ObjectiveTo explore the effects of astragalin （AST） on autophagy and apoptosis of astrocytes in the L_4-5 dorsal horn of the spinal cord in mice with inflammatory pain induced by complete Freund's adjuvant （CFA）. MethodsTwenty-four male C57BL/6 mice， aged six months， were randomly assigned to four groups： control group， saline group， CFA model group， and CFA+AST group， six mice in each group. The inflammatory pain model was established by injection of 10 µL CFA into the right lateral malleolus fossa. The saline group were injected with an equal amount of normal saline at the same site. The inflammatory pain mice in CFA+AST group were further treated with AST （60 mg/kg） intraperitoneally once a day for 21 consecutive days. Multiplex immunofluorescence staining was used to detect the coexpression of autophagy-related factors including ATG 12 and Beclin-1， apoptosis-related factors including Cleaved-Caspase3 and Caspase9， and the astrocyte marker such as GFAP in the L_4-5 spinal dorsal horn of the mice in each group. Western blot was used to examine the protein expression levels of autophagy-related proteins（ATG12， Beclin-1） and apoptosis-related proteins（Caspase 3， Caspase 9） in the L_4-5 spinal dorsal horn of mice. ResultsImmunofluorescent staining showed that in the L_4-5 dorsal horn of the spinal cord， the fluorescence intensity of ATG12 （P<0.000 1） and Beclin-1 （P<0.000 1） was significantly increased， while that of Cleaved-Caspase 3 （P<0.001） and Caspase 9 （P<0.000 1） was decreased in the CFA+AST group when compared to the CFA model group. Furthermore， AST could inhibit the activation of astrocytes. Western blot further confirmed that AST significantly upregulated the expression of ATG12 （P<0.000 1） and Beclin-1 （P<0.000 1） in the L_4-5 spinal cord of CFA mice， and downregulated the expression of Caspase 3 （P<0.01） and Caspase 9 （P<0.001）. ConclusionsAST promotes autophagy of astrocytes and inhibits their apoptosis in the L_4-5 spinal dorsal horn of CFA mice.

AIM:To investigate the effect of 3% diquafosol sodium eye drops on tear film homeostasis in patients wearing overnight orthokeratology lenses.METHODS:Retrospective study. A total of 340 patients(564 eyes)fitted with night-worn orthokeratology lenses from June to December 2022 were respectively divided into a diquafosol sodium group(200 cases, 323 eyes, treated with 3% diquafosol sodium eye drops)and a sodium hyaluronate group(140 cases, 241 eyes, treated with sodium hyaluronate eye drops). The uncorrected visual acuity(LogMAR), ocular surface disease index(OSDI), non-invasive tear film break-up time(NIBUT), meibomian gland infrared imaging score, and corneal epithelial fluorescein staining were analyzed and compared between the two groups.RESULTS:Compared to baseline, both groups showed significant improvements in uncorrected visual acuity(LogMAR)at 1 wk, 1, and 3 mo after lens wear(all P<0.01). However, no statistically significant difference in uncorrected visual acuity(LogMAR)was observed between the two groups at any time point(all P>0.05). No significant differences in NIBUT or OSDI scores were found between the groups before and at 1 wk after lens wear(all P>0.05). At the 1- and 3 mo follow-ups, the 3% diquafosol sodium group demonstrated significantly longer NIBUT(all P<0.001)and lower OSDI scores(all P<0.001)compared to the sodium hyaluronate group. After wearing lens for 3 mo, the meibomian gland infrared imaging scores were significantly better in the diquafosol sodium group(P<0.001), whereas no significant intergroup difference was observed in corneal fluorescein staining(P>0.05). Furthermore, the incidence of adverse events during the study period did not differ significantly between the two groups(P>0.05).CONCLUSION:Compared with sodium hyaluronate, 3% diquafosol sodium eye drops were more effective in maintaining tear film homeostasis in patients wearing overnight orthokeratology lenses.

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a severe dose-limiting adverse event of chemotherapy. Presently, the mechanism underlying the induction of CIPN remains unclear, and no effective treatment is available. In this study, through metabolomics analyses, we found that nab-paclitaxel therapy markedly increased serum serotonin [5-hydroxtryptamine (5-HT)] levels in both cancer patients and mice compared to the respective controls. Furthermore, nab-paclitaxel-treated enterochromaffin (EC) cells showed increased 5-HT synthesis, and serotonin-treated Schwann cells showed damage, as indicated by the activation of CREB3L3/MMP3/FAS signaling. Venlafaxine, an inhibitor of serotonin and norepinephrine reuptake, was found to protect against nerve injury by suppressing the activation of CREB3L3/MMP3/FAS signaling in Schwann cells. Remarkably, venlafaxine was found to significantly alleviate nab-paclitaxel-induced CIPN in patients without affecting the clinical efficacy of chemotherapy. In summary, our study reveals that EC cell-derived 5-HT plays a critical role in nab-paclitaxel-related neurotoxic lesions, and venlafaxine co-administration represents a novel approach to treating chronic cumulative neurotoxicity commonly reported in nab-paclitaxel-based chemotherapy.
Paclitaxel/toxicity* ; Animals ; Albumins/adverse effects* ; Serotonin/metabolism* ; Mice ; Humans ; Male ; Female ; Venlafaxine Hydrochloride/therapeutic use* ; Neurotoxicity Syndromes/metabolism* ; Middle Aged ; Schwann Cells/metabolism* ; Peripheral Nervous System Diseases/drug therapy* ; Antineoplastic Agents

Objective To investigate the distribution of abnormal karyotypes and their associations with clinical manifestations of the infertile patients in southern Sichuan Province.Methods A total of 4 157 infertile patients who attended the Reproductive Medicine Center of our hospital from July 2018 to June 2021 were included.The chromosome karyotype in peripheral blood was detected by G-banding,and their semen analysis results,uterine development and other clinical data were collected.Results Among the 4 157 patients,chromosomal polymorphisms were found in 239 cases(5.75％),and abnormal karyotypes wee found 137 cases(3.30％).The abnormal karyotypes included 57 cases(41.61％)of sex chromosome aneuploidy,6 cases(4.38％)of Robertsonian transloca-tions,32 cases(23.36％)of balanced translocations,21 cases(15.33％)of chromosomal inversions,9 cases(6.57％)of mosai-cism,8 cases(5.84％)of marker chromosomes,3 cases(2.19％)of sex reversal and 1 case(0.73％)of sex chromosome deletion.In male patients with abnormal karyotypes,91.58％showed abnormal semen parameters,while in those with polymorphic karyotypes,55％had abnormal semen parameters.The patients with Turner syndrome had significantly smaller uterine dimensions(longitudinal,transverse,and anteroposterior)compared to the normal control group(P＜0.01).Conclusion Chromosomal abnormalities should be the important cause of infertility.Conducting karyotype analysis combining with clinical manifestations is crucial examination for the di-agnosis and reproductive guidance of infertile patients.

Clinical pathway has great similarity with DRG,and plays an important role in standardizing diagnosis and treatment behavior and controlling medical expenses.Based on the analysis of the relationship between DRG payment method reform and clinical pathway,taking a public hospital in Wuhan City,Hubei Province as an example,the clinical pathway implementation strategy of large public hospitals under the DRG payment method reform was explored from five aspects:management system,suitable disease types,doctor's order setting,information system,training and assessment.

Objective To explore the clinical effect of personalized pars plana vitrectomy(PPV)for proliferative di-abetic retinopathy(PDR).Methods In this retrospective case study,76 patients(86 eyes)diagnosed with PDR and re-ceiving PPV in the Department of Ophthalmology of Songjiang Hospital affiliated to Shanghai Jiao Tong University School of Medicine,from October 2019 to November 2022,were divided into the observation group(40 patients,46 eyes)and the control group(36 patients,40 eyes).Patients in the obseration group were treated with personalized PPV,while patients in the control group were treated with conventional PPV,After treatment,all patients were followed up for 12 months.The operation time,intraoperative use of heavy water and silicone oil,incidence of iatrogenic retinal tears and heavy water resi-dues,proportion of scleral buckling,preoperative and postoperative best corrected visual acuity(BCVA)and intraocular pressure(IOP),retinal reattachment rate at 12 months after surgery,and the incidence of post-vitrectomy vitreous hemor-rhage(PVH),diabetic macular edema(DME)and neovascular glaucoma(NVG)were compared between the two groups.Results The operation time of patients in the observation group was shorter than that in the control group(P＜0.05).Intraoperative use of heavy water and silicone oil in the observation group was lower than that in the control group(both P＜0.05).The incidence of iatrogenic retinal tears and heavy water residues and the proportion of scleral buckling showed no statistically significant difference between the two groups(all P＞0.05).There was no statistically significant difference between the two groups in BCVA preoperatively,3,6 and 12 months postoperatively(all P＞0.05).BCVA in the observa-tion group was better than that in the control group at 1 day,1 week and 1 month after surgery(all P＜0.05).Compared with the preoperative value,BCVA increased in the observation group at 1 day,1 week,1 month,3 months,6 months,and 12 months after surgery(all P＜0.05);in the control group,BCVA increased slightly at 1 day and 1 week(both P＞0.05)and then increased significantly at 1 month,3 months,6 months,and 12 months after surgery(all P＜0.05).The two groups showed no statistically significant difference in IOP at 1 day,1 week,1 month,3 months,6 months,and 12 months postoperatively(all P＞0.05).There was no statistically significant difference in the retinal reattachment rate and the inci-dence of complications such as PVH,DME,and NVG between the two groups at 12 months postoperatively(all P＞0.05).Conclusion Personalized PPV can shorten the operation time,reduce the intraoperative use of heavy water and silicone oil,enhance the efficiency of the operation,and rapidly improve the visual acuity of PDR patients.

Objective To establish a high-performance liquid chromatography-tandem mass spectrometry(LC-MS/MS)method for the simultaneous determination of seven vitamin Bs(VBs)in rat plasma.Methods The plasma samples were pretreated using the protein precipitation method.The chromatographic separation was achieved using an Agilent ZORBAX SB-Aq column(2.1 mm×150 mm,3.5 μm),with a mobile phase composed of 0.01%formic acid(A)and methanol(B)in a gradient elution mode.The flow rate was set at 0.3 mL·min-1 and the column temperature was maintained at 30℃.Mass spectrometric detection was performed using positive ion mode in multiple reaction monitoring.2,4,5,6-Deuteronicotinamide was used as the internal standard.Results Methodological validation results showed that the lowest limits of quantitation(LOQs)for the seven VBs ranged from 7.5 to 300 ng/mL,while the highest LOQs ranged from 1 000 to 20 000 ng·mL-1.Within a certain concentration range,all compounds showed a good linearity(r2>0.992 2).The accuracies ranged from 86.0%to 117.6%,and both intra-and inter-batch precision were less than 20%.Additionally,all analytes demonstrated extraction recoveries greater than 86.1%.No significant matrix effects were observed,and the stability was good.The established validation method was successfully applied to the pharmacokinetics study of single intragastric administration of VB solution in SD rats.Conclusion The analytical method established in this study is simple,rapid,sensitive,and exclusive for the simultaneous determination of VB in real plasma samples.This LC-MS/MS method provides a new analytical tool for further exploring the physiological and pathological effects of VB.

AIM:To investigate the effects of astragalin(AST)on activation status of astrocytes and the ex-pression level of autophagy-related proteins in the cortex of the anterior cingulate cortex of mice with a complete Freund's adjuvant(CFA)-induced inflammatory pain model.METHODS:Twenty-four 6-month-old male C57BL/6 mice were ran-domly divided into four groups:control group,saline group,CFA model group and CFA+60 mg/kg AST administration group,and six mice in each group.Mice in the AST administration group received 60 mg/kg AST by intraperitoneal injec-tion on a body weight basis for 21 d.The paw withdrawal threshold in each group of mice was evaluated by the von Frey test.The expression levels of autophagy-related factors LC3,p62,ATG12 and beclin-1,and astrocyte activation were de-tected by multiplex immunofluorescence staining in the anterior cingulate cortex of mice in each group.Western blot was used to measure the levels of autophagy-related proteins LC3,p62,ATG12 and beclin-1 in the anterior cingulate cortex of mice in each group.RESULTS:Behavioural tests showed that AST significantly increased mechanical pain thresholds in CFA mice(P＜0.05).The results from multiple immunofluorescent staining showed that AST significantly increased the fluorescence intensity of LC3(P＜0.01),ATG12(P＜0.01)and beclin-1(P＜0.05),attenuated the fluorescence intensi-ty of p62(P＜0.05),and inhibited the activation of astrocytes in the anterior cingulate cortex of CFA mice.Western blot results further confirmed that AST significantly increased the expressions of LC3(P＜0.01),ATG12(P＜0.01),beclin-1(P＜0.01),and decreased the expression of p62(P＜0.05)in the anterior cingulate cortex of CFA mice.CONCLU-SION:AST relieves CFA-induced inflammatory pain of mice,and its analgesic mechanism may be related to the inhibi-tion of activation of cortical astrocytes in the anterior cingulate cortex and the promotion of autophagy in CFA mice.

Coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. It is highly contagious and can cause death in severe cases. As reported by the World Health Organization (WHO), as of 6:36 pm Central European Summer Time (CEST), 12 August 2022, there had been 585 950 285 confirmed cases of COVID-19, including 6 425 422 deaths (WHO, 2022).
Humans ; COVID-19 ; SARS-CoV-2 ; Mental Health ; Cohort Studies ; Quality of Life ; China/epidemiology* ; Health Personnel ; Hospitals ; Lung

Objective:To explore the values of ultrasound, pathology combined with inflammatory indicators in predicting high nodal burden (HNB) in patients with early breast cancer and to construct a nomogram to provide reference for individualized diagnosis and treatment.Methods:The ultrasonographic, pathological features and preoperative inflammatory indicators of 378 female patients diagnosed with early breast cancer confirmed by pathology in the South Hospital of the Sixth People′s Hospital Affiliated to Shanghai Jiaotong University from January 2014 to July 2022 were retrospectively analyzed. They were randomly divided into training set ( n=302) and test set ( n=76) in a ratio of 8∶2, and the baseline data of the two groups were compared. The optimal cutoff values of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and lymphocyte to monocyte ratio (LMR) were obtained by ROC curve. In the training set, with axillary high lymph node load (≥3 metastatic lymph nodes) as the dependent variable, independent influencing factors of HNB were identified by univariate and multivariate Logistic regression analyses, and the nomogram was established. The test set data were used to verify the model. The discrimination, calibration and clinical applicability of the model were assessed by the area under the ROC curve (AUC), C-index, the calibration curve, Brier score and the decision curve analysis, respectively. Results:There were no significant differences in all variables between the training set and the test set (all P>0.05). ROC curve analysis results showed that AUCs of NLR, PLR and LMR were 0.578, 0.547 and 0.516, respectively, and the optimal cut-off values were 2.184, 150 and 3.042, respectively. Univariate Logistic regression analysis showed that age, pathological type, histological grade, Ki-67, lymphovascular invasion, NLR, PLR, ultrasonic characteristics (maximum diameter of primary tumor, shape, long/short diameter of lymph node, cortical thickness, cortical and medullary boundary, lymph node hilum, lymph node blood flow pattern) were correlated with HNB of early breast cancer (all P<0.05). Multivariate Logistic regression analysis showed that ultrasonic characteristics (maximum diameter of primary tumor >2 cm, effacement of lymph node hilum, non-lymphatic portal blood flow), lymphovascular invasion, Ki-67>14% and NLR>2.184 were independent risk factors for HNB in early breast cancer ( OR=7.258, 8.784, 6.120, 8.031, 3.394 and 3.767, respectively; all P<0.05) and were used to construct the nomogram model. The AUC of the training set was 0.914 (95% CI=0.878-0.949), C-index was 0.914; The AUC of the test set was 0.871 (95% CI=0.769-0.973), C-index was 0.871, indicating good discrimination. Calibration curve and Brier score were 0.090, indicating high calibration degree of the model. The clinical decision curve indicated good clinical benefit. Conclusions:The nomogram based on ultrasonic characteristics (maximum diameter of primary tumor, lymph node hilum, lymph node blood flow pattern), lymphovascular invasion, Ki-67 and NLR can effectively predict the risk of HNB in patients with early breast cancer, and provide a reference for precision diagnosis and treatment to avoid excessive or insufficient treatment.