ObjectiveTo identify the direct target proteins for the anti-obesity effect of resveratrol （Res） via chemical proteomic analysis and systematically explore the molecular mechanisms by which Res inhibits lipid accumulation in adipocytes from mitochondrial function regulation， adipocyte browning， and inflammation inhibition， thus providing new targets and experimental evidence for the prevention and treatment of obesity and related metabolic diseases. MethodsThe cell counting kit-8 （CCK-8） assay was adopted to detect the safe and effective doses （7.5， 15， 30 μmol·L^-1） of Res for treating 3T3-L1 cells based on the cell survival rate. After being induced to differentiate into mature adipocytes， the cells were assigned into the blank ［treated with dimethyl sulfoxide （DMSO）］ group and the Res （7.5， 15， 30 μmol·L^-1） groups and treated for 48 h. Oil red O staining and total triglyceride （TG） content were assessed to measure lipid accumulation in adipocytes. Target protein identification of Res was conducted through IAA-P-based chemical proteomics combined with high-resolution mass spectrometry. Target proteins of Res were validated by cellular thermal shift assay （CETSA） combined with Western blot analysis. Furthermore， the expression of browning markers peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α） and mitochondrial uncoupling protein 1 （UCP1）， as well as the target proteins NADH-ubiquinone oxidoreductase core subunit S8 （NDUFS8） and high-mobility group protein B1 （HMGB1） were determined by Western blot. The ATP assay kit was used to measure the ATP concentration. Mitochondrial biogenesis was characterized with MitoTracker Green， on the basis of which the regulatory effect of Res on mitochondrial function was analyzed. The level of the inflammatory cytokine tumor necrosis factor-α （TNF-α） was measured by enzyme-linked immunosorbent assay （ELISA）， on the basis of which the anti-inflammatory effect of Res on adipocytes was evaluated. ResultsCompared with the control group， Res demonstrated safety and efficacy within the range of 7.5-30 μmol·L^-1， without significantly affecting cell viability. Compared with the control group， different concentrations of Res reduced lipid accumulation in 3T3-L1 adipocytes （P<0.01）， promoted the expression of NDUFS8 （P<0.01）， increased the ATP concentration and the protein levels of UCP1 and PGC-1α， elevated the level of TNF-α （P<0.05， P<0.01）. ConclusionNDUFS8 and HMGB1were identified as the target proteins of Res in mitigating obesity. Res promotes mitochondrial biogenesis to induce the browning of 3T3-L1 adipocytes via targeting NDUFS8 and it inhibits the TNF-α-mediated inflammatory signaling via targeting HMGB1， thus inhibiting lipid accumulation and ameliorating obesity.

Objective To explore the deeper understanding of the pregnancy and delivery experience of three-child pregnant and matemal women,and to provide a basis for healthcare personnel to provide more systematic,safe,and targeted perinatal healthcare services and care measures for three-child pregnant and matemal women.Methods Purposive sampling method was used to select 17 cases of three-child pregnant and matemal women who were admitted and delivered in a tertiary level-A matemal and child healthcare hospital in Nanjing from August 2022 to June 2023 for semi-structured interviews,and Colaizzi 7-step process of analyzing,summarizing,and refining the themes was used.Results A total of 4 themes were extracted,including determination of willingness to become pregnant,perceived risks of childbirth,perceived benefits to themselves and their families,diversified support needs.Conclusion The establishment of pregnancy intention of three-child pregnant women is affected by many factors.Relevant departments should actively implement the supporting measures of the three-child birth policy;healthcare workers should strengthen perinatal healthcare services for three-child mothers to reduce the risk of giving birth,actively strengthen their sense of benefits related to pregnancy,and establish a whole process of support system to promote the health of mothers and infants.

OBJECTIVES: To investigate the efficacy of Ag₂Se nanoparticles for eliminating intracellular Porphyromonas gingivalis (P. gingivalis) in esophageal cancer and examine the effect of P. gingivalis clearance on progression of esophageal cancer. METHODS: Ag₂Se nanoparticles were synthesized via a chemical synthesis method. The effects of Ag₂Se nanoparticles on P. gingivalis viability and colony-forming ability were assessed using fluorescence staining and colony formation assays. In a mouse model bearing subcutaneous murine esophageal cancer cell allograft with P. gingivalis infection, the effect of treatment with Ag₂Se nanoparticles on the abundance of P. gingivalis in the tumor tissues was quantified using RNAscope in situ hybridization and quantitative polymerase chain reaction (qPCR), and the changes in tumor volume were monitored. The biosafety of Ag₂Se nanoparticles was assessed by examining liver and kidney functions and pathological changes in the major organs of the mice. RESULTS: Transmission electron microscopy revealed that the synthesized Ag₂Se nanoparticles were uniformly dispersed spherical particles with a diameter around 50 nm. In vitro experiments demonstrated that exposure to Ag₂Se nanoparticles significantly reduced the viability and clonal proliferation capacity of P. gingivalis in a dose-dependent manner. In the tumor-bearing mice, treatment with Ag₂Se nanoparticles significantly reduced the abundance of P. gingivalis in tumor tissues and suppressed tumor cell proliferation. No significant damages to the liver and kidney functions or the major organs were observed in Ag₂Se nanoparticle-treated mice, demonstrating good biocompatibility of Ag₂Se nanoparticles. CONCLUSIONS Ag₂Se nanoparticles exhibit significant bactericidal and inhibitory effects against P. gingivalis, and can effectively eliminate intracellular P. gingivalis to suppress the growth of esophageal cancer allograft in mice, suggesting the potential of Ag₂Se nanoparticles in the treatment of esophageal cancer.
Animals ; Porphyromonas gingivalis/drug effects* ; Mice ; Esophageal Neoplasms/pathology* ; Nanoparticles ; Metal Nanoparticles ; Bacteroidaceae Infections ; Cell Line, Tumor

Objective To explore the association between the growth condition of mandibular third molars(M3)and the parameters of mandibular dental arch through a retrospective cross-sectional study on M3 in adults,and to provide a basis for the selection of clini-cal treatment of M3.Methods A total of 221 adult patients were randomly selected for our study.Dolphin software was used to analyze the CBCT of all the patients.Parameters of the mandibular dentition including the entire dental crowding(EDC)were recorded.Then the association between M3 growth condition and these parameters was analyzed.Results The mesio-impacted angle of M3 was posi-tively correlated with EDC(P＜0.05),and negatively correlated with the retromolar space(RMS,P＜0.0 1).It was worth noting that me-dian mesio-impacted M3 significantly increased EDC(P＜0.01),and the erupting M3 in the vertical orthotopic position significantly in-creased RMS(P＜0.01).Conclusion For patients with median mesio-impacted M3 or insufficient RMS,preventive removal of M3 may be considered clinically,which may help to reduce crowding and prevent relapse after orthodontic treatment.

Objective To explore the association between the growth condition of mandibular third molars(M3)and the parameters of mandibular dental arch through a retrospective cross-sectional study on M3 in adults,and to provide a basis for the selection of clini-cal treatment of M3.Methods A total of 221 adult patients were randomly selected for our study.Dolphin software was used to analyze the CBCT of all the patients.Parameters of the mandibular dentition including the entire dental crowding(EDC)were recorded.Then the association between M3 growth condition and these parameters was analyzed.Results The mesio-impacted angle of M3 was posi-tively correlated with EDC(P＜0.05),and negatively correlated with the retromolar space(RMS,P＜0.0 1).It was worth noting that me-dian mesio-impacted M3 significantly increased EDC(P＜0.01),and the erupting M3 in the vertical orthotopic position significantly in-creased RMS(P＜0.01).Conclusion For patients with median mesio-impacted M3 or insufficient RMS,preventive removal of M3 may be considered clinically,which may help to reduce crowding and prevent relapse after orthodontic treatment.

Objective To explore the deeper understanding of the pregnancy and delivery experience of three-child pregnant and matemal women,and to provide a basis for healthcare personnel to provide more systematic,safe,and targeted perinatal healthcare services and care measures for three-child pregnant and matemal women.Methods Purposive sampling method was used to select 17 cases of three-child pregnant and matemal women who were admitted and delivered in a tertiary level-A matemal and child healthcare hospital in Nanjing from August 2022 to June 2023 for semi-structured interviews,and Colaizzi 7-step process of analyzing,summarizing,and refining the themes was used.Results A total of 4 themes were extracted,including determination of willingness to become pregnant,perceived risks of childbirth,perceived benefits to themselves and their families,diversified support needs.Conclusion The establishment of pregnancy intention of three-child pregnant women is affected by many factors.Relevant departments should actively implement the supporting measures of the three-child birth policy;healthcare workers should strengthen perinatal healthcare services for three-child mothers to reduce the risk of giving birth,actively strengthen their sense of benefits related to pregnancy,and establish a whole process of support system to promote the health of mothers and infants.

Objective:To explore the risk factors of septic acute kidney injury (sAKI) in patients with sepsis, construct a predictive model for sAKI, verify the predictive value of the model, and develop a dynamic nomogram to help clinical doctors identify patients with high-risk sAKI earlier and more easily.Methods:A cross-sectional study was conducted. A total of 245 patients with sepsis admitted to intensive care unit (ICU) of the Affiliated Hospital of Jining Medical University from May 2013 to November 2023 were enrolled as the research subjects. The patients were divided into sAKI group and non-sAKI group based on whether they suffered from sAKI during ICU hospitalization. The differences of the demographic, clinical and laboratory indicators of patients between the two groups were compared. Logistic ordinal regression analysis was performed to analyze the imbalanced variables between the two groups, and to construct a sAKI predictive model. The predictive value of the sAKI predictive model was evaluated through 5-fold cross validation, calibration curve, and decision curve analysis (DCA), and to develop an online dynamic nomogram for the predictive model.Results:A total of 245 patients were enrolled in the final analysis. 110 (44.9%) patients developed sAKI during ICU hospitalization and 135 (55.1%) patients did not develop sAKI. Compared with the non-sAKI group, the patients in the sAKI group had higher ratios of female, hypertension, invasive mechanical ventilation (IMV), renal replacement therapy (RRT), vasopressin usage, and neutrophil count (NEU), aspartate aminotransferase (AST), blood urea nitrogen (BUN), serum creatinine (SCr), uric acid (UA), Na +, K +, procalcitonin (PCT), acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, and sequential organ failure assessment (SOFA) score. Multivariate Logistic ordinal regression analysis showed that female [odd ratio ( OR) = 2.208, 95% confidence interval (95% CI) was 1.073-4.323, P = 0.020], hypertension ( OR = 2.422, 95% CI was 1.255-5.073, P = 0.012), vasopressin usage ( OR = 2.888, 95% CI was 1.380-6.679, P = 0.002), and SCr ( OR = 1.015, 95% CI was 1.009-1.024, P < 0.001) were independent risk factors for sAKI in septic patients, and a sAKI predictive model was constructed: ln[ P/(1+ P)] = -4.665+0.792×female+0.885×hypertension+1.060×vasopressin usage+0.015×SCr. The 5-fold cross validation showed that the average area under the receiver operator characteristic curve (AUC) was 0.860, indicating the sAKI predictive model had a good performance. The calibration curve analysis showed that the calibration degree of the sAKI predictive model was good. DCA showed that the net profit of the sAKI predictive model was relatively high. A static nomogram and an online dynamic nomogram were constructed for the sAKI predictive model. Compared with the static nomogram, the dynamic nomogram allowed for manual selection of corresponding patient characteristics and viewing the corresponding sAKI risk directly. Conclusions:Female, hypertension, vasopressin usage, and SCr are the main risk factors for sAKI in patients with sepsis. The sAKI predictive model constructed based on these factors can help clinical doctors identifying high-risk patients as early as possible, and intervene in a timely manner to provide preventive effects. Compared with the common static nomogram, online dynamic nomogram can make predictive models clearer, more intuitive, and easier.

ObjectiveTo observe the effects of Danggui Buxuetang on the mitochondrial fission and apoptosis of podocytes in the rat model of diabetic kidney disease （DKD） and to explore the protective effect and mechanism of Danggui Buxuetang on DKD rats. MethodSD rats were randomized into a modeling group （n=65， fed with a high-sugar and high-fat diet） and a normal group （n=10， fed with a normal diet）. After 6 weeks， the modeled rats were injected intraperitoneally with streptozotocin （STZ） for the modeling of type 2 diabetes mellitus （T2DM）. Sixty T2DM rats were randomized into model， irbesartan （0.014 g·kg^-1）， and low-， medium-， and high-dose （0.36， 0.72， 1.44 g·kg^-1， respectively） Danggui Buxuetang groups and administrated with corresponding drugs by gavage for 16 weeks. The levels of fasting blood glucose （FBG） and 24 h urinary protein （24 h UTP） were determined at the end of the 16th week. The pathological changes of the renal tissue were observed by hematoxylin-eosin and Masson staining. The mitochondrial ultrastructure of rat podocytes was observed by transmission electron microscopy. The level of reactive oxygen species （ROS） in the renal tissue of rats was measured by the fluorescent probe labeling of dihydroethidium （DHE）. The apoptosis of renal cells was detected by terminal-deoxynucleotidyl transferase-mediated dUTP nick end labeling （TUNEL）. The expression levels of Synaptopodin， Podocin， and cleaved caspase-3 in renal podocytes were detected by the immunohistochemical method （IHC）. Western blot was employed to determine the protein levels of A-kinase anchoring protein 1 （AKAP1）， phosphorylated dynamin-related protein 1 （p-Drp1）， mitofusin-2 （Mfn2）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. ResultCompared with the control group， the model group showed elevated levels of FBG and 24 h UTP， mesangial hyperplasia， basement membrane thickening， mitochondrial swelling， mitochondrial crista breakage and disorder， and increased ROS and TUNEL-positive cells. In addition， the model group showcased down-regulated expression of Synaptopodin and Podocin， increased expression of cleaved Caspase-3， up-regulated protein levels of AKAP1 and p-Drp1 ， and down-regulated protein levels of Mfn2 and Bcl-2/Bax （P<0.01）. Compared with the model group， high-dose Danggui Buxuetang lowered the levels of FBG and 24 h UTP， alleviated the pathological injuries of the renal tissue and the mitochondrial injury of podocytes， decreased ROS and TUNEL-positive cells， promoted the expression of Synaptopodin and Podocin， inhibited the expression of cleaved Caspase-3， down-regulated the protein levels of AKAP1 and p-Drp1， and up-regulated the protein levels of Mfn2 and Bcl-2/Bax （P<0.05， P<0.01）. ConclusionDanggui Buxuetang may inhibit mitochondrial fission and apoptosis of podocytes and reduce urine protein by regulating the AKAP1/Drp1 pathway， thereby delaying the progression of DKD.

Objective:To investigate the effectiveness and safety of low-dose oral misoprostol solution for cervical ripening in late gestation.Methods:This was a prospective cohort study including 396 primiparas with singleton pregnancy who received low-dose oral misoprostol solution for cervical ripening (oral group) in Peking University Third Hospital from March to October 2022. They were further allocated to receive oral misoprostol alone (OA group, n=167) or oral misoprostol in combination with oxytocin/amniotomy (OC group, n=229). Moreover, 218 cases who received vaginal misoprostol for cervical ripening (vaginal group) during the same period in 2021 were reviewed (a retrospective cohort). Among them, 77 were given vaginal misoprostol alone (VA group) and 141 received vaginal misoprostol in combination with oxytocin/amniotomy (VC group). The OA group and VA group (72 and 73 cases) as well as the OC group and VC group (108 and 103 cases) were matched using propensity scores. Basic clinical information, hospital stay, duration of labor induction, uterine hyperstimulation, rate of labor initiation, vaginal delivery rate, rate of delivery within 24 h, duration of labor, neonatal condition, adverse pregnancy outcomes, and other information were compared between different groups. All data were statistically analyzed using independent sample t test, analysis of variance, nonparametric test, Chi-square test, or Fisher's exact probability test. Logistic regression model was used to analyze the factors affecting the labor initiation and the failure of labor induction. Results:The average hospital stay, the duration from medication to labor initiation and the duration from medication to vaginal delivery were significantly shorter in the oral group than those in the vaginal group [(5.4±2.4) vs. (6.5±2.6) d, (34.2±24.1) vs. (38.9±25.7) h, (45.8±25.8) vs. (53.4±27.8) h; t=5.24, 2.10 and 3.39; all P<0.05]. The total labor initiation rate and vaginal delivery rate in the oral group were significantly higher than those in the vaginal group [92.9% (368/396) vs. 83.5% (182/218), 72.2% (286/396) vs. 60.1% (131/218); χ 2=13.43 and 9.50; both P<0.05]. The incidence of failed induction of labor, uterine hyperstimulation, fetal distress, and intrauterine infection in the oral group were lower than those in the vaginal group [2.0% (8/396) vs. 6.9% (15/218), 4.3% (17/396) vs. 17.9% (39/218), 8.8% (35/396) vs. 14.7% (32/218), 1.3% (5/396) vs. 3.7% (8/218); χ 2=9.21, 31.36, 4.93 and 3.93; all P<0.05]. The duration from medication to labor initiation and to vaginal delivery in the OA group were higher than those in the VA group [(25.8±17.0) vs. (17.4±10.8) h, (37.2±18.8) vs. (29.7±13.5) h; t=3.49 and 2.74; both P<0.05]. There were no significant differences in the labor initiation rate, vaginal delivery rate, rate of delivery within 24 h or the incidence of failed induction of labor between the OA and VA groups (all P>0.05). Women in the VA group were more likely to develop uterine hyperstimulation than those in the OA group [19.2% (14/73) vs. 4.2% (3/72), χ2=7.89, P=0.005]. There were no significant differences in the duration from medication to labor initiation or to vaginal delivery between the VC and OC groups (both P>0.05), but the duration were significantly longer than those in the corresponding medication alone group (VC vs. VA groups: (49.7±24.6) vs. (17.4±10.8) h and (61.6±25.7) vs. (29.7±13.5) h, t=5.31 and 5.13, both P<0.05; OC vs. OA groups: (45.3±26.6) vs. (25.8±17.0) h and (56.1±27.2) vs. (37.2±18.8) h, t=10.35 and 9.78, both P<0.05]. The labor initiation rate, vaginal delivery rate and rate of delivery within 24 h in the OC group were higher than those in the VC group [88.9% (96/108) vs. 77% (87/113), 63.0% (68/108) vs. 47.8% (54/113), 10.3% (7/108) vs. 0.0% (0/113); χ 2=5.49, 5.14 and 7.56; all P<0.05]. The incidence of uterine hyperstimulation in the OC group was 4.6% (5/108), which was lower than that in the VC group [18.6% (21/113), χ 2=10.37, P=0.001]. Logistic regression analysis showed that oral misoprostol and gestational age were positively correlated with labor initiation [ OR (95% CI): 2.18 (1.24-3.90) and 1.43 (1.14-1.79)], while maternal age was negatively correlated with labor initiation [ OR (95% CI): 0.90 (0.82-0.98)]. Moreover, failed induction of labor was negatively correlated with oral misoprostol [ OR (95% CI): 0.37 (0.14-0.91)], but positively correlated with maternal age [ OR (95% CI): 1.21 (1.05-1.40)]. Conclusions:Oral administration of low-dose misoprostol solution is as effective as vaginal misoprostol in promoting cervical ripening. Besides, it can shorten the average hospital stay and reduce the incidence of uterine hyperstimulation, suggesting that low-dose oral misoprostol solution is relatively safer and can be used to promote cervical ripening in late gestation.

Depression is a common cause of human disability and death.Some patients are not sensitive to antidepressants,and also the recurrence rate is very high.Unfortunately,there are many problems with existing antidepressants.So,it is urgent to find a new antidepressant aiming at multiple targets.Recently,researchers have found that soluble N-ethylmaleimide-sensitive factor attachment protein receptor(SNARE)complex is closely related to the progression of depression.This review discusses the potential mechanisms of the SNARE complex in glial cells,and hopes to contribute to the understanding of depression and provide new ideas for clinical development of novel antidepressant drugs.