Background and aims:Primary sclerosing cholangitis(PSC)is an autoimmune liver disease characterized by complex pathogenesis and limited available therapeutic options.The mechanisms underlying the development and progression of PSCs remain unclear.Liver X receptor beta(LXR-β)is recognized to modulate lipid metabolism and immune response,but its specific involvement in the PSC has not been elucidated.Here,we explored the role and mechanism of LXR-β in PSC induced by 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-collidine(DDC).Methods:CRISPR-Cas9 technology was applied to generate Abcb4(coding MDR2,next named as Mdr2),Nr1h2(coding LXR-β,next named as Lxrβ),and Rag2(coding RAG2)knockout mice.DDC was used to induce PSC.Hematoxylin and eosin and Sirius red staining were used to assess the extent of hepatic injury and fibrosis.Flow cytometry was used to observe immune cell subsets.Results:We observed a declining trend in hepatic Lxrβ in the PSC model.Unexpectedly,Lxrβ knockout failed to modulate DDC-induced PSC pathogenesis.Concomitantly,assessment of the influence of Rag2 deficiency on PSC progression revealed the absence of aggravated or alleviated hepatic injury or fibrosis in the Rag2-/-DDC mice.However,Lxrβ depletion intensified DDC-induced PSC in the Rag2-/-mice,with more abundant infiltrative inflammatory cells and more severe liver fibrosis.Compared with Rag2-/-DDC mice,Lxrβ-/-Rag2-/-DDC mice had higher serum ALT and AST levels and mRNA expression of proinflammatory and profibrotic genes.Flow cytometry showed that LXR-β deficiency resulted in a diminished population of hepatic innate immune cells.Conclusion:This study indicated innate immune cell LXR-β deficiency can exacerbate hepatic injury and fibrosis in murine models of PSC suggesting that LXR-β may regulate the function of innate immunity in the fibrotic advancement of PSC.

Objective To compare the long-term efficacy of intradiscal injection of autologous platelet-rich plasma(PRP)and intradiscal injection of autologous PRP combined with pulsed radiofrequency(PRF)therapy for discogenic back pain(DBP).Methods Prospective inclusion of 98 DBP patients who received treatment at Hai'an People's Hospital from July 2019 to December 2023 was conducted.The patients were randomly divided into study group(receiving PRP combined with PRF,n=50)and control group(receiving PRP only,n=48).The preoperative and the postoperative 1-,3-,6-,and 12-month baseline data,visual analog scale(VAS)score,Roland-Morris Disability Questionnaire(RMDQ)score,Leeds Neurological Symptoms and Signs Score(LANSS),European Society for Quality of Life Five Dimensional Questionnaire(EQ-5D)score,and the use of non-steroidal anti-inflammatory and analgesic drugs were compared between the two groups.Results There was no statistically significant differences in the baseline data and the incidence of intraoperative and postoperative adverse reactions between the two groups(both P＞0.05).At 12 months after surgery,the VAS,RMDQ,LANSS,EQ-5D scores,and the use of non-steroidal anti-inflammatory and analgesic drugs in all patients were significantly better than those before surgery(all P＜0.05).The postoperative 3-,6-,and 12-month VAS,RMDQ,LANSS,EQ-5D scores,and the analgesic dosage in the study group were significantly better than those in the control group(all P＜0.05),and the percentages of patients with pain relief greater than 50％and greater than 80％were also significantly higher than those in the control group(all P＜0.01).Conclusion for the treatment of DBP,both CT-guided intradiscal injection of autologous PRP and CT-guided intradiscal injection of autologous PRP combined with PRF can significantly improve pain,body function,and quality of life in DBP patients,and significantly reduce the use of non-steroidal anti-inflammatory and analgesic drugs.The efficacy of autologous PRP combined with PRF is remarkably better than that of autologous PRP alone.

AIM: To evaluate the changes in corneal epithelial thickness(CET)and corneal optical density(CD)after smart pulse technology(SPT)-assisted transepithelial photorefractive keratectomy(TPRK)and analyze their correlation.METHODS: The prospective study included 60 patients(120 eyes)with myopia and myopic astigmatism who underwent SPT-TPRK in the ophthalmology department at the First Affiliated Hospital of Xinxiang Medical University between February and August 2023. Changes in CET and CD were evaluated preoperatively and at 1 wk, 1 and 3 mo postoperatively.RESULTS: A total of 14 cases(28 eyes)were lost to follow-up, and 3 patients(6 eyes)with postoperative haze were excluded from this study, resulting in a final inclusion of 43 patients(86 eyes). At 1 wk after SPT-TPRK, CET had statistically significantly thickened compared to preoperative levels(P<0.05), particularly in the CET at 0-2 mm central corneal area(P<0.05). At 1 mo after SPT-TPRK, the CET at 0-2 mm area had statistically significantly decreased(P<0.05). At 3 mo after SPT-TPRK, the CET at 0-2 mm had essentially reached preoperative levels. Postoperative CD values increased, with a positive correlation between CET in the 0-2 mm area and CD in the whole 0-2 mm area(r=0.256, P<0.05), and a positive correlation between CET in the 2-5 mm area and CD in the anterior 2-6 mm area(r=0.319, P<0.05).CONCLUSION: Corneal epithelial remodeling takes 3 mo in areas within 2 mm of the central cornea; areas with thinner CET have faster postoperative corneal epithelial remodeling and greater thickening in the early postoperative period; CD increases in the early postoperative period compared to the preoperative value, and in some areas, there is a positive correlation between CET and CD value.

Objective: To explore the associations of physical activity and sleep quality with anxiety and depressive symptoms in college students, in order to provide empirical support and theoretical guidance for mental health intervention among college students. Methods: From March to April 2023, 2 099 college students from universities in 6 different provinces were selected by a convenient sampling method. Physical activity, sleep quality, anxiety and depressive symptoms were evaluated by the International Physical Activity Questionnaire Short Form (IPAQSF), the Pittsburgh Sleep Quality Index (PSQI), the Center for Epidemiologic Studies Depression Scale (CESD) and the Anxiety SelfRating Scale (SAS), respectively. Descriptive statistics and Logistic regression models were used to analyze the data. Results: The reporting rates of lowintensity, moderateintensity, and highintensity physical activity among college students were 30.3%, 45.3%, and 24.4%, respectively. Moreover, among the participants, anxiety was detected in 21.6% and depressive symptoms in 39.9%, while 62.3% experienced poor sleep quality. Compared with males, females exhibited a lower proportion of highintensity physical activity (22.3% vs 42.8%), while reported higher proportions of moderateintensity (48.1% vs 40.8%) and lowintensity physical activity (29.5% vs 16.4%). Additionally, the proportion of females reporting poor sleep quality (65.0%) was higher than that of males (58.0%) (χ2=110.15, 10.70, P<0.05). The proportion of girls (43.8%) with depressive sypmtoms was higher than that of boys (33.9%) (χ2=20.48, P<0.05). Logistic regression analysis showed that high physical activity was negatively correlated with anxiety and depression (OR=0.45, 0.33), poor sleep quality was positively correlated with anxiety and depressive symptoms (OR=3.89, 3.94) (P<0.01).The interaction effect between high physical activity and good sleep quality was associated with the reduction of anxiety and depression among college students (OR=0.14, 0.08, P<0.01). Conclusions Physical activity and sleep quality are associated with anxiety and depressive symptoms among college students. The interventions for mental health problems such as depression and anxiety among college students should aim to improve physical activity and sleep quality.

Objective: To examine the association of 24 hour movement behaviors with emotional and behavioral problems among left behind children, so as to provide a theoretical reference for the practice of 24 hour activity interventions to promote emotional and behavioral problems in this population. Methods: From February to May 2023, 1 117 left behind children in grades 4-6 from 10 primary schools in five cities in Zhejiang Province were selected using a convenient cluster sampling method to conduct a questionnaire survey examining 24 hour movement behaviors, as well as emotional and behavioral problems. The general linear model was adopted to analyze the association between satisfying the 24 hour movement behavior guidelines, and emotional and behavioral problems among left behind children. Results: The sleep duration compliance rate was the highest (52.19%), while the moderate-to-vigorous PA (MVPA) compliance rate was the lowest (17.73%). The compliance rate of the three activities accounted for 7.43 %. There was a dose response between the number of guidelines satisfied, and the emotional and behavior of left behind children; that was, satisfaction of a higher number of guidelines was associated with a lower risk of emotional and behavioral problems among left behind children (difficulty factor: β=-0.56, 95%CI =-1.23--0.19; strength factor: β=0.50, 95%CI =-0.48-1.22, P < 0.01). Compared to satisfying none of the guidelines, satisfying the guidelines for screen time ( β=-0.23, 95%CI =-2.18- -0.14 ) and sleep duration ( β=-0.13, 95%CI =-1.66--0.11) was negatively correlated with the difficulty factor, while satisfying the guideline for MVPA ( β=0.13, 95%CI =0.09-1.08) and sleep duration ( β=0.18, 95%CI =0.09-1.40) was positively associated with the strength factor. In addition, satisfying two or all three of the guidelines was more strongly associated with these outcomes than satisfying one of the recommendations ( P <0.01). Conclusions Meeting the 24 hour movement behavior guidelines can improve emotional and behavioral problems among left behind children. It is necessary to raise their awareness of the effect of satisfying the 24 hour movement behavior guidelines and formulate comprehensive intervention measures.

Objective:To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods:The prospective multicenter study was conducted in Zhejiang, China from May 1 st, 2019 to January 31 st, 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results:A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P<0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95% CI 0.593-0.771, P<0.01). Conclusion:In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.

Objective:To evaluate the long-term efficacy and safety of B cell maturation antigen(BCMA)-chimeric antigen receptor-T(CAR-T)cells in the treatment of recurrent/refractory multiple myeloma(R/R MM).Methods:A retrospective analysis was conducted on the clinical data of 20 patients with R/R MM who received BCMA CAR-T-cell therapy at The First Affiliated Hospital of Nanchang University between July 2018 and July 2023.The follow-up period was up to December 31,2023.Overall survival and progression-free survival(PFS)rates were eval-uated using Kaplan-Meier analysis,and adverse effects were recorded.Results:Of all 20 cases with R/R MM,the median number of previ-ous treatment lines was three(range:two to six),total objective response rate(ORR)was 75%,and complete response(CR)rate was 50%.The median follow-up duration was 29 months,with a median PFS of 26 months.Among ten patients with CR,five were still in remission at the last follow-up,with the shortest duration of remission being 6 months and the longest being 48 months.In the subgroup analysis,PFS was significantly worse in patients with extramedullary infiltration,high tumor burden,and 17p deletion high-risk cytogenetic features(P<0.05).Cytokine release syndrome(CRS)was the most common(90%)adverse event,and it was mostly mild,with an incidence rate of grade 3 or higher of 35%.Few long-term adverse effects occurred and no CAR-T cell treatment-related deaths were observed.Conclusions:BCMA CAR-T-cell therapy was effective and safe for patients with R/R MM.Patients with extramedullary diseases and high tumor burden can also benefit from this treatment;however,their persistent response is not satisfactory.It is worth exploring the differences and design-ing prospective clinical studies to consolidate and maintain the efficacy in these patients.

BACKGROUND: Preliminary studies have indicated that Shexiang Baoxin Pill (MUSKARDIA) has a coronary artery dilation effect and increases the coronary blood flow, relieving the symptoms of angina. This study aimed to evaluate the benefit of MUSKARDIA on patients with stable coronary artery disease (CAD) and diabetes mellitus (DM). METHODS: This was a subgroup analysis of a multicenter, randomized, placebo-controlled phase IV trial. CAD patients with a medical history of DM or baseline fasting blood glucose (FBG) ≥7.0 mmol/L were grouped according to the treatment (standard therapy plus MUSKARDIA or placebo). The primary outcome was major adverse cardiovascular events (MACEs), which was the composite outcome of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. The secondary outcome was the composite outcome of all-cause death, non-fatal myocardial infarction, non-fatal stroke, hospitalization for unstable angina or heart failure, and coronary angioplasty. RESULTS: MACEs occurred in 2.6% (9/340) and 4.8% (18/376) of patients in the MUSKARDIA and placebo groups, respectively ( P  = 0.192). Secondary composite outcome was significantly less frequent with MUSKARDIA than with placebo (15.3% [52/340] vs . 22.6% [85/376], P  = 0.017). Risk of MACEs (hazard ratio [HR] = 0.69, 95% confidence interval [CI]: 0.31-1.57) was comparable between two groups. In patients with uncontrolled DM (≥4 measurements of FBG ≥7 mmol/L in five times of follow-up), the risk of secondary outcome was significantly lower with MUSKARDIA (5/83, 6.0%) than with placebo (15/91, 16.5%) (HR = 0.35, 95%CI: 0.13-0.95). CONCLUSION: As an add-on to standard therapy, MUSKARDIA shows a trend of reduced MACEs in patients with stable CAD and DM. Furthermore, MUSKARDIA may reduce the frequency of all-cause death, hospitalization, and coronary angioplasty in this population, especially in those with uncontrolled DM. TRIAL REGISTRATION ChiCTR.org.cn, ChiCTR-TRC-12003513.
Humans ; Coronary Artery Disease/complications* ; Diabetes Mellitus, Type 2/drug therapy* ; Myocardial Infarction/complications* ; Stroke/epidemiology*

Objective: To explore the relationship between 24 hour movement behavior and physical fitness in college students, so as to provide a reference for physical fitness interventions for college students. Methods: A survey was conducted from September 23 to November 12, 2022, involving 342 college students selected from one comprehensive college among Shanghai City, Hubei Province and Zhejiang Province. Accelerometers were used to measure 24 hour movement behavior, and programs specified in the National Physical Fitness Standards for Students (2014 revision) were used to evaluate physical fitness. Compositional linear regression was used to analyze the association between 24 hour movement behavior and physical fitness. The effects of compositional isotemporal substitution of 24 hour movement behavior on physical fitness were also examined. Results: The geometric means for sleep, sedentary behavior, light physical activity (LPA), and moderate to vigorous physical activity (MVPA) were 515.89, 678.88 , 196.30, 48.92 min/d, respectively, and the comprehensive physical fitness score was (73.09±8.55). The proportion of participants who passed the fitness test was 72.51%. Overall, 20.76% had excellent or good scores, whereas 6.73% failed. Compositional linear regression indicated that physical fitness was significantly positively associated with MVPA ( β =2.55) and LPA ( β = 5.88 )( P <0.05), but no significantly associated with sleep ( β =-5.18) and sedentary behavior ( β =-3.24)( P >0.05). Isotemporal substitution indicated that reallocation of 15 minutes from sleep and sedentary behavior to MVPA resulted in a 0.71 and 0.64 point increase in physical fitness, respectively. Similarly, reallocating the same duration to LPA led to a 0.50 and 0.43 point increase in physical fitness, respectively. Dose response analysis revealed that the mutual substitution of LPA with sedentary behavior and sleep had symmetry, whereas the mutual substitution of MVPA with sedentary behavior and sleep had asymmetry. The effectiveness of replacing sleep or sedentary behavior with MVPA in improving physical fitness decreased with increasing allocation time, whereas the adverse effects of replacing MVPA with sleep or sedentary behavior increased with increasing allocation time. Conclusion In the context of 24 hour movement behavior, increasing the time spent on LPA and MVPA is beneficial for physical fitness among college students. It should be recommend that college students actively transition from sedentary behavior to engaging in physical activity, with a particular emphasis on incorporating MVPA.