Objective To investigate the influencing factors of adverse pregnancy outcomes in patients with preeclampsia and the predictive value of serum trace elements in the second trimester.Methods A total of 98 patients with preeclampsia admitted to Qujing First People's Hospital from January 2019 to June 2022 were enrolled in the study.Patients were divided into poor outcome group and good outcome group according to whether they had adverse pregnancy outcomes.The clinical data of all patients enrolled in the study were col-lected and the serum levels of trace elements calcium,copper,zinc and iron were detected in the second trimes-ter.Univariate analysis and multivariate Logistic regression were used to analyze the influencing factors of ad-verse pregnancy outcomes in patients with preeclampsia.The levels of serum trace elements in the second tri-mester of pregnancy were compared between the poor outcome group and the good outcome group.The re-ceiver operating characteristic(ROC)curve was used to evaluate the predictive value of serum trace elements calcium,copper,zinc and iron for adverse pregnancy outcomes in patients with preeclampsia.Results Univari-ate analysis showed that compared with the good outcome group,the poor outcome group had significantly higher systolic blood pressure,24 h urinary protein quantitation,and D-dimer level(P＜0.05)and significantly less gestational age and platelet count at admission(P＜0.05).Multivariate Logistic regression analysis showed that 24 h urinary protein quantification,D-dimer and platelet count were the influencing factors of ad-verse pregnancy outcomes in patients with preeclampsia(P＜0.05).The levels of serum trace elements calci-um,copper,and zinc in the poor outcome group were significantly lower than those in the good outcome group(P＜0.05),and the level of iron was significantly higher than that in the good outcome group(P＜0.05).ROC curve analysis showed that the areas under the curves(AUCs)of serum calcium,copper,zinc,and iron in the second trimester of pregnancy for predicting adverse pregnancy outcomes in preeclampsia patients were 0.830(95％CI:0.780-0.880),0.855(95％CI:0.805-0.905),0.847(0.797-0.897)and 0.861(95％CI:0.811-0.911),respectively.Conclusion Adverse pregnancy outcomes in patients with preeclampsia are re-lated to 24 h urine protein,D-dimer and platelet count.The levels of serum trace elements calcium,copper,zinc and iron in the second trimester of pregnancy change significantly in patients with adverse pregnancy out-comes,which may become predictive markers of adverse pregnancy outcomes.

Purpose To explore the clinicopathological features of cholangitis lenta.Methods The clinical data of 12 patients with cholangitis Lenta were collected,HE staining,his-tochemical staining and immunohistochemistry were used to de-tect the clinicopathological changes in 12 cases of cholangitis lenta,and the relevant literature was reviewed.Results All the 12 patients with cholangitis Lenta had acute history and ab-normal liver function,9 cases(75.0％)had abnormal white blood cell count,11 cases(91.7％)had abdominal infection,8 cases(66.7％)had systemic inflammatory response syndrome(SIRS)and 8 cases(66.7％)were diagnosed as sepsis.The common pathological manifestations included spotty necrosis(100％),piecemeal necrosis(100％),confluent necrosis(75.0％),bridging necrosis(66.7％),hepatocyte and capil-lary cholestasis(75.0％),and mild edema in portal area(33.3％).12 cases showed proliferation of bile ductules around the portal area,inspissated bile in dilated bile ductules and no cholestasis in interlobular bile ducts.12 cases had the basis of primary liver disease.2 patients(16.7％)died after being transferred to another hospital for treatment,and 10 patients(83.3％)survived,which lasted for 7 to 55 months.Conclu-sion Cholangitis Lenta shows unique clinical manifestations and morphological features,it is often accompanied by underly-ing diseases.The pathological manifestation of cholangitis Lenta in liver biopsy suggests that patients may have sepsis and/or ab-dominal infection,and therefore its diagnosis should be com-bined with clinical features,laboratory examination and imaging manifestations.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

Receptors, Purinergic ; Signal Transduction/physiology*

Purpose: Neoadjuvant therapy modality can increase the operability rate and mitigate pathological risks in locally advanced cervical cancer, but treatment response varies widely. It remains unclear whether genetic alterations correlate with the response to neoadjuvant therapy and disease-free survival (DFS) in locally advanced cervical cancer. Materials and Methods: A total of 62 locally advanced cervical cancer (stage IB-IIA) patients who received neoadjuvant chemoradiation plus radical hysterectomy were retrospectively analyzed. Patients’ tumor biopsy samples were comprehensively profiled using targeted next generation sequencing. Pathologic response to neoadjuvant treatment and DFS were evaluated against the association with genomic traits. Results: Genetic alterations of PIK3CA were most frequent (37%), comparable to that of Caucasian populations from The Cancer Genome Atlas. The mutation frequency of genes including TERT, POLD1, NOS2, and FGFR3 was significantly higher in Chinese patients whereas RPTOR, EGFR, and TP53 were underrepresented in comparison to Caucasians. Germline mutations were identified in 21% (13/62) of the cohort and more than half (57%) had mutations in DNA damage repair genes, including BRCA1/2, TP53 and PALB2. Importantly, high tumor mutation burden, TP53 polymorphism (rs1042522), and KEAP1 mutations were found to be associated with poor pathologic response to neoadjuvant chemoradiation treatment. KEAP1 mutations, PIK3CA-SOX2 co-amplification, TERC copy number gain, and TYMS polymorphism correlated with an increased risk of disease relapse. Conclusion We report the genomic profile of locally advanced cervical cancer patients and the distinction between Asian and Caucasian cohorts. Our findings highlight genomic traits associated with unfavorable neoadjuvant chemoradiation response and a higher risk of early disease recurrence.

OBJE CTIVE To explore the rational application and management of antibiotics in burn department of our hospital based on disease diagnosis related groups （DRGs）. METHODS Patients discharged from the burn department of our hospital from July 2020 to June 2021 were selected as the research objects to collect DRG data. The overall application of antibiotics in DRG group with more than 10 cases were analyzed ，and the application of antibiotics in typical disease groups were evaluated horizontally and vertically. RESULTS Among 3 732 discharged cases in the burn department of our hospital ，a total of 3 515 cases were included in 66 DRG groups ，21 DRG groups of which were included in the study. Among 21 DRG groups ，the maximum antibiotics use density （AUD）of antibiotics was 102.20 DDDs/（100 person·d）in AH 11 group，the utilization ratio of antibiotics was 100％，and the combined use rate of antibiotics was 81.82％；case-mix index （CMI）value was 11.49. The minimum AUD was 1.01 DDDs/（100 person·d）in XR 19 group，the utilization ratio of antibiotics was 5.06％，and the combined use rate of antibiotics was 0；CMI value was 0.81. Within the same core group ，AUD increased with the increase of CMI. The horizontal comparison and analysis of WB 11 group showed that there was a large gap in AUD among different physicians. The vertical comparison of AUD in WB11 group showed relatively small changes over time. CONCLUSIONS The horizontal and vertical evaluation of antibiotics based on DRGs can provide new clues for the control of antibiotics and help to realize the fine specialized management of antibiotics.

Objective To determine the consistency of urogenital hiatus ( U H ) data between the semi‐automatic measurement and manual measurement using transperineal pelvic floor ultrasonography . Methods Total of 286 three‐dimensional images of minimal U H dimension were obtained . And they were divided into study group ( 100 images) and test group ( 186 images) randomly . T hree experts traced and created the w hole profile of the U H of those images in the study group by M AT LAB . T hen the semi‐automatic software was obtained through machine learning algorithms . In the test group , 6 parameters of U H ( including anterioposterior diameter , transverse diameter ,circumference , area ,left and right levator urethral gap distance) were measured by two experts ( D 1 and D2 ) both manually and semi‐automatically . T he time experts spent on measuring was also recorded and compared . Results T he time used for semi‐automatic measurement was significantly shorter than that for manual measurement [ ( 7 .49 ± 1 .51 ) s vs ( 42 .42 ± 11 .08) s ,( 7 .52 ± 1 .37) s vs ( 43 .45 ± 9 .09) s for D1 and D2 , t ＝ －12 .09 ,－13 .64 ,all P＝0 .00] . T he Pearson correlation coefficients between semi‐automatic and manual measurements of 6 parameters were 0 .857 －0 .985 ( P ＜ 0 .01) ,0 .853 －0 .979 ( P ＜ 0 .01 ) in D1 and D2 ,respectively . T he interclass correlation coefficients ( ICC) of six parameters were ranged from 0 .846 －0 .985 for D1 and 0 .843～0 .979 for D2 ( all P ＜ 0 .01 ) . T he Bland Altman plot also showed good agreement between two methods . Conclusions Intellectual recognition and semi‐automatic measurement has simplified the process for U H measurement ,and it is proved to be a reliable and timesaving method that is practical for clinical use .

Objective To investigate the role of the ATP binding box C subfamily 2 transporter protein (ABCC2) gene in drug-resistant epilepsy.Methods From February 2014 to February 2018,204 epileptic patients were treated in our hospital,including 41 cases of drug resistance epilepsy (drug resistance group),163 cases of non drug resistant epilepsy (sensitive group).The rs717620 polymorphism of ABCC2 gene and the level of P-glycoprotein (P-gp) in cerebrospinal fluid and serum were detected in two groups.Results The proportion of genotype TT and gene frequency T in the drug resistant group were 24.39％ and 41.46％,respectively,which were significantly higher than those in the sensitive group (P ＜ 0.05).The concentration of P-gp in cerebrospinal fluid of drug resistant group was (21.03 ± 4.21) ng/ml,which was significantly higher than that of the sensitive group (P ＜ 0.05).There was no significant difference in serum P-gp concentration between the drug resistant group and the sensitive group (P ＞ 0.05);The concentration of P-gp in cerebrospinal fluid of patients with genotype TT in drug resistance group was (24.03 ± 3.57) ng/ml,which was significantly higher than that of type CC and CT (P ＜ 0.05).There was no significant difference in the concentration of P-gp in the patients with different genotypes in the drug resistant group (P ＞ 0.05).Conclusions The rs717620 polymorphism of ABCC2 gene may be associated with drug-resistant epilepsy,and may be related to P-gp level in the cerebrospinal fluid.

Objective To evaluate combined sampling at multiple sites of gastric mucosa for Helicobacter pylori (HP) culture.Methods A total of 258 patients with upper gastrointestinal symptoms received 13C-urea breath test between August 2014 and May 2015.During endoscopy,gastric mucosa biopsy samples from the lesser curvature of the antrum (A),the greater curvature of the antrum (B),gastric angle (C) and the body of the stomach (D) were collected to isolate HP strains.The positive rates of HP based on combined sampling and single site sampling were compared with a Nemenyi test.Results Consistency between 13C-urea breath test and HP culture was 82.56％.There was significant difference between the single site sampling and two-site sampling in the positive rate of HP,except for the body of the stomach (P＜0.05).There was significant difference in the positive rate of HP between the single site sampling and three-site sampling (P ＜ 0.05).There was no significant difference between any two-site sampling in the lesser curvature of the antrum and the body of the stomach,gastric angle and the body of the stomach,the greater curvature of the antrum and the body of the stomach,and any three-site sampling (P＞0.05).Conclusion The combined sampling of the lesser curvature of the antrum and the body of the stomach have the highest cost-effectiveness in HP culture compared with the single site sampling and three-site sampling.

Aim To investigate the anti-proliferation effect of resveratrol (Res)on human colon cancer cells and dissect the possible mechanism underlaying this effect.Methods We introduced crystal violet staining and Western blot to analyse the anti-proliferation effect of Res on HCT1 1 6 cells.Then,we used flow cytome-try and Western blot assay to detect the Res induced apoptosis in HCT1 1 6 cells.Next,we employed the well established TCF4 /LEF luciferase reporter to meas-ure the effect of Res on Wnt/β-catenin signaling trans-duction.Finally,we took Western blot and PCR assay to analyse the effect of Res on the expression of β-cate-nin in HCT1 1 6 cells.Results Crystal violet staining and Western blot analysis showed that Res could inhib-it the proliferation of HCT1 1 6 cells in a concentration-and time dependent fashion.What’s more,Res could promote apoptosis in HCT1 1 6 cells.The transcriptional activities of TCF4 /LEF reporter were reduced by Res in a concentration-dependent fashion (P <0.05 when the concentration of Res was 20 μmol·L -1 ,and P <0.01 when the concentration of Res was 40 μmol·L -1 or 80 μmol·L -1 ).Res could decrease not only the protein level of β-catenin in HCT1 1 6 cells,but also the mRNA expression of β-catenin.Conclusion Res can inhibit the proliferation of HCT1 1 6 cells,which may be mediated at least by down-regulating the ex-pression of β-catenin to inhibit the Wnt/β-catenin sig-naling transduction.