AIM:To investigate whether the expression of perilipin 2(PLIN2)in renal tubular cells could predict a decline in renal function in diabetic kidney disease(DKD)patients,and to explore the potential mechanisms in-volved in renal tubular cell injury induced by PLIN2 during the progression of DKD.METHODS:Control individuals(n=12)and DKD patients(n=51)were enrolled in this retrospective cohort study.Demographic and laboratory data were col-lected.A simplified linear mixed-effects model was applied to assess the estimated glomerular filtration rate(eGFR)slope.The relationship between PLIN2 and renal function decline in DKD patients was predicted by Spearman correlation analysis and a generalized linear model.BKS-db/db diabetic mice and streptozotocin-induced diabetic mice were used.Primary renal tubular cells were treated with glucose and transfected with small interfering RNA or plasmid.Western blot-ting and immunofluorescence staining were used to detect PLIN2 expression.Lipid droplets were stained with oil red O.The oxygen consumption rate(OCR)of mitochondria was measured using an extracellular flux analyser.RESULTS:The expression of PLIN2 was markedly higher in the tubules of DKD patients than in those of control subjects.After 24(12,39)months of follow-up,the eGFR slope of DKD patients was-7.42(-19.77,-2.09)mL/(min·1.73 m2·year).An in-crease in the baseline percentage of PLIN2-positive tubules was significantly associated with the eGFR slope during the fol-low-up period[hazard ratio(HR)=1.90,95%confidence interval(CI):1.00～3.58],indicating that tubular PLIN2 could predict a decrease in renal function in DKD patients.Both the accumulation of lipid droplets and the expression of PLIN2 were markedly greater in the tubules of diabetic mice than in those of control mice.Glucose treatment induced lipid droplet accumulation and PLIN2 expression in renal tubular cells.Knockdown of PLIN2 significantly alleviated glucose-in-duced lipid droplet accumulation,whereas PLIN2 overexpression aggravated glucose-induced lipid droplet accumulation.The decrease in mitochondrial OCR in renal tubular cells induced by glucose treatment was alleviated after PLIN2 knock-down.However,overexpression of PLIN2 directly decreased the mitochondrial OCR.CONCLUSION:The PLIN2 ex-pression in tubules predicts a decline in renal function in patients with DKD.The PLIN2 suppresses mitochondrial aerobic respiration and contributes to the accumulation of lipid droplets in renal tubular cells to promote the progression of DKD.

Objective To observe the value of intratumoral and peritumoral radiomics models combined with clinical and routine CT features for differentiating adenocarcinoma in situ(AIS)and microinvasive adenocarcinoma(MIA)of lung.Methods Totally 180 patients with isolated AIS and 180 with isolated MIA were retrospectively included,among them 160 AIS cases and 160 MIA cases were randomly selected into training set(n=320),while the other 20 AIS cases and 20 MIA cases were selected into test set(n=40).In training set,clinical and conventional CT features being statistically different between AIS and MIA were obtained to construct clinical model.Besides,radiomics features were extracted from intratumoral(CTi)ROI,intra-and peritumoral 2 mm(CTi+p2mm)ROI and intra-and peritumoral 4 mm(CTi+p4mm)ROI,and then CTi model,CTi+p2mm model and CTi+p4mm model for differentiating MIA and AIS were constructed.The optimal radiomics model for predicting MIA was selected using the area under the curve(AUC)of receiver operating characteristic(ROC)curve,and a combined model was built based on the optimal radiomics model combining with clinical and conventional CT features.The AUC,calibration and net benefit of the clinical model,the optimal radiomics model and the combined model were assessed.Results In training set,the larger nodular diameter,higher percentage of inhomogeneous density and ratio of nodules with vascular signals were observed in MIA compared with those in AIS(all P＜0.05).In test set,CTi+p2mm model had the highest efficacy(AUC=0.838)for differentiating MIA from AIS(P＜0.05),and the combined model had better efficacy(AUC=0.867,P＜0.05).The calibration of combined model was good,and the net benefit was high in 0.60-0.90 threshold probability range.Conclusion The radiomics model constructed with intratumoral and peritumoral 2 mm ROI based on plain CT was effective for differentiating MIA from AIS.Combining with clinical and routine CT features could furtherly improve differential diagnostic efficacy.

Objective:To investigate the rates of low disease activity and clinical remission in patients with systemic lupus erythematosus(SLE)in a real-world setting,and to analyze the related factors of low disease activity and clinical remission.Methods:One thousand patients with SLE were enrolled from 11 teaching hospitals.Demographic,clinical and laboratory data,as well as treatment regimes were collec-ted by self-completed questionnaire.The rates of low disease activity and remission were calculated based on the lupus low disease activity state(LLDAS)and definitions of remission in SLE(DORIS).Charac-teristics of patients with LLDAS and DORIS were analyzed.Multivariate Logistic regression analysis was used to evaluate the related factors of LLDAS and DORIS remission.Results:20.7％of patients met the criteria of LLDAS,while 10.4％of patients achieved remission defined by DORIS.Patients who met LLDAS or DORIS remission had significantly higher proportion of patients with high income and longer disease duration,compared with non-remission group.Moreover,the rates of anemia,creatinine eleva-tion,increased erythrocyte sedimentation rate(ESR)and hypoalbuminemia was significantly lower in the LLDAS or DORIS group than in the non-remission group.Patients who received hydroxychloroquine for more than 12 months or immunosuppressant therapy for no less than 6 months earned higher rates of LLDAS and DORIS remission.The results of Logistic regression analysis showed that increased ESR,positive anti-dsDNA antibodies,low level of complement(C3 and C4),proteinuria,low household in-come were negatively related with LLDAS and DORIS remission.However,hydroxychloroquine usage for longer than 12 months were positively related with LLDAS and DORIS remission.Conclusion:LLDAS and DORIS remission of SLE patients remain to be improved.Treatment-to-target strategy and standar-dized application of hydroxychloroquine and immunosuppressants in SLE are recommended.

Objective To analyze the evaluation indicators of pre-hospital first aid for adult patients with acute severe trauma to provide the evidence-based basis for the initiation of "zero channel" in first aid work.Methods The literatures such as expert consensus,clinical research,guideline and systematic review were retrieved from PubMed,Medline,Embase,Cochrane Central Register of Controlled Trials,and China Knowledge Network by computer.The retrieval time was from January 2013 to November 2023.After screen-ing the literatures according to the standard,the quality evaluation and evidence grading were conducted by a-dopting different tools.Results A total of 8 literatures were included,including 4 clinical studies,2 expert consensus and 2 systematic reviews.Finally,10 evidence-based evidences for the initiation of "zero channel" in adult patients with acute severe trauma were summarized.Conclusion This study summarizes the relevant in-dicators of "zero channel" initiation in the adult patients with acute severe trauma,which is helpful for clinical medical staff to start the first aid "zero channel" in time and increase the success rate of rescue.

Fusobacterium nucleatum (F. nucleatum) is an early pathogenic colonizer in periodontitis, but the host response to infection with this pathogen remains unclear. In this study, we built an F. nucleatum infectious model with human periodontal ligament stem cells (PDLSCs) and showed that F. nucleatum could inhibit proliferation, and facilitate apoptosis, ferroptosis, and inflammatory cytokine production in a dose-dependent manner. The F. nucleatum adhesin FadA acted as a proinflammatory virulence factor and increased the expression of interleukin(IL)-1β, IL-6 and IL-8. Further study showed that FadA could bind with PEBP1 to activate the Raf1-MAPK and IKK-NF-κB signaling pathways. Time-course RNA-sequencing analyses showed the cascade of gene activation process in PDLSCs with increasing durations of F. nucleatum infection. NFκB1 and NFκB2 upregulated after 3 h of F. nucleatum-infection, and the inflammatory-related genes in the NF-κB signaling pathway were serially elevated with time. Using computational drug repositioning analysis, we predicted and validated that two potential drugs (piperlongumine and fisetin) could attenuate the negative effects of F. nucleatum-infection. Collectively, this study unveils the potential pathogenic mechanisms of F. nucleatum and the host inflammatory response at the early stage of F. nucleatum infection.
Humans ; Fusobacterium nucleatum/metabolism* ; NF-kappa B/metabolism* ; Periodontal Ligament/metabolism* ; Signal Transduction ; Fusobacterium Infections/pathology* ; Stem Cells/metabolism*

Background: Cervical cancer is still present a major public health problem, especially in developing countries. In International Federation of Gynaecology and Obstetrics 2018, allowing assessment of retroperitoneal lymph nodes by imaging and/or pathological findings and, if deemed metastatic, the case is designated as stage IIIC (with r and p notations). Patients with lymph node metastases have lower overall survival (OS), progression free survival (PFS), and survival after recurrence, especially those who have unresectable macroscopical positive lymph nodes. Retrospective analysis suggests that there may be a benefit to debulking macroscopic nodes that would be otherwise difficult to sterilize with standard doses of radiation therapy. However, there are no prospective study reporting that resecting macroscopic nodes before concurrent chemoradiation therapy (CCRT) would improve PFS or OS of cervical cancer and no guidelines for surgical resection of bulky lymph nodes. The CQGOG0103 study is a prospective, multicenter and randomized controlled trial (RCT) evaluating lymph node dissection on stage IIICr of cervical cancer. Methods Eligible patients are histologically confirmed cervical squamous cell carcinoma, adenocarcinoma, adeno-squamous cell carcinoma. Stage IIICr (confirmed by computed tomography [CT]/magnetic resonance imaging/positron emission tomography/CT) and the short diameter of image-positive lymph node ≥15 mm. 452 patients will be equally randomized to receive either CCRT (pelvic external-beam radiotherapy [EBRT]/extended-field EBRT + cisplatin [40 mg/m2] or carboplatin [the area under curve=2] every week for 5 cycles + brachytherapy) or open/minimally invasive pelvic and para-aortic lymph node dissection followed by CCRT. Randomization is stratified by status of para-aortic lymph node. The primary endpoint is PFS. Secondary endpoints are OS and surgical complications. A total of 452 patients will be enrolled from multiple hospitals in China within 4 years and followed up for 5 years.

Objective:To explore the effects of standard meal and treadmill exercise test on body surface gastrointestinal electrogram in healthy subjects, and to provide more evidence for the clinical application of gastrointestinal electrogram.Methods:From January to June 2021, a total of 100 healthy asymptomatic volunteers underwent gastrointestinal electrogram after fasting, standard meal and treadmill exercise test. After the subjects fasted for more than 8 hours, the gastrointestinal electrogram was performed after the subjects were lying flat, quiet, and breathing steadily, electrodes were placed on the the body surface projection positions of the gastric body, the lesser curvature, the greater curvature, the antrum, the ascending colon, the transverse colon, the descending colon, and the rectum. The fasting gastrointestinal electrogram was recorded for 6 min. Then lay for 5 to 10 min after the standard meal (100 g bread, 250 mL milk), the postprandial gastrointestinal electrogram was recorded for 6 min. And lay for 5 to 10 min after treadmill exercise test, then the postexercise gastrointestinal electrogram was recorded for 6 min. The frequency and amplitude of gastrointestinal electrogram waveforms of the three time points were compared, and the percentage of gastrointestinal electrical rhythm disorder, and slow wave frequency instability coefficient were also compared. Stratified analysis of gastric motility was performed according to age, sex and body mass index. Paired t-test, Pearson Chi-squared test, continuity correction Chi-squared test, Fisher′s exact method and Speraman correlation were used for statistical analysis. Results:The standard meal did not obviously affect the mean frequency of the gastric electrocardiogram, however the mean amplitude of gastric electrocardiogram significantly increased after standard meal compared with that of fasting, especially in the electrodes placed at lesser curvature((148.5±8.7) μV vs.(113.2±5.0)μV ), greater curvature((176.3±11.3) μV vs.(126.1±7.3) μV), and antrum((161.8±10.6) μV vs.(117.6±4.91) μV), and the differences were statistically significant( t=4.63, 4.63 and 3.99, all P< 0.001). There were no significant changs in rhythm and stability of the gastric electrocardiogram. The mean frequency of intestinal electrograms at the ascending colon, the transverse colon, the descending colon, and the rectum decreased after the standard meal compared with that of fasting ((10.8±0.2) count per minute(cpm) vs.(11.5±0.2) cpm, (10.5±0.2) cpm vs.(11.2±1.6) cpm, (10.9±0.2) cpm vs.(11.7±0.2) cpm, (11.1±0.2) cpm vs.(11.8±0.2) cpm), and the differences were statistically significant ( t=3.82, 4.55, 4.39, and 3.98, all P<0.001); the mean amplitude of the ascending colon, the transverse colon, and the rectum increased compared with that of fasting ((129.8±6.1) μV vs. (110.9±6.4) μV, (119.6±4.1) μV vs. (101.3±4.7) μV, (124.1±4.6) μV vs. (106.2±5.7) μV), and the differences were statistically significant ( t=2.62, 3.76, and 3.16; P=0.010, <0.001, =0.002); and the number of leads with enteroelectric rhythm disorder increased (398 vs. 389, the total number of leads is 400), and the difference was statistically significant( χ2=7.31, P=0.026). The mean frequency of gastric electricity after treadmill exercise in electrode placed at antrum increased compared with that after standard meal ((3.4±0.4) cpm vs.(3.3±0.3) cpm), and the differences were statistically significant( t=2.45, P=0.016), and the mean amplitude of gastric electricity in electrodes placed at gastric body, lesser curvature and antrum increased compared with those after standard meal((160.2±8.6) μV vs. (133.9±6.4) μV, (178.1±10.0) μV vs. (148.5±8.7) μV, (202.5±10.2) μV vs. (161.8±10.6) μV), and the differences were statistically significant ( t=2.30, 2.35, and 2.48; P=0.024, 0.021, and 0.015). Treadmill exercise affected the rhythm and stability of gastric electricity, and the number of electrodes with instable and abnormal coefficient frequency slow-wave significantly increased (25 vs. 1, the total number of electrodes is 400), and the difference was statistically significant( χ2=22.90, P<0.001). There was no significant change in the mean frequency of the colonic electricity after treadmill exercise compared with that after standard meal, however the mean amplitude of intestinal electrical waveform at the ascending colon, the transverse colon, the descending colon, and the rectum increased compared with those after standard meal((171.2±8.4) μV vs. (129.8±6.1) μV, (166.1±7.7) μV vs. (119.6±4.1) μV, (147.2±7.2) μV vs. (121.1±4.9) μV, (149.6±7.3) μV vs. (124.1±4.6) μV), and the differences were statistically significant( t=3.51, 5.49, 3.09, and 2.83; P=0.001, <0.001, =0.003, and=0.006), which affected the rhythm and stability of the colonic electricity, and the number of electrodes with instable and abnormal coefficient frequency slow-wave significantly increased (10 vs. 3, the total number of electrodes is 400, χ2=4.04, P=0.040). Gender was correlated with mean frequency of gastric electricity after standrdmeal and treadmill exercise test and mean amplitude of fasting and standard postprandial gastric electricity( r=0.242, -0.272, 0.286, 0.242; P=0.015, 0.006, 0.004, 0.015), and with mean amplitude of fasting and standard postprandial electricity( r=0.225, 0.460; P=0.024, <0.001). Age was only associated with mean frequency of fasting gastric electricity( r=-0.214, P=0.033). Body mass index was correlated with mean gastric electrical amplitude after fasting, standard meal and treadmill exercise( r=-0.347, -0.260, -0.211; P<0.001, =0.009, =0.036), as well as with the mean gastric electricity frequency after treadmill exercise ( r=0.242, P=0.016). Body mass index was correlated with the mean amplitude and frequency of fasting and standard postprandial intestinal electricity ( r=-0.261, -0.296, -0.400, -0.286; P=0.009, =0.003, < 0.001, =0.003). In the healthy volunteers with female gender and body mass index < 24 kg/m 2, there were statistically significant differences in the changes of gastric motility after standard meal (Fisher′s exact method, P=0.022 and 0.024). Conclusion:Both standard meal and treadmill exercise test affect gastrointestinal electrical activity, and exercise caused more changes in gastrointestinal electrical activity than standard meal.

Objective:To investigate the clinical settings, antibiotic susceptibilities, management and outcomes of streptococcal endophthalmitis.Methods:A retrospective observational case series study. Fifty six eyes of 56 patients diagnosed with streptococcal endophthalmitis in Eye & ENT Hospital, Fudan University from 2012 to 2022 were collected. The treatment followed the general principles of relevant guidelines, including pars plana vitrectomy (PPV), vitreous injection of antibiotics (IVI), vitreous injection of glucocorticoids and systemic application of antibiotics. The follow-up time was (11.9±17.0) months. Patients' clinical characteristics, pathogenic distribution and antibiotic susceptibilities, treatment and outcomes in their medical records were retrospectively collected and analyzed.Results:All 56 patients had monocular onset, including 39 (69.6%, 39/56) males and 17 (30.4%, 17/56) females, 26 (46.4%, 26/56) with left eyes involved and 30 (53.6%, 30/56) with right eyes involved. Their average age was (25.0±24.4) years. Ocular trauma was the leading cause of streptococcal endophthalmitis (73.2%, 41/56), followed by ophthalmic surgery (23.2%, 13/56) and endogenous infection (3.6%, 2/56). The streptococcal species included Streptococcus viridans (50.0%, 28/56), Streptococcus pneumoniae (18/56, 32.1%) and β-hemolytic Streptococcus (17.9%, 10/56). The susceptibility rates of Streptococcus to penicillin, cefatriaxone, vancomycin and levofloxacin were 66.0%, 57.1%, 94.1% and 92.4%, respectively. Patients received PPV+IVI and IVI as initial treatment were 49 eyes (87.5%, 49/56) and 7 eyes (12.5%, 7/56), respectively. Vitreous injection of glucocorticoids were performed in 17 eyes (30.4%, 17/56); and systemic antibiotics were applied in 52 cases (92.9%, 52/56). At the final follow-up, 47 eyes were recorded with visual acuity. Twenty (35.7%, 20/56) had best corrected visual acuity (BCVA)≥0.05 and 27 (48.2%, 27/56) had BCVA <0.05, of which 1 (1.8%, 1/56) had an eyeball enucleation. The etiology of endophthalmitis, streptococcal species, initial treatment with PPV, vitreous injection of glucocorticoids, and systemic antibiotics did not significantly affect patients' visual outcomes ( P>0.05). Timely visit to the hospital after the onset of symptoms (≤3 days) was significantly associated with achieving a final BCVA above 0.05 ( P=0.025). Conclusions:Ocular trauma was the primary cause of streptococcal endophthalmitis. Streptococcus viridans is the most common pathogenic bacterium. Streptococci had high susceptibility to vancomycin, but patients' visual outcomes were poor.

Background The community is the main place for people's daily activities. A livable environment will improve the subjective well-being of residents. Objective To understand the current status of subjective well-being of residents in Pudong, Shanghai, and explore the impact of community environmental factors on residents' subjective well-being. Methods Using quota sampling, 6000 permanent residents from 12 sub-districts or towns in Pudong, Shanghai were selected to participate in an questionnaire survey. The questionnaire included three parts: participants' basic information, community environmental factors (neighborhood aesthetics, fitness environment, public service and security, natural environment), and subjective well-being. Using a multiple regression model, the influence of community environmental factors on the subjective well-being of residents was analyzed. Results A total of 5887 questionnaires were recovered, and the valid recovery rate was 98.1%. The subjective well-being score of the survey respondents was (7.03±1.61) points. There was no statistical difference in the subjective well-being score of study subjects of different gender and marital status groups; while those with different ages, education levels, occupations, and self-evaluated economic status showed statistical differences in their subjective well-being score (P<0.05). The multiple logistic regression analysis results showed that after controlling general demographic characteristics, with the low level as the control group (according predetermined cut-off values of 33.3% and 66.7%, the community environmental factors were divided into high-, medium-, and low-level groups), the OR values of subjective well-being of the high- and medium-level neighborhood aesthetics groups were 1.393 (95%CI: 1.173-1.654) and 1.235 (95%CI: 1.080-1.412); the OR values of the high- and medium-level fitness environment groups were 2.297 (95%CI: 1.929-2.734) and 1.349 (95%CI: 1.166-1.560); the OR values of the high- and medium-level public service and security groups were 1.101 (95%CI: 0.943-1.285) and 1.039 (95%CI: 0.905-1.193); the OR values of the high- and medium-level natural environment groups were 4.248 (95%CI: 3.321-5.434) and 1.652 (95%CI: 1.374-1.986), respectively. Conclusion Community environment factors could affect residents' subjective well-being, and good neighborhood aesthetics, fitness environment, natural environment have positive effects.

Objective:To investigate the effect of long non-coding RNA 068 (lncRNA 068) on the migration of a melanoma cell line A375, and to explore its mechanism of action.Methods:From December 2015 to November 2020, 21 patients with pathologically confirmed cutaneous melanoma were collected from Department of Dermatology, Affiliated Hospital of Nantong University, and quantitative PCR (qPCR) was performed to determine the expression of lncRNA 068 in melanoma and paracancerous tissues. LncRNA 068 was overexpressed or knocked down via lentiviral transfection in A375 human melanoma cells in the following experiments. Specifically, A375 cells were divided into lentiviral vector (LV) -green fluorescent protein (GFP) group and LV-lncRNA 068 group to be transfected with a GFP-expressing LV and a LV containing lncRNA 068 respectively in the overexpression experiment, and were divided into LV-LacZ short hairpin RNA (shRNA) group and LV-lncRNA 068 shRNA group to be transfected with a LV containing the reporter gene LacZ-specific shRNA and a LV containing the lncRNA 068-targeting shRNA respectively in the low-expression experiment, with the LV-GFP group and LV-LacZ shRNA group serving as the control groups. Transwell and scratch assays were performed to evaluate cell migration, EdU cell proliferation assay and cell counting kit-8 (CCK8) assay to determine the proportion of proliferative cells and cell viability respectively, and immunofluorescence staining was conducted to evaluate epithelial-mesenchymal transformation in the above groups. Lentivirus-transfected A375 cells from the above groups were inoculated into the axillae of BALB/c nude mice, and tumor volume was measured and calculated every 3 days. After 30 days, all mice were sacrificed, and tumor tissues were resected to measure the tumor volume and weight. Cultured B16F10 cells were subcutaneously inoculated into the back and foot of BALB/c nude mice to construct mouse models of subcutaneously transplanted B16F10 melanoma. After 2 weeks, the mice were sacrificed, and qPCR and Western blot analysis were performed to determine the mRNA expression of inflammatory factors in transplanted B16F10 melanoma and paracancerous tissues, and expression of IκB kinase (IKK) /P65 signaling pathway-related proteins, respectively. Comparisons between 2 groups were done by t test, and comparisons of tumor volume and weight at different time points among groups were done by repeated measures analysis of variance. Results:qPCR showed that the relative expression of lncRNA 068 was significantly lower in human melanoma tissues and transplanted B16F10 murine melanoma tissues (0.414 ± 0.109, 0.717 ± 0.041, respectively) than in the corresponding paracancerous tissues (1.050 ± 0.103, 1.011 ± 0.023, t = 19.48, 10.83, respectively, both P < 0.001). Transwell and scratch assays both showed that the cellular migratory ability was significantly lower in the LV-lncRNA 068 group than in the LV-GFP group (both P < 0.01), and significantly higher in the LV-lncRNA 068 shRNA group than in the LV-LacZ shRNA group (both P < 0.05). Immunofluorescence assay showed significantly increased fluorescence intensity of E-cadherin and decreased fluorescence intensity of N-cadherin in the LV-lncRNA 068 group compared with the LV-GFP group (both P < 0.001), but significantly decreased fluorescence intensity of E-cadherin and increased fluorescence intensity of N-cadherin in the LV-lncRNA 068 shRNA group compared with the LV-LacZ shRNA group (both P < 0.05). In vivo tumor formation experiment in nude mice showed that there were no significant differences in the volume or weight of melanoma between the LV-lncRNA 068 group and LV-GFP group (both P > 0.05), as well as between the LV-lncRNA 068 shRNA group and LV-LacZ shRNA group (both P > 0.05). As qPCR and Western blot analysis showed, the mRNA and protein expression of interleukin-10 (IL-10) and claudin-1 in A375 cells were significantly higher in the LV-lncRNA 068 group than in the LV-GFP group (both P < 0.05), but significantly lower in the LV-lncRNA 068 shRNA group than in the LV-LacZ shRNA group (both P < 0.05). Compared with the paracancerous tissues, B16F10 melanoma tissues showed significantly decreased mRNA expression of IL-10 ( P < 0.01), but significantly increased mRNA expression of IL-6 and tumor necrosis factor-α, as well as protein expression of phosphorylated P65 and phosphorylated IKK ( P < 0.01) . Conclusion:Overexpression of lncRNA 068 can inhibit the migration of A375 melanoma cells, and may affect the development of inflammation and inhibit the epithelial-mesenchymal transformation by inhibiting the IKK/P65 signaling pathway.