ObjectiveTo investigate whether photoreceptor-specific knockout of lanosterol synthase （Lss） induces age-related retinal degeneration and to elucidate the underlying molecular mechanisms. MethodsPhotoreceptor-specific Lss knockout mice （Lss^flox/flox； Rho-Cre， CKO） models were established. Retinal structure and function were assessed at 1， 4， and 8 months of age using fundus photography， optical coherence tomography （OCT）， scotopic electroretinogram （ERG） and hematoxylin and eosin （HE） staining. The mouse photoreceptor cell line 661W served as an in vitro model. Lss was knocked down via siRNA， followed by analyses including Seahorse XF mitochondrial stress test， JC-1， MitoSOX Red and DCFH-DA probes to evaluate mitochondrial function and oxidative stress， glycolytic rate assay for glycolysis ability， RT-qPCR for inflammatory factors， γH2AX immunofluorescence for double-strand DNA damage detection， and transcriptome sequencing to identify differentially expressed genes and enriched pathways. ResultsCompared with controls， 1-month-old CKO mice showed no abnormalities. Mild fundus lesions appeared at 4 months. By 8 months， CKO mice exhibited significant thinning of the outer nuclear layer， disorganization of the inner/outer segment structure， and markedly reduced amplitudes of the dark-adapted ERG a- and b-waves （P<0.05）. Transcriptome analysis revealed 1 842 differentially expressed genes （826 up-regulated， 1 016 down-regulated）， with Lss being the most significantly downregulated gene； these genes significantly enriched in sterol biosynthesis， oxidative phosphorylation， aerobic electron transport chain， and ATP synthesis （P<0.05）. In 661W cells， knockdown of Lss significantly reduced mitochondrial basal respiration （P=0.006）， ATP production （P=0.015）， maximal respiration （P<0.001）， and spare respiratory capacity （P<0.001）， while basal glycolysis （P=0.005） and compensatory glycolysis （P=0.028） were increased. These changes were accompanied by mitochondrial membrane potential depolarization （P<0.001）， elevated mitochondrial reactive oxygen species （ROS） levels （P<0.001）， and increased total ROS levels （P=0.013）. Additionally， the mRNA expression of inflammatory factors， including Ccl2 （P=0.004）， Ccl5 （P=0.012）， Cxcl1 （P<0.001）， Cxcl5 （P<0.000 1）， Tgfb （P=0.008）， Hgf （P<0.000 1） and Mmp3 （P=0.003） was significantly upregulated. Moreover， γH2AX fluorescence intensity was increased （P=0.002）. ConclusionsPhotoreceptor-specific Lss deficiency induces mitochondrial dysfunction， oxidative stress and cellular inflammation， ultimately leading to age-dependent retinal degeneration. This study provides novel mechanistic insights and potential therapeutic targets for hereditary and age-related retinal degenerative diseases.

Objective To evaluate the impact of traditional Chinese medicine(TCM)syndromes on percutaneous microwave ablation(MWA)treatment in patients with colorectal cancer liver metastases(CRLM)and to construct a multidimensional prediction model prognostic based on TCM syndrome classification.Methods Clinical data were collected from 86 CRLM patients who underwent MWA at Zhongshan Hospital of Traditional Chinese Medicine between October 2012 and October 2023.The clinical information covered TCM syndrome types of qi-blood deficiency and spleen-kidney yang deficiency,tumor characteristics,and treatment parameters.Logistic regression was used to screen feature variables for constructing the prognostic predication model,and cross validation was performed to evaluate the prognostic predictive performance.Results(1)Among the 86 CRLM patients,31(36.05%)had spleen-kidney yang deficiency syndrome,while 55(63.95%)had qi-blood deficiency syndrome.(2)Compared to the patients with spleen-kidney yang deficiency syndrome,patients with qi-blood deficiency syndrome exhibited significantly long progression-free survival(PFS)and high progression-free survival rate(P＜0.01),while no significant differences were presented in the incidences of postoperative adverse events such as pain,fever,infection,liver function impairment,or ascites/pleural effusion among the patients with the two syndrome types(P＞0.05).(3)Multivariate logistic regression analysis revealed that TCM syndrome type,maximum diameter of metastatic liver tumor,timing of liver metastasis,and Ki-67 expression rate of primary tumors were the independent prognostic factors for 1-year PFS(P＜0.05 or P＜0.01).(4)The constructed model demonstrated high predictive accuracy for PFS,with an area under the receiver operating characteristic(ROC)curve(AUC)of 0.905(95%CI:0.830-0.980).Conclusion TCM syndromes have significant influence on the prognosis of CRLM patients undergoing MWA,and the patients with qi-blood deficiency syndrome have favorable prognosis.This study pioneers a multidimensional prognostic prediction model integrating TCM syndromes for MWA-treated CRLM patients,highlighting the unique value of TCM syndromes in assessing disease progression and predicting prognosis.

OBJECTIVE To provide reference for the establishment and improvement of the regulatory system of patients'medicine instructions in China.METHODS Through searching the official website of the European Medicines Agency(EMA)and related literature,the definition,basic nature,and content of patients'medicine instructions in the European Union were introduced,and the characteristics of the management system of patients'medicine instructions in the European Union were analyzed in terms of the management department,approval and change procedures,readability requirements and information accessibility requirements.At the same time,the pilot situation of patients'medicine instructions in China,as well as problems in the paths of classification and management,readability of content,and information timeliness were analyzed to put forward suggestions.RESULTS & CONCLUSIONS European Union had a dedicated department for the management of medicine instructions;the approval and change procedures for patients'medicine instructions were clear,the readability requirements were detailed,the readability verification program with patient participation was established,and multi-channel and timely information disclosure was adopted.It is recommended that China establish a mechanism to categorize and manage professionals'and patients'medicine instructions,guide multiple parties to participate in the design of patients'medicine instructions and refine the readability requirements,and improve the mechanism for disclosure of medicine instructions to enhance the timeliness of medication information.

ObjectiveTo understand the acceptance of sex-related behaviors， sexual safety awareness， and refusal skills among junior high school students and conduct association analysis， and to provide a reference for the implementation of sex and reproductive health education for adolescents. MethodsA questionnaire survey related to knowledge of sexual and reproductive health was conducted among 478 students from two junior high schools in Jiading District， Shanghai. ResultsThe pass rate for sex and reproductive health knowledge among junior high school students was only 36.6%， with acceptance rates for dating， watching pornography， engaging in sexual behavior， pregnancy， and artificial abortion at 24.5%， 11.1%， 5.6%， 4.8%， and 5.9%， respectively. Binary logistic regression analysis showed that students who passed the sexual and reproductive health assessment had a significantly lower acceptance rate of sex-related behaviors than those who did not （aOR=1.666， 95%CI： 1.124‒2.470， P=0.011）. Adolescents with a passing knowledge of sexual and reproductive health （aOR=1.607， 95%CI： 1.060‒2.438， P=0.026） or a lower acceptance of sex-related behaviors （aOR=4.199， 95%CI： 2.804‒6.289， P<0.001） had higher awareness of sexual safety. Adolescents with a passing knowledge of sexual and reproductive health （aOR=1.691， 95%CI： 1.066‒2.684， P=0.026）， a lower acceptance of sex-related behaviors （aOR=1.756， 95%CI： 1.130‒2.729， P=0.012）， or higher awareness of sexual safety （aOR=2.872， 95%CI： 1.826‒4.516， P<0.001） had stronger skills to refuse sex-related behaviors. ConclusionSexual and reproductive attitudes， sexual safety awareness， and refusal skills for sex-related behaviors among junior high school students in Jiading District need to be improved. Schools should focus on cultivating adolescents’ sexual and reproductive knowledge and related skills， and advocate for relevant institutions to provide appropriate sexual healthcare services to meet their needs for reproductive healthcare.

OBJECTIVE To analyze the practices of electronic drug instructions in the European Union （EU）， the United States （US） and Japan， so as to provide references for promoting electronic drug instructions under Chinese existing regulatory systems. METHODS By searching the official websites of FDA， European Medicines Agency （EMA） and Pharmaceuticals and Medical Devices Agency （PMDA）， as well as relevant literature， the practice and system of electronic drug instructions in different countries/regions were compared and analyzed. The problems of regulatory system， accessibility form and management system of electronic drug instructions in China were analyzed to put forward the suggestions. RESULT ＆＆ CONCLUSIONS The EU， the US and Japan had established relevant laws for the implementation of electronic drug instructions， issued guidance to specify management requirements and work processes， and set up information platforms to standardize data requirements and enrich search channels. In contrast， the practice of electronic drug instructions in China is still in its infancy， the implementation of electronic drug instructions in China still lacks legislative support， and its accessibility form and future regulatory system need to be further explored. It is suggested to take the opportunity to carry out the pilot reforms of the age-friendly and barrier-free environment for drug instructions in China， improve the regulatory system of electronic drug instructions， promote the readability of drug instructions by exploring the accessibility form of electronic drug instructions in stages， establish and improve the regulatory system of electronic drug instructions， actively build an electronic information platform for it， and promote the development and implementation of electronic drug instructions.

Objective:To explore the oxidative stress of cerebral white matter lesion (WML) and normal-appearing white matter (NAWM) with in vivo proton exchange rate (k ex) MRI on relapse-remitting multiple sclerosis (RRMS) patients. Methods:Clinical and imaging data of 37 patients (case group) with RRMS patients of Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology were analyzed retrospectively from November 2018 to November 2021, including 11 males and 26 females aged 18-41 (29±7) years. Another 22 age-matched healthy volunteers (control group) were recruited for the same period, including 4 males and 18 females aged 23-44 years with a median age of 25 (24, 28.25) years. All subjects received conventional MR protocols and chemical exchange saturation transfer imaging. The manifestation of WML on the k ex map and T 1WI images were assessed while the k ex values of WML, NAWM and normal white matter (NWM) of control group were quantitatively evaluated. Student′s t test was used to compare the k ex difference of WML and NAWM in the case group, NAWM in the case group and NWM in the control group, low-signal and isosignal WML in T 1WI. Spearman rank correlation was used to analyze the correlation of the k ex values of WML with patients′ expanded disability status scale (EDSS) score. Results:A total of 272 WML were found in the 37 RRMS patients, and 25.4% (69/272) were T 1-hypointense. The k ex value of WML in the case group [(932±108) s -1] was higher than that of NAWM [(771±26) s -1], and the difference was statistically significant ( t=8.95, P<0.001); the k ex value of NAWM in the case group [(771±26) s -1 ] was higher than that of NWM [(745±26) s -1] in the control group, and the difference was statistically significant ( t=3.96, P<0.001). The k ex value [(1 039±110) s -1] of WML with low signal at T 1WI was higher than that of WML with equal signal [(895±79) s -1], with a statistically significant difference ( t=9.78, P<0.001). Correlation analysis showed that the k ex value of WML in the case group was positively correlated with the EDSS score ( r=0.54, P<0.001). Conclusions:The elevated k ex values of WML and NAWM reflect the cerebral oxidative stress of RRMS patients and are positively correlated to the severity of tissue damage, which suggests the role of oxidative stress in RRMS lesion formation and brain atrophy.

Objective To explore the application of the standard of Chinese lymph node dissection in minimally invasive esophagectomy.Methods Methods Between April 2014 to September 2015,63 patients with esophageal carcinoma received minimally invasive esophagectomy by the same group of surgeons.Wedescribed in detail the methods of thoracic esophagus mobilization and lymph node dissection in the peri-esophageal space.We analyzed the surgical effect,postoperative complications and follow-up results.Resnits The average operation time was(280.48 ± 44.28) mins,the median intraoperative blood loss was 100 ml,the mean number of lymph nodes was 22.25-± 11.18;the incidence of postoperative pulmonary infection in 28.57％,hoarseness was 17.46％,anastomotic leakage was 12.70％,postoperative 1 year survival rate was 84.1％,3 year survival rate of 61.1％.Conclusion Mobilization of thoracic esophagus based on peri-esophageal space and dissection lymph nodes guided by the Chinese standard of grouping lymph node would achieve good clinical effects.

Objective To observe the effects of early rehabilitation training on endothelial progenitor cells (EPCs),stromal cell-derived factor alpha 1 (SDF-lα) and motor function recovery in hemiplegic patients with acute cerebral infarction.Methods Fifty hemiplegic patients after a first acute cerebral infarction were randomly divided into a control group (n =25) and an experimental group (n =25).Both groups of patients were given routine drug therapy,while the experimental group also received early rehabilitation (within 48 hours of onset).EPCs and SDF-1α levels in peripheral blood were measured before and after one week of treatment,and Fugl-Meyer assessments and modified Barthel index scoring were conducted at admission and after three months of treatment.Results There was no difference between the 2 groups before the treatment.After a week of treatment,however,the EPC and SDF-1α values of both groups had increased,with those of the experimental group increasing significantly more than in the control group.Spearman rank correlation analysis showed that the increase in EPCs was positively correlated with the SDF-1α increment in the first week.After 3 months of treatment,the average FMA and MBI results of the experimental group were significantly better than those of the control group.Conclusion Early rehabilitation training can help to further improve the recovery of motor function for hemiplegic patients after acute cerebral infarction.This may be related to its effect in upregulating the expression of SDF-1α,thus contributing to the mobilization of EPCs in the bone marrow.

ObjectiveTo evaluate the protective effect of Xuebijing injection against renal injury in patients with sepsis, and to explore its possible mechanism.Methods A prospective randomized controlled trial (RCT) was conducted in which 62 severe patients with sepsis and septic shock admitted in Department of Critical Care Medicine of Jiangsu Province Traditional Chinese Medicine Hospital from June 2013 to December 2013 were randomly divided into control group and Xuebijing group, with 31 patients in each group. The patients in both groups received basic treatment for sepsis, and the patients in Xuebijing group were additionally given intravenous injection of Xuebijing 100 mL once a day for 7 days. In both groups, the changes in acute physiology and chronic health evaluationⅡ (APACHEⅡ) score were observed before treatment and 1, 3, 7 days after treatment, and the changes in the levels of interleukins (IL-6, IL-10), prothrombin time (PT), fibrinogen (Fib), activated partial thromboplastin time (APTT), serum creatinine (SCr), and Cystain C (Cys C) were determined before treatment and 1 day and 3 days after treatment.Results There was no statistically significant difference in APACHEⅡ score before treatment between two groups, however, the APACHEⅡ scores were significantly decreased in both groups 3 days and 7 days after treatment compared with those before treatment, and the degree of decrease in Xuebijing group was more obvious 7 days after treatment (13.61±7.62 vs. 16.34±8.70,P< 0.05). Serum concentrations of Cys C, SCr, IL-6, IL-10, PT, APTT, and Fib showed no difference between two groups before treatment (allP> 0.05), while after treatment the degrees of improvement of above indexes in Xuebijing group were obviously superior to those in control group, especially 3 days after treatment[Cys C (mg/L):1.12±0.11 vs. 1.35±0.14, SCr (μmol/L): 115.0±31.0 vs. 135.0±24.0, IL-6 (ng/L): 54.27±28.79 vs. 73.35±31.01,PT (s): 13.50±0.11 vs. 15.71±0.11, APTT (s): 43.66±0.31 vs. 48.03±0.55, Fib (g/L): 1.91±0.51 vs. 1.51±0.52, P< 0.05 orP< 0.01].ConclusionXuebijing injection has certain renal protective effect in patients with sepsis, and its mechanism is possibly related to the regulation and improvement of uncontrolled inflammatory response and coagulation function in sepsis.

Objective To explore the effect of electroacupuncture on CD 34 +VEGFR2 +endothelial progenitor cell (EPC)-derived vessels and stromal cell-derived factor-1α(SDF-1α)/CXCR4, and study its mechanism of promoting an-giogenesis in hippocampus after focal cerebral ischemia /reperfusion .Methods A total of 180 healthy male adult Sprague Dawley (SD) rats were randomly divided into sham operation (sham) group, model (I/R) group, electroacupuncture (I/RE) group, I/RE plus AMD3100 (A specific antagonist of CXCR4) group (I/REA) and AMD3100 (I/RA) group. The rats received filament occlusion of the right middle cerebral artery for 2 hours followed by reperfusion .Electroacupunc-ture was applied to “Baihui” (GV20)/“Siguan” (Hegu LI 4/Taichong LR 3) acupoints for 30 min, once a day.The mR-NA expression of SDF-1αand CXCR4 were detected by reverse transcription-polymerase chain reaction ( RT-PCR) .Double immunofluorescence was used to stain CD 34 +VEGFR2 +EPC-derived vessels.Results Compared with the sham group, the mRNA expressions of SDF-1αand CXCR4 were significantly upregulated in I/R and I/RE group ( P<0.05 ) , but that in I/RE group was more significantly increased than I/R group(P<0.05).In addition, the mRNA expression of SDF-1αand CXCR4 were highly increased on day 1 in the I/REA group than that of I/RE group, but decreased than that of I/RE group on day 7 after reperfusion (P<0.01).CD34 +VEGFR2 +EPCs-derived vessels were obviously increased on 3d and 7d in the I/RE group compared with that of the I/R group, and significantly decreased on 7d in the I/REA group compared with that of the I/RE group ( P<0.01) .Conclusions Electroacupuncture can effectively promote an-giogenesis through upregulating the expression of SDF-1αand CXCR4 in rat ischemic hippocampus after focal cerebral is-chemia/reperfusion.