Dry eye disease (DED) is a prevalent and intractable ocular disease induced by a variety of causes. Elevated sphingomyelin (SM) levels and pro-inflammatory cytokines were detected on the ocular surface of DED patients, particularly in the meibomian glands. Sphingomyelin synthase 2 (SMS2), one of the proteins involved in SM synthesis, would light a novel way of developing a DED therapy strategy. Herein, we report the design and optimization of a series of novel thiophene carboxamide derivatives to afford 14l with an improved highly potent inhibitory activity on SM synthesis (IC_{50, SMS2} = 28 nmol/L). Moreover, 14l exhibited a notable protective effect of anti-inflammation and anti-apoptosis on human corneal epithelial cells (HCEC) under TNF-α-hyperosmotic stress conditions in vitro, with an acceptable ocular specific distribution (corneas and meibomian glands) and pharmacokinetics (PK) profiles (t _{1/2, cornea} = 1.11 h; t _{1/2, meibomian glands} = 4.32 h) in rats. Furthermore, 14l alleviated the dry eye symptoms including corneal fluorescein staining scores and tear secretion in a dose-dependent manner in mice. Mechanically, 14l reduced the mRNA expression of Tnf-α, Il-1β and Mmp-9 in corneas, as well as the proportion of very long chain SM in meibomian glands. Our findings provide a new strategy for DED therapy based on selective SMS2 inhibitors.

Objective To explore the action targets and related mechanisms of pogostemon cablin in the treatment of glioma based on network pharmacology and cellular experiments.Methods The active ingredi-ents and action targets of pogostemon cablin were collected by using databases such as the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and the Traditional Chinese Med-icine Comprehensive Database(TCMID).The relevant targets of glioma were collected through databases such as Gene Cards and OMIM,and the network diagrams of"drug-target"and"disease-target"were estab-lished by using Cytoscape3.7.1 software.The intersection targets of pogostemon cablin for treating glioma were obtained and STRING database was used to analyzed,and their protein-protein interaction(PPI)net-work diagram was established.Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis on key targets were performed by using the DAVID database.In vitro cell experiments on key signaling pathways were conducted,U87 glioma cells were collected and divided into the control group(added to basic culture medium)and the 60,90,120 μg/mL pog-ostemon cablin groups(added to culture medium containing 60,90,and 120 μg/mL pogostemon cablin,respec-tively).CCK-8 assay and wound healing assay were used to detect the proliferation and migration ability of each group of cells,and the protein expression levels of mitogen activated protein kinase 1(MAPK1),recom-binant V-rel reticuloendotheliosis viral oncogene homolog A(RELA)phosphatidylinositol 3-kinase(PI3K),protein kinase B(Akt),phosphorylated-PI3K(p-PI3K),and phosphorylated-Akt(p-Akt)in each group of cells were detected by Western blot.Results A total of 94 main chemical constituents of pogostemon cablin were obtained.According to the screening conditions,9 effective active ingredients,239 drug target proteins,4 526 glioma related genes and 121 drug and disease common targets were identified.Protein interaction net-works discovered that Akt1,c-Jun N-terminal kinase(JUN),MAPK1,RELA,interleukin(IL)-6 and epider-mal growth factor receptor(EGFR)may be the key targets of pogostemon cablin in the treatment of glioma.GO function enrichment analysis identified 1 819 items in biological processes,109 items of cellular compo-nents and 216 items of molecular functions,which involved various aspects such as the positive regulation of the cellular metabolic process,the activity of protein homodimers,kinase activation,and membrane rafts.KEGG pathway enrichment analysis identified 181 related signaling pathways,involving anti-cancer,inflamma-tion,cell apoptosis,endocrine,immune regulation and so on,mainly including the PI3K/Akt pathway,ad-vanced glycation advanced glycation end products(AGE)/recepter for advanced glycation end products(RAGE)pathway,IL-6 pathway,and HIF-1 pathway,TNF pathway and so on.The in vitro experimental re-sults showed that compared with the control group,with the increase of the dose of the alcohol extract of pog-ostemon cablin,the cell activity decreased,the cell migration ability decreased,and the expression levels of MAPK1,RELA,p-PI3K and p-Akt proteins decreased(P＜0.05).Conclusion Pogostemon cablin can syner-gistically inhibit the development of glioma through multiple targets and pathways,and can suppress cell pro-liferation of U87 cells through the PI3K/Akt pathway.

OBJECTIVE To evaluate the effictiveness and safety of recombinant human endostatin combined with afatinib and teggio in the treatment of advanced lung squamous cell carcinoma. METHODS A total of 25 patients with driver-negative advanced lung squamous cell carcinoma were included in this single-arm prospective study, and the enrolled patients were treated with recombinant human endostatin combined with afatinib and teggio as scheduled. Progression-free survival(PFS), overall survival(OS), disease control rate(DCR), objective response rate(ORR), and adverse reactions(AR) were observed and analyzed. RESULTS The 25 enrolled patients received at least 2 cycles of second-line treatment, and were followed up as of March 31, 2023. Among them, 4 patients had partial remission, 17 patients had stable disease, and 4 patients experienced progressive disease. The ORR confirmed by the researchers was 16%(95%CI, 4.5%−36.1%), DCR was 84%(95%CI, 63.9%−95.5%), and median PFS was 5.3 months(95%CI, 3.5−6.9 months). The median OS had not yet been achieved. The entire group of patients had good treatment tolerance, and the most common level Ⅲ or Ⅳ adverse events related to treatment were leukopenia(20%) and rash(12%), with no reported treatment-related deaths. CONCLUSION Recombinant human endostatin combined with afatinib and teggio in the second line treatment of advanced lung squamous cell carcinoma can prolong the progression free survival period of patients and is relatively safe, which is worth further exploration and promotion.

Objective To investigate the application value of the MHSeqTyper47 kit in kinship identification.Methods Multiplexed amplification and library preparation were performed for DNA samples from 113 related individuals by using the MHSeqTyper47 kit.The libraries were sequenced on a MiSeq FGx sequencer,and the data were analyzed using MHTyper for microhaplotype genotyping.The kinship indexes were calculated to evaluate the application efficiency of this kit in kinship identification and compared with those of the GlobalFilerTM kit.Results For the MHSeqTyper47 kit,the CPI values in trio identification were 1.43× 1011～6.15×1018.The CPI values in duo identification were 1.02× 105～1.53× 1013.The CFSI values in full sibling identification were 7.73×101～2.59×1016.Trios,duos and full siblings could be completely distinguished from unrelated pairs.The combined efficiency of these two kits in 2nd-degree kinship identification was 0.466 2.Conclusion The application value of MHSeqTyper47 kit is relatively higher in the identification of lst-degree kinships.If jointly used with the GlobalFilerrM kit,2nd-degree kinship identification could be achieved in some cases.

Hidden absenteeism refers to the behavior of employees who insist on going to work even when they are in poor health,but its work efficiency is low and affects the productivity.This paper reviews and sorts out the related researches on hidden absenteeism of nurses in China,expounds the definition of the con-cept of hidden absenteeism,evaluation tools,current situation and influencing factors of hidden absenteeism of nurses in China,and puts forward the suggestions on the countermeasures of hidden absenteeism,in order to provide reference for nursing managers in China on the management of hidden absenteeism.

The advancements in colorectal minimally invasive surgical techniques represent not merely technological innovation but also a significant leap in surgical philosophy.Over the past half-century,we have witnessed the historic transition from traditional open surgery to minimally invasive procedures,a change propelled by continuous innovations in surgical platforms and techniques.The innovations of platforms encompass developments in imaging platforms,energy platforms,instrumentation platforms.Furthermore,innovations in surgical techniques primarily focus on exploring variables within five key elements of surgical techniques:the approach,extent of bowel resection,lymph node dissection,reconstruction of the digestive tract,and specimen extraction.The progress in colorectal minimally invasive surgery has significantly reduced surgical trauma,and enhanced patients' postoperative quality of life and the overall safety of surgeries.This progress is underpinned by stringent quality control throughout the surgical process,ensuring standardized and homogeneous execution of procedures.Moving forward,the ongoing drive to innovate surgical techniques and philosophies will continue to improve the efficacy and safety of colorectal minimally invasive surgeries.This journey not only necessitates the relentless advancement of medical technologies,but also requires surgeons to continuously deepen and actively pursue surgical philosophies.

Objective To explore the expression of mocro RNA(miR)-142-5p and suppressor of cytokine signaling 1(SOCS1)mRNA in peripheral blood mononuclear cells(PBMC)of mice and clinical patients with ankylosing spondylitis(AS)and their impact on immune function.Methods The mRNA levels of miR-142-5p and SOCS1 in PBMC of 30 patients with AS(Patient group)and 30 healthy controls(Health group)treated in the First People's Hospital of Shangqiu from January 2022 to March 2023 were measured by quantitative real time PCR(qRT-PCR).AS mice models were induced by bovine proteoglycan combined with complete Freund's adjuvant,and these mice were divided into control group,model group,NC group and antagomir group.Normal saline was injected into tail vein in control group and model group,and NC-antagomir and miR-142-5p-antagomir were injected into tail vein in NC group and antagomir group,respectively.After 2 weeks of treatment,the arthritis symptom scores of mice in each group were evaluated.The morphology of ankle joint was evaluated by hematoxylin eosin(HE)staining.The levels of Th1 cytokine interferon-γ(IFN-γ),Th2 cytokine interleukin-4(IL-4),Th17 cytokine interleukin-17(IL-17)and Treg cytokine forkhead box protein P3(FOXP3)in PBMC of mice were detected by ELISA method.The mRNA and protein expression of miR-142-5p,SOCS1,IFN-γ,IL-4,IL-17 and FOXP3 in PBMC and ankle joints were detected by qRT-PCR and Western blot.Results Compared with Health group,the level of miR-142-5p in PBMC of patient group was increased(1.00±0.21 vs 3.03±0.99,t=10.997,P＜0.001),while the level of SOCS1 mRNA was decreased(1.00±0.18 vs 0.41±0.09,t=15.956,P＜0.001).Compared with control group,miR-142-5p level(1.00±0.04 vs 4.00±0.52)and the mRNA and protein levels of IFN-γ and IL-17 in ankle joint tissue of model group were increased,while the mRNA and protein levels of SOCS1,IL-4 and FOXP3 were decreased,with significant differences(t=23.356,31.420,48.056,47.224,38.035,29.007,54.183,28.123,55.155,26.758,45.346,all P＜0.05).The arthritis symptom score was increased(7.83±0.94 vs 0.00±0.00,t=22.212,P＜0.05),and the ankle joint structure was damaged.Serum IFN-γ,IL-17 levels,IFN-γ/IL-4 ratio(0.81±0.08 vs 2.08±0.33)and IL-17/FOXP3 ratio(0.41±0.03 vs 1.27±0.10)were increased,and the differences were statistically significant(t=15.382,35.779,8.934,35.130,all P＜0.05).Compared with NC group,miR-142-5p level(3.89±0.33 vs 1.47±0.10),the mRNA and protein levels of IFN-γ and IL-17 in ankle joint tissue of antagomir group were decreased,while the mRNA and protein levels of SOCS1,IL-4 and FOXP3 were increased,and the differences were statistically significant(t=18.846,22.969,43.454,32.617,23.259,20.881,41.832,11.994,32.977,15.190,35.834,all P＜0.05).The arthritis symptom score was decreased(7.42±1.24 vs 2.75±0.75,t=13.233,P＜0.05),and the shape of the ankle joint of the rats was improved.Serum IFN-γ,IL-17 levels,IFN-γ/IL-4 ratio(1.22±0.11 vs 1.91±0.19)and IL-17/FOXP3 ratio(0.69±0.05 vs 1.23±0.12)were decreased,and the differences were statistically significant(t=8.688,22.972,3.785,22.007,all P＜0.05).Conclusion MiR-142-5p was highly expressed in AS.Down-regulation of miR-142-5p using antagonists may reduce Th1/Th2 ratio and Th17/Treg ratio through up-regulation of SOCS1,there by improving the immune balance of AS mice and inhibiting the progression of AS.

Objective:To evaluate the long-term impact of three different outdoor activity intervention strategies on the prevalence of myopia among school-aged children in China.Methods:Cross-sectional data from the Refractive Error Study in Children (RESC) on the baseline prevalence of myopia and 10-year longitudinal data from the Guangzhou Twin Eye Study (GTES) on the baseline incidence of myopia were utilized.The effect size of outdoor activity intervention was derived from longitudinal data of the Guangzhou Outdoor Activity Longitudinal Study (GOALS). Three intervention strategies were proposed: intervention for children in grades 1 to 6 (Strategy A), intervention for children in grades 1 to 3 (Strategy B), and intervention for children from the last year of kindergarten to grade 3 (Strategy C). Outdoor activity interventions across all strategies included an extra 40 minutes of daily outdoor activity time.Simulated analyses assumed that the prevalence of myopia would decrease with declining incidence and increasing school grade, and the degree of myopia among highly myopic children would decrease with delayed myopia onset.This study was approved by the Ethics Committee of Zhongshan Ophthalmic Center (No.2006-5).Results:With prolonged intervention time, the overall prevalence of myopia in children showed a significant declining trend.After 5 years of implementation, Strategy A resulted in a decrease in myopia prevalence from 34.67% to 25.71%, which decreased to 24.89% after 10 years, with an average annual reduction of 0.98%.Strategies B and C had similar long-term effects, with myopia prevalence after 10 years being 26.00% and 26.20% respectively, with an average annual reductions of 0.87% and 0.85%.Strategy A yielded the greatest reduction in myopia severity, with a decrease of -5.94 D after 5 years and -5.88 D after 10 years in the initial 15-year-old highly myopic individuals.Strategy B followed with -6.08 D and -6.02 D after 5 and 10 years, respectively.Conclusions:Implementing intensified outdoor activity intervention among children in grades 1 to 6 may be the recommended strategy to reduce the overall prevalence of myopia in regions with high rates of myopia among school-aged children.

Objective:To explore and analyze the changes of miRNA-138 and miRNA-26b before and after transsphenoidal surgery for pituitary tumors and their clinical significance.Methods:86 patients with functional pituitary tumors who underwent transsphenoidal surgery in Linyi People’s Hospital from Apr. 2020 to Apr. 2021 were retrospectively analyzed. The recurrence within 1 year after operation was followed up and the patients were divided into unrecovered group (24 cases) and cured group (62 cases) . Clinical data such as age, gender, tumor pathological type, Knosp grade, first operation, tumor diameter, intraoperative tumor residue, Ki-67 and adjuvant therapy were collected. Fasting venous blood was collected before surgery and the next morning after surgery. Quantitative real-time PCR was used to detect the serum levels of mircoRNA-138 (miRNA-138) and miRNA-26b (mirNA-26B) , and the changes of serum miRNA-138 and miRNA-26b levels before and after surgery. Univariate and multivariate logistic regression were used to analyze the relationship between serum miRNA-138 and miRNA-26b levels and postoperative prognosis, and ROC curve was drawn to analyze their predictive value for postoperative prognosis.Results:Univariate analysis showed that Knosp grade, tumor diameter, intraoperative tumor residual, Ki-67, and adjuvant therapy were associated with the recurrence of body tumor after transsphenoidal surgery ( P<0.05) . After operation, the expression of miRNA-138 in serum was higher than that before operation, and the expression of miRNA-138 in unhealed group (4.13±1.12) was higher than that in cured group (3.56±0.84) ( P<0.05) . The expression of miRNA-26b in serum after operation was lower than that before operation, and the expression of miRNA-26b in the unhealed group (2.34±0.62) was lower than that in the cured group (2.75±0.58) ( P<0.05) . Pituitary tumor hormone increased before operation and returned to normal after operation. Multivariate logistic regression analysis showed that tumor diameter ≥40cm (OR=3.476, 95%CI: 1.267-9.539) , postoperative tumor residual (OR=3.155, 95%CI: 1.236-8.052) , Ki-67≥3% (OR=3.885, 95%CI: 2.038-7.403) , postoperative serum miRNA-138 expression ≤3.62 (OR=2.323, 95%CI: 1.536-3.513) , postoperative serum miRNA-26b expression ≥2.59 (OR0.453, 95 %CI: 0.286-0.717) was an independent risk factor for the recurrence of pituitary tumors after transsphenoidal surgery ( P<0.05) . When the optimal cut-off value of serum miRNA-138 was 3.62, the area under the curve for predicting the recurrence of pituitary tumors after transsphenoidal surgery was 0.78, the sensitivity was 81.35%, and the specificity was 71.46%; the optimal cut-off value of serum miRNA-26b When it was 2.59, the area under the curve for predicting and predicting the recurrence of pituitary tumors after transsphenoidal surgery was 0.75, at this time, the sensitivity was 78.62%, and the specificity was 72.33%. The lower area was 0.83, the sensitivity was 85.47%, and the specificity was 72.38%. Conclusion:The expression of serum miRNA-138 was up-regulated and the expression of miRNA-26b was down-regulated after transsphenoidal surgery for pituitary tumors, and its abnormal expression was associated with postoperative recurrence, which has a good predictive value for predicting postoperative recurrence.

Objective:To investigate the influences of anxiety on postoperative efficacy in elderly patients with complex proximal humerus fractures.Methods:A retrospective case control study was conducted to analyze the clinical data of 297 elderly patients with complex proximal humerus fractures admitted to 5 tertiary hospitals in Shanghai from January 2017 to December 2018. There were 121 males and 176 females, aged 65-85 years [(74.2±8.5)years]. The fracture types included Neer type III in 176 patients and Neer type IV in 121 patients. Two days after admission, patients were analyzed by self-rating anxiety scale (SAS) and anxiety factors questionnaire (participated by Shanghai Mental Health Center) and they were divided into anxiety group (SAS>35) and nonanxiety group (SAS≤35). Anxiety group included 68 patients, among which 7 had conservative treatments. Nonanxiety group contained 229 patients, among which 7 had conservative treatments. Both groups underwent with proximal reduction of humerus fractures accepted the operations. Operative patient in both groups underwent open reduction and plate fixation. The surgery rate and length of hospital stay were compared between groups. After 1 year of follow-up, Constant-Murley score was used to evaluate the effect of shoulder joint and dual-energy X-ray absorptiometry (DXA) was taken to observe the wrist joint bone mineral density. Postoperative complications were recorded.Results:All operative patients were followed up for 10-28 months, with an average of 13.6 months. The surgery rate was 89.7% (61/68) in anxiety group and 96.9% (222/229) in nonanxiety group ( P<0.05). The hospital stay was (6.8±3.4)days for non-surgery patients and (10.2±2.8)days for surgery patients in anxiety group and (4.2±1.6)days for non-surgery patients and (7.4±2.2)days for surgery patients in nonanxiety group ( P<0.05). In anxiety group and nonanxiety group, the excellent and good rate of Constant-Murley score was respective 75.4% (46/61) and 88.3% (196/222) and the wrist joint bone mineral density was respective (-3.1±0.5)SD and (-2.9±0.6)SD (both P<0.05). The incidence of complications was 8.2% (5/61) in anxiety group and 4.5% (10/222) in nonanxiety group ( P>0.05). Conclusions:Anxiety has a significant negative influence on the surgery rate, length of hospital stay, shoulder joint function, wrist joint bone mineral density. Intervention on anxiety in elderly patients with complex proximal humerus fractures should be valued attention by clinical orthopedic surgeons.