Clinically significant changes in anal sphincter hiatal area in patients with gestational diabetes mellitus and pelvic organ prolapse

BACKGROUND The prevalence of pelvic organ prolapse(POP)increases with age and parity.Specifically,the prevalence of POP among women aged 20 to 39 is 9.7%,while it rises to 49%among women over 80 years old.Additionally,as the number of deliveries increases,the prevalence of POP also rises accordingly,with a rate of 12.8%for women with one delivery history,18.7%for those with two deliveries,and 24.6%for women with three or more deliveries.It causes immense suffering for pregnant women.AIM To evaluate the relationship between the levator ani muscle’s hiatus(LH)area and POP in patients with gestational diabetes mellitus(GDM)using perineal ultrasound.METHODS The study cohort comprised 104 patients aged 29.8±3.7 years who sought medical care at our institution between January 2021 and June 2023.All were singleton pregnancies consisting of 75 primiparas and 29 multiparas,with an average parity of 1.7±0.5.According to the POP diagnostic criteria,the 104 subjects were divided into two groups with 52 members each:POP group(patients with GDM combined with POP)and non-POP group(patients with GDM without POP).Perineal ultrasound was used to measure differences in the anteroposterior diameter,transverse diameter,and LH area.Receiver operating characteristic curves were drawn to determine the optimal cutoff values for the LH anteroposterior diameter,transverse diameter,and area for diagnosing POP.RESULTS Statistically significant increase in the LH area,anteroposterior diameter,and lateral diameter were observed in the POP group compared with the non-POP group(P<0.05).Both groups exhibited markedly elevated incidence rates of macrosomia and stress urinary incontinence.For the POP group,the area under the curve(AUC)for the LH area was 0.906 with a 95%confidence interval(CI):0.824-0.988.The optimal cutoff was 13.54cm²,demonstrating a sensitivity of 83.2%and a specificity of 64.4%.The AUC for the anteroposterior diameter reached 0.836 with a 95%CI:0.729-0.943.The optimal cutoff was 5.53 cm with a sensitivity of 64.2%and a specificity of 73.4%.For the lateral diameter,its AUC was 0.568 with a 95%CI:0.407-0.729.The optimal cutoff was 4.67 cm,displaying a sensitivity of 65.9%and a specificity of 69.3%.Logistic regression analysis unveiled that age,body weight,number of childbirths,total number of pregnancies,and gestational weight gain constituted the independent risk factors for the cooccurrence of GDM and POP.CONCLUSION Three-dimensional perineal ultrasonography of LH size and shape changes can effectively diagnose POP.Age,weight,number of births,number of pregnancies,and weight gain during pregnancy are independent risk factors affecting the cooccurrence of GDM and POP.GDM can increase the LH area in patients,and an enlarged LH leads to an increased incidence of POP.

基于文献病例的他克莫司致急性胰腺炎临床特征分析

目的探讨他克莫司相关急性胰腺炎(AP)的临床特征。方法检索CNKI、WanFang Data、VIP、PubMed和Web of Science等中英文文献数据库(截至2023年3月10日),收集他克莫司相关AP的病例报告文献,提取相关数据并进行描述性统计分析。结果共收集17篇文献共19例病例,其中男性10例,女性9例;年龄3~65岁。共发生他克莫司相关AP 21例次。11例次AP发作时他克莫司血药浓度水平>15 ng·mL^(-1),其中8例次接近或超过30 ng·mL^(-1)。19例次患者首次应用他克莫司后诱导AP时间为3 d~7年,中位时间为20 d,2例再诱发AP时间分别为37 d和75 d。他克莫司相关AP的临床症状、实验室、影像学检查结果与其他药物引起的AP类似,主要症状为腹痛,部分患者伴有恶心、呕吐、腹泻,少部分患者合并糖尿病或糖尿病酮症症状,严重者合并休克。诊断AP后,20例次有停药或对症支持治疗的描述,15例次患者及时停用或降低他克莫司剂量。15例次症状缓解或好转,5例死亡,其中与AP相关的死亡2例。结论他克莫司可能会引起AP,一般预后较好,严重者可出现死亡。早期识别并及时处理至关重要,特别是对于合并使用多种药物患者应密切监测他克莫司血药浓度。

Association of TNF-α-238G/A and 308 G/A Gene Polymorphisms with Pulmonary Tuberculosis among Patients with Coal Worker’s Pneumoconiosis

Objectives Tumor necrosis factor-α （TNF-α） may play an important role in host＇s immune response to mycobacterium tuberculosis （M. tuberculosis） infection. This study was to investigate the association of TNF-α gene polymorphism with pulmonary tuberculosis （TB） among patients with coal worker＇s pneumoconiosis （CWP）. Methods A case-control study was conducted in 113 patients with confirmed CWP complicated with pulmonary TB and 113 non-TB controls with CWP. They were matched in gender, age, job, and stage of pneumoconiosis. All participants were interviewed with questionnaires and their blood specimens were collected for genetic determination with informed consent. The TNF-α gene polymorphism was determined with polymerase chain reaction of restriction fragment length polymorphism （PCR-RFLP）. Frequency of genotypes was assessed for Hardy-Weinberg equilibrium by chi-square test or Fisher＇s exact probability. Factors influencing the association of individual susceptibility with pulmonary TB were evaluated with logistic regression analysis. Gene-environment interaction was evaluated by a multiplieative model with combined OR. All data were analyzed using SAS version 8.2 software. Results No significant difference in frequency of the TNF-α-308 genotype was found between CWP complicated with pulmonary TB and non-TB controls （2,2=5.44, P=-0.07）. But difference in frequency of the TNF-α-308 A allele was identified between them （2,2-5.14, P=0.02）. No significant difference in frequencies of the TNF-α-238 genotype and allele （P=0.23 and P=0.09, respectively） was found between cases and controls either, with combined （GG and AA） OR of 3.96 （95% confidence interval of 1.30-12.09） at the -308 locus of the TNF-α gene, as compared to combination of the TNF-α-238 GG and TNF-α-308 GG genotypes. Multivariate-adjusted odds ratio of the TNF-α-238 GG and TNF-α-308 GA genotypes was 1.98 （95% CI of 1.06-3.71） for risk for pulmonary TB in patients with CWP. There was a synergic interaction between the TNF-a-308 GG genotype and body mass index （OR=4.92）, as well as an interaction between the TNF-α-308 GG genotype and history of BCG immunization or history of TB exposure. And, the interaction of the TNF-α-238 GG genotype and history of BCG immunization or TB exposure with risk for pulmonary TB in them was also indicated. Conclusions TNF-α-308 A allele is associated with an elevated risk for pulmonary TB, whereas TNF-α-238 A allele was otherwise.

Baicalin and geniposide inhibit the development of atherosclerosis by increasing Wntl and inhibiting dickkopf-related protein-1 expression

Background Our previous study showed that the combined Chinese herbs containing scutellaria baicalensis georgi and gardenia jasminoids ellis inhibited atherosclerosis. In this study, we sought to determine if baicalin and geniposide could inhibit atherosclerosis through Wntl and dickkopf-related protein-1 （DKK1）. Methods The wild-type and ApoE-/- mice were treated with baicalin, geniposide, and baicalin plus geniposide daily by gavage for 12 weeks. Blood lipid levels were measured with an automatic biochemistry analyzer. Aortic atherosclerotic lesion areas were analyzed with Image-ProPlus software. The mRNA and protein expression of DKK1, Wntt and nuclear factor-r,B （NF-κB） were measured with RT-PCR and Westem Blot. Serum levels of interleukin-12 （IL-12） were quantified with ELISA. Results The baicalin or geniposide monotherapy as well as combination therapy inhibited the development of atherosclerotic lesions, increased Wntl and decreased DKKI expression and elevated the ratio of Wntl/DKK1 compared with high-lipid diet group. However, only baicalin or geniposide monotherapy decreased NF-κB expression. Moreover, baicalin and geniposide monoor combination therapy lowered IL-12 levels. Geniposide reduced both serum total cholesterol and low density lipoprotein levels, while baicalin either alone or in combination with geniposide did not affect serum lipid levels. In human, umbilical vein endothelial ceils stimulated by oxidized low density lipoprotein, baicalin and geniposide also increased Wntl and decreased DKK1 expression and elevated the ratio of Wntl/DKK1. Condusions Baicalin and geniposide exert inflammation-regulatory effects and may prevent atherosclerotic lesions through enhancing Wntl and inhibit- ing DKK1 expression.

Correlation between Histone Deacetylase 9 and Regulatory T Cell in Patients with Chronic Heart Failure

Heart failure （HF） is the end stage of various kinds of cardiovascular diseases and leads to a high mortality worldwide. Numerous studies have demonstrated that frequencies of CD4＋CD25＋Foxp3＋ regulatory T cells （Tregs） are reduced in HF patients and properly expanding Tregs attenuates HF progression. Histone deacetylase （HDAC） 9 has been revealed to contribute to several cardiovascular and cerebrovascular diseases. Plenty of studies showed that HDAC9 negatively regulated the number and function of Tregs. Thus, we aim to investigate the expression of HDAC 9 in patients with chronic heart failure （CHF） and the relationship among HDAC9, Tregs and CHF. Our research showed a reduced number of Tregs and an increased expression of HDAC9 mRNA in CHF patients. Patients with CHF were divided into two groups by heart function grade of New York Heart Association （NYHA）, we found that the HDAC9 mRNA expression level in NYHA grade Ⅱ -Ⅲ group were lower than that in NYHA grade IV group. More importantly, the correlation study suggested that the expression of HDAC9 mRNA was negatively correlated to Tregs frequency and left ventricular ejection fraction （LVEF）, whereas positively correlated to larger left ventricular end-diastolic dimension （LVEDD） and B-type natriuretic peptide （BNP） in patients with CHF. The correlation studies also showed a positive correlation between HDAC9 and the severity of CHF. Our research suggests that HDAC9 may be a new indicator for assessing CHF and it may offer a new direction for research of CHF.

Free dendritic growth model based on nonisothermal interface and microscopic solvability theory

Considering both the effect of nonisothermal nature of the solid/liquid interface and the microscopic solvability theory (MicST), a further improved version of free dendritic growth model for pure materials was proposed. Model comparison indicates that there is a higher temperature at the tip of dendrite predicted by the present model compared with the corresponding model with the isothermal solid/liquid interface assumption. This is attributed to the sidewise thermal diffusion, i.e. the gradient of temperature along the nonisothermal interface. Furthermore, it is indicated that the distinction between the stability criteria from MicST and marginal stability theory (MarST) is more significant with the increase of bath undercoolings. Model test also indicates that the present model can give an agreement with the available experimental data. It is finally concluded that the nonisothermal nature of the solid/liquid interface and the stability criterion from MicST should be taken into account in modeling free dendritic growth.

Influence of sintering temperature on the thermoelectric properties of Ba_8Ga_(16)Si_(30) clathrate treated by spark plasma sintering

A series of Ba8Ga16Si30 clathrate samples were prepared by arc melting, ball milling, acid washing, and spark plasma sintering （SPS）. X-ray diffraction analysis revealed that the lattice of the Ba8Ga16Si30 samples expanded as the SPS temperature was increased from 400 to 750℃. Lattice contraction recurred when the SPS temperature was further increased in the range of 750-1000℃. This phenomenon can be explained by the variation of Ga content in the lattice. The thermoelectric figure of the merit ZT value of clathrates increased with the increase in SPS temperature and reached a maximum when the sample was subjected to SPS at 800℃. A further increase in SPS temperature did not contribute to the improvement of ZT. The variation of the lattice parameter a vs. SPS temperature T was similar to the variation ob-served in the ZT-T curve.

Free dendritic growth model considering both interfacial nonisothermal nature and effect of convection for binary alloy

Considering both the effect of the nonisothermal nature of the interface as well as the effect of forced convection,an extended free dendritic growth model for binary alloys was proposed.Comparative analysis indicates that the effect of convection on solute diffusion is more remarkable compared with the ignorable effect of convection on thermal diffusion at low bath undercooling,due to the fact that solute diffusion coefficient is usually three orders of magnitude less than thermal diffusion coefficient.At high bath undercooling,the effect of convection on the dendritic growth is very slight.Furthermore,a satisfying agreement between the model predictions with the available experiment data for the Cu70Ni30 alloy was obtained,especially at low bath undercoolings,profiting from the higher values of interfacial migration velocity predicted by the present model with nonideal fluid case than that predicted by the one ignoring the effect of convection.

Comparison of involved-field intensity-modulated radiotherapy combined with S-1 vs radiotherapy alone for elderly patients with esophageal cancer

BACKGROUND It is estimated that about 30%of esophageal cancer(EC)patients are over 70 years old.Therefore,there is less evidence on the diagnosis and management of elderly EC patients.It is important to explore how elderly EC patients benefit from radical radiochemotherapy regimens,including the target area of radiotherapy(RT),radiation dose and fraction,and choice of chemotherapy drugs.AIM To compare the efficacy of involved-field intensity-modulated RT(IF-IMRT)combined with S-1 vs RT alone in the treatment of elderly EC patients in terms of safety,short-term response,and survival.METHODS Thirty-four EC patients aged>70 years were prospectively enrolled between December 2017 and December 2019.Based on the random number table,they were divided into an IF-IMRT+S-1 group and an IF-IMRT alone group,with 17 patients in each group.All patients were treated with IF-IMRT at a dose of 50.4-56 Gy in 28-30 fractions(1.8-2 Gy/fraction,5 fractions/wk).Oral S-1 was administered concomitantly in the IF-IMRT+S-1 group for 14 consecutive days,and a second cycle was started 7 d after drug withdrawal.After RT,4 cycles of S-1 treatment were offered as the consolidation chemotherapy.The safety,short-term response,and survival were observed after the treatment.RESULTS As of April 2022,these 34 patients had been followed up for 15.2-32.5 mo,with a median follow-up period of 24.5 mo.Complete efficacy indicators were obtained from all the patients.The objective response rate was 88.2%vs 76.5%,respectively,in the IF-IMRT+S-1 group and the RT alone group,where as the disease control rate was 100%vs 82.4%,respectively.The incidence of adverse events including grade 1-2 fatigue,granulocytopenia,thrombocytopenia,anemia,radiation esophagitis,radiation-induced skin injury,and radiation-induced lung injury was not significantly different between these two groups,so was the incidence of the grade 3 radiation esophagitis(0%vs 5.7%).The rate of progressive disease(PD)was 52.9%(n=9)in the IF-IMRT+S-1 group and 64.7%(n=11)in the RT alone group.The median progression-free survival(PFS)was 23.4 mo vs 16.3 mo,and the 2-year PFS rate was 42%vs 41.2%.The median overall survival(OS)was 27.0 mo vs 23.0 mo,and the 2-year OS rate was 58.8%vs 47.1%.Multivariate analysis showed that age was a significant prognostic factor(P=0.0019);patients aged<75 years had a significant survival advantage over patients aged≥75 years.The locations of EC also affected the prognosis.In the IFIMRT+S-1 group,the number of chemotherapy cycles was a significant prognostic factor(P=0.0125),and the risk of PD was significantly lower in EC patients who had received 6 cycles of chemotherapy than those who had received 2-5 cycles of chemotherapy.CONCLUSION Compared with IF-IMRT alone,IF-IMRT+S-1 shows the benefits of preventing PD and prolonging survival without increasing adverse reactions.Therefore,this concurrent radiochemotherapy deserves clinical application.

Screening antimicrobial peptides and probiotics using multiple deep learning and directed evolution strategies

Owing to their limited accuracy and narrow applicability,current antimicrobial peptide(AMP)prediction models face obstacles in industrial application.To address these limitations,we developed and improved an AMP prediction model using Comparing and Optimizing Multiple DEep Learning(COMDEL)algorithms,coupled with high-throughput AMP screening method,finally reaching an accuracy of 94.8%in test and 88%in experiment verification,surpassing other state-of-the-art models.In conjunction with COMDEL,we employed the phage-assisted evolution method to screen Sortase in vivo and developed a cell-free AMP synthesis system in vitro,ultimately increasing AMPs yields to a range of 0.5-2.1 g/L within hours.Moreover,by multi-omics analysis using COMDEL,we identified Lactobacillus plantarum as the most promising candidate for AMP generation among 35 edible probiotics.Following this,we developed a microdroplet sorting approach and successfully screened three L.plantarum mutants,each showing a twofold increase in antimicrobial ability,underscoring their substantial industrial application values.

Corticosteroid-induced Osteonecrosis of the Femoral Head:Detection,Diagnosis,and Treatment in Earlier Stages

Objective： This review aimed to provide a current recommendation to multidisciplinary physicians for early detection, diagnosis, and treatment of corticosteroid-induced osteonecrosis of the femoral head （ONFH） based on a comprehensive analysis of the clinical literature. Data Sources： For the purpose of collecting potentially eligible articles, we searched for articles in the PubMed, Cochrane Library, Embase, and CNKI databases up to February 2017, using the following key words： ＆quot;corticosteroid＆quot;, ＆quot;osteonecrosis of the femoral head＆quot;,＆quot;risk factors＆quot;, ＆quot;diagnosis＆quot;, ＆quot;prognosis＆quot;, and ＆quot;treatment＆quot;. Study Selection： Articles on relationships between corticosteroid and ONFH were selected for this review. Articles on the diagnosis, prognosis, and intervention of earlier-stage ONFH were also reviewed. Results： The incidence of corticosteroid-induced ONFH was associated with high doses of corticosteroids, and underlying diseases in certain predisposed individuals mainly occurred in the first 3 months of corticosteroid prescription. The enhanced awareness and minimized exposure to the established risk factors and earlier definitive diagnosis are essential for the success of joint preservation. When following up patients with ONFH, treatment should be started if necessary. Surgical treatment yielded better results than conservative therapy in earlier-stage ONFH. The ideal purpose of earlier intervention and treatment is permanent preservation of the femoral head without physical restrictions in daily living. Conclusions： Clinicians should enhance their precaution awareness of corticosteroid-induced ONFH. For high-risk patients, regular follow-up is very important in the 1st year after high-dose prescription of corticosteroids. Patients with suspected ONFH should be referred to orthopedists for diagnosis and treatment in its earlier stage to preserve the joint.

Scalable synthesis of nanoporous high entropy alloys for electrocatalytic oxygen evolution

High entropy alloys(HEAs)containing five or more equimolar components have shown promising catalytic performance due to their unique chemical and mechanical properties.However,it is still challenging to prepare scalable and efficient nanoporous HEAs as catalysts.Here,we present a facile strategy to synthesize largescale nanoporous HEAs particles by combing vacuum induction melting,gas atomization,and acidic etching procedure.The application of HEAs to energy conversion is evaluated with electrocatalytic oxygen evolution reaction(OER)on AlCrCuFeNi HEAs.The HEAs exhibit a low OER overpotential of 270 mV to achieve a current density of 10 mA·cm^(-2),a small Tafel slope of 77.5 mV·dec^(-1),and long-term stability for over 35 h in 1 mol·L^(-1) KOH,which is comparable to the state-of-the-art OER electrocatalyst RuO2.The findings in this paper not only provide an industrial approach to produce nanoporous HEAs powder but also inspire the applications of HEAs as catalysts.

Cognitive impairment and the associated risk factors among the elderly in the Shanghai urban area:a pilot study from China

Objectives:Our study aimed to investigate the prevalence of cognitive impairment(CI)and the associated risk factors among elderly people in Shanghai urban area,China.Methods:A population-based survey was conducted among people aged 55 years or older in urban areas of Shanghai.Face-to-face interviews were carried out to collect information including demographic characteristics,medical history,and medication use,etc.The validated Chinese version of the Mini-Mental State Examination(MMSE)was used to screen subjects with CI,and the criteria of CI were adjusted for education levels.Results:A total of 3,176 home-living residents(≥55 years old)were included in the study.Among them,266 people(102 men and 164 women)were identified as cognition impaired,with a prevalence of 8.38%(266/3,176,95%CI:(8.26,8.49))for both genders,9.21%(102/1,107,95%CI:(9.18,9.33))for men and 7.93%(164/2,069,95%CI:(7.80,8.09))for women,respectively.Furthermore,we found that several significant risk factors,including social factors(education,number of children,marriage status,and family structure),physiological factors(age,blood glucose level,and obesity),factors on living styles(physical exercise,diet&chronic diseases),and genetic factor(ApoE),associated with CI onset.Conclusions:This study confirms the high prevalence of CI among the elderly population in the Shanghai urban in China,similar to previous epidemiologic studies in Western countries.The putative risk factors associated with CI merit further investigated.

Visualization and Characterization of High-Order Chromatin Fibers under Light Microscope during Interphase and Mitotic Stages in Plants

Using genomic in situ hybridization with genomic DNA, high-order chromatin fibers were successfully exhibited under a light microscope through the cell cycle in barley, rice, maize and field bean. From the interphase to prophase and metaphase of mitosis, the fibers were basically similar. Each was estimated to be around 200 nm in diameter, but the strength of signals was not the same along the fiber length. Through the cell cycle a series of dynamic distribution changes occurred in the fibers. In the interphase, they were unraveled. At the early prophase they were arranged with parallel and mirror symmetry. During late-prophase and metaphase, the fibers were bundled and became different visible chromosomes. The parallel coiling and mirror symmetry structures were visible clearly until the metaphase. In anaphase they disappeared. During telophase, in peripheral regions of congregated chromosome group, borderlines of the chromosomes disappeared and the fibers were unraveled. This demonstrated that mitotic chromosomes are assembled and organized by parallel and adjacent coiling of the fibers and the fibers should be the highest order structure for DNA coiling.

Facile synthesis of CF_3-substituted dienamides via one-pot tandem reactions

A one-pot reaction sequence of sequential phosphine-promoted tandem annulations of aryl trifluoromethyl ketones and MBH（Morita-Baylis-Hillman） carbonates and DBU-mediated aminolysis was developed. This method provides a step-economical approach to trifluoromethylated dienamides with diverse structural complexity from readily available starting materials in moderate yields.