BACKGROUND:Macrophage migration inhibitory factor(MIF)is a pleiotropic cytokine,which is secreted in different types of stem cells and can regulate the proliferation,differentiation and migration of various types of stem cells.Our previous research has confirmed that human embryonic stem cells secrete MIF and that its concentration in the culture medium is relatively stable.However,whether MIF is involved in the survival,proliferation and differentiation of human embryonic stem cells remains unclear. OBJECTIVE:To investigate the effects of MIF on survival,proliferation,and differentiation of human embryonic stem cells. METHODS:(1)Human embryonic stem cells H9 were cultured.The growth curve of cells was detected and plotted by CCK-8 assay.Enzyme-linked immunosorbent assay was used to determine the level of MIF in the medium.(2)To determine the effects of exogenous MIF on the survival and proliferation of human embryonic stem cells,different groups were established:the control group,which was cultured in stem cell medium without any modifications;the exogenous MIF group,which was treated with different concentrations(30,100,300 ng/mL)of MIF in the stem cell medium;the MIF inhibitor ISO-1 group,which was treated with different concentrations(2,7,21 μmol/L)of ISO-1 in the stem cell medium;and the MIF+ISO-1 group,which was treated with different concentrations of ISO-1 along with 100 ng/mL of MIF.Cell viability was assessed using the CCK-8 assay.(3)To further elucidate the effect of MIF gene on survival and proliferation of human embryonic stem cell,the MIF knockout H9 cell line was constructed by CRISPR-Cas 9 technology to observe the lineage establishment.(4)To determine the effect of high concentrations of MIF on human embryonic stem cell differentiation,100 ng/mL MIF and 100 ng/mL of CXCR4 neutralizing antibody were separately added to the normal stem cell culture medium.The expression levels of self-renewal factors(KLF4,c-MYC,NANOG,OCT4,and SOX2)and differentiation transcription factors(FOXA2,OTX2)were measured using real-time quantitative polymerase chain reaction,immunofluorescence staining,and western blot analysis. RESULTS AND CONCLUSION:(1)The logarithmic growth phase of H9 cells was between 3-6 days.Under normal growth conditions,human embryonic stem cells secreted MIF at a concentration of approximately 20 ng/mL,independent of cell quantity.(2)Compared to the control group,the addition of different concentrations of MIF had no effect on the proliferation of human embryonic stem cells(P>0.05).ISO-1 significantly inhibited the proliferation of human embryonic stem cells,with a stronger inhibition observed at higher concentrations of ISO-1(P<0.05).The addition of MIF in the presence of ISO-1 reduced the inhibitory effect of ISO-1(P<0.05).(3)Real-time quantitative polymerase chain reaction showed that knocking out 50%of the MIF gene resulted in a significant decrease in the growth vitality of human embryonic stem cells and failure to establish cell lines.(4)Adding 100 ng/mL exogenous MIF to the culture medium resulted in a decrease in the mRNA,protein,and fluorescence expression levels of the self-renewal transcription factor KLF4,while the mRNA,protein,and fluorescence expression levels of the differentiation factor FOXA2 increased.(5)When 100 ng/mL CXCR4 neutralizing antibody was added to the culture medium,the mRNA and protein expression levels of KLF4 increased,while the mRNA and protein expression levels of FOXA2 decreased,contrary to the expression trend observed in the MIF group.In conclusion,the endogenous secretion of MIF by human embryonic stem cells is essential for their survival.The addition of MIF to the culture medium does not promote the proliferation of human embryonic stem cells.However,it can lead to a decrease in the expression of the self-renewal factor KLF4 and an increase in the expression of the transcription factor FOXA2.This provides a clue for further investigation into the effects and mechanisms of MIF on the differentiation of human embryonic stem cells.The MIF-CXCR4 axis plays a regulatory role in this process.

BackgroundAs a high prevalence disorder， schizophrenia has caused significant burden to family and society due to the impairment of occupational and social function. Currently， the dominant vocational training model in China follows a paternalistic， clinician-led decision-making approach. Although it improves patients' social function to some extent， it undermines their autonomy and treatment adherence. Therefore， it is urgently necessary to explore a new intervention method to enhance treatment compliance and social function in patients. ObjectiveTo explore the impact of shared decision-making oriented vocational training on social function in hospitalized schizophrenia patients， so as to provide references for rehabilitation interventions. MethodsA total of 68 patients diagnosed with schizophrenia according to the International Classification of Diseases， tenth edition （ICD-10） criteria were consecutively enrolled from January to June 2024 at The Third People's Hospital of Wenjiang Distric， Chengdu. Participants were randomly allocated into the research group （n=34） and the control group （n=34） using a random number table method. Both groups received routine rehabilitation training， while the research group received shared decision-making oriented vocational training for 12 weeks， 2 times a week for 2 hours each time. Before and at the 4^th and 12^th week of intervention， two groups were evaluated by General Self-Efficacy Scale （GSES）， Stigma Scale for Mental Illness （SSMI）， Scale of Social function of Psychosis Inpatients （SSFPI） and Inpatient Psychiatric Rehabilitation Outcome Scale （IPROS）. ResultsA total of 63 participants completed the study， with 30 cases in the research group and 33 cases in the control group. Repeated measures ANOVA revealed statistically significant time effects and interaction effects in both groups for GSES， SSMI， SSFPI and IPROS scores （F=20.451， 16.022； 26.193， 12.944； 23.957， 5.023； 11.776， 3.985， P<0.05 or 0.01）， while no significant group effects were observed （F=0.188， 0.742， 1.878， 0.474， P>0.05）. At the 12^th week of intervention， there were statistically significant differences in GSES， SSMI， SSFPI and IPROS scores between the two groups. ConclusionShared decision-making oriented vocational training may help to improve social function in patients with schizophrenia. ［Funded by 2023 Chengdu Medical Research Project （number， 2023468）］

Objective To investigate the antimicrobial susceptibility of clinical isolates of Corynebacterium striatum and the clinical characteristics of the patients infected or colonized with these strains.Methods The C.striatum strains isolated from clinical specimens were collected in Quanzhou First Hospital Affiliated to Fujian Medical University from July 2020 to September 2022.The clinical data were analyzed to examine the clinical characteristics of patients with C.striatum colonization or infection.The susceptibility of these strains to 18 antimicrobial agents were tested by broth microdilution method.The gyrA gene related to quinolone resistance determining region was amplified and sequenced to analyze the position of amino acid mutations.The ribosomal methylase gene ermX and aminoglycoside enzyme gene aphA1 were amplified by PCR and sequenced.Results Antimicrobial susceptibility testing indicated that all of the 72 strains were susceptible to vancomycin,linezolid and daptomycin.All stains were resistant to ceftriaxone,ciprofloxacin and moxifloxacin.The C.striatum strains showed high resistance rate to penicillin(87.5％),cefepime(95.8％),meropenem(95.8％),trimethoprim-sulfamethoxazole(90.3％),erythromycin(98.6％)and clindamycin(98.6％),but relatively lower resistance rate to gentamycin(25.0％),tetracycline(30.6％)and rifampicin(23.6％).Sequencing analysis indicated that 3 strains of C.striatum had single mutation of gyrA gene(Ser87Val),67 strains had double mutations(Ser87Phe,Asp91Ala or Ser87Tyr,Asp91Ala)and 2 strains had three point mutations(Ser87Phe,Ala88Pro and Asp91 Ala),which was newly identified in this study.The ermXgene was detected in all of the isolates and the prevalence of aphA1 gene was 43.1％.The 72 strains of C.striatum were mainly isolated from ICU(65.2％)and lower respiratory tract specimen(91.6％).The average age of patients was 68.0±15.3 years old.About 72.2％(52/72)of the C.striatum strains were isolated from the patients with infection and 27.8％(20/72)were colonizers.Compared to the patients colonized with C.striatum,the patients with C.striatum infection had statistically significant higher percentages of hospital stay ≥ 28 days,cerebral hemorrhage,disturbance of consciousness and disease deterioration(P＜0.05).Conclusions All of the 72 C.striatum isolates were multidrug resistant,and the outcome of patients with C.striatum infection was relatively poor.

Critical care medicine-related treatment is an interdisciplinary and multi-professional process,often leading to secondary or concomitant mental disorders in clinical practice.Currently,there is no consensus on the pharmacological treatment of related mental illnesses in China.The Chinese Society of Psychosomatic Medicine collaborated with the Critical Care Medicine expert group to form a consensus writing expert group.After a systematic review of relevant literature,summarizing published domestic and foreign literature,and extensive discussions,the consensus was developed.The consensus elaborates on the principles and processes of the standardized use of psychotropic drugs in critical care medicine,as well as the clinical indications,precautions,and specific drug selection of various psychiatric medications,providing feasible suggestions and guidance for the clinical application of psychiatric medications in the intensive care unit.

Objective:To analyze the clinical characteristics, muscle imaging and pathological features of patients with anti-signal recognition particle positive immune-mediated necrotizing myopathy (SRP-IMNM).Methods:Nine patients with SRP-IMNM were collected in the Neuromuscular Disease Center of Jiaozuo People′s Hospital from May 2018 to May 2023, who were confirmed by skeletal muscle pathology and myositis-specific autoantibodies detection, and their clinical manifestations, muscle imaging and muscle pathology characteristics were systematically summarized.Results:Among the 9 patients with SRP-IMNM, there were 7 females and 2 males. The age of onset ranged from 18 to 59 years. All the patients presented proximal muscle weakness. Seven patients experienced neck weakness, and dysphagia was present in 5 patients. Laboratory examinations showed elevated serum creatine kinase levels in all 9 patients (1 866-6 725 U/L). Eight patients were combined with other antibodies positivity, except for anti-SRP antibody. Among them, 7 patients were combined with anti-Ro-52 antibody positivity, 4 patients combined with anti-Ro-52 antibody positivity alone, and 3 patients combined with 3 or more positive antibodies simultaneously. Those patients who presented with interstitial lung disease and cardiac involvement were all combined with other antibodies positivity. Seven patients completed thigh muscle magnetic resonance imaging (MRI), which showed diffuse skeletal muscle oedema, partial muscle atrophy and fatty replacement, primarily affecting the posterior thigh muscle group. Two patients underwent shank muscle MRI. The soleus involvement was evident, while the tibialis anterior muscle and gastrocnemius muscles were involved in 1 patient. All 9 patients showed varying degrees of scattered muscle fiber necrosis and regeneration on muscle biopsies. In 1 patient, a small amount of inflammatory cell infiltration was observed. Pipestem capillaries were observed in 4 patients. Immunohistochemical staining revealed a small number of CD68-positive lymphocytes in 8 patients. Additionally, 5 patients showed upregulation of major histocompatibility complex Ⅰ expression on the muscle fiber membrane, while 6 patients showed deposition of membrane attack complex (C5b-9) on non-necrotic muscle fibers and capillaries. P62 staining showed homogeneous fine-granular in sarcoplasm in 6 patients.Conclusions:In addition to proximal muscle weakness, patients with SRP-IMNM often experience neck weakness and dysphagia. Those with multiple antibodies are more likely to develop interstitial lung disease and cardiac involvement. SRP-IMNM patients have diffuse oedema in the affected muscles, and the posterior thigh muscles are more prone to atrophy and fatty tissue formation. C5b-9 deposition and pipestem capillaries are significant pathological features of SRP-IMNM, which provide additional evidence for clinical diagnosis.

Objective:To study the epidemiological and genetic characteristics of coxsackievirus B3 (CVB3) circulating in Guangdong Province from 2008 to 2021.Methods:This study collected the specimens of hand, foot, and mouth disease (HFMD) cases from 2008 to 2021 that were positive for other enteroviruses except for enterovirus 71 (EV71), coxsackievirus A16 (CVA16), and CVA6, as well as the specimens of herpangina and neonatal infection cases from 2020 to 2021. Enteroviruses in these specimens were detected and their types were identified. CVB3 strains were isolated and the entire VP1 sequences of CVB3 strains were amplified and sequenced. The genetic features of CVB3 strains were analyzed using DNAStar 7.1 and MEGA 6.06 software packages.Results:Among 3 484 HFMD cases positive for other enteroviruses from 2008 to 2021, CVB3-positive cases accounted for 1.6% (57/3 484); among 560 cases of herpangina from 2020 to 2021, CVB3-positive cases accounted for 2.1% (12/560); one neonatal infection case in 2021 was positive for CVB3. CVB3-positive cases accounted for 67.1% (47/70) in 2021 and 18.6% (13/70) in 2020, while there were less than five cases in other years. Forty-eight CVB3 strains were isolated and the entire VP1 sequences of 26 CVB3 strains were obtained. Phylogenetic analysis indicated that the CVB3 strains could be divided into eight genotypes (A-H) and the strains of genotypes A, D and E were prevalent in the Chinese mainland. The 26 CVB3 strains isolated in Guangdong Province shared 80.2%-100.0% nucleotide homology, and belonged to two genotypes of D and E, with genotype D prevalent from 2008 to 2017 and genotype E prevalent from 2020 to 2021.Conclusions:CVB3 is prevalent sporadically in Guangdong Province from 2008 to 2017, but the epidemic intensity increased during 2020 and 2021. CVB3 strains of genotypes D and E are prevalent in Guangdong Province during 2008 to 2021, with genotype E being the prevalent genotype during 2020 and 2021.

Inguinal hernia is one of the most common surgical diseases, mainly in men and elderly people, and its occurrence and development are related to many risk factors. At present, inguinal hernia can only be cured with surgery, which requires the selection of surgical methods based on patients′ conditions, medical resources and surgeons′ skills. With the aging of the popula-tion, it is expected that the number of inguinal hernia patients will continue to increase. The authors review the epidemiology, risk factors and characteristics of surgical treatment mode of inguinal hernia based on the epidemiological studies of inguinal hernia in recent years.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective We systematically analyze the changes in the count and function of platelet at the early sepsis based on clinical study and single cell sequencing.Methods Clinical data of sepsis patients at the early stage were collected and had been compared between different prognostic groups in the prospective case-control study.The independent risk factors of death were analyzed by logistic regression,and the predictive efficacy of clini-cal indicators was evaluated by receiver operating characteristic(ROC)curve.The healthy volunteers and sepsis patients were recruited.Clinical researchers collected peripheral venous blood samples for sorting cell samples to carry out single-cell RNA sequencing(sc-RNA seq).Through bioinformatics techniques,we analyzed the changes in platelet count,the significantly differential-expressed genes and its enriched functional signaling pathways in the early stages of sepsis.Results(1)A total of 224 patients were enrolled,with a 90 day survival rate of 70.5%.Compared with the survival group,the count of platelet and MAP in the death group at the early stage of sepsis were significantly lower,but the plasma lactate content and SOFA score were significantly higher.(2)Based on single cell sequencing technology,cells are annotated as six groups.The proportion of innate immune cells(neutrophils,monocytes,and dendritic cells)was significantly increased in the early stage of sepsis compared to the healthy volun-teers(2.15∶1),while platelets significantly decreased(0.31∶1).(3)Through bioinformatics technology,CD41/CD42a/CD61 was identified as platelet specific molecules,with significantly increased expression levels in sepsis.Three molecules can distinguish platelets together.(4)771 genes were significantly upregulated and 1101 genes were significantly downregulated in platelets of patients with sepsis,including core molecules involved in physiological functions such as cell adhesion,chemotaxis,and immune response.Functional analysis suggests that differentially expressed genes are enriched in coagulation,immune functions and cell death,participating in oxidative phosphory-lation,leukocyte chemotaxis,iron death,and NOD like receptor signaling pathways.Conclusion Reduced platelet count is associated with poor prognosis in the early stage of sepsis.The specific high expression molecules CD41/CD42a/CD61 that are significantly upregulated in platelets can serve as biomarkers for platelets.Platelets not only mediate cell adhesion and coagulation cascade,but also participate in functional changes such as immune cell chemotaxis,inflammatory response,and the pathological death of inflammatory cells.

Objective Visual electrophysiology and optical correlation tomography angiography(OCTA)were used to investigate differences in preoperative retinal function in patients with type 2 diabetic cataract(DC)without obvious retinopathy(NDR)and to determine the clinical application of whole-process blood glucose man-agement(WBGM)for improving postoperative vision in DC patients.Methods This study investigated the preop-erative and postoperative visual electrophysiology(N75,P100,photopic FERG,and scotopic FERG),peripapil-lary retinal nerve fiber layer(pRNFL)and peripapillary capillary vessel density(ppVD)data,as well as trends in these data changes during blood glucose management intervention.Results As the course of T2DM progressed,FBG and HbA1c increased,the N75 and P100 lategraduancy periods of patients gradually lengthened,and the photopic FERG,scotopic FERG,pRNFL,and ppVD values decreased at each postoperative time point.At the same time,the best corrected visual acuity(BCVA)of patients after surgery gradually decreased(P<0.05).Compared with that at 1 week after surgery,the BCVA of Group A(without whole-process blood glucose manage-ment)gradually increased at 1 month and 3 months after surgery but showed a downward trend at 1 year after sur-gery.The BCVA of Group B(with whole-process blood glucose management)gradually stabilized at 1 month after surgery,and at all time points after surgery,the BCVA of Group B was better than that of Group A.The results showed that N75 and P100 in Group A were greater than those in Group B,while the photopic and scotopic FERG,pRNFL,and ppVD(%)in Group A were lower than those in Group B.In addition,N75 and P100 in Group A showed a gradual prolongation trend at various time points after surgery,while photopic FERG,scotopic FERG,pRNFL,and ppVD(%)showed a gradually decreasing trend.However,the above data in Group B gradu-ally stabilized at 3 months after DC surgery,approaching the preoperative level of the group(P<0.05).In the state of whole blood glucose management,although N75 and P100 both reached their longest durations at 1 week af-ter surgery,N75,P100,photopic FERG,scotopic FERG,and pRNFL showed a gradually decreasing trend at 1 month and 3 months after surgery,while ppVD(%)gradually increased(P<0.05).At various time points from 3 months to 1 year after surgery,the overall trend of the above indicators remained stable and close to the preoperative values(P>0.05).Conclusion According to the results of the quantitative analysis of visual electrophysiology and OCTA,in DC patients without obvious retinopathy and with the worsening of diabetes,retinal function decreased,but whole-process blood glucose management effectively restored retinal function and improved visual quality after surgery.