Background: and Purpose Therapeutic target selection in noninvasive brain stimulation for poststroke motor recovery typically relies on the interhemispheric inhibition model, which is effective for mildly affected patients but offers limited benefits for severely affected individuals. The mechanisms governing recovery from moderate-to-severe stroke remain poorly understood, which hinders the development of targeted interventions. Methods: We analyzed resting-state functional magnetic resonance imaging data from patients with unilateral subcortical stroke and moderate-to-severe upper limb deficits, both pre- and postintervention, along with data from healthy controls. We developed a novel dynamic lag analysis method for identifying recovery-related homotopic sensorimotor regions with altered interhemispheric interactions. To further uncover the global reorganization pathway, we developed dynamic lateralization approaches to detect large-scale functional connectivity (FC) alterations associated with the identified regions in transient lateralization states. Results: Dynamic time-lag analysis revealed significantly reduced synchronized states in the homotopic dorsal premotor cortex (PMd) post-intervention compared with pre-intervention, which correlated with motor recovery. Further dynamic lateralization analysis revealed a prolonged segregation state in patients, characterized by weakened interhemispheric and strengthened intrahemispheric interactions. In this state, patients showed decreased FC in the ipsilesional PMd and increased FC in the contralesional PMd with bilateral subcortical networks. These recoveryrelated alterations were absent in the traditional static analysis. Conclusions Dynamic analyses targeting interhemispheric interactions are valuable for understanding neural reorganization after stroke. The diminished interactions between the homotopic PMd indicate a compensatory mechanism. Importantly, a state-dependent compensatory pathway was identified, wherein the contralesional PMd assumes the functions of the ipsilesional PMd through enhanced interactions with subcortical structures, potentially guiding more effective interventions.

Objective·To explore the antitumor effects and potential mechanisms of combining phosphoinositide 3-kinase,FYVE-type zinc finger containing(PIKfyve)inhibitor YM201636 with the stimulator of interferon genes(STING)agonist diABZI in STING pathway-deficient melanoma.Methods·The mRNA and protein expression levels of STING in human cancer cell lines were obtained from the Cancer Cell Line Encyclopedia(CCLE)and UniProt databases.Based on median expression values,melanoma cell lines with high STING mRNA but low protein expression were identified.Quantitative real-time PCR(qRT-PCR)and Western blotting were performed to validate STING mRNA and protein expression in human melanoma cells.The murine melanoma cell line YUMM1.7,characterized by low STING protein expression,was selected through Western blotting.The ability of YM201636 to restore STING protein expression in YUMM1.7 cells was evaluated.STING agonist diABZI was then applied in combination with YM201636 to analyze the synergistic tumor cell-killing effect through CCK-8 assay.Western blotting was used to detect the phosphorylation of TANK-binding kinase 1(TBK1)and interferon regulatory factor 3(IRF3),and qRT-PCR was used to evaluate type Ⅰ interferon expression.A mouse melanoma model was established and treated with YM201636,diABZI,or their combination.Tumor volume was measured,and treatment efficacy was assessed.RNA sequencing and immunofluorescence staining were performed to analyze immune cell infiltration in the tumor microenvironment.Results·Database analyses,qRT-PCR,and Western blotting confirmed that some human melanoma cell lines exhibited high STING mRNA expression but low STING protein levels.YM201636 significantly increased STING protein expression in YUMM1.7 cells(P<0.001).Combined treatment with YM201636 and diABZI significantly enhanced phosphorylation of TBK1 and IRF3(P<0.05),indicating effective activation of the STING signaling pathway.This combination also promoted the expression of type Ⅰ interferons(P<0.001)and enhanced tumor cell killing in vitro.In vivo,the combination therapy markedly suppressed melanoma growth compared to monotherapy.Immune profiling of the tumor microenvironment revealed significantly increased infiltration of CD4? T cells and CD8? T cells in the combination treatment group(P<0.05).Conclusion·The PIKfyve inhibitor YM201636 could restore STING protein expression in STING-deficient melanoma and enhance the antitumor efficacy of the STING agonist diABZI,offering a promising therapeutic strategy for tumors with defective STING signaling.

The visual crowding effect refers to the phenomenon that the observers' ability to identify the target object significantly decreases when it is flanked by surrounding objects.A variety of ophthalmic diseases,including amblyopia,strabismus,glaucoma,macular degeneration and nystagmus,involve structural or functional abnormalities in different parts of the visual system.These abnormalities will exacerbate the visual crowding effect,thereby impairing the ability in multi-line visual identification,reading and other daily visual activities of patients.Since intervention on visual crowding can im-prove patients' ability to process complex visual information,optimize the use of residual vision and improve prognosis,it is of great clinical value to develop targeted intervention methods.This article systematically reviews the characteristics of visual crowding in patients with oculopathy and its impact on functional vision,and summarizes the current intervention strategies,in order to provide theoretical basis and practical guidance for future clinical practice.

Objective To retrospective analysis summarized the effectiveness and safety of the"triple"conversion therapy regimen combining immune,targeted and local therapy.Methods From February 2019 to June 2023,52 patients with advanced liver cancer from February 2019 to June 2023 in XI,an Jiao Tong university medicine college affiliated 3201 hospital were admitted and received conversion treatment regimens combining sintilimab with bevacizumab and combined with local treatment,analyzed the surgical resection rate and pathological complete response rate(pCR),complete response rate(CR),partial response rate(PR),progression of disease(PD),stable disease(SD),objective response rate(ORR)and disease control rate(DCR).To evaluated the effect of conversion therapy and adverse reactions.Results 21 cases had recived operative resection in the 52 patients with primary liver cancer receiving sintilimab and bevacizumab.The postoperative resection rate was 40.4％(21/52),pCR 42.9％(9/21).The other 31 cases have complete response 5.8％(3/52),PR 25.0％(13/52),PD 11.5％(6/52),SD 17.3％(9/52).The overall objective response rate(ORR)was71.2％(37/52),and the disease control rate(DCR)was 88.5％(46/52).Adverse reactions manifest as Grade 1-2 skin-related damage primarily affecting the epidermis.Conclusions For patients with potentially resectable primary liver cancer in middle and advanced stage,the"triple"conversion therapy with sintilimab combined with bevacizumab as systematic treatment and combined with local therapy can achieve good conversion treatment effect with controllable safety.

Objective To investigate the correlation between the expression of human leukocyte antigen class I(HLA-I)and programmed cell death ligand 1(PD-L1)with clinicopathological features and cellular immune infiltration.Methods A total of 150 patients with bladder cancer diagnosed and treated in Anhui Provincial Hospital from May 2020 to April 2023 were retrospectively selected as the study objects.The positive expression rates and positive scores of HLA-I and PD-L1 were compared between cancerous tissues and adjacent tissues.The positive scores of HLA-I and PD-L1 in cancer tissues of patients with different clinical characteristics were compared,and the correlation between HLA-I,PD-L1 and clinical characteristics of patients with bladder cancer was analyzed by Kendall's tau-b method.Logistic regression model was used to establish the combined model parameters of HLA-I and PD-L1 positive scores,and receiver operating characteristic(ROC)curve was drawn to analyze the HLA-I and PD-L1 positive scores and the area under the curve(AUC),sensitivity and specificity of the combined diagnosis of bladder cancer.Results The positive expression rate of HLA-I in cancer tissues was lower than that in paracancer tissues[38.67%(58/150)vs 81.33%(122/150)],while the positive expression rate of PD-L1 was higher than that in paracancer tissues[57.33%(86/150)vs 14.00%(21/150)],and the differences were statistically siginficant(χ2=56.889,61.377,all P<0.05).The HLA-I positive score of cancer tissues was lower than that of paracancer tissues[2.00(1.00,3.00)vs 3.00(3.00,5.00)],while the PD-L1 positive score was higher than that of paracancer tissues[3.00(2.00,5.00)vs 2.00(1.00,2.00)],and the fifferences were statistically significant(Z=-8.409,-6.346,all P<0.05).There was no significant difference in HLA-I and PD-L1 positive scores among different sex,age and tumor diameter(ZHLA-1=-1.834,-0.622,-0.543;ZPD-L1=0.811,0.812,0.919,all P＞0.05).The difference of HLA-I and PD-L1 positive scores among different pathological stages,lymph node metastasis,differentiation degree,CD4+,CD8+and CD68+were statistically significant(ZHLA-1=-7.034～3.814;ZPD-L1=-4.479～3.257,all P＜0.05).Kendall's tau-b correlation analysis showed that HLA-I was negatively correlated with pathological stage,lymph node metastasis,degree of differentiation,and positively correlated with negative infiltration of CD4+,CD8+and CD68+(r=-0.528～-0.286,all P<0.05).PD-L1 was positively correlated with pathological stage,lymph node metastasis,degree of differentiation and negatively correlated with negative infiltration of CD4+,CD8+and CD68+(r=-0.243～0.334,all P<0.05).ROC curve analysis showed that the positive scores of HLA-I and PD-L1 and the AUC values of the combined diagnosis of bladder cancer were 0.773,0.702 and 0.856,respectively.Sensitivity was 61.30%,57.30%and 82.00%.The specificity was 81.30%,86.00%and 73.30%.Conclusion The expression of HLA-I and PD-L1 is abnormal in patients with bladder cancer,and their expression is affected by the positive infiltration of immune cells.Observing the positive expression of HLA-I and PD-L1 is beneficial to provide guidance for clinical diagnosis and treatment.

Objective To retrospective analysis summarized the effectiveness and safety of the"triple"conversion therapy regimen combining immune,targeted and local therapy.Methods From February 2019 to June 2023,52 patients with advanced liver cancer from February 2019 to June 2023 in XI,an Jiao Tong university medicine college affiliated 3201 hospital were admitted and received conversion treatment regimens combining sintilimab with bevacizumab and combined with local treatment,analyzed the surgical resection rate and pathological complete response rate(pCR),complete response rate(CR),partial response rate(PR),progression of disease(PD),stable disease(SD),objective response rate(ORR)and disease control rate(DCR).To evaluated the effect of conversion therapy and adverse reactions.Results 21 cases had recived operative resection in the 52 patients with primary liver cancer receiving sintilimab and bevacizumab.The postoperative resection rate was 40.4％(21/52),pCR 42.9％(9/21).The other 31 cases have complete response 5.8％(3/52),PR 25.0％(13/52),PD 11.5％(6/52),SD 17.3％(9/52).The overall objective response rate(ORR)was71.2％(37/52),and the disease control rate(DCR)was 88.5％(46/52).Adverse reactions manifest as Grade 1-2 skin-related damage primarily affecting the epidermis.Conclusions For patients with potentially resectable primary liver cancer in middle and advanced stage,the"triple"conversion therapy with sintilimab combined with bevacizumab as systematic treatment and combined with local therapy can achieve good conversion treatment effect with controllable safety.

Objective To evaluate the performance of the artificial intelligence (AI)-enabled snail identification system for recognition of Oncomelania hupensis robertsoni and Tricula in schistosomiasis-endemic areas of Yunnan Province. Methods Fifty O. hupensis robertsoni and 50 Tricula samples were collected from Yongbei Township, Yongsheng County, Lijiang City, a schistosomiasis-endemic area in Yunnan Province in May 2024. A total of 100 snail sample images were captured with smartphones, including front-view images of 25 O. hupensis robertsoni and 25 Tricula samples (upward shell opening) and back-view images of 25 O. hupensis robertsoni and 25 Tricula samples (downward shell opening). Snail samples were identified as O. hupensis robertsoni or Tricula by schistosomiasis control experts with a deputy senior professional title and above according to image quality and morphological characteristics. A standard dataset for snail image classification was created, and served as a gold standard for recognition of snail samples. A total of 100 snail sample images were recognized with the AI-enabled intelligent snail identification system based on a WeChat mini program in smartphones. Schistosomiasis control professionals were randomly sampled from stations of schistosomisis prevention and control and centers for disease control and prevention in 18 schistosomiasis-endemic counties (districts, cities) of Yunnan Province, for artificial identification of 100 snail sample images. All professionals are assigned to two groups according the median years of snail survey experiences, and the effect of years of snail survey experiences on O. hupensis robertsoni sample image recognition was evaluated. A receiver operating characteristic (ROC) curve was plotted, and the sensitivity, specificity, accuracy, Youden’s index and the area under the curve (AUC) of the AI-enabled intelligent snail identification system and artificial identification were calculated for recognition of snail sample images. The snail sample image recognition results of AI-enabled intelligent snail identification system and artificial identification were compared with the gold standard, and the internal consistency of artificial identification results was evaluated with the Cronbach’s coefficient alpha. Results A total of 54 schistosomiasis control professionals were sampled for artificial identification of snail sample image recognition, with a response rate of 100% (54/54), and the accuracy, sensitivity, specificity, Youden’s index, and AUC of artificial identification were 90%, 86%, 94%, 0.80 and 0.90 for recognition of snail sample images, respectively. The overall Cronbach’s coefficient alpha of artificial identification was 0.768 for recognition of snail sample images, and the Cronbach’s coefficient alpha was 0.916 for recognition of O. hupensis robertsoni snail sample images and 0.925 for recognition of Tricula snail sample images. The overall accuracy of artificial identification was 90% for recognition of snail sample images, and there was no significant difference in the accuracy of artificial identification for recognition of O. hupensis robertsoni (86%) and Tricula snail sample images (94%) (χ² = 1.778, P > 0.05). There was no significant difference in the accuracy of artificial identification for recognition of snail sample images with upward (88%) and downward shell openings (92%) (χ² = 0.444, P > 0.05), and there was a significant difference in the accuracy of artificial identification for recognition of snail sample images between schistosomiasis control professionals with snail survey experiences of 6 years and less (75%) and more than 6 years (90%) (χ² = 7.792, P < 0.05). The accuracy, sensitivity, specificity and AUC of the AI-enabled intelligent snail identification system were 88%, 100%, 76% and 0.88 for recognition of O. hupensis robertsoni snail sample images, and there was no significant difference in the accuracy of recognition of O. hupensis robertsoni snail sample images between the AI-enabled intelligent snail identification system and artificial identification (χ² = 0.204, P > 0.05). In addition, there was no significant difference in the accuracy of artificial identification for recognition of snail sample images with upward (90%) and downward shell openings (86%) (χ² = 0.379, P > 0.05), and there was a significant difference in the accuracy of artificial identification for recognition of snail sample images between schistosomiasis control professionals with snail survey experiences of 6 years and less and more than 6 years (χ² = 5.604, P_adjusted < 0.025). Conclusions The accuracy of recognition of snail sample images is comparable between the AI-enabled intelligent snail identification system and artificial identification by schistosomiasis control professionals, and the AI-enabled intelligent snail identification system is feasible for recognition of O. hupensis robertsoni and Tricula in Yunnan Province.

BackgroundAtypical antipsychotics have been widely used in patients with chronic schizophrenia， and aripiprazole and risperidone are the most commonly used drugs. The mechanism of action of the two is different， while previous studies have provided insufficient credible evidence from multiple perspectives to support the comparative efficacy of the two drugs in improving symptoms in patients with chronic schizophrenia. ObjectiveTo compare the efficacy of aripiprazole and risperidone on the improvement of symptoms， prepulse inhibition （PPI）， cognitive functioning and neurotrophic factors in patients with chronic schizophrenia， so as to provide effective treatment regimens for these patients. MethodsA total of 86 patients with chronic schizophrenia attending the psychiatry department of the Third People's Hospital of Fuyang from March 2021 to March 2023 and fulfilling the diagnostic criteria of International Classification of Diseases， tenth edition （ICD-10） were enrolled and grouped using random number table method， each with 43 cases. Aripiprazole group was given oral aripiprazole once daily at an initial dose of 5 mg for one week and then gradually increased to a maximum dose of 25 mg. Risperidone group received oral risperidone twice daily at an initial dose of 0.5 mg for one week and then gradually increased to a maximum dose of 3 mg. Treatment in both groups lasted 3 months. Before treatment and 3 months after treatment， Patients were required to complete Positive and Negative Symptom Scale （PANSS）， detection of both strong and weak PPIs in a startle modification passive attention paradigm， Wisconsin Card Sorting Test （WCST） and the measurement of neurotrophic factors at baseline and after treatment. The adverse reactions were recorded. Analysis of covariance was used to test the difference between the PANSS score， PPI， WCST and neurotrophic factor levels of the groups， with the pretest used as the covariate. Results3 months after treatment， no statistical difference was found in the scores of PANSS general psychopathology subscale， positive symptom subscale， negative symptom subscale and total score between two groups after treatment （F=0.621， 0.815， 0.743， 0.752， P>0.05）. There were no statistically significant differences between the two groups in PPI inhibition rate， single intense stimulus amplitude， single intense stimulus latency， prepulse inhibition amplitude， or prepulse inhibition latency （F=0.174， 0.001， 0.183， 0.171， 0.001， P>0.05）. There was no statistically significant difference in the total number of WCST tests between two groups （F=0.512， P>0.05）， whereas aripiprazole group reported significantly larger total numbers of categories completed and correct responses as well as smaller total numbers of random errors and perseverative errors compared to risperidone group （F=3.737， 4.621， 4.892， 5.130， P<0.05）. A significant increase in brain-derived neurotrophic factor （BDNF） and nerve growth factor （NGF） along with a reduction in glial fibrillary acidic protein （GFAP） were documented in risperidone group when compared to risperidone group （F=4.414， 3.781， 6.319， P<0.05）. No significant difference was demonstrated in the incidence of adverse reactions between the two groups （χ²=0.261， P>0.05）. ConclusionAripiprazole may be more beneficial than risperidone in improving cognitive functioning and neurotrophic factor levels in patients with chronic schizophrenia. ［Funded by Scientific Research Project of Fuyang Municipal Health Commission in 2021 （number， FY2021-147）］

Medical fiber endoscope is one kind of medical device that utilizes fiber technique to realize visual detection for internal organs or cavities.In clinical applications,medical fiber endoscope not only need to complete fiber optic imaging but also need possess the functions of delivering water and air,and operating device.Therefore,its routine management and maintenance for fault is more and more payed attention by the staffs of using medical fiber endoscope in department.The system of delivering water and air is a key structure for some of medical fiber endoscopes,which has higher maintenance matters and frequency of maintaining fault.Based on the above reasons,this research analyzed the working principle of medical fiber endoscopes,and summarized the ideas and methods of repairing common faults through focused on the structural composition of delivering system of water and air of medical fiber endoscopes,so as to improve the management level for this type of medical device.

Objective To comparatively analyze the disparities in informatization construction between primary healthcare institu-tions in remote and non-remote areas,clarify the causes and manifestations of regional digital divides,and provide empirical evidence for optimizing resource allocation in remote areas and promoting health equity.The study also offers policy insights for advancing the"Internet+Healthcare"strategy based on local conditions.Methods A stratified sampling survey was conducted among 1 255 primary healthcare institutions in Sichuan Province to systematically compare informatization construction differences between remote and non-remote areas.Results Compared with non-remote areas,remote areas exhibited significant gaps in the coverage of informa-tization infrastructure and the construction of core system integration platforms.Remote areas also had higher absence rates of clinical service systems and notable disparities in institutional informatization investment and the allocation of dedicated IT person-nel.However,remote areas demonstrated strengths in the deployment of health terminals(e.g.,integrated health devices,smart follow-up kits,and wearable devices)and the construction of systems for infection control/communicable disease management and patient follow-up management.Conclusion Regional digital divides are primarily constrained by three factors:fiscal invest-ment,talent reserves,and technical adaptability.A differentiated policy support system is needed to address these challenges.