[Objective] : To explore the clinical characteristics and methods for syndrome differentiation prediction, as well as to construct a predictive model for Qi deficiency and blood stasis syndrome in patients with acute ischemic stroke (AIS). [Methods] : This study employed a retrospective case-control design to analyze patients with AIS who received inpatient treatment at the Neurology Department of The First Hospital of Hunan University of Chinese Medicine from January 1, 2013 to December 31, 2022. AIS patients meeting the diagnostic criteria for Qi deficiency and blood stasis syndrome were stratified into case group, while those without Qi deficiency and blood stasis syndrome were stratified into control group. The demographic characteristics (age and gender), clinical parameters [time from onset to admission, National Institutes of Health Stroke Scale (NIHSS) score, and blood pressure], past medical history, traditional Chinese medicine (TCM) diagnostic characteristics (tongue and pulse), neurological symptoms and signs, imaging findings [magnetic resonance imaging-diffusion weighted imaging (MRI-DWI)], and biochemical indicators of the two groups were collected and compared. The indicators with statistical difference (P < 0.05) in univariate analysis were included in multivariate logistic regression analysis to evaluate their predictive value for the diagnosis of Qi deficiency and blood stasis syndrome, and the predictive model was constructed by receiver operating characteristic (ROC) curve analysis. [Results] : The study included 1 035 AIS patients, with 404 cases in case group and 631 cases in control group. Compared with control group, patients in case group were significantly older, had extended onset-to-admission time, lower diastolic blood pressure, and lower NIHSS scores (P < 0.05). Case group showed lower incidence of hypertension history (P < 0.05). Regarding tongue and pulse characteristics, pale and dark tongue colors, white tongue coating, fine pulse, astringent pulse, and sinking pulse were more common in case group. Imaging examinations demonstrated higher proportions of centrum semiovale infarction, cerebral atrophy, and vertebral artery stenosis in case group (P < 0.05). Among biochemical indicators, case group showed higher proportions of elevated fasting blood glucose and glycated hemoglobin (HbA1c), while lower proportions of elevated white blood cell count, reduced hemoglobin, and reduced high-density lipoprotein cholesterol (HDL-C) (P < 0.05). Multivariate logistic regression analysis identified significant predictors for Qi deficiency and blood stasis syndrome including: fine pulse [odds ratio (OR) = 4.38], astringent pulse (OR = 3.67), superficial sensory abnormalities (OR = 1.86), centrum semiovale infarction (OR = 1.57), cerebral atrophy (OR = 1.55), vertebral artery stenosis (OR = 1.62), and elevated HbA1c (OR = 3.52). The ROC curve analysis of the comprehensive prediction model yielded an area under the curve (AUC) of 0.878 [95% confidence interval (CI) = 0.855 – 0.900]. [Conclusion] This study finds out that Qi deficiency and blood stasis syndrome represents one of the primary types of AIS. Fine pulse, astringent pulse, superficial sensory abnormalities, centrum semiovale infarction, cerebral atrophy, vertebral artery stenosis, elevated blood glucose, elevated HbA1c, pale and dark tongue colors, and white tongue coating are key objective diagnostic indicators for the syndrome differentiation of AIS with Qi deficiency and blood stasis syndrome. Based on these indicators, a syndrome differentiation prediction model has been developed, offering a more objective basis for clinical diagnosis, and help to rapidly identify this syndrome in clinical practice and reduce misdiagnosis and missed diagnosis.

ObjectivesTo investigate the effect of the Bioinformatics Infrared Liver Therapeutic （BILT） instrument on portal vein blood flow， liver stiffness， and spleen stiffness in patients with liver cirrhosis， and to preliminarily explore the therapeutic effect and mechanism of the BILT instrument. MethodsA total of 78 patients with compensated liver cirrhosis who attended the outpatient service or were hospitalized in Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from October 2017 to December 2021 were enrolled， among whom 68 patients completed the 12-week treatment and were randomly divided into BILT group and simulated instrument group， with 34 patients in each group. In addition to basic treatment， the patients in the BILT group received irradiation with the BILT instrument， while those in the simulated instrument group received irradiation with the simulated instrument， for 30 minutes each time， twice a day； the course of treatment was 12 weeks for both groups. The two groups were compared in terms of laboratory markers （liver function， renal function， and routine blood test results）， liver and spleen ultrasound morphology， color Doppler blood flow detection （portal vein diameter， portal vein cross-sectional area， mean portal vein velocity， peak portal vein velocity， and mean portal vein flow）， and liver/spleen stiffness measurement before and after treatment. The independent samples t-test was used for comparison of normally distributed continuous data between two groups， and the non-parametric Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between groups. The paired samples correlation test was performed for the data before and after treatment within each group， and the paired samples t-test or the non-parametric Wilcoxon signed-rank test was performed for data with significant correlations. ResultsThe paired samples correlation test showed no correlation in spleen attenuation parameter before and after treatment， suggesting that the results of spleen fat measured by FibroTouch could not be used for statistical analysis. After 12 weeks of treatment， compared with the control group， the treatment group had significantly greater increases in portal vein diameter， portal vein cross-sectional area， and mean portal vein flow and a significantly greater reduction in liver stiffness measurement （all P0.05）. At week 0 before treatment and after 12 weeks of treatment， comparison of the immediate effect after 30 minutes of BILT irradiation showed that the treatment group had significant increases in portal vein diameter， portal vein cross-sectional area， mean portal vein velocity， and mean portal vein flow （all P0.05）， while the control group showed no significant changes after irradiation （all P0.05）； compared with the control group， the treatment group had significantly greater changes in all indicators except peak portal vein flow at week 0 （all P0.05）. No adverse events were observed in either group. ConclusionThe BILT instrument can improve portal vein blood flow in the liver and alleviate liver stiffness/fibrosis in patients with liver cirrhosis.

Objective To analyze and compare the change of disease burden attributed to high temperature in the Chinese population in 2019 compared with 1990. Methods Based on the global burden of disease study data in 2019, the number of deaths, mortality, disability-adjusted life years (DALY) and DALY rate attributable to high temperature in Chinese population of different ages and genders in 1990 and 2019 were extracted to analyze the changing trend of disease burden attributable to high temperature exposure in Chinese population and its main causes. The Joinpoint regression model was used to analyze the trend of changes in standardized attributable DALY rates. Results Compared with 1990, the number of disease deaths attributable to high temperature in China in 2019 increased from 10 700 to 13 900, and the attributable DALY decreased from 532,200 to 276 100 person-years. The standardized mortality and DALY rates decreased by 35.25% and 65.20%, respectively. The burden attributable to high temperature was higher in males than in females, and the burden was relatively heavier in the population aged 70 and above. In 2019, chronic non-communicable diseases were the main cause of the attributable burden of high temperature exposure, and ischemic heart disease had the highest DALY burden, with an age-standardized DALY rate of 4.64/100 000. Conclusion The absolute death burden attributable to high temperature exposure in Chinese population is still increasing. It is necessary to pay more attention to high-risk groups such as men and the elderly, continue to strengthen environmental protection, and formulate relevant interventions in a targeted way to further reduce the disease burden caused by high temperature exposure.

Objective:To explore the clinical characteristics and related socio-demographic factors of schizo-phrenia patients with different ages of onset.Methods:Totally 2 016 patients with schizophrenia aged 15 to 70 were selected according to the diagnostic criteria for schizophrenia in the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition.All of the patients were interviewed by psychiatrists using the Mini International Neuropsy-chiatric Interview to diagnose schizophrenia,Clinical-Rated Dimensions of Psychosis Symptom Severity(CRDPSS)and the Positive and Negative Syndrome Scale(PANSS)to assess symptoms.The cut-off points were 18 and 25 years old for three age groups,i.e.early onset(EOS),youth onset(YOS)and adult onset(AOS).Statistical analy-ses were performed by analysis of variance Pearson correlation analysis,and multivariate linear regression.Results:The early-onset patients had the highest total PANSS score(73.8±28.0)and CRDPSS score(11.7±5.4).Fe-male gender,high education level,Han ethnicity,early onset age,and slower onset of illness were negatively corre-lated with the total and dimension score of PANSS scale and CRDPSS scale(standardized regression coefficient:0.04-0.47),and income level and smoking were negatively correlated with those score(standardized regression coefficient:-0.04--0.14).Conclusion:Early-onset schizophrenia patients have more severe symptoms,and fe-male,high education level,early-onset disease,and chronic onset are the risk factors of symptom severity in patients with schizophrenia.

Objective: To investigate the effects of acupotomy on skeletal muscle fibrosis and collagen deposition in a rabbit knee osteoarthritis (KOA) model. Methods: Rabbits (n = 18) were randomly divided into control, KOA, and KOA + acupotomy (Apo) groups (n = 6). The rabbits in the KOA and Apo groups were modeled using the modified Videman's method for 6 weeks. After modeling, the Apo group was subjected to acupotomy once a week for 3 weeks on the vastus medialis, vastus lateralis, rectus femoris, biceps femoris, and anserine bursa tendons around the knee. The behavior of all animals was recorded, rectus femoris tissue was obtained, and histomorphological changes were observed using Masson staining and transmission electron microscopy. The expression of transforming growth factor-β1 (TGF-β1), Smad 3, Smad 7, fibrillar collagen types I (Col-I) and III (Col-III) was detected using Western blot and real-time polymerase chain reaction (RT-PCR). Results: Histological analysis revealed that acupotomy improved the microstructure and reduced the collagen volume fraction of rectus femoris, compared with the KOA group (P = .034). Acupotomy inhibited abnormal collagen deposition by modulating the expression of fibrosis-related proteins and mRNA, thus preventing skeletal muscle fibrosis. Western blot and RT-PCR analysis revealed that in the Apo group, Col-I, and Col-III protein levels were significantly lower than those in the KOA group (both P < .01), same as Col-I and Col-III mRNA levels (P = .0031; P = .0046). Compared with the KOA group, the protein levels of TGF-β1 and Smad 3 were significantly reduced (both P < .01), as were the mRNA levels of TGF-β1 and Smad 3 (P = .0007; P = .0011). Conversely, the levels of protein and mRNA of Smad 7 were significantly higher than that in the KOA group (P < .01; P = .0271). Conclusion Acupotomy could alleviate skeletal muscle fibrosis and delay KOA progress by inhibiting collagen deposition through the TGF-β/Smad pathway in the skeletal muscle of KOA rabbits.

Objective To investigate the feasibility, safety, and short-term efficacy of minimally invasive McKeown esophagectomy (MIME) in patients with locally advanced thoracic esophageal squamous cell carcinoma (TESCC) after neoadjuvant immunotherapy. Methods The clinical data of the patients with locally advanced TESCC in the First Affiliated Hospital of University of Science and Technology of China from July 2022 to March 2023 were restrospectively analyzed. They were divided into a neoadjuvant immunotherapy (NI) group and a non-neoadjuvant immunotherapy (NNI) group according to different preoperative neoadjuvant therapy. The perioperative clinical data and 3-month follow-up data were compared between the two groups. Results A total of 47 patients were collected, including 31 males and 16 females with a mean age of (67.57±7.64) years. There were 29 patients in the NI group and 18 patients in the NNI group. There were no statistical differences in baseline data, perioperative complications, short-term complications, surgical time, intraoperative bleeding, postoperative adjuvant therapy, metastasis/recurrence within 3 months, R0 resection rate, postoperative pathological staging decline, or College of American Pathologists (CAP) tumor regression grade between the two groups (P＞0.05). Conclusion Neoadjuvant immunotherapy combined with minimally invasive McKeown esophagectomy can be safely and effectively performed for patients with locally advanced TESCC without increasing operation time, intraoperative blood loss and perioperative complications.

Objective To explore the pharmacodynamic substances of Simiao Wan for the treatment of hyperuricemia and gout.Methods The pharmacological model of hyperuricemia was established.The chemical components in vivo and in vitro of Simiao Wan were analyzed by UPLC-Q-Exactive-MS.Based on the components absorbed in blood,the"active ingredient-target-pathway"network of Simiao Wan for regulating hyperuricemia and gout was constructed by network pharmacology method.The key ingredients were used for molecular docking with key targets[uricogenase(XDH),uric acid transporter(ABCG2,GLUT9,OAT1,URAT1)and inflammatory targets(PTGS2,TLR2,TLR4)]of hyperuricemia and gout.Finally,experimental verification was conducted according to the results of molecular docking.Our aim is to identify the key pharmacodynamic substances of Simiao Wan for the treatment of hyperuricemia and gout.Results Eighty-nine components of Simiao Wan were identified by UPLC-Q-Exactive-MS analysis,including 74 components absorbed in blood,which were confirmed as candidate ingredients.Network pharmacology was used to constructed"components absorbed in blood-target-pathway"network,and components absorbed in blood were matched with 116 targets of hyperuricemia and 173 targets of gout.It is involved in the regulation of biological processes,such as glucose and lipid metabolism,oxidative stress,inflammatory response,ERK1 and ERK2 cascade,MAPK cascade,PI3K signal transduction.Moreover,Simiao Wan plays a role in regulating the network of hyperuricemia and gout through regulating blood lipids and atherosclerosis,apoptosis,AGE-RAGE,TNF,PI3K-Akt,MAPK,TLRs,JAK-STAT,NF-κB and other signaling pathways.Molecular docking studies showed that berberine,phellodendrine,magnoflorine,jatrorrhizine,palmatine,obacunone,limonin,atractylodin,taxifolin,atractylenolide Ⅲ and β-ecdysterone had good affinity with uric acid synthase,uric acid transporter and inflammatory targets.Western Blot test showed that taxifolin negatively regulates the expression of URAT1.The above-mentioned compounds were the main pharmacodynamic substances of Simiao Wan for the treatment of hyperuricemia and gout.Conclusion This article describes the main pharmacodynamic substances of Simiao Wan in the regulation of hyperuricemia and gout,which can provides a scientific basis for the clinical application,improvement in quality evaluation and standard of Simiao Wan.

Objective To improve the efficiency of induced differentiation of primitive neural epithelial cells derived from human induced pluripotent stem cells(hiPSCs-NECs)into functional midbrain dopaminergic progenitor cells(DAPs).Methods HiPSCs were cultured in mTeSRTM medium containing DMH1(10 μmol/L),SB431542(10 μmol/L),SHH(200 ng/mL),FGF8(100 ng/mL),purmorphamine(2 μmol/L),CHIR99021(3 μmol/L),and N2(1%)for 12 days to induce their differentiation into primitive neuroepithelial cells(NECs).The hiPSCs-NECs were digested with collagenase IV and then cultured in neurobasal medium supplemented with 1%N2,2%B27-A,BDNF(10 ng/mL),GDNF(10 ng/mL),AA,TGF-β,cAMP,and 1%GlutaMax in the presence of different concentrations of Rho kinase inhibitor Y27632,and the culture medium was changed the next day to remove Y27632.Continuous induction was performed until day 28 to obtain DAPs.Results Human iPSCs expressed the pluripotency markers OCT4,SOX2,Nanog,and SSEA1 and were positive for alkaline phosphatase staining.The hiPSCs-NECs were obtained on day 13 in the form of neural rosettes expressing neuroepithelial markers SOX2,nestin,and PAX6.In digested hiPSCs-NECs,the addition of 5 μmol/L Y27632 significantly promoted survival of the adherent cells,increased cell viability and the proportion of S-phase cells(P<0.01),and reduced the rate of apoptotic cells(P<0.05).On day 28 of induction,the obtained cells highly expressed the specific markers of DAPS(TH,FOXA2,NURR1,and Tuj1).Conclusion Treatment with Y27632(5 μmol/L)for 24 h significantly promotes the survival of human iPSCs-NECs during their differentiation into DPAs without affecting the cell differentiation,which indirectly enhances the efficiency of cell differentiation.

Objective To investigate the binding and carrying effects of human serum albumin(HSA)from various sources on sphingosine-1-phosphate(S1P).Methods Utilizing human plasma-derived HSA(pHSA)and recombinant HSA(rHSA)samples as the focal points of our investigation,LC-MS/MS technology was employed to meticulously compare and an-alyze the disparities in S1P content among the aforementioned samples.Subsequently,under physiological concentration condi-tions,S1P was directly introduced to HSA samples for loading processing,facilitating a comprehensive comparison of the bind-ing efficacy of HSA from different sources to S1P.Within a serum-free culture setting,HSA samples from various sources were co-cultured with HUVEC cells.The alterations in S1P content within the cell culture supernatant across different treatment groups were meticulously analyzed,allowing for a nuanced comparison of the S1P carry effects exerted by HSA from different sources on cells.The interaction between HSA and S1P molecules from different sources was analyzed and their affinity was cal-culated using surface plasmon resonance(SPR)technology.Furthermore,leveraging AutoDock Vina software and the Mol-prophet platform,the molecular docking analysis of HSA and S1P was conducted,aiming to predict the key binding pocket do-main of S1P within HSA.Results All pHSA samples exhibited detectable levels of S1P(ranging from 3.31±0.03 to 30.35±0.07 μg/L),with significant variations observed among pHSA samples from different manufacturers(P＜0.001).Conversely,S1P was undetectable in all rHSA samples.Upon load treatment,the binding affinity of HSA from diverse sources to S1P dem-onstrated significant discrepancies(P＜0.001),with rHSA exhibiting approximately double the average S1P loading compared to pHSA(ΔCrHSA=801.75±142.45 μg/L vs ΔCpHSA=461.94±85.73 μg/L;P＜0.001,t=5.006).Co-culture treatment out-comes revealed a significant elevation in S1P concentration within the supernatant after 6 hours of co-culture across all HSA sample processing groups with HUVEC cells,while no changes were observed in the supernatant of the blank control group.Notably,significant differences in supernatant S1P concentration were observed among treatment groups at 6 h,12 h,and 24 h(P＜0.001).SPR analysis unveiled a stronger affinity of pHSA for S1P compared to rHSA(KDpHSA-S1P:2.38E-06,KDrHSA-S1P:3.72E-06).Molecular docking analysis and binding pocket prediction suggested that the key binding pocket of HSA and S1P may reside in the IB subdomain of the HSA molecule.Conclusion HSA from various sources exhibits distinct binding and carrying effects on S1P,which appear to be closely associated with the IB subdomain of the HSA molecule.

Objective To improve the efficiency of induced differentiation of primitive neural epithelial cells derived from human induced pluripotent stem cells(hiPSCs-NECs)into functional midbrain dopaminergic progenitor cells(DAPs).Methods HiPSCs were cultured in mTeSRTM medium containing DMH1(10 μmol/L),SB431542(10 μmol/L),SHH(200 ng/mL),FGF8(100 ng/mL),purmorphamine(2 μmol/L),CHIR99021(3 μmol/L),and N2(1%)for 12 days to induce their differentiation into primitive neuroepithelial cells(NECs).The hiPSCs-NECs were digested with collagenase IV and then cultured in neurobasal medium supplemented with 1%N2,2%B27-A,BDNF(10 ng/mL),GDNF(10 ng/mL),AA,TGF-β,cAMP,and 1%GlutaMax in the presence of different concentrations of Rho kinase inhibitor Y27632,and the culture medium was changed the next day to remove Y27632.Continuous induction was performed until day 28 to obtain DAPs.Results Human iPSCs expressed the pluripotency markers OCT4,SOX2,Nanog,and SSEA1 and were positive for alkaline phosphatase staining.The hiPSCs-NECs were obtained on day 13 in the form of neural rosettes expressing neuroepithelial markers SOX2,nestin,and PAX6.In digested hiPSCs-NECs,the addition of 5 μmol/L Y27632 significantly promoted survival of the adherent cells,increased cell viability and the proportion of S-phase cells(P<0.01),and reduced the rate of apoptotic cells(P<0.05).On day 28 of induction,the obtained cells highly expressed the specific markers of DAPS(TH,FOXA2,NURR1,and Tuj1).Conclusion Treatment with Y27632(5 μmol/L)for 24 h significantly promotes the survival of human iPSCs-NECs during their differentiation into DPAs without affecting the cell differentiation,which indirectly enhances the efficiency of cell differentiation.