Objective To explore the effect and mechanism of Baicalein in the treatment of hyperuricemia.Methods The mouse model of hyperuricemia was established by yeast extract combined with potassium oxazinate.The effect and potential mechanism of Baicalein in the treatment of hyperuricemia were studied by biochemical indexes,pathological changes,non-target metabonomics and network pharmacology.Results Baicalein could reduce the contents of serum uric acid,creatinine and blood urea nitrogen,reduce the inflammatory injury of renal tissue,up-regulate the expression level of uric acid excretion protein and down-regulate the expression level of uric acid reabsorption protein.Nine disease-related targets such as BCL2,SIRT1 and XDH were screened by network pharmacology.Six key metabolic pathways including nicotinic acid and nicotinamide metabolism,caffeine metabolism and purine metabolism were screened by metabonomics analysis.Conclusions Baicalein can treat hyperuricemia and reduce renal injury,and its mechanism may be related to the metabolic pathways of nicotinic acid and nicotinamide regulated by SIRT1 and quinolinate.

Objective:To learn about the operation of arsenic reduction and water improvement projects and the present situation of arsenic level in drinking water in drinking water type endemic arsenic poisoning areas in Jinzhong City, Shanxi Province.Methods:From May to August 2023, in accordance with the requirements of the "Investigation Plan for Arsenic Content in Drinking Water of Residents in Arsenic Exposed Areas of Shanxi Province", 29 high arsenic villages in the drinking water type endemic arsenic poisoning historical areas of Pingyao County, Jiexiu City and Qi County in Jinzhong City, Shanxi Province were selected as monitoring villages to investigate the operation of water improvement projects. The drinking water samples of village residents were collected and water arsenic level was measured by hydride atomic fluorescence spectrophotometry. At the same time, monitoring of the operation of water improvement projects and water arsenic level for residents within adjacent local areas were carried out in townships where 29 high arsenic villages located.Results:In 2023, a total of 29 high arsenic villages in 3 counties (cities) of Jinzhong City, Shanxi Province were monitored, all of which had undergone water improvement and all water improvement projects were operating normally. The range of water arsenic level was 0.000 - 0.047 mg/L, with 27 high arsenic villages had water arsenic level < 0.01 mg/L. A total of 81 natural villages within the adjacent local areas of high arsenic villages in Jinzhong City were monitored, all of which had undergone water improvement and the water improvement projects were operating normally. The range of water arsenic level was 0.000 - 0.043 mg/L, and there were 4, 7, and 2 natural villages in Pingyao County, Jiexiu City and Qi County with water arsenic level ranging from 0.01 to 0.05 mg/L.Conclusions:All high arsenic villages in Jinzhong City, Shanxi Province have completed water improvement, and the water improvement projects are operating normally. The water arsenic level in most high arsenic villages meets the national drinking water standard (< 0.01 mg/L).

Objective:To analyze the review results of salt iodine monitoring in the county-level laboratories of iodine deficiency disorders in Jinzhong City, and to learn about the quality of the monitoring in the county-level laboratories, so as to provide scientific basis for formulating iodine deficiency disorders prevention and control strategies.Methods:From 2021 to 2023, Jinzhong Center for Disease Control and Prevention used the systematic random sampling method to select 5% (15 samples each) of all edible salt samples (short for salt samples) tested by 11 county-level iodine deficiency disorders laboratories under its jurisdiction for retesting each year. The salt iodine was determined by the redox titration method in accordance with the "General Test Method in Salt Industry-Determination of Iodine" (GB/T 13025.7-2012). Comparisons between groups for count data were analyzed using the χ 2 test, and the comparisons between groups for measurement data were analyzed using a random group design t-test. Results:From 2021 to 2023, the municipal laboratories reviewed and tested 165 salt samples (495 in total over 3 years). The proportion of households using adquately iodized salt tested by county-level laboratories was 92.53% (458/495), with annual rates of 89.70% (148/165), 93.33% (154/165), and 94.55% (156/165), respectively. The proportion of households using adquately iodized salt detected by municipal laboratories was 94.95% (470/495), with annual rates of 90.91% (150/165), 96.36% (159/165), and 97.58% (161/165), respectively. There was no significant difference in the proportion of households using adquately iodized salt detected by the two-level laboratories from 2021 to 2023 (χ 2 = 2.48, P = 0.116). The proportion of salt samples with relative error > 20% in the salt iodine detection results of county-level laboratories reviewed at the municipal laboratory from 2021 to 2023 were 20.00% (33/165), 16.97% (28/165), and 8.48% (14/165), respectively. The differences between different years were statistically significant (χ 2 = 8.49, P = 0.004). Compared with 2023, in 2021 and 2022, the differences were statistically significant ( P < 0.05). The proportion of salt samples with relative error > 30% were 7.88% (13/165), 6.06% (10/165), and 3.64% (6/165), respectively. There was no significant difference among different years (χ 2 = 2.69, P = 0.101). The comparison of laboratory test results between the two-level laboratories showed statistically significant differences ( t = 6.05, P < 0.001). Among the group data reviewed, there were a total of 16 groups with statistical significance, including 4 groups in 2021, 7 groups in 2022, and 5 groups in 2023. Conclusions:The review results indicate that the quality of salt iodine monitoring in county-level laboratories in Jinzhong City continues to improve, and the testing data are authentic and reliable. In the future, training for county-level laboratory inspectors should be increased to enhance their operational skills and minimize testing result errors.

OBJECTIVE: To explore the laboratory phenotype and molecular pathogenesis in a Chinese pedigree affected with Hereditary coagulation factor Ⅻ (FⅫ) deficiency. METHODS: A male proband admitted to Ningbo No.2 Hospital on July 17, 2021 due to chronic gastritis and members of his pedigree (7 individuals from three generations) were selected as the study subjects. Prothrombin time (PT), activated partial thromboplastin time (APTT), FⅧ activity (FⅧ: C), FⅨ activity (FⅨ: C), FⅪ activity (FⅪ: C), FⅫ activity (FⅫ: C), and FⅫ antigen (FⅫ: Ag) were determined. All of the exons, exon-intronic boundaries, as well as the 5'- and 3'-untranslated regions of the F12 gene were subjected to Sanger sequencing. Candidate variants were verified by cloning sequencing. The effect of candidate variants on the protein function was analyzed by bioinformatics software. RESULTS: The proband, a 47-year-old male, had significantly prolonged APTT (180.0 s) and decreased FⅫ:C and FⅫ:Ag levels (< 1%). His father, mother, brother and two sons also showed certain degrees of reduction. Genetic testing revealed that the proband has harbored compound heterozygous variants of the F12 gene, namely c.1092_1093insC (p.Lys365Glnfs*69) in exon 10 and c.1792_1796delGTCTA (p.Val579Hisfs*32) in exon 14. His mother and elder son were heterozygous for the c.1092_1093ins variant, whilst his father, brother, and younger son were heterozygous for the c.1792_1796delGTCTA variant. Analysis of the promoter region of exon 1 also showed that the proband and both sons had harbored a 46T/T polymorphism, whilst other family members were 46C/T. Bioinformatic analysis suggested that the p.Val579 is a highly conserved site. Protein model analysis showed that, with the p.Val579Hisfs*32 variant, a benzene ring was added and the hydrogen bond of surrounding amino acids was changed. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.1792_1796delGTCTA was classified as a pathogenic variant (PVS1+PM2_Supporting+PM4). CONCLUSION The c.1092_1093insC (p.Lys365Glnfs*69) and c.1792_1796delGTCTA (p.Val579Hisfs*32) compound heterozygous variants of the F12 gene probably underlay the decreased FXII levels in this pedigree. Above finding has also enriched the mutational spectrum for FⅫ deficiency.
Male ; Humans ; Aged ; Middle Aged ; Pedigree ; East Asian People ; Exons ; Introns ; Family ; Factor XII Deficiency/genetics* ; 3' Untranslated Regions ; Factor XII/genetics*

Objective To explore the clinical efficacy of using rituximab and atoxiban in the treatment of cervical incompetence after emergency cervical cerclage surgery.Methods Sixty patients with cervical incompetence admitted from May 2020 to February 2022 were selected as the study subjects.Divide into control group A,control group B,and trial group C using random number table method,with 20 cases in each group.All three groups underwent emergency cervical cerclage surgery.After the surgical treatment,control group A received treatment with rituximab hydrochloride,control group B received treatment with atoxiban,and experimental group C received treatment with atoxiban on the basis of rituximab hydrochloride.Analyze and compare the inhibitory effects of uterine contractions,incidence of adverse reactions,and neonatal outcomes among three groups.Results The inhibition rate of uterine contractions in control group A and test group C was higher than that in control group B(P<0.05);The incidence of postoperative complications in experimental group C was lower than that in control group A and control group B,with a statistically significant difference(P<0.05);Compared with control group A and control group B,the incidence of fetal loss,neonatal asphyxia,and low birth weight infant outcomes in experimental group C was not statistically significant(P>0.05).Compared with control group A and control group B,experimental group C had a longer gestational week extension and a higher Apgar score for newborns,with statistically significant differences(P<0.05).Conclusion The combination treatment of rituximab and atoxiban after emergency cervical cerclage surgery for this disease has good effects,can better inhibit uterine contractions,appropriately prolong gestational age,improve neonatal outcomes and prognosis,and reduce adverse drug reactions in pregnant women.

OBJECTIVE To optimite the purification technology of total triterpenoid extracts from Inonotus obliquus ，and to investigate the anti -tumor activity of its purified products . METHODS Using inotodiol as control ，the method was established for the content determination of total triterpenoid in I. obliquus. The type of macroporous adsorption resin ，sample volume ，sample concentration，sample flow rate ，eluent volume ，eluent dosage and elution flow rate were selected by single factor experiments . The purification technology of the crude extract was determined and verified . The effects of total triterpenoid purified from I. obliquus on the proliferation ，migration and apoptosis of human cervical cancer HeLa cells were detected by cell proliferation test ， migration test ，flow cytometry and AO/EB kit . RESULTS The best purification technology of total triterpenoid crude extracts from I. obliquus was as follows ：AB-8 macroporous adsorption resin was used ；mass concentration of the sample solution was 2.0 mg/mL；sample volume was 140 mL，and the flow rate was 1.0 mL/min；the impurity was removed with 50% ethanol 40 mL， then eluted with 95% ethanol 160 mL，at the elution flow rate of 3.0 mL/min. After purification ，mass concentration of total triterpenoid from I. obliquus increased from 34.36% to 73.39%. The total triterpenoid of I. obliquus could inhibit the proliferation of HeLa cells ，and the 50% inhibitory concentration was 184.20 μg/mL. Compared with control group ，the purified products could significantly inhibit the migratio n and promote the apoptosis of HeLa cells （P＜0.05 or P＜0.01）. CONCLUSIONS The purification technology of total triterpenoids extracts from I. obliquus is successfully optimited . The purified product could inhibit the proliferation and migration of HeLa cells and induce their apoptosis.

Objective:To observe the clinical features of uveal metastases from lung carcinoma.Methods:A retrospective case study. From 1983 to 2014, 14 patients with uveal metastases of lung cancer confirmed by ocular examination in Peking Union Medical College Hospital were included in the study. Among them, 7 were male, 7 were female; 11 were monocular and 3 were binocular. The mean age was 54.5±9.6 years. Pathologic examination showed primary bronchial lung cancer, including 13 patients of non-small cell lung cancer (10, 2 and 1 patients of lung adenocarcinoma, squamous cell carcinoma and adenosquamous cell carcinoma, respectively) and 1 patient of small cell lung cancer. Four patients (28.6%) were diagnosed with lung cancer before ophthalmology consultation, and 10 patients (71.4%) were first diagnosed with ophthalmology due to ocular symptoms. The duration from ocular symptoms to lung cancer diagnosis was 1 week to 6 months. The course from diagnosis of lung cancer to ophthalmological consultation was ranged from 10 to 60 months, and the average course was 29.5±19.0 months. There were 7, 4 and 3 patients with impaired vision, occlusion of visual objects and deformation of visual objects, respectively. All patients underwent visual acuity, slit lamp microscope, B-mode ultrasound and UBM examinations. FFA was performed in 8 eyes, and 2 eyes were examined for ICGA. Orbital MRI was performed in 5 patients. Vitreoretinal surgery was performed on 1 eye. The clinical characteristics of the patients were analyzed and observed.Results:In 17 eyes, there were 2 eyes with visual acuity of light perception, 3 eyes of hand movement to counting finger before the eyes, 5 eyes of 0.1- 0.3, 4 eyes of 0.4-0.6, 3 eyes of greater than 0.8. Metastatic cancer was located in iris in 1 eye, it presents as a red mass with irregular shape on the surface, which is full of small nourishing blood vessels. Metastatic cancer were located in choroid in 16 eyes, they presented yellowish-white or grayish-yellow lumps under the posterior pole or equatorial retina, including 14 eyes with a single lesion and 2 eyes with 2 lesions, with retinal detachment in 8 eyes and increased intraocular pressure in 5 eyes. B-mode ultrasonography showed posterior polar flat or surface irregular wavy intraocular space occupying lesions with localized or extensive retinal detachment. FFA and ICGA showed the focal, apical and patchy fluorescence of the tumor. MRI showed that T 1WI medium and high signal consistent with the vitreous body, while T 2WI showed low signal. Conclusions:Uveal metastatic may be the first manifestation of lung cancer, and visual impairment, part of solid mass lesions with fundus flattening may be accompanied by secondary glaucoma and retinal detachment as the main clinical manifestations. Most of the metastatic sites are located in choroid, which is more common in single eye and single lesion. Adenocarcinoma is the most common type of uveal metastasis in non-small cell lung cancer.

OBJECTIVE： To study early toxicity of paracetamol （APAP） to drug-induced liver injury in mice based on lipid metabonomics research， and to provide reference for finding potential biological marker. METHODS： Totally 20 mice were randomly divided into normal group and APAP liver injury group， with 10 mice in each group. APAP liver injury group was given intraperitoneal injection of APAP 300 mg/kg to establish acute liver injury model； normal group was given constant volume of normal saline intraperitoneally. 1 h later， the blood of mice was collected to isolate plasma. UPLC-Triple-TOF-MS method was used to detect plasma metabolites and perform metabonomics analysis. PCA， PLS-DA and OPLS-DA analysis distinguished the difference of metabolism profiles between groups. The lipid metabolites were screened and identified according to HMDB， Metlin and LIPID MAPS databases. Meanwhile， the changes of APAP level in plasma of mice were detected. The lipid metabolites with variable influence in the projection （VIP） greater than 1 and P＜0.05 in OPLS-DA analysis were identified as differential metabolites. The correlation between lipid differential metabolites and plasma APAP level was analyzed. RESULTS： PCA， PLS-DA and OPLS-DA results showed that sample points in normal group and APAP liver injury group were located in different areas with good differentiation. Compared with liver injury group and normal group， levels of 5 fatty acid metabolites were significantly increased or decreased； levels of 8 glycerophospholipids were significantly decreased and one sphingolipids was significantly increased. 9-thiastearic acid， tetradecanedioic acid， 9-hydrogen peroxide-10，12-octadecadienoic acid， L-myristoyl carnitine （fatty acid） and scyphostation A （sphingolipids） levels had a significant correlation with APAP level in plasma. CONCLUSIONS： The plasma lipid metabolomics showed abnormal changes 1 hour after acetaminophen exposure. A total of 14 related lipid differential metabolites are found， and 5 of which are significantly correlated with APAP level in plasma.

OBJECTIVETo detect numerical chromosomal aberrations and copy number variations (CNVs) in abortus tissue samples with a benchtop semiconductor sequencing platform (SSP).

METHODSOne hundred and forty patients with early spontaneous abortions at between 7 and 16 weeks were selected. Following DNA extraction, library preparation, high-throughput sequencing was carried out.

RESULTSChromosomal anomalies were detected in 82 cases (58.57%), which included 67 aneuploidies and 15 CNVs. Trisomies 16, 21, 22, and X/Y were the most common. A significant difference was found in the anomaly rates between women <35 and ≥35 years old (P< 0.01).

CONCLUSIONThe SSP platform can detect chromosomal aneuploidies and CNVs among abortus tissues. Numerical chromosomal aberration is the main cause of early spontaneous abortion, and advance maternal age is a high risk factor for chromosomal abnormality.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are confirmed to be expressed in bladder interstitial Cajal-like cells (ICC-LCs), but little is known about their possible role in cystitis-associated bladder dysfunction. The present study aimed to determine the functional role of HCN channels in regulating bladder function under inflammatory conditions. Sixty female wild-type C57BL/6J mice and sixty female HCN1-knockout mice were randomly assigned to experimental and control groups, respectively. Cyclophosphamide (CYP)-induced cystitis models were successfully established in these mice. CYP treatment significantly enhanced HCN channel protein expression and I(h) density and significantly altered bladder HCN1 channel regulatory proteins. Carbachol (CCH) and forskolin (FSK) exerted significant effects on bladder ICC-LC [Ca²⁺]i in CYP-treated wild-type (WT) mice, and HCN1 channel ablation significantly decreased the effects of CCH and FSK on bladder ICC-LC [Ca²⁺]i in both naive and CYP-treated mice. CYP treatment significantly potentiated the spontaneous contractions and CCH (0.001-10 µM)-induced phasic contractions of detrusor strips, and HCN1 channel deletion significantly abated such effects. Finally, we demonstrated that the development of CYP-induced bladder overactivity was reversed in HCN1 -/- mice. Taken together, our results suggest that CYP-induced enhancements of HCN1 channel expression and function in bladder ICC-LCs are essential for cystitis-associated bladder hyperactivity development, indicating that the HCN1 channel may be a novel therapeutic target for managing bladder hyperactivity.
Animals ; Carbachol ; Colforsin ; Cyclophosphamide ; Cystitis ; Female ; Humans ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels* ; Mice* ; Telocytes* ; Up-Regulation* ; Urinary Bladder*