Hydrogels offer tissue-like softness,stretchability,fracture toughness,ionic conductivity,and compatibility with biological tissues,which make them promising candidates for fabricating flexible bioelectronics.A soft h...Hydrogels offer tissue-like softness,stretchability,fracture toughness,ionic conductivity,and compatibility with biological tissues,which make them promising candidates for fabricating flexible bioelectronics.A soft hydrogel film offers an ideal interface to directly bridge thin-film electronics with the soft tissues.However,it remains difficult to fabricate a soft hydrogel film with an ultrathin configuration and excellent mechanical strength.Here we report a biological tissue-inspired ultrasoft microfiber composite ultrathin(<5μm)hydrogel film,which is currently the thinnest hydrogel film as far as we know.The embedded microfibers endow the composite hydrogel with prominent mechanical strength(tensile stress~6 MPa)and anti-tearing property.Moreover,our microfiber composite hydrogel offers the capability of tunable mechanical properties in a broad range,allowing for matching the modulus of most biological tissues and organs.The incorporation of glycerol and salt ions imparts the microfiber composite hydrogel with high ionic conductivity and prominent anti-dehydration behavior.Such microfiber composite hydrogels are promising for constructing attaching-type flexible bioelectronics to monitor biosignals.展开更多
Advances in antibody engineering have led to the generation of more innovative antibody drugs,such as bispecific antibodies(bs Abs).Following the success associated with blinatumomab,bs Abs have attracted enormous int...Advances in antibody engineering have led to the generation of more innovative antibody drugs,such as bispecific antibodies(bs Abs).Following the success associated with blinatumomab,bs Abs have attracted enormous interest in the field of cancer immunotherapy.By specifically targeting two different antigens,bs Abs reduce the distance between tumor and immune cells,thereby enhancing tumor killing directly.There are several mechanisms of action upon which bs Abs have been exploited.Accumulating experience on checkpoint-based therapy has promoted the clinical transformation of bs Abs targeting immunomodulatory checkpoints.Cadonilimab(PD-1×CTLA-4)is the first approved bs Ab targeting dual inhibitory checkpoints,which confirms the feasibility of bs Abs in immunotherapy.In this review we analyzed the mechanisms by which bs Abs targeting immunomodulatory checkpoints and their emerging applications in cancer immunotherapy.展开更多
In this study,an X-band standing-wave biperiodic linear accelerator was developed for medical radiotherapy that can accel-erate electrons to 9 MeV using a 2.4-MW klystron.The structure works atπ/2 mode and adopts mag...In this study,an X-band standing-wave biperiodic linear accelerator was developed for medical radiotherapy that can accel-erate electrons to 9 MeV using a 2.4-MW klystron.The structure works atπ/2 mode and adopts magnetic coupling between cavities,generating the appropriate adjacent mode separation of 10 MHz.The accelerator is less than 600-mm long and constitutes four bunching cells and 29 normal cells.Geometry optimizations,full-scale radiofrequency(RF)simulations,and beam dynamics calculations were performed.The accelerator was fabricated and examined using a low-power RF test.The cold test results showed a good agreement with the simulation and actual measurement results.In the high-power RF test,the output beam current,energy spectrum,capture ratio,and spot size at the accelerator exit were measured.With the input power of 2.4 MW,the pulse current was 100 mA,and the output spot root-mean-square radius was approximately 0.5 mm.The output kinetic energy was 9.04 MeV with the spectral FWHM of 3.5%,demonstrating the good performance of this accelerator.展开更多
BACKGROUND In the translational therapy of giant hepatocellular carcinoma(HCC),hepatic arterial infusion chemotherapy(HAIC)combined with anti-PD-1 immunotherapy and tyrosine kinase inhibitors(TKI)after laparoscopic po...BACKGROUND In the translational therapy of giant hepatocellular carcinoma(HCC),hepatic arterial infusion chemotherapy(HAIC)combined with anti-PD-1 immunotherapy and tyrosine kinase inhibitors(TKI)after laparoscopic portal vein ligation(PVL)is extremely rare.This is a dual conversion therapy that combines surgery and oncology.Here,we report two cases of successful surgical completion after dual conversion therapy.CASE SUMMARY We report that a 54-year-old man and a 69-year-old woman were diagnosed with primary HCC combined with hepatitis B cirrhosis(case 2 also combined with fatty liver)on physical examination.Due to the insufficient residual liver volume assessed before surgery,laparoscopic right PVL was performed,followed by HAIC combined with anti-PD-1 immunotherapy and TKI.Finally,surgical resection was successfully completed,and pathology confirmed that the tumor was mostly necrotic(90%)in one case,and no live tumor tissue was found in the other case.CONCLUSION In the process of surgical transformation,our treatment plan takes into account the control and transformation of oncology at the same time,which is expected to provide more opportunities for radical hepatectomy and improve the prognosis of patients with large liver cancer.展开更多
[Objectives]To determine the optimal reflux extraction process conditions for Compound Coptis Ointment.[Methods]The study employed the orthogonal experimental design method and drug-sensitive disc agar diffusion metho...[Objectives]To determine the optimal reflux extraction process conditions for Compound Coptis Ointment.[Methods]The study employed the orthogonal experimental design method and drug-sensitive disc agar diffusion method to evaluate the extraction rate,berberine hydrochloride content,and bacteriostatic ring diameter of the extract as comprehensive indices,and optimized the extraction process conditions of Compound Coptis Ointment using ethanol reflux.[Results]Based on the results of comprehensive indices,the optimal reflux extraction conditions for Compound Coptis Ointment were determined to be soaking in 1.5 times the amount of 70%ethanol for 2 h,followed by two extractions with 6 times the amount of 70%ethanol for 1 h each time.Three verification tests were conducted under the optimal process conditions.The yield of the extract was 28.32%±0.53%,the content of berberine hydrochloride was 4.68%±0.45%,and the diameter of the bacteriostatic ring was(2.5±0.2)cm.[Conclusions]The extract had higher drug content and exhibited better antibacterial effects.The optimized extraction process is simple,stable,and reliable,and can be effectively used to optimize the extraction process of Compound Coptis Ointment.展开更多
Cerebral ischemic injury is the main manifestation of stroke,and its incidence in stroke patients is 70–80%.Although ischemic stroke can be treated with tissue-type plasminogen activator,its time window of effectiven...Cerebral ischemic injury is the main manifestation of stroke,and its incidence in stroke patients is 70–80%.Although ischemic stroke can be treated with tissue-type plasminogen activator,its time window of effectiveness is narrow.Therefore,the incidence of paralysis,hypoesthesia,aphasia,dysphagia,and cognitive impairment caused by cerebral ischemia is high.Nerve tissue regeneration can promote the recovery of the aforementioned dysfunction.Neural stem cells can participate in the reconstruction of the damaged nervous system and promote the recovery of nervous function during self-repair of damaged brain tissue.Neural stem cell transplantation for ischemic stroke has been a hot topic for more than 10 years.This review discusses the treatment of ischemic stroke with neural stem cells,as well as the mechanisms of their involvement in stroke treatment.展开更多
Transcranial magnetic stimulation,a type of noninvasive brain stimulation,has become an ancillary therapy for motor function rehabilitation.Most previous studies have focused on the effects of repetitive transcranial ...Transcranial magnetic stimulation,a type of noninvasive brain stimulation,has become an ancillary therapy for motor function rehabilitation.Most previous studies have focused on the effects of repetitive transcranial magnetic stimulation(rTMS)on motor function in stroke patients.There have been relatively few studies on the effects of different modalities of rTMS on lower extremity motor function and corticospinal excitability in patients with stroke.The MEDLINE,Embase,Cochrane Library,ISI Science Citation Index,Physiotherapy Evidence Database,China National Knowledge Infrastructure Library,and ClinicalTrials.gov databases were searched.Parallel or crossover randomized controlled trials that addressed the effectiveness of rTMS in patients with stroke,published from inception to November 28,2019,were included.Standard pairwise meta-analysis was conducted using R version 3.6.1 with the“meta”package.Bayesian network analysis using the Markov chain Monte Carlo algorithm was conducted to investigate the effectiveness of different rTMS protocol interventions.Network meta-analysis results of 18 randomized controlled trials regarding lower extremity motor function recovery revealed that low-frequency rTMS had better efficacy in promoting lower extremity motor function recovery than sham stimulation.Network meta-analysis results of five randomized controlled trials demonstrated that highfrequency rTMS led to higher amplitudes of motor evoked potentials than low-frequency rTMS or sham stimulation.These findings suggest that rTMS can improve motor function in patients with stroke,and that low-frequency rTMS mainly affects motor function,whereas high-frequency rTMS increases the amplitudes of motor evoked potentials.More highquality randomized controlled trials are needed to validate this conclusion.The work was registered in PROSPERO(registration No.CRD42020147055)on April 28,2020.展开更多
AIM:To present computed tomography(CT) findings of different histological subtypes of parotid gland masses in detail and to establish diagnostic strategy.METHODS:From January 2009 to November 2011,56 patients were col...AIM:To present computed tomography(CT) findings of different histological subtypes of parotid gland masses in detail and to establish diagnostic strategy.METHODS:From January 2009 to November 2011,56 patients were collected through the histopathology and Picture Archiving and Communication Systems records,which revealed 5 basal cell adenoma(BCA),16 pleomorphic adenoma(PA),25 Warthin's tumor(War-T),3 Kimura's disease(KD) and 7 parotid carcinoma(PCa) cases.All the CT images were retrospectively analyzed by two radiologists in consensus,based on their description of morphology(location,number,size,margin and fibrous capsule) and enhancement patterns of masses.In addition,the diagnostic efficiency of diagnostic strategy is tested.RESULTS:War-T and BCA patients' mean age was 59.9 ± 12.6 years and 58.4 ± 18.2 years;the significant difference was seen in War-T vs PA and BCA vs PA.About 40% of War-Ts presented with bilateral multifocal lesions,a higher ratio than others.Seventy two percent of War-Ts were limited to the superficial lobe,followed by BCA 60% and PA 40%.Vessel facing sign and enlarged lymph nodes were both frequent in War-T,which respectively accounts for 84% and 76% of cases.Rapid contrast enhancement and decreases were unique for War-T.BCA and PA showed obvious delayed enhancement.The diagnostic strategy of parotid gland tumor had a good diagnostic efficiency,with high accuracy,sensitivity and specificity.CONCLUSION:Determination of the histological subtypes of parotid gland masses might be possible based on CT findings and clinical data.A diagnostic strategy with high diagnostic efficiency was established.展开更多
AIM:To investigate the impact of different anesthetic techniques on T-helper(Th) cell subsets in hepatocellular carcinoma(HCC) patients undergoing hepatectomy.METHODS:Sixty-one HCC patients who received hepatectomies ...AIM:To investigate the impact of different anesthetic techniques on T-helper(Th) cell subsets in hepatocellular carcinoma(HCC) patients undergoing hepatectomy.METHODS:Sixty-one HCC patients who received hepatectomies were randomized into an epidural combined general anesthesia(G + E;n = 31) or a general anesthesia(G;n = 30) group.Blood samples were obtained the morning before the operation(d0),and on the second(d2) and seventh(d7) day after the operation.Th cell contents were evaluated using flow cytometry,realtime reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay.RESULTS:In all 61 patients,Th1 and Th2 cell frequencies,and interferon-(IFN-) mRNA expression markedly increased on d2,compared to d0.They recovered slightly on d7,and the Th1/Th2 ratio increased markedly on d7,compared with d2.In contrast,Th17,regulatory T cell(Treg),and interleukin-17(IL-17) levels and FOXP3 mRNA expression showed no significant change on d2,and then markedly decreased on d7.Similarly,plasma IFN-concentration on d2 was much higher than that on d0,and then partly recovered on d7.As compared with the G group,in the G + E group,Th1 cell frequencies and the Th1/Th2 ratio were slightly higher on d2 and significantly higher on d7,while Th2,Th17,and Treg cell frequencies were slightly lower on d2,and significantly lower on d7.Consistently,on d7,IFN-mRNA and protein levels and the IFN-/IL-4 ratio in the G + E group were higher than those in the G group.In contrast,the IL-17 mRNA level,and IL-17 and transforming growth factor-1 concentrations in the G + E group were lower than those in the G group.CONCLUSION:G + E is superior to G in shifting the Th1/Th2 balance towards Th1,while decreasing Th17 and Treg,potentially benefiting HCC patients by promoting anti-tumor Th polarization.展开更多
A large number of studies have demonstrated that depression patients have cognitive dysfunction. With recently developed brain functional imaging, studies have focused on changes in brain function to investigate cogni...A large number of studies have demonstrated that depression patients have cognitive dysfunction. With recently developed brain functional imaging, studies have focused on changes in brain function to investigate cognitive changes. However, there is still controversy regarding abnormalities in brain functions or correlation between cognitive impairment and brain function changes. Thus, it is important to design an emotion-related task for research into brain function changes. We selected positive, neutral, and negative pictures from the International Affective Picture System. Patients with major depressive disorder were asked to judge emotion pictures. In addition, functional MRI was performed to synchronously record behavior data and imaging data. Results showed that the total correct rate for recognizing pictures was lower in patients compared with normal controls. Moreover, the consistency for recognizing pictures for depressed patients was worse than normal controls, and they frequently recognized positive pictures as negative pictures. The consistency for recognizing pictures was negatively correlated with the Hamilton Depression Rating Scale. Functional MRI suggested that the activation of some areas in the frontal lobe, temporal lobe, parietal lobe, limbic lobe, and cerebellum was enhanced, but that the activation of some areas in the frontal lobe, parietal lobe and occipital lobe was weakened while the patients were watching positive and neutral pictures compared with normal controls. The activation of some areas in the frontal lobe, temporal lobe, parietal lobe, and limbic lobe was enhanced, but the activation of some areas in the occipital lobe were weakened while the patients were watching the negative pictures compared with normal controls. These findings indicate that patients with major depressive disorder have negative cognitive disorder and extensive brain dysfunction. Thus, reduced activation of the occipital lobe may be an initiating factor for cognitive disorder in depressed patients.展开更多
BACKGROUND The treatment of difficult common bile duct stones(CBDS)remains a big challenge around the world.Biliary stenting is a widely accepted rescue method in patients with failed stone extraction under endoscopic...BACKGROUND The treatment of difficult common bile duct stones(CBDS)remains a big challenge around the world.Biliary stenting is a widely accepted rescue method in patients with failed stone extraction under endoscopic retrograde cholangiopancreatography.Fully covered self-expanding metal stent(FCSEMS)has gained increasing attention in the management of difficult CBDS.AIM To manufacture a drug-eluting FCSEMS,which can achieve controlled release of stone-dissolving agents and speed up the dissolution of CBDS.METHODS Customized covered nitinol stents were adopted.Sodium cholate(SC)and disodium ethylene diamine tetraacetic acid(EDTA disodium,EDTA for short)were used as stone-dissolving agents.Three different types of drug-eluting stents were manufactured by dip coating(Stent I),coaxial electrospinning(Stent II),and dip coating combined with electrospinning(Stent III),respectively.The drugrelease behavior and stone-dissolving efficacy of these stents were evaluated in vitro to sort out the best manufacturing method.And the selected stonedissolving stents were further put into porcine CBD to evaluate their biosecurity.RESULTS Stent I and Stent II had obvious burst release of drugs in the first 5 d while Stent III presented controlled and sustainable drug release for 30 d.In still buffer,the final stone mass-loss rate of each group was 5.19%±0.69%for naked FCSEMS,20.37%±2.13%for Stent I,24.57%±1.45%for Stent II,and 33.72%±0.67%for Stent III.In flowing bile,the final stone mass-loss rate of each group was 5.87%±0.25%for naked FCSEMS,6.36%±0.48%for Stent I,6.38%±0.37%for Stent II,and 8.15%±0.27%for Stent III.Stent III caused the most stone mass-loss no matter in still buffer or in flowing bile,which was significantly higher than those of other groups(P<0.05).In vivo,Stent III made no difference from naked FCSEMS in serological analysis(P>0.05)and histopathological examination(P>0.05).CONCLUSION The novel SC and EDTA-eluting FCSEMS is efficient in diminishing CBDS in vitro.When conventional endoscopic techniques fail to remove difficult CBDS,SC and EDTA-eluting FCSEMS implantation may be considered a promising alternative.展开更多
Background: N6-Methyladenosine(m^6A), the most prevalent modification in mammalian m RNA, plays important roles in numerous biological processes. Several m^6A associated proteins such as methyltransferase like 3(METTL...Background: N6-Methyladenosine(m^6A), the most prevalent modification in mammalian m RNA, plays important roles in numerous biological processes. Several m^6A associated proteins such as methyltransferase like 3(METTL3),methyltransferase like 14(METTL14), α-ketoglutarate-dependent dioxygenase Alk B homolog 5(ALKBH5) and YTH domain containing 2(YTHDC2) are involved in the regulation of spermatogenesis and oogenesis. However, the role of the first detected m^6A demethylase, fat mass and obesity associate protein(FTO), in germ cells remains elusive.Elucidation of FTO roles in the regulation of germ cell fate will provide novel insights into the mammalian reproduction.Methods: Mouse GC-1 spg cells were treated with the ester form of meclofenamic acid(MA2) to inhibit the demethylase activity of FTO. The cellular m^6A and m^6Amlevel were analyzed through high performance liquid chromatography combined with tandem mass spectrometry(HPLC/MS-MS). The cell apoptosis was detected via TUNEL and flow cytometry. The cell proliferation was detected through Ed U and western blot. The m RNA level of core cyclin dependent kinases(CDKs) was quantified via q-PCR. RNA decay assay were performed to detect RNA stability. Dual fluorescence assay was conducted to study whether MA2 affects the expression of CDK2 dependent on the m^6A modification at 3’UTR.Results: MA2 significantly increased the cellular m^6A level and down-regulated the expression of CDK1, CDK2, CDK6 and Cd C25 a, resulting in arrest of G1/S transition and decrease of cell proliferation. MA2 downregulated CDK2 m RNA stability. Additionally, mutation of the predicted m^6A sites in the Cdk2–3’UTR could mitigated the degradation of CDK2 m RNA after MA2 treatment.Conclusion: MA2 affected CDKs expression through the m^6A-dependent m RNA degradation pathway, and thus repressed spermatogonial proliferation.展开更多
AIM: To identify an appropriate therapeutic regimen for using aconite cake-separated moxibustion to treat diarrhea-predominant irritable bowel syndrome(D-IBS).METHODS: A factorial design was employed to examine the tw...AIM: To identify an appropriate therapeutic regimen for using aconite cake-separated moxibustion to treat diarrhea-predominant irritable bowel syndrome(D-IBS).METHODS: A factorial design was employed to examine the two factors of moxibustion frequency and number of cones. The two tested frequencies were three or six moxibustion sessions per week, and the two tested doses were one or two cones per treatment. A total of 166 D-IBS patients were randomly divided into four treatment groups, which included each combination of the examined frequencies and doses. The bilateral Tianshu acupoints(ST25) and the Qihai acupoint(RN6) were selected for aconite cake-separated moxibustion. Each patient received two courses of treatment, and each course had a duration of 2 wk. For each group, the scores on the Birmingham irritable bowel syndrome(IBS) symptom questionnaire, the IBS Quality of Life scale, the Self-Rating Depression Scale(SDS), the Self-Rating Anxiety Scale(SAS), the Hamilton Depression(HAMD) scale, and the Hamilton Anxiety(HAMA) scale were determined before treatment, after the first course of treatment, and after the second course of treatment. RESULTS: The symptom, quality of life, SDS, SAS, HAMD, and HAMA scores of the patients in all 4 aconite cake-separated moxibustion groups were significantly lower after the first and second courses of treatment than before treatment(P < 0.001 for all). The symptom, quality of life, SDS, SAS, HAMD, and HAMA scores of the patients in all four aconite cake-separated moxibustion groups were significantly lower after the second course of treatment than after the first course of treatment(P < 0.001 for all). Between-group comparisons after the second course of treatment revealed that the symptom scores for group 1(1 cone, 3 treatments/wk) and group 3(2 cones, 3 treatments/wk) were significantly lower than that for group 2(1 cone, 6 treatments/wk)(5.55 ± 5.05 vs 10.45 ± 6.61, P < 0.001; 5.65 ± 4.00 vs 10.45 ± 6.61, P < 0.001). Regarding the two levels of the two examined factors for aconite cake-separated moxibustion, after the first course of treatment, the changes in HAMA scores weresignificantly different for the two tested moxibustion frequencies(P = 0.011), with greater changes for the "6 treatments/wk" groups than for the "3 treatments/wk" groups; in addition, there were interaction effects between the number of cones and moxibustion frequency(P = 0.028). After the second course of treatment, changes in symptom scores for the 2 tested moxibustion frequencies were significantly different(P = 0.002), with greater changes for the "3 treatments/wk" groups than for the "6 treatments/wk" groups.CONCLUSION: An aconite cake-separated moxibustion treatment regimen of 3 treatments/wk and 1 cone/treatment appears to produce better therapeutic effects for D-IBS compared with the other tested regimens.展开更多
Extremely low frequency electromagnetic fields(ELF-EMF) can improve the learning and memory impairment of rats with Alzheimer's disease, however, its effect on cerebral ischemia remains poorly understood.In this s...Extremely low frequency electromagnetic fields(ELF-EMF) can improve the learning and memory impairment of rats with Alzheimer's disease, however, its effect on cerebral ischemia remains poorly understood.In this study, we established rat models of middle cerebral artery occlusion/reperfusion.One day after modeling, a group of rats were treated with ELF-EMF(50 Hz, 1 mT) for 2 hours daily on 28 successive days.Our results showed that rats treated with ELF-EMF required shorter swimming distances and latencies in the Morris water maze test than those of untreated rats.The number of times the platform was crossed and the time spent in the target quadrant were greater than those of untreated rats.The number of BrdU~+/NeuN~+ cells, representing newly born neurons, in the hippocampal subgranular zone increased more in the treated than in untreated rats.Up-regulation in the expressions of Notch1, Hes1, and Hes5 proteins, which are the key factors of the Notch signaling pathway, was greatest in the treated rats.These findings suggest that ELF-EMF can enhance hippocampal neurogenesis of rats with cerebral ischemia, possibly by affecting the Notch signaling pathway.The study was approved by the Institutional Ethics Committee of Sichuan University, China(approval No.2019255A) on March 5, 2019.展开更多
基金supported by the National Natural Science Foundation of China(Nos.52071069,U1332110)the Liaoning Revitalization Talents Program,China(No.XLYC1902097)。
基金the funding support from the fellowship of the China Postdoctoral Science Foundation (2022M722329, 2021M700097)the National Natural Science Foundation for Distinguished Young Scholars of China (62125112)+2 种基金the National Natural Science Foundation of China (62071462, 62071463, 62271479, 22109173)the Jiangxi Provincial Natural Science Foundation (20224ACB212001)the support from Nano-X Vacuum Interconnected Workstation&Key Laboratory of Multifunctional Nanomaterials and Smart Systems of Suzhou Institute of Nano-Tech and Nano-Bionics (SINANO),Chinese Academy of Sciences (CAS)
文摘Hydrogels offer tissue-like softness,stretchability,fracture toughness,ionic conductivity,and compatibility with biological tissues,which make them promising candidates for fabricating flexible bioelectronics.A soft hydrogel film offers an ideal interface to directly bridge thin-film electronics with the soft tissues.However,it remains difficult to fabricate a soft hydrogel film with an ultrathin configuration and excellent mechanical strength.Here we report a biological tissue-inspired ultrasoft microfiber composite ultrathin(<5μm)hydrogel film,which is currently the thinnest hydrogel film as far as we know.The embedded microfibers endow the composite hydrogel with prominent mechanical strength(tensile stress~6 MPa)and anti-tearing property.Moreover,our microfiber composite hydrogel offers the capability of tunable mechanical properties in a broad range,allowing for matching the modulus of most biological tissues and organs.The incorporation of glycerol and salt ions imparts the microfiber composite hydrogel with high ionic conductivity and prominent anti-dehydration behavior.Such microfiber composite hydrogels are promising for constructing attaching-type flexible bioelectronics to monitor biosignals.
基金supported by the National Natural Science Foundation of China(Grant Nos.82130077 and 81961128025)。
文摘Advances in antibody engineering have led to the generation of more innovative antibody drugs,such as bispecific antibodies(bs Abs).Following the success associated with blinatumomab,bs Abs have attracted enormous interest in the field of cancer immunotherapy.By specifically targeting two different antigens,bs Abs reduce the distance between tumor and immune cells,thereby enhancing tumor killing directly.There are several mechanisms of action upon which bs Abs have been exploited.Accumulating experience on checkpoint-based therapy has promoted the clinical transformation of bs Abs targeting immunomodulatory checkpoints.Cadonilimab(PD-1×CTLA-4)is the first approved bs Ab targeting dual inhibitory checkpoints,which confirms the feasibility of bs Abs in immunotherapy.In this review we analyzed the mechanisms by which bs Abs targeting immunomodulatory checkpoints and their emerging applications in cancer immunotherapy.
基金the Key R&D Project of the Ministry of Science and Technology of China(No.2022YFC2402300).
文摘In this study,an X-band standing-wave biperiodic linear accelerator was developed for medical radiotherapy that can accel-erate electrons to 9 MeV using a 2.4-MW klystron.The structure works atπ/2 mode and adopts magnetic coupling between cavities,generating the appropriate adjacent mode separation of 10 MHz.The accelerator is less than 600-mm long and constitutes four bunching cells and 29 normal cells.Geometry optimizations,full-scale radiofrequency(RF)simulations,and beam dynamics calculations were performed.The accelerator was fabricated and examined using a low-power RF test.The cold test results showed a good agreement with the simulation and actual measurement results.In the high-power RF test,the output beam current,energy spectrum,capture ratio,and spot size at the accelerator exit were measured.With the input power of 2.4 MW,the pulse current was 100 mA,and the output spot root-mean-square radius was approximately 0.5 mm.The output kinetic energy was 9.04 MeV with the spectral FWHM of 3.5%,demonstrating the good performance of this accelerator.
文摘BACKGROUND In the translational therapy of giant hepatocellular carcinoma(HCC),hepatic arterial infusion chemotherapy(HAIC)combined with anti-PD-1 immunotherapy and tyrosine kinase inhibitors(TKI)after laparoscopic portal vein ligation(PVL)is extremely rare.This is a dual conversion therapy that combines surgery and oncology.Here,we report two cases of successful surgical completion after dual conversion therapy.CASE SUMMARY We report that a 54-year-old man and a 69-year-old woman were diagnosed with primary HCC combined with hepatitis B cirrhosis(case 2 also combined with fatty liver)on physical examination.Due to the insufficient residual liver volume assessed before surgery,laparoscopic right PVL was performed,followed by HAIC combined with anti-PD-1 immunotherapy and TKI.Finally,surgical resection was successfully completed,and pathology confirmed that the tumor was mostly necrotic(90%)in one case,and no live tumor tissue was found in the other case.CONCLUSION In the process of surgical transformation,our treatment plan takes into account the control and transformation of oncology at the same time,which is expected to provide more opportunities for radical hepatectomy and improve the prognosis of patients with large liver cancer.
基金Supported by Key Research Project of Wuhan Municipal Health Commission(WZ21A08).
文摘[Objectives]To determine the optimal reflux extraction process conditions for Compound Coptis Ointment.[Methods]The study employed the orthogonal experimental design method and drug-sensitive disc agar diffusion method to evaluate the extraction rate,berberine hydrochloride content,and bacteriostatic ring diameter of the extract as comprehensive indices,and optimized the extraction process conditions of Compound Coptis Ointment using ethanol reflux.[Results]Based on the results of comprehensive indices,the optimal reflux extraction conditions for Compound Coptis Ointment were determined to be soaking in 1.5 times the amount of 70%ethanol for 2 h,followed by two extractions with 6 times the amount of 70%ethanol for 1 h each time.Three verification tests were conducted under the optimal process conditions.The yield of the extract was 28.32%±0.53%,the content of berberine hydrochloride was 4.68%±0.45%,and the diameter of the bacteriostatic ring was(2.5±0.2)cm.[Conclusions]The extract had higher drug content and exhibited better antibacterial effects.The optimized extraction process is simple,stable,and reliable,and can be effectively used to optimize the extraction process of Compound Coptis Ointment.
基金supported by the National Natural Science Foundation of China,No.0040205401797(to QG)the General Research Fund of China,No.15164216(to BWML)
文摘Cerebral ischemic injury is the main manifestation of stroke,and its incidence in stroke patients is 70–80%.Although ischemic stroke can be treated with tissue-type plasminogen activator,its time window of effectiveness is narrow.Therefore,the incidence of paralysis,hypoesthesia,aphasia,dysphagia,and cognitive impairment caused by cerebral ischemia is high.Nerve tissue regeneration can promote the recovery of the aforementioned dysfunction.Neural stem cells can participate in the reconstruction of the damaged nervous system and promote the recovery of nervous function during self-repair of damaged brain tissue.Neural stem cell transplantation for ischemic stroke has been a hot topic for more than 10 years.This review discusses the treatment of ischemic stroke with neural stem cells,as well as the mechanisms of their involvement in stroke treatment.
基金supported by the 1·3·5 project for disciplines of excellence-Clinical Research Incubation Project,West China Hospital,Sichuan University,China,No.2020HXFH051(to QG).
文摘Transcranial magnetic stimulation,a type of noninvasive brain stimulation,has become an ancillary therapy for motor function rehabilitation.Most previous studies have focused on the effects of repetitive transcranial magnetic stimulation(rTMS)on motor function in stroke patients.There have been relatively few studies on the effects of different modalities of rTMS on lower extremity motor function and corticospinal excitability in patients with stroke.The MEDLINE,Embase,Cochrane Library,ISI Science Citation Index,Physiotherapy Evidence Database,China National Knowledge Infrastructure Library,and ClinicalTrials.gov databases were searched.Parallel or crossover randomized controlled trials that addressed the effectiveness of rTMS in patients with stroke,published from inception to November 28,2019,were included.Standard pairwise meta-analysis was conducted using R version 3.6.1 with the“meta”package.Bayesian network analysis using the Markov chain Monte Carlo algorithm was conducted to investigate the effectiveness of different rTMS protocol interventions.Network meta-analysis results of 18 randomized controlled trials regarding lower extremity motor function recovery revealed that low-frequency rTMS had better efficacy in promoting lower extremity motor function recovery than sham stimulation.Network meta-analysis results of five randomized controlled trials demonstrated that highfrequency rTMS led to higher amplitudes of motor evoked potentials than low-frequency rTMS or sham stimulation.These findings suggest that rTMS can improve motor function in patients with stroke,and that low-frequency rTMS mainly affects motor function,whereas high-frequency rTMS increases the amplitudes of motor evoked potentials.More highquality randomized controlled trials are needed to validate this conclusion.The work was registered in PROSPERO(registration No.CRD42020147055)on April 28,2020.
文摘AIM:To present computed tomography(CT) findings of different histological subtypes of parotid gland masses in detail and to establish diagnostic strategy.METHODS:From January 2009 to November 2011,56 patients were collected through the histopathology and Picture Archiving and Communication Systems records,which revealed 5 basal cell adenoma(BCA),16 pleomorphic adenoma(PA),25 Warthin's tumor(War-T),3 Kimura's disease(KD) and 7 parotid carcinoma(PCa) cases.All the CT images were retrospectively analyzed by two radiologists in consensus,based on their description of morphology(location,number,size,margin and fibrous capsule) and enhancement patterns of masses.In addition,the diagnostic efficiency of diagnostic strategy is tested.RESULTS:War-T and BCA patients' mean age was 59.9 ± 12.6 years and 58.4 ± 18.2 years;the significant difference was seen in War-T vs PA and BCA vs PA.About 40% of War-Ts presented with bilateral multifocal lesions,a higher ratio than others.Seventy two percent of War-Ts were limited to the superficial lobe,followed by BCA 60% and PA 40%.Vessel facing sign and enlarged lymph nodes were both frequent in War-T,which respectively accounts for 84% and 76% of cases.Rapid contrast enhancement and decreases were unique for War-T.BCA and PA showed obvious delayed enhancement.The diagnostic strategy of parotid gland tumor had a good diagnostic efficiency,with high accuracy,sensitivity and specificity.CONCLUSION:Determination of the histological subtypes of parotid gland masses might be possible based on CT findings and clinical data.A diagnostic strategy with high diagnostic efficiency was established.
基金supported by the National Natural Science Foundation of China (Nos. 51871012, 52071021)Beijing Natural Science Foundation (No. 2162024)+1 种基金Fundamental Research Funds for the Central Universities, China (No. FRF-GF-20-20B)the National Key Basic Research Program of China (No. 2011CB605502)。
基金Supported by The State 863 High Technology R and D Project of China,No.2007AA02Z479National Natural Science Foundation of China,No.30972949+3 种基金Shanghai Rising-Star Program, No.10QA1401300FANEDD,No.201183Science and Technology Commission of Shanghai Municipality,No.114119a4400Shanghai "Chen Guang" Project,No.11CG02
文摘AIM:To investigate the impact of different anesthetic techniques on T-helper(Th) cell subsets in hepatocellular carcinoma(HCC) patients undergoing hepatectomy.METHODS:Sixty-one HCC patients who received hepatectomies were randomized into an epidural combined general anesthesia(G + E;n = 31) or a general anesthesia(G;n = 30) group.Blood samples were obtained the morning before the operation(d0),and on the second(d2) and seventh(d7) day after the operation.Th cell contents were evaluated using flow cytometry,realtime reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay.RESULTS:In all 61 patients,Th1 and Th2 cell frequencies,and interferon-(IFN-) mRNA expression markedly increased on d2,compared to d0.They recovered slightly on d7,and the Th1/Th2 ratio increased markedly on d7,compared with d2.In contrast,Th17,regulatory T cell(Treg),and interleukin-17(IL-17) levels and FOXP3 mRNA expression showed no significant change on d2,and then markedly decreased on d7.Similarly,plasma IFN-concentration on d2 was much higher than that on d0,and then partly recovered on d7.As compared with the G group,in the G + E group,Th1 cell frequencies and the Th1/Th2 ratio were slightly higher on d2 and significantly higher on d7,while Th2,Th17,and Treg cell frequencies were slightly lower on d2,and significantly lower on d7.Consistently,on d7,IFN-mRNA and protein levels and the IFN-/IL-4 ratio in the G + E group were higher than those in the G group.In contrast,the IL-17 mRNA level,and IL-17 and transforming growth factor-1 concentrations in the G + E group were lower than those in the G group.CONCLUSION:G + E is superior to G in shifting the Th1/Th2 balance towards Th1,while decreasing Th17 and Treg,potentially benefiting HCC patients by promoting anti-tumor Th polarization.
基金supported by the National Natural Science Foundation of China,No.30971054,30770770,81171290
文摘A large number of studies have demonstrated that depression patients have cognitive dysfunction. With recently developed brain functional imaging, studies have focused on changes in brain function to investigate cognitive changes. However, there is still controversy regarding abnormalities in brain functions or correlation between cognitive impairment and brain function changes. Thus, it is important to design an emotion-related task for research into brain function changes. We selected positive, neutral, and negative pictures from the International Affective Picture System. Patients with major depressive disorder were asked to judge emotion pictures. In addition, functional MRI was performed to synchronously record behavior data and imaging data. Results showed that the total correct rate for recognizing pictures was lower in patients compared with normal controls. Moreover, the consistency for recognizing pictures for depressed patients was worse than normal controls, and they frequently recognized positive pictures as negative pictures. The consistency for recognizing pictures was negatively correlated with the Hamilton Depression Rating Scale. Functional MRI suggested that the activation of some areas in the frontal lobe, temporal lobe, parietal lobe, limbic lobe, and cerebellum was enhanced, but that the activation of some areas in the frontal lobe, parietal lobe and occipital lobe was weakened while the patients were watching positive and neutral pictures compared with normal controls. The activation of some areas in the frontal lobe, temporal lobe, parietal lobe, and limbic lobe was enhanced, but the activation of some areas in the occipital lobe were weakened while the patients were watching the negative pictures compared with normal controls. These findings indicate that patients with major depressive disorder have negative cognitive disorder and extensive brain dysfunction. Thus, reduced activation of the occipital lobe may be an initiating factor for cognitive disorder in depressed patients.
基金the National Natural Science Foundation of China,No.81470904and Shanghai Committee of Science and Technology,No.14411963000
文摘BACKGROUND The treatment of difficult common bile duct stones(CBDS)remains a big challenge around the world.Biliary stenting is a widely accepted rescue method in patients with failed stone extraction under endoscopic retrograde cholangiopancreatography.Fully covered self-expanding metal stent(FCSEMS)has gained increasing attention in the management of difficult CBDS.AIM To manufacture a drug-eluting FCSEMS,which can achieve controlled release of stone-dissolving agents and speed up the dissolution of CBDS.METHODS Customized covered nitinol stents were adopted.Sodium cholate(SC)and disodium ethylene diamine tetraacetic acid(EDTA disodium,EDTA for short)were used as stone-dissolving agents.Three different types of drug-eluting stents were manufactured by dip coating(Stent I),coaxial electrospinning(Stent II),and dip coating combined with electrospinning(Stent III),respectively.The drugrelease behavior and stone-dissolving efficacy of these stents were evaluated in vitro to sort out the best manufacturing method.And the selected stonedissolving stents were further put into porcine CBD to evaluate their biosecurity.RESULTS Stent I and Stent II had obvious burst release of drugs in the first 5 d while Stent III presented controlled and sustainable drug release for 30 d.In still buffer,the final stone mass-loss rate of each group was 5.19%±0.69%for naked FCSEMS,20.37%±2.13%for Stent I,24.57%±1.45%for Stent II,and 33.72%±0.67%for Stent III.In flowing bile,the final stone mass-loss rate of each group was 5.87%±0.25%for naked FCSEMS,6.36%±0.48%for Stent I,6.38%±0.37%for Stent II,and 8.15%±0.27%for Stent III.Stent III caused the most stone mass-loss no matter in still buffer or in flowing bile,which was significantly higher than those of other groups(P<0.05).In vivo,Stent III made no difference from naked FCSEMS in serological analysis(P>0.05)and histopathological examination(P>0.05).CONCLUSION The novel SC and EDTA-eluting FCSEMS is efficient in diminishing CBDS in vitro.When conventional endoscopic techniques fail to remove difficult CBDS,SC and EDTA-eluting FCSEMS implantation may be considered a promising alternative.
基金supported in part by the National Natural Science Foundation of China(Grant No.31572401)to WZ
文摘Background: N6-Methyladenosine(m^6A), the most prevalent modification in mammalian m RNA, plays important roles in numerous biological processes. Several m^6A associated proteins such as methyltransferase like 3(METTL3),methyltransferase like 14(METTL14), α-ketoglutarate-dependent dioxygenase Alk B homolog 5(ALKBH5) and YTH domain containing 2(YTHDC2) are involved in the regulation of spermatogenesis and oogenesis. However, the role of the first detected m^6A demethylase, fat mass and obesity associate protein(FTO), in germ cells remains elusive.Elucidation of FTO roles in the regulation of germ cell fate will provide novel insights into the mammalian reproduction.Methods: Mouse GC-1 spg cells were treated with the ester form of meclofenamic acid(MA2) to inhibit the demethylase activity of FTO. The cellular m^6A and m^6Amlevel were analyzed through high performance liquid chromatography combined with tandem mass spectrometry(HPLC/MS-MS). The cell apoptosis was detected via TUNEL and flow cytometry. The cell proliferation was detected through Ed U and western blot. The m RNA level of core cyclin dependent kinases(CDKs) was quantified via q-PCR. RNA decay assay were performed to detect RNA stability. Dual fluorescence assay was conducted to study whether MA2 affects the expression of CDK2 dependent on the m^6A modification at 3’UTR.Results: MA2 significantly increased the cellular m^6A level and down-regulated the expression of CDK1, CDK2, CDK6 and Cd C25 a, resulting in arrest of G1/S transition and decrease of cell proliferation. MA2 downregulated CDK2 m RNA stability. Additionally, mutation of the predicted m^6A sites in the Cdk2–3’UTR could mitigated the degradation of CDK2 m RNA after MA2 treatment.Conclusion: MA2 affected CDKs expression through the m^6A-dependent m RNA degradation pathway, and thus repressed spermatogonial proliferation.
基金Supported by National Basic Research Program of China(973 Program),No.2009CB522900,2009CB522901Shanghai Top Clinical Medical Center of Acupuncture,Moxibustion and TuinaNational Natural Sciences Foundation of China,Nos.81303031 and 81202752
文摘AIM: To identify an appropriate therapeutic regimen for using aconite cake-separated moxibustion to treat diarrhea-predominant irritable bowel syndrome(D-IBS).METHODS: A factorial design was employed to examine the two factors of moxibustion frequency and number of cones. The two tested frequencies were three or six moxibustion sessions per week, and the two tested doses were one or two cones per treatment. A total of 166 D-IBS patients were randomly divided into four treatment groups, which included each combination of the examined frequencies and doses. The bilateral Tianshu acupoints(ST25) and the Qihai acupoint(RN6) were selected for aconite cake-separated moxibustion. Each patient received two courses of treatment, and each course had a duration of 2 wk. For each group, the scores on the Birmingham irritable bowel syndrome(IBS) symptom questionnaire, the IBS Quality of Life scale, the Self-Rating Depression Scale(SDS), the Self-Rating Anxiety Scale(SAS), the Hamilton Depression(HAMD) scale, and the Hamilton Anxiety(HAMA) scale were determined before treatment, after the first course of treatment, and after the second course of treatment. RESULTS: The symptom, quality of life, SDS, SAS, HAMD, and HAMA scores of the patients in all 4 aconite cake-separated moxibustion groups were significantly lower after the first and second courses of treatment than before treatment(P < 0.001 for all). The symptom, quality of life, SDS, SAS, HAMD, and HAMA scores of the patients in all four aconite cake-separated moxibustion groups were significantly lower after the second course of treatment than after the first course of treatment(P < 0.001 for all). Between-group comparisons after the second course of treatment revealed that the symptom scores for group 1(1 cone, 3 treatments/wk) and group 3(2 cones, 3 treatments/wk) were significantly lower than that for group 2(1 cone, 6 treatments/wk)(5.55 ± 5.05 vs 10.45 ± 6.61, P < 0.001; 5.65 ± 4.00 vs 10.45 ± 6.61, P < 0.001). Regarding the two levels of the two examined factors for aconite cake-separated moxibustion, after the first course of treatment, the changes in HAMA scores weresignificantly different for the two tested moxibustion frequencies(P = 0.011), with greater changes for the "6 treatments/wk" groups than for the "3 treatments/wk" groups; in addition, there were interaction effects between the number of cones and moxibustion frequency(P = 0.028). After the second course of treatment, changes in symptom scores for the 2 tested moxibustion frequencies were significantly different(P = 0.002), with greater changes for the "3 treatments/wk" groups than for the "6 treatments/wk" groups.CONCLUSION: An aconite cake-separated moxibustion treatment regimen of 3 treatments/wk and 1 cone/treatment appears to produce better therapeutic effects for D-IBS compared with the other tested regimens.
基金supported by the National Natural Science Foundation of China,No.81201513 (to QG)。
文摘Extremely low frequency electromagnetic fields(ELF-EMF) can improve the learning and memory impairment of rats with Alzheimer's disease, however, its effect on cerebral ischemia remains poorly understood.In this study, we established rat models of middle cerebral artery occlusion/reperfusion.One day after modeling, a group of rats were treated with ELF-EMF(50 Hz, 1 mT) for 2 hours daily on 28 successive days.Our results showed that rats treated with ELF-EMF required shorter swimming distances and latencies in the Morris water maze test than those of untreated rats.The number of times the platform was crossed and the time spent in the target quadrant were greater than those of untreated rats.The number of BrdU~+/NeuN~+ cells, representing newly born neurons, in the hippocampal subgranular zone increased more in the treated than in untreated rats.Up-regulation in the expressions of Notch1, Hes1, and Hes5 proteins, which are the key factors of the Notch signaling pathway, was greatest in the treated rats.These findings suggest that ELF-EMF can enhance hippocampal neurogenesis of rats with cerebral ischemia, possibly by affecting the Notch signaling pathway.The study was approved by the Institutional Ethics Committee of Sichuan University, China(approval No.2019255A) on March 5, 2019.
