Objectives:To investigate the effect of non-optimal temperature exposure during pregnancy on the risk for preterm birth and identify the susceptible exposure window. At the same time, the interaction between non-optimal temperature and pollutants exposure during pregnancy on preterm birth was analyzed, in order to provide strong clues for the influence of non-optimal temperature exposure during pregnancy on the risk for preterm birth.Methods:A total of 1 852 pregnant women were recruited from September 2021 to June 2023 in Fujian Provincial Maternal and Child Health Care Center. Questionnaire survey was conducted, and their health records were analyzed. The permanent address of each pregnant woman was matched with Fifth Generation European Centre for Medium-Range Weather Forecasts Atmospheric Reanalysis of the Global Climate and a geo-statistical combination model based on satellite remote sensing data collection, then follow-up for pregnancy outcome was conducted. Distributed lag nonlinear model was used to assess the association between exposure to non-optimal temperature during pregnancy and the risk for preterm birth and a multiplicative interaction model was used to assess the interaction between exposure to pollutants and non-optimal temperatures during pregnancy on the risk for preterm birth.Results:After adjusting for potential confounders such as maternal age, occupation, Gross Domestic Product of the region, pre-pregnancy preconception BMI, newborn sex, the weekly susceptibility windows of extreme low temperature ( P1, P3, P5) were week 1-22 , and the weekly susceptibility windows of extreme high temperature ( P95, P97, P99) were week 27 and week 32-36. Extreme low temperature [ P1 ( OR=1.147, 95% CI: 1.041-1.265), P5 ( OR=1.284, 95% CI: 1.035-1.501)] and extreme high temperature [ P97 ( OR=1.146, 95% CI: 1.039-1.263), P99 ( OR=1.216, 95% CI: 1.099-1.345)] exhibited multiplicative interaction with PM 2.5. Conclusions:Exposure to non-optimal temperature during pregnancy was associated with an increased risk for preterm birth. The susceptible exposure windows of extreme low temperature were mainly in early and mid-pregnancy, and the susceptible exposure windows of extreme high temperature were mainly in late-pregnancy. Exposure to non-optimal temperatures and pollutants during pregnancy was associated with an increased risk for preterm birth.

OBJECTIVES: To elucidate the anti-aging effect of β-sitosterol (BS), an important component in the fruits of Alpinia oxyphylla Miq., in C. elegans and its regulatory effect on ETS-5 gene to modulate ferroptosis. METHODS: C. elegans treated with 10 µg/mL BS were monitored for survival time and changes in body length, motility, and reproductive function. The effect of ETS-5 gene knockdown on survival time of C. elegans was observed, and the changes in fat accumulation and lipid redox homeostasis in the transfected C. elegans were assessed using Oil Red O staining and by detecting MDA levels and the GSH/GSSG ratio. The mRNA expression levels of ferroptosis-related genes (FTN-1, GPX-1 and AAT-9) were detected using qPCR. The effects of BS treatment and ETS-5 knockdown on AAT-9 enzyme activity in C. elegans were examined. The effect of BS on nuclear localization of FEV (the human homolog of ETS-5) was validated in cultured human umbilical venous endothelial cells (HUVECs). RESULTS: Both BS treatment and ETS-5 knockdown significantly prolonged the lifespan, promoted lipid accumulation and reduced lipid peroxidation in C. elegans. ETS-5 knockdown resulted in upregulated expressions of the ferroptosis repressors GPX-1, AAT-9 and FTN-1 and increased the GSH/GSSG ratio in C. elegans. CONCLUSIONS BS inhibits ferroptosis in C. elegans by suppressing the expression of ETS-5 transcription factor and hence the activity of AAT-9 enzyme, a key gene for ferroptosis, which in turn prolongs the lifespan of C. elegans.
Animals ; Caenorhabditis elegans/physiology* ; Ferroptosis/drug effects* ; Alpinia/chemistry* ; Sitosterols/pharmacology* ; Longevity/drug effects* ; Fruit/chemistry* ; Humans

Objectives:To investigate the effect of non-optimal temperature exposure during pregnancy on the risk for preterm birth and identify the susceptible exposure window. At the same time, the interaction between non-optimal temperature and pollutants exposure during pregnancy on preterm birth was analyzed, in order to provide strong clues for the influence of non-optimal temperature exposure during pregnancy on the risk for preterm birth.Methods:A total of 1 852 pregnant women were recruited from September 2021 to June 2023 in Fujian Provincial Maternal and Child Health Care Center. Questionnaire survey was conducted, and their health records were analyzed. The permanent address of each pregnant woman was matched with Fifth Generation European Centre for Medium-Range Weather Forecasts Atmospheric Reanalysis of the Global Climate and a geo-statistical combination model based on satellite remote sensing data collection, then follow-up for pregnancy outcome was conducted. Distributed lag nonlinear model was used to assess the association between exposure to non-optimal temperature during pregnancy and the risk for preterm birth and a multiplicative interaction model was used to assess the interaction between exposure to pollutants and non-optimal temperatures during pregnancy on the risk for preterm birth.Results:After adjusting for potential confounders such as maternal age, occupation, Gross Domestic Product of the region, pre-pregnancy preconception BMI, newborn sex, the weekly susceptibility windows of extreme low temperature ( P1, P3, P5) were week 1-22 , and the weekly susceptibility windows of extreme high temperature ( P95, P97, P99) were week 27 and week 32-36. Extreme low temperature [ P1 ( OR=1.147, 95% CI: 1.041-1.265), P5 ( OR=1.284, 95% CI: 1.035-1.501)] and extreme high temperature [ P97 ( OR=1.146, 95% CI: 1.039-1.263), P99 ( OR=1.216, 95% CI: 1.099-1.345)] exhibited multiplicative interaction with PM 2.5. Conclusions:Exposure to non-optimal temperature during pregnancy was associated with an increased risk for preterm birth. The susceptible exposure windows of extreme low temperature were mainly in early and mid-pregnancy, and the susceptible exposure windows of extreme high temperature were mainly in late-pregnancy. Exposure to non-optimal temperatures and pollutants during pregnancy was associated with an increased risk for preterm birth.

Objective To elucidate the anti-aging effect of β-sitosterol(BS),an important component in the fruits of Alpinia oxyphylla Miq.,in C.elegans and its regulatory effect on ETS-5 gene to modulate ferroptosis.Methods C.elegans treated with 10 μg/mL BS were monitored for survival time and changes in body length,motility,and reproductive function.The effect of ETS-5 gene knockdown on survival time of C.elegans was observed,and the changes in fat accumulation and lipid redox homeostasis in the transfected C.elegans were assessed using Oil Red O staining and by detecting MDA levels and the GSH/GSSG ratio.The mRNA expression levels of ferroptosis-related genes(FTN-1,GPX-1 and AAT-9)were detected using qPCR.The effects of BS treatment and ETS-5 knockdown on AAT-9 enzyme activity in C.elegans were examined.The effect of BS on nuclear localization of FEV(the human homolog of ETS-5)was validated in cultured human umbilical venous endothelial cells(HUVECs).Results Both BS treatment and ETS-5 knockdown significantly prolonged the lifespan,promoted lipid accumulation and reduced lipid peroxidation in C.elegans.ETS-5 knockdown resulted in upregulated expressions of the ferroptosis repressors GPX-1,AAT-9 and FTN-1 and increased the GSH/GSSG ratio in C.elegans.Conclusion BS inhibits ferroptosis in C.elegans by suppressing the expression of ETS-5 transcription factor and hence the activity of AAT-9 enzyme,a key gene for ferroptosis,which in turn prolongs the lifespan of C.elegans.

A young female patient with acne and elevated testosterone level underwent plasma steroid hormones testing and found a significant increase in aldosterone. We excluded testing interference and verified the absence of hypertension, hypokalemia, and adrenal occupancy, as well as primary and secondary hyperaldosteronism. During follow-up, a temporal correlation was found between aldosterone levels and the use of drospirenone and ethinylestradiol tablets. It was observed that the combination of drospirenone and ethinylestradiol could lead to the increase of aldosterone level and the concentration ratio of aldosterone to direct renin through different mechanisms. Drospirenone exerts an antagonistic effect on mineralocorticoid receptor to prevent the development of hypertension or hypokalemia. In clinical practice, it is necessary to pay attention to the effect of this drug on screening markers for primary aldosteronism. In the laboratory examination, when female patients with no symptoms of hypertension and hypokalemia but with elevated aldosterone levels are encountered, it can be verified whether they have a history of use of compound estrogen-progestin such as drospirenone and ethinylestradiol tablets, and appropriate tips are provided in the report.

Objective To investigate the effect of verbascoside(VB)on endothelial dysfunction in atherosclerotic(AS)rats by regulating high-mobility group protein B1(HMGB1)/receptor for advanced glycation endproducts(RAGE)/nuclear factor κB(NF-κB)signal pathway.Methods The rat model of AS was established by high fat feeding combined with vitamin D3 solution intraperitoneal injection.Rats were divided into the control group(n=10),the model group(n=12),the low(VB-L),medium(VB-M)and high dose(VB-H)VB groups(2,5 and 10 mg/kg,n=10),and the positive control group(simvastatin,5 mg/kg,n=10).The serum level of blood lipids was detected by automatic biochemical analyzer.Pathological changes of aorta were observed by HE staining.Serum levels of inflammatory factors and vascular endothelial cytokines were detected by enzyme-linked immunosorbent assay(ELISA).The level of oxidative stress in rats was detected by micro-method kit.The expression of HMGB1/RAGE signal pathway protein in aorta was detected by Western blot assay.Results Compared with the control group,the intima of aorta in the model group was thickened,plaque appeared in blood vessels,accompanied by lipid deposition and inflammatory cell infiltration.Serum levels of total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),C-reactive protein(CRP),matrix metalloproteinase-9(MMP-9),endothelin-1(ET-1),visfatin,intercellular adhesion molecule-1(ICAM-1)and malondialdehyde(MDA),and HMGB1,RAGE and phosphorylation levels of NF-κB in aorta were obviously increased.Serum levels of high-density lipoprotein cholesterol(HDL-C),nitric oxide(NO),superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)were obviously decreased(P＜0.05).Compared with the model group,pathological changes of rats were obviously improved in the VB-L,VB-M and VB-H groups and the simvastatin group.Serum levels of TC,TG,LDL-C,TNF-α,IL-1β,CRP,MMP-9,ET-1,visfatin,ICAM-1,MDA,and HMGB1,RAGE,phosphorylation levels of NF-κB in aorta were obviously decreased,and serum levels of HDL-C,NO,SOD and GSH-Px were obviously increased(P＜0.05).Conclusion VB can down-regulate the expression of HMGB1/RAGE/NF-κB signal pathway protein,inhibit inflammation and oxidative stress in AS rats,and improve lipid metabolism and vascular endothelial function.

Thimerosal has been widely used as a preservative in drug and vaccine products for decades.Due to the strong propensity to modify thiols in proteins,conformational changes could occur due to covalent bond formation between ethylmercury(a degradant of thimerosal)and thiols.Such a conformational change could lead to partial or even complete loss of desirable protein function.This study aims to investigate the effects of thimerosal on the capsid stability and antigenicity of recombinant human papillomavirus(HPV)18 virus-like particles(VLPs).Dramatic destabilization of the recombinant viral capsid upon thimerosal treatment was observed.Such a negative effect on the thermal stability of VLPs preserved with thimerosal was shown to be dependent on the thimerosal concentration.Two highly neutralizing antibodies,13H12 and 3C3,were found to be the most sensitive to thimerosal treatment.The kinetics of antigenicity loss,when monitored with 13H12 or 3C3 as probes,yielded two distinctly different sets of kinetic parameters,while the data from both monoclonal antibodies(mAbs)followed a biphasic expo-nential decay model.The potential effect of thimerosal on protein function,particularly for thiol-containing proteinaceous active components,needs to be comprehensively characterized during formulation development when a preservative is necessary.

Objective:To analyze the interim clinical efficacy of laparoscopic and open distal gastrectomy for gastric cancer in elderly patients.Methods:The prospective randomized controlled study was conducted. The clinicopathological data of 102 patients aged ≥65 years who underwent distal gastrectomy for gastric cancer in the Nanfang Hospital of Southern Medical University from September 2014 to May 2018 were collected. After excluding 6 patients, 96 patients were finally included. Based on random number table, patients were allocated into two groups. Patients undergoing laparoscopic distal gastrectomy were allocated into laparoscopic group, and patients undergoing open distal gastrectomy were allocated into open group, respectively. Obser-vation indicators: (1) grouping situations of the enrolled patients; (2) intraoperative situations; (3) postoperative situations; (4) follow-up. Follow-up using outpatient examination and telephone interview was conducted to detect complications in the postoperative 30 days up to July 2018. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M( P25, P75) or M(range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Comparison of ordinal data was analyzed using the non-parameter Mann-Whitney U test. Results:(1) Grouping situations of the enrolled patients: a total of 96 patients were selected for eligibility. There were 66 males and 30 females, aged from 65 to 85 years, with a median age of 69 years. There were 49 of 96 patients in the laparoscopic group and 47 patients in the open group. (2) Intraoperative situations: patients in the two groups underwent distal gastrectomy successfully with D 2 lymphadenectomy, without intra-operative conversion to laparotomy. The volume of intraoperative blood loss and surgical incision length were 50 mL(50 mL,100 mL) and (7.1±1.7)cm for the laparoscopic group, respectively, versus 100 mL(100 mL,200 mL) and (19.1±1.7)cm for the open group, showing significant differences between the two groups ( Z=?3.779, t=?34.880, P<0.05) . (3) Postoperative situations: the number of lymph node dissected, time to postoperative initial out-of-bed activities, time to postoperative first flatus, time to postoperative first liquid food intake, time to postoperative first semi-liquid food intake, time to drainage tube removal, duration of postoperative hospital stay were 49(35,62), 1.9 days(1.3 days,2.9 days), 2.6 days(2.2 days,2.9 days), 3.4 days(2.7days,4.0 days), 5.9 days(4.7 days,7.7 days), 4.9 days(3.5 days,6.8 days), 7.7 days(6.7 days,8.9 days) for the laparoscopic group, respectively, versus 40(27,51), 2.5 days (1.8 days,3.3 days), 2.6 days(2.2 days,2.9 days), 3.9 days(2.9 days,5.7 days), 4.9 days(3.9 days, 5.9 days), 6.3 days(4.7 days,8.9 days), 8.7 days(6.9 days,11.7 days), showing significant differences between the two groups ( Z=?2.354, ?2.210, ?2.743, ?2.474, ?2.906, ?2.503, ?2.359, P<0.05). (4) Follow-up: patients in the two groups received 30 days of follow-up. During the follow-up, 8 patients in the laparoscopic group had postoperative complications, including 1 case with Clavien-Dindo grade Ⅰ complications, 7 cases with Clavien-Dindo grade Ⅱ complications, and no patient with Clavien-Dindo grade Ⅲ complications. Thirteen patients in the open group had postoperative complications, including 2 cases with Clavien-Dindo grade Ⅰ complications, 10 cases with Clavien-Dindo grade Ⅱ complications, and 1 case with Clavien-Dindo grade Ⅲ complications. There was no significant difference in the above indicators between the two groups ( χ2=1.135, 1.973, 1.054, P>0.05). The overall complication rate was 16.3%(8/49) and 27.7%(13/47) for the laparoscopic group and open group, respectively, showing no significant difference between the two groups ( χ2=1.803, 99.7% confidence interval as ?∞ to 2.4%, P>0.05). The upper limit of 99.7% confidence interval was less than non-inferiority level of 15%, interim analysis of which showed that the complication rate of the laparoscopic group was non-inferior to the open group. Conclusion:For elderly patients undergoing laparoscopic or open distal gastrectomy for gastric cancer, laparoscopic surgery does not increase intraoperative or postoperative complications, and has advantages of minimally invasiveness, fine operation, quicker recovery, and shorter hospital stay. Registry: this study was registered at clinicaltrials.gov in United States, with the registry number of NCT02246153.

Objective:This study evaluates the efficacy and safety of dasatinib combined with a multi-agent chemotherapy regimen of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) patients. Methods:This prospective, single-arm, and open clinical study enrolled 30 adult Ph + ALL patients who were newly diagnosed and treated from January 2016 to April 2018 in the center of this study. Standard induction chemotherapy was given for 4 weeks. However, dasatinib (100 mg/d) was continuously administered from day 8 until the end of the whole therapy in the induction therapy. Patients who are available for allogeneic or autologous stem cell transplantation (SCT) received transplantation when the disease was evaluated as complete remission. Results:All 30 patients achieved hematological complete remission (HCR) after the induction chemotherapy, and 70.0% (21/30) of them achieved the accumulated molecular complete remission (MCR) . The patients were followed up with a median follow-up time of 37.8 months (32.0-46.6) . The 3 year overall survival (OS) and 3 year hematological relapse-free survival (HRFS) were 68.1% and 61.6%, respectively. Moreover, 63.3% and 43.3% of the patients achieved molecular major remission and MCR, respectively. Consequently, 60.0% of the patients achieved MCR until 6 months. The patients who achieved MCR within 6 months had superior OS ( P=0.004) , HRFS ( P=0.049) , and event-free survival (EFS; P=0.001) . Fifteen patients (50.0%) received SCT at the first HCR. However, HRFS ( P=0.030) and EFS ( P=0.010) in the SCT group were better than those in the chemotherapy group. Conclusions:The regimen of dasatinib combined with a multi-agent chemotherapy was proven safe and effective in the treatment of newly diagnosed adult Ph + ALL patients. Clinical trial registration:ClinicalTrials.gov, NCT02523976.

OBJECTIVE： To screen the best proportion of Astragalus membranaceus injection combined with Erigeron breviscapus injection against cerebral ischemia-reperfusion injury in rats. METHODS： Male SD rats were randomly divided into sham operation group， model group and administration group [different A. membranaceus injection-E. breviscapus injection proportion groups， being A（0 ∶ 10）， B（2 ∶ 8）， C（4 ∶ 6）， D（6 ∶ 4）， E（8 ∶ 2）， F（10 ∶ 0）groups， set by baseline geometric proportion increasing and decreasing design]， with 8 rats in each group. Except for sham operation group， reperfusion injury model of middle cerebral artery occlusion were induced by modified suture method in rats. The each administration group was given relevant medicine intraperitoneally once immediately after inducing model， and then given again after 24 hours （medication interval between the two injections of 30 min）. Constant volume of normal saline was given to rats in sham operation group and model group. Forty-eight hours after reperfusion， Longa scoring method was used to evaluate neurological impairment of rats， and neurological impairment score was recorded. Serum content of MDA and activity of SOD were measured by colorimetry assay. TTC assay was used to detect cerebral infraction， and cerebral infarction rate was calculated. Kim’s formula was used to calculate the synergistic index （q） of rats in administration groups. RESULTS： Compared with sham operation group， neurological impairment score and serum content of MDA were increased significantly in model group， while activity of SOD was decreased significantly （P＜0.01）. The area of cerebral infarction increased significantly， and the rate of cerebral infarction increased significantly （P＜0.01）. Compared with model group， neurological impairment scores and serum contents of MDA were decreased significantly in group A， B， C， D and E； neurological impairment score of group C was significantly lower than those of group A and F； serum contents of MDA in group B， C， D and E were significantly lower than that of group F （P＜0.05 or P＜0.01）. Activities of SOD in group A， B， C， D and E were increased significantly， and group C was significantly higher than group F （P＜0.05 or P＜0.01）. The cerebral infarction area of rats in each administration group was reduced to varying degrees. The cerebral infarction rates of rats in group B， C， D and E were significantly reduced， and group C and D were significantly lower than group F， while group C was significantly lower than group A （P＜0.05 or P＜0.01）. The q values of group B， C， D and E were 0.90， 1.30， 1.00， 0.70 （neurological impairment score） and 0.79， 1.27， 0.98， 0.82 （cerebral infarction rate）. CONCLUSIONS： Different ratios of A. membranaceus injection and E. breviscapus injection have certain protective effects on cerebral ischemia-reperfusion injury model rats， can relieve their neurological deficits， alleviate their oxidative stress and reduce their cerebral infarction areas. The effect of the combination of the two drugs is better than that of single use， and the optimum ratio is 4 ∶ 6.