ObjectiveTo investigate the mechanism by which 2，3，5，4'-tetrahydroxyldiphenylethylene-2-O-glucoside （THSG） mitigates cerebral ischemia/reperfusion （CI/R） injury by regulating mitochondrial calcium overload and promoting mitophagy. MethodsSixty male SD rats were randomized into sham， model， SAS （40 mg·kg^-1）， and low-， medium- and high-dose （10， 20， 40 mg·kg^-1， respectively） THSG groups， with 10 rats in each group. The middle cerebral artery occlusion/reperfusion （MCAO/R） model was established by the modified Longa suture method. An oxygen-glucose deprivation/reoxygenation （OGD/R） model was constructed in PC12 cells. Neurological deficits were assessed via Zea Longa scoring， and cerebral infarct volume was measured by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Structural and functional changes of cortical neurons in MCAO/R rats were assessed by hematoxylin-eosin and Nissl staining. PC12 cell viability was detected by cell counting kit-8 （CCK-8） assay， and mitochondrial calcium levels were quantified by Rhod-2 AM. Immunofluorescence was used to detect co-localization of PTEN-induced kinase 1 （PINK1） and leucine zipper/EF-hand-containing transmembrane protein 1 （LETM1） in neurons. Transmission electron microscopy （TEM） was employed to observe mitochondrial morphology in neurons. Western blot was employed to analyze the expression of translocase of outer mitochondrial membrane 20 （TOMM20）， autophagy-associated protein p62， microtubule-associated protein light chain 3 （LC3）， cysteinyl aspartate-specific proteinase-9 （Caspase-9）， B-cell lymphoma 2-associated protein X （Bax）， and cytochrome C （Cyt C）. ResultsCompared with the sham group， the model group exhibited increased infarct volume （P<0.01） and neurological deficit scores （P<0.01）， neuronal structure was disrupted with reduced Nissl bodies. （P<0.01）， mitochondrial swelling/fragmentation， decreased PINK1/LETM1 co-localization （P<0.01）， upregulated protein levels of LC3Ⅱ/LC3Ⅰ， TOMM20， Caspase-9， Bax， and Cyt C （P<0.01）， downregulated protein level of p62 （P<0.05）， weakened PC12 viability （P<0.01）， and elevated mitochondrial calcium level （P<0.01）. Compared with the model group， THSG and SAS groups showed reduced infarct volumes （P<0.05，P<0.01） and neurological deficit scores （P<0.05，P<0.01）， mitigated mitochondrial damage， and increased PINK1/LETM1 co-localization （P<0.01）. Medium/high-dose THSG and SAS alleviated the neurological damage， increased Nissl bodies （P<0.05，P<0.01）， downregulated the protein levels of p62， TOMM20， Caspase-9， Bax， and Cyt C （P<0.05，P<0.01）， and elevated the LC3Ⅱ/LC3Ⅰ level （P<0.05，P<0.01）. High-dose THSG enhanced PC12 cell viability （P<0.01）， increased PINK1/LETM1 co-localization （P<0.01）， and reduced mitochondrial calcium （P<0.01）. ConclusionTHSG may exert the neuroprotective effect on CI/R injury by activating the PINK1-LETM1 signaling pathway， reducing the mitochondrial calcium overload， and promoting mitophagy.

ObjectiveTo investigate the mechanism by which 2，3，5，4'-tetrahydroxyldiphenylethylene-2-O-glucoside （THSG） mitigates cerebral ischemia/reperfusion （CI/R） injury by regulating mitochondrial calcium overload and promoting mitophagy. MethodsSixty male SD rats were randomized into sham， model， SAS （40 mg·kg^-1）， and low-， medium- and high-dose （10， 20， 40 mg·kg^-1， respectively） THSG groups， with 10 rats in each group. The middle cerebral artery occlusion/reperfusion （MCAO/R） model was established by the modified Longa suture method. An oxygen-glucose deprivation/reoxygenation （OGD/R） model was constructed in PC12 cells. Neurological deficits were assessed via Zea Longa scoring， and cerebral infarct volume was measured by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Structural and functional changes of cortical neurons in MCAO/R rats were assessed by hematoxylin-eosin and Nissl staining. PC12 cell viability was detected by cell counting kit-8 （CCK-8） assay， and mitochondrial calcium levels were quantified by Rhod-2 AM. Immunofluorescence was used to detect co-localization of PTEN-induced kinase 1 （PINK1） and leucine zipper/EF-hand-containing transmembrane protein 1 （LETM1） in neurons. Transmission electron microscopy （TEM） was employed to observe mitochondrial morphology in neurons. Western blot was employed to analyze the expression of translocase of outer mitochondrial membrane 20 （TOMM20）， autophagy-associated protein p62， microtubule-associated protein light chain 3 （LC3）， cysteinyl aspartate-specific proteinase-9 （Caspase-9）， B-cell lymphoma 2-associated protein X （Bax）， and cytochrome C （Cyt C）. ResultsCompared with the sham group， the model group exhibited increased infarct volume （P<0.01） and neurological deficit scores （P<0.01）， neuronal structure was disrupted with reduced Nissl bodies. （P<0.01）， mitochondrial swelling/fragmentation， decreased PINK1/LETM1 co-localization （P<0.01）， upregulated protein levels of LC3Ⅱ/LC3Ⅰ， TOMM20， Caspase-9， Bax， and Cyt C （P<0.01）， downregulated protein level of p62 （P<0.05）， weakened PC12 viability （P<0.01）， and elevated mitochondrial calcium level （P<0.01）. Compared with the model group， THSG and SAS groups showed reduced infarct volumes （P<0.05，P<0.01） and neurological deficit scores （P<0.05，P<0.01）， mitigated mitochondrial damage， and increased PINK1/LETM1 co-localization （P<0.01）. Medium/high-dose THSG and SAS alleviated the neurological damage， increased Nissl bodies （P<0.05，P<0.01）， downregulated the protein levels of p62， TOMM20， Caspase-9， Bax， and Cyt C （P<0.05，P<0.01）， and elevated the LC3Ⅱ/LC3Ⅰ level （P<0.05，P<0.01）. High-dose THSG enhanced PC12 cell viability （P<0.01）， increased PINK1/LETM1 co-localization （P<0.01）， and reduced mitochondrial calcium （P<0.01）. ConclusionTHSG may exert the neuroprotective effect on CI/R injury by activating the PINK1-LETM1 signaling pathway， reducing the mitochondrial calcium overload， and promoting mitophagy.

Uveitis, a complex ocular disorder with numerous etiologies, can result from infection, autoimmune, and various physicochemical and mechanical injury factors. The treatment of this disease is difficult, and failure to receive timely and effective treatment can often lead to blindness. With the deepening of people's understanding of uveitis and its related mechanisms, various new sustained-release drug delivery systems for uveitis have been studied. However, due to the existence of various anatomical and physiological barriers in the eye, there are multiple obstacles to the sustained release treatment of uveitis. In this paper, the main research results in this field in recent years are reviewed, and the innovations and limitations of various new sustained-release drug delivery systems are discussed in order to provide new ideas for the sustained-release drug delivery treatment of uveitis in the future. These new sustained-release drug delivery systems will help to completely change the traditional treatment mode of uveitis with side effects and poor compliance in the future, bringing longer targeted sustained release and less toxic reactions.

ObjectiveTo investigate the mechanism of Baihuan Xiaoyao Decoction （Xiaoyaosan added with Lilii Bulbus and Albiziae Cortex） in alleviating depression-like behaviors of juvenile rats by regulating the polarization of microglia. MethodSixty juvenile SD rats were randomized into normal control， model， fluoxetine， and low-， medium-， and high-dose （5.36， 10.71， 21.42 g·kg^-1， respectively） Baihuan Xiaoyao decoction groups. The rat model of juvenile depression was established by chronic unpredictable mild stress （CUMS）. The sucrose preference test （SPT） was carried out to examine the sucrose preference of rats. Forced swimming test （FST） was carried out to measure the immobility time of rats. The open field test （OFT） was conducted to measure the total distance， the central distance， the number of horizontal crossings， and the frequency of rearing. Morris water maze （MWM） was used to measure the escape latency and the number of crossing the platform. The immunofluorescence assay was employed to detect the expression of inducible nitric oxide synthase （iNOS， the polarization marker of M1 microglia） and CD206 （the polarization marker of M2 microglia）. Real-time polymerase chain reaction was employed to determine the mRNA levels of iNOS， CD206， pro-inflammatory cytokines ［tumor necrosis factor （TNF）-α， interleukin （IL）-1β， and IL-6］ and anti-inflammatory cytokines （IL-4 and IL-10） in the hippocampus. Western blotting was employed to determine the protein levels of iNOS and CD206 in the hippocampus. The levels of IL-4 and IL-6 in the hippocampus were detected by enzyme-linked immunosorbent assay. ResultCompared with the normal control group， the model rats showed a reduction in sucrose preference （P<0.05）， an increase in immobility time （P<0.05）， decreased motor and exploratory behaviors （P<0.05）， and weakened learning and spatial memory （P<0.05）. In addition， the model rats showed up-regulated mRNA and protein levels of iNOS and mRNA levels of IL-1β， IL-6， and TNF-α （P<0.05）. Compared with the model group， Baihuan Xiaoyao decoction increased the sucrose preference value （P<0.05）， shortened the immobility time （P<0.01）， increased the motor and exploratory behaviors （P<0.05）， and improved the learning and spatial memory （P<0.01）. Furthermore， the decoction down-regulated the positive expression and protein level of iNOS， lowered the levels of TNF-α， IL-1β， and IL-6 （P<0.01）， promoted the positive expression of CD206， and elevated the levels of IL-4 and IL-10 （P<0.01） in the hippocampus of the high dose group. Moreover， the high-dose Baihuan Xiaoyao decoction group had higher sucrose preference value （P<0.01）， shorter immobility time （P<0.01）， longer central distance （P<0.01）， stronger learning and spatial memory （P<0.01）， higher positive expression and protein level of iNOS （P<0.01）， lower levels of TNF-α， IL-1β， and IL-6 （P<0.05， P<0.01）， lower positive expression and mRNA level of iNOS （P<0.05）， and higher levels of IL-4 and IL-10 （P<0.05， P<0.01） than the fluoxetine group. ConclusionBaihuan Xiaoyao decoction can improve the depression-like behavior of juvenile rats by inhibiting the M1 polarization and promoting the M2 polarization of microglia in the hippocampus.

Objective To investigate the effect of transcranial direct current stimulation(tDCS)in the left posterior sylvia temporal-parietal association area on language function in patients with post-stroke conductive aphasia.Methods The post-stroke aphasia patients admitted to the Department of Rehabilitation Medicine,Xuanwu Hospital,Capital Medical University were prospectively included from June 2021 to April 2024.A self-cross randomized controlled trial was performed in this study.The patients enrolled were assessed as conductive aphasia by Western aphasia test kit diagnostic criteria.Twelve patients with post-stroke conductive aphasia were completely randomly divided into group A(treatment sequence:stage A—washout period—stage B)and group B(treatment sequence:stage B—washout period—stage A),with 6 cases in each group.Stage A performed true tDCS therapy combined with speech and language training,and stage B performed sham tDCS therapy combined with speech and language training.During washout period,only speech and language training was performed,and each stage was trained for 5 days.The tDCS anode is the stimulation electrode and is placed at the stimulation target.The cathode is the reference electrode and is placed on the right shoulder.The intensity of tDCS was 1.4 mA,the true stimulation was 20 min/time,and the sham stimulation stopped automatically after only 30 s/time,both twice/d,and a total of 10 times treatment were performed.Speech and language training was performed 30 min/time,2 times/d,a total of 10 times treatment.The function of rehearsal and picture naming(training item and non-training item)were examined before and after treatment of stage A and B immediately,and the difference of function scores of rehearsal and picture naming(training item and non-training item)before and after treatment of stage A and B were compared.Results(1)There were no significant differences in gender,age,course of disease and educational level between group A and group B(all P＞0.05).(2)Before and after washout period,there were no statistical significance in functional scores of rehearsal and picture naming(training items and non-training items)in both group A and group B(all P＞0.05).(3)There were no significant differences in functional scores of rehearsal and picture naming(training items and non-training items)between group A and group B before and after washout treatment(all P＞0.05).(4)Compared with the difference before and after treatment of stage B,the function scores difference before and after treatment of stage A in rehearsal function,picture naming(training item)and picture naming(non-training item)were higher([6.9±1.4]scores vs.[2.2±1.0]scores,t=9.604;[6.2±1.2]scores vs.[1.8±1.1]scores,t=9.277;[6.5±1.0]scores vs.[1.5±1.0]scores,t=12.247;all P＜0.01).Conclusions Preliminary analysis suggested that tDCS intervention in the brain tissue of the temporoparietal association area of the left posterior lateral cleft may help improve the rehearsal and picture naming(training and non-training items)ability in conductive aphasia patients after stroke.The sample size of this study is small,and the results need to be further explored.

Objective:To explorethe relationship between internet use and loneliness among the elderly,as well as the moderating role of physical health.Methods:Data from the 2018 China Longitudinal Aging Social Sur-vey(CLASS2018)were analyzed,including 8 260 older adults.Loneliness was measured withthe UCLA Loneliness Scale-3-item short version(UCLA-3),Internet use was measured with whether or not participants used the internet and for what purposes(Latent class analysis identified three types of internet users,namely multi-functional use group,communication group,and information acquisition group),and physical health was assessed with activities of daily living and chronic disease status.Results:Multiple linear regression analysis revealed that the elderly who used the internet had significantly lower scores on the loneliness scale than those who did not use the internet(β=-0.08).Multi-functional use group had significantly lower loneliness scores than information acquisition group and communication group(β=0.06,0.12).Two-way ANOVA found that physical health moderated the association be-tween internet use,internet use type,and loneliness(Ps＜0.05).Conclusion:Internet use helps the elderly to allevi-ate loneliness,and the use of multiple Internet functions has a cumulative effect on reducing loneliness.However,the relationship between internet use and loneliness among the elderly may vary depending on their physical health status.

Triple-negative breast cancer(TNBC)is one of the prognosis poorer molecular subtypes of breast cancer with limited conventional treatments,however,it is characterized by a strong immune microenvironmental activity,which provides a certain biological basis for immunotherapy as well as antibody-drug conjugates(ADCs).Nowadays,the combination of immune checkpoint inhibitors and chemotherapy,as well as the successive introduction of ADCs such as sacituzumab govitecan and trastuzumab deruxtecan,has changed the therapeutic pattern of TNBC and provided new ideas for the development of new drugs for TNBC.In this paper,the clinical research progress of immunotherapy and ADCs for the treatment of TNBC is reviewed,in order to provide a reference for the strategy selection of clinical drugs,that is,the future research and development trend.

Objective To observe the effect of Qixian Tongluo Formula on contralateral corticospinal tract(CST)remodeling and motor functional recovery in rats with cerebral infarction,and to explore its potential molecular mechanism from the perspective of regulating factors related to never remodeling.Methods The rat middle cerebral artery occlusion(MCAO)model was established by silk thread ligation.Fifty model rats were randomly divided into model group,citicoline group(0.054 g·kg-1),Qixian Tongluo Formula low-,medium-and high-dose(7.83,15.66,31.32 g·kg-1)groups,and sham operation group,with 10 rats in each group.The intervention administration was started on the 3rd day after operation once a day for 26 consecutive days.On the 3rd,14th and 28th day after operation,the gross motor function was evaluated by Longa score,and the fine motor function was evaluated by beam-walking test(BWT)score.The contralateral motor cortex was injected with the nerve tracer biotin dextran amine(BDA)on the 14 th day after operation to anterogradely trace the CST.On the 28th day after operation,the expression of axonal growth associated protein-43(GAP-43)and BDA positive fibers in the contralateral motor cortex and cervical spinal cord were detected by immunohistochemistry.The co-localization areas of BDA positive fibers and presynaptic marker protein vesicular glutamate transporter 1(VGLUT1)in the cervical spinal cord gray matter were detected by immunofluorescence.The expressions of brain-derived neurotrophic factor(BDNF),glial cell-derived neurotrophic factor(GDNF),nerve growth factor(NGF)and nerve remodeling-associated inhibitory factor[Nogo-A,oligodendrocyte myelin glycoprotein(OMgp)and myelin-associated glycoprotein(MAG)]in the contralateral motor cortex were detected by Western Blot.Pearson correlation analysis was used to analyze the correlation between Longa score or BWT score and BDA/VGLUT1 co-localization area,respectively.Results Compared with the sham operation group,rats in the model group had obvious symptoms of motor function deficits,and the Longa scores were significantly increased(P＜0.01)and the BWT scores were significantly decreased(P＜0.05,P＜0.01)at each time point.The expression of GAP-43 in the contralateral motor cortex and cervical spinal cord was up-regulated(P＜0.05),the number of edge-crossing fibers from the posterior funiculus in cervical cord was increased(P＜0.05),the co-localization area of BDA/VGLUT1 in the gray matter of the cervical spinal cord was increased(P＜0.05),the expressions of BDNF,GDNF and NGF in the contralateral motor cortex were up-regulated(P＜0.05),while the expressions of Nogo-A,OMgp and MAG were down-regulated(P＜0.05).Compared with the model group,the Longa scores in each administration group on the 14th and 28th day after MCAO operation were significantly decreased(P＜0.01),the BWT scores were significantly increased(P＜0.01),the expression of GAP-43 in the contralateral motor cortex and cervical spinal cord was significantly up-regulated(P＜0.01).The number of edge-crossing fibers from the posterior funiculus in cervical cord was significantly increased(P＜0.01),the co-localization area of BDA/VGLUT1 in the gray matter of the cervical spinal cord was significantly increased(P＜0.01).The expressions of BDNF,GDNF and NGF in the contralateral motor cortex were significantly up-regulated(P＜0.01,P＜0.05),while the expressions of Nogo-A,OMgp and MAG were significantly down-regulated(P＜0.05),and the most significant effect was observed in the high dose group.The Longa score was negatively correlated with the co-localization area of BDA/VGLUT1(r=-0.89,P＜0.01),and the BWT score was positively correlated with the co-localization area of BDA/VGLUT1(r=0.84,P＜0.01).Conclusion Qixian Tongluo Formula can improve motor function through promoting contralateral CST remodeling in MCAO rats after cerebral infarction,and the molecular mechanism may be related to the regulation of the expression of nerve remodeling-associated factor in the contralateral motor cortex.

Objective:To investigate the causes and prognosis of salvage cholecystectomy for relapsing cholecystolithiasis after gallbladder-preserving gall stones removal surgery.Methods:From Jul 2015 to Dec 2019, 24 referral patients with gallstone recurrence after gallbladder-preserving cholelithotomy surgery received salvage cholecystectomy. The clinical data was analyzed to explore the causes for re-operation and the prognosis.Results:Twenty-two cases had definite gallstone recurrence, among them 19 cases were symptomatic, 2 cases were operated on suspected gallbladder tumor and common bile duct stones induced acute cholangitis. Laparoscopic cholecystectomy was successfully performed in 23 cases and 1 case was converted to open surgery. No severe complication were observed in all the patients.Conclusions:Symptomatic gallstone recurrence is the most common causes of salvage cholecystectomy after gallbladder-preserving cholelithotomy. Laparoscopic surgery procedure is still highly successful.

Objective:To explore the application effect of problem-based learning (PBL) combined with WeChat assisted teaching pattern in teaching rounds of encephalopathy department.Methods:Undergraduate interns of Batch 2018 from the encephalopathy department were enrolled in the study. The observation group ( n=36) was taught by PBL combined with WeChat teaching mode. The control group ( n=36) was taught by the conventional teaching mode. At the end of rotation, the scores of theoretical and practical skills tests of the two groups were compared, and at the same time, the results of the survey were compared according to the questionnaire. SPSS 19.0 was used for statistical analysis of the data. Results:The test scores of the observation group were significantly higher than those of the control group ( P<0.05). The recognition in nine aspects of the observation group was also significantly higher than that of the control group, such as the interaction with the teaching teachers, the effect of improving clinical learning interest and the ability of inspiring thinking and innovation ( P<0.05). There was no significant difference in recognition about improving the efficiency of clinical teaching rounds between two groups ( P>0.05). Conclusion:PBL combined with WeChat teaching rounds model has certain advantages over traditional rounds in TCM clinical teaching, which are mainly manifested in the mastery of clinical knowledge, the communication ability of interns, the ability of interaction and cooperation, the ability of innovation and thinking, and the improvement of learning initiative.