ObjectiveTo investigate the genetic polymorphism and structure of 47 autosomal microhaplotypes in the Han population in Changshu City, Jiangsu Province, and to evaluate the forensic efficiencies and forensic parameters. MethodsThe DNA library of unrelated individual samples was prepared according to MHSeqTyper47 kit manual and sequenced on the MiSeq FGx platform. Microhaplotype genotyping and sequencing depth statistics were processed using MHTyper. The genetic information of samples was then evaluated. The fixation index and genetic distance between the Jiangsu Changshu population and the reference populations in the 1000 Genomes Project phase 3 (1KG) were calculated, and forensic parameters were evaluated. ResultsThe fixation index and genetic distance between the Han population in Changshu, Jiangsu, and the CHB (Han Chinese in Beijing, China) reference population in 1KG were the lowest. The effective allele number (A_e) of each locus is also the closest between the two populations. The combined matching probability (CMP) of the Changshu Han population is close to the 5 populations of the East Asian reference super-population in 1KG, which is 1.25×10^-36, and the combined probability of exclusion reached 0.999 999 999 964 1. ConclusionThis study reported the genetic polymorphism and allele frequency of 47 microhaplotypes in a Han population in Changshu City, Jiangsu Province. This information provides a data basis for 47 microhaplotypes in forensic applications. In addition, the polymorphism differences between the 1KG reference population and the Han population in Changshu, Jiangsu were compared, and the genetic structure of 47 microhaplotypes in the Han population in Changshu, Jiangsu was revealed. In general, the reference data of the East Asian super-population in 1KG is more in line with the genetic characteristics of Han population in Changshu, Jiangsu.

Objective To investigate surgical methods and long-term treatment outcomes of urinary mesh/sling urinary tract exposure after pelvic floor reconstruction.Methods A retrospective analysis was performed for 9 patients admitted to the Department of Urology,West China Hospital of Sichuan University during Nov.2011 and Sep.2020 due to urinary tract exposure to mesh or sling after pelvic floor reconstruction.Results The median age of the 9 patients was 53(39-73)years and the median body mass index was 23.0(19.5-27.3).Six patients underwent transvaginal mesh implantation for pelvic organ prolapse,and the remaining 3 patients underwent mid-urethral sling(MUS)surgery due to urinary incontinence.Of the 6 patients who experienced mesh exposure after transvaginal mesh implantation,3 underwent transvaginal mesh removal,and the remaining 3 cystoscopic holmium laser ablation.Among patients who experienced mesh exposure after mid-urethral sling,2 patients underwent transurethral removal and 1 cystoscopic holmium laser ablation.The median follow-up was 69(16-121)months.At the last follow-up,none of the patients had mesh/sling exposure.Conclusion Both transvaginal and transurethral mesh/sling removal are effective surgical methods for the treatment of urinary tract mesh/sling exposure after pelvic floor reconstruction.

AIM To establish a UPLC-MS/MS method for the simultaneous content determination of Asp,Guad,Adeno,Arg,Ade,Cyti,Phe,Leu,Ile,Glu,Ser,Gln,Gly,Ala,Hyp,Thr,Pro and Lys in Asini Corii Colla.METHODS The analysis was performed on a 45℃ thermostatic Waters BEH C18column(2.1 mm×50 mm,1.7 μm),with the mobile phase comprising of acetonitrile(containing 0.1% formic acid)-water flowing at 0.35 mL/min in a gradient elution manner,and electron spray ionization source was adopted in positive ion scanning with multiple reaction monitoring mode.Subsequently,chemical pattern recognition was performed by hierarchical clustering analysis,principal component analysis and orthogonal partial least squares-discriminant analysis.RESULTS Eighteen nucleosides and free amino acids showed good linear relationships within their own ranges(r≥0.999 0),whose average recoveries were 98.0%-104.9% with the RSDs of 1.6%-4.9% .Seventeen batches of samples were clustered into two categories,two principal components demonstrated the accumulative variance contribution rate of 60.75%,Leu,Phe,Ade and Guad were potential index constituents.CONCLUSION This stable and reliable method can be used for the quality control of Asini Corii Colla.

Objective:To explore the cost-effectiveness and cost-benefit of chronic obstructive pulmonary disease (COPD) screening and intervention based on family doctor contract services.Methods:From January 2023 to October 2023, using purposive sampling and a cross-sectional survey method, 1 040 individuals aged 60 to 75 years who underwent physical examinations at community health service centers in Shanghai Minhang district were selected as research subjects. The subjects were divided into a control group ( n=532) and a study group ( n=508). The control group received conventional community health education and participated in a COPD screening and intervention program provided by the examination center. The study group received COPD screening and intervention provided by contracted family doctors under a tightly integrated medical consortium. The screening content for both groups included initial and follow-up risk assessment questionnaires, pulmonary function tests, bronchodilator tests, and CT scans. A comparative analysis was conducted on the screening compliance rate, positive rate, and cost-effectiveness and cost-benefit between the two groups. Results:A total of 251 individuals at high risk for COPD and confirmed COPD patients were identified through initial and re-screening in both groups, accounting for 24.13% of the subjects, including 222 individuals at high risk (21.35%) and 29 confirmed patients (2.79%). The study group had significantly higher compliance rates in questionnaire-based initial screening, questionnaire-based re-screening+pulmonary function tests, bronchodilator experiments, diagnosis, and subsequent CT scans than the control group ( &chi;2=33.563, 41.425, 24.842, 17.363, all P<0.05).There were significant higher proportions of high-risk individuals and patients identified through screening in the study group than those in the control group ( &chi;2=44.880, all P<0.05). The study group had significantly higher positive rates of questionnaire-based initial screening, pulmonary function tests, bronchodilator experiments, and CT scans than the control group ( &chi;2=29.191, 11.313, 12.370, 4.429, all P<0.05). The overall costs of the screening in the control and study groups were 36 100 and 53 900 yuan, respectively. The cost of pulmonary function tests in the screening for the control and study groups was 1.44 million and 2.45 million yuan, respectively, accounting for 43.19% of the total cost, which was the highest proportion among all costs. The per capita cost for identifying one high-risk individual or patient with COPD was 358.46 Yuan, and the cost in study groups was significantly lower than that in the control group (322.75 vs. 429.45 yuan, &chi;2=20.396, P<0.05). The per capita net benefits and cost-benefit ratios for the overall subjects in the two groups were 0.37 million yuan and 43.50, respectively. The average net benefit of the study group and the control group was 0.49 million yuan and 0.26 million yuan respectively. The average net benefit of the study group was 0.23 million yuan higher than that of the control group. The cost-benefit ratio of the study group and the control group were 46.77 and 38.61, respectively. The cost-benefit ratio of the study group was 8.16 higher than that of the control group. Conclusion:The screening and intervention for COPD based on family doctor contract services have significant effectiveness, with a marked improvement in screening compliance and high cost-effectiveness, and can be used in community medical institutions with relatively sound family doctor and medical consortium services for targeted COPD screening.

This study aimed to investigate the underlying mechanism of Zhenwu Decoction in the treatment of heart failure by regulating electrical remodeling through the transient outward potassium current(I_(to))/voltage-gated potassium(Kv) channels. Five normal SD rats were intragastrically administered with Zhenwu Decoction granules to prepare drug-containing serum, and another seven normal SD rats received an equal amount of distilled water to prepare blank serum. H9c2 cardiomyocytes underwent conventional passage and were treated with angiotensin Ⅱ(AngⅡ) for 24 h. Subsequently, 2%, 4%, and 8% drug-containing serum, simvastatin(SIM), and BaCl_2 were used to interfere in H9c2 cardiomyocytes for 24 h. The cells were divided into a control group [N, 10% blank serum + 90% high-glucose DMEM(DMEM-H)], a model group(M, AngⅡ + 10% blank serum + 90% DMEM-H), a low-dose Zhenwu Decoction-containing serum group(Z1, AngⅡ + 2% drug-containing serum of Zhenwu Decoction + 8% blank serum + 90% DMEM-H), a medium-dose Zhenwu Decoction-containing serum group(Z2, AngⅡ + 4% drug-containing serum of Zhenwu Decoc-tion + 6% blank serum + 90% DMEM-H), a high-dose Zhenwu Decoction-containing serum group(Z3, AngⅡ + 8% drug-containing serum of Zhenwu Decoction + 2% blank serum + 90% DMEM-H), an inducer group(YD, AngⅡ + SIM + 10% blank serum + 90% DMEM-H), and an inhibitor group(YZ, AngⅡ + BaCl_2 + 10% blank serum + 90% DMEM-H). The content of ANP in cell extracts of each group was detected by ELISA. The relative mRNA expression levels of ANP, Kv1.4, Kv4.2, Kv4.3, DPP6, and KChIP2 were detected by real-time quantitative PCR. The protein expression of Kv1.4, Kv4.2, Kv4.3, DPP6, and KChIP2 was detected by Western blot. I_(to) was detected by the whole cell patch-clamp technique. The results showed that Zhenwu Decoction at low, medium, and high doses could effectively reduce the surface area of cardiomyocytes. Compared with the M group, the Z1, Z2, Z3, and YD groups showed decreased ANP content and mRNA level, increased protein and mRNA expression of Kv4.2, Kv4.3, DPP6, and KChIP2, and decreased protein and mRNA expression of Kv1.4, and the aforementioned changes were the most notable in the Z3 group. Compared with the N group, the Z1, Z2, and Z3 groups showed significantly increased peak current and current density of I_(to). The results indicate that Zhenwu Decoction can regulate myocardial remodeling and electrical remodeling by improving the expression trend of Kv1.4, Kv4.2, Kv4.3, KChIP2, and DPP6 proteins and inducing I_(to) to regulate Kv channels, which may be one of the mechanisms of Zhenwu Decoction in treating heart failure and related arrhythmias.
Rats ; Animals ; Myocytes, Cardiac ; Atrial Remodeling ; Rats, Sprague-Dawley ; Heart Failure/metabolism* ; RNA, Messenger/metabolism* ; Potassium

OBJECTIVE: To investigate the feasibility of using thyroid ^99mTcO₄^- imaging ROI ratio instead of 24 h radioactive iodine uptake (RAIU) for estimating ¹³¹I dose in individualized treatment of hyperthyroidism. METHODS: We retrospectively analyzed the clinical data of 132 patients receiving ¹³¹I treatment in our department between January and June, 2019. According to their 3 h/24 h RAIU peak ratio, the patients were divided into peak forward (≥80%) group and no peak forward (< 80%) group. In the former group, the therapeutic ¹³¹I dose was calculated based the Marinelli formula (¹³¹I dose=thyroid mass×planned amount/24 h RAIU), and in the latter group, the correlation between the ROI ratio and the 24 h RAIU was analyzed, and the ¹³¹I dose was calculated using a modified Marinelli formula where 24 h RAIU was replaced by a converted ROI ratio. The two groups of patients were compared for antithyroid drug type and discontinuation time, thyroid hormones and related antibodies, thyroid area, thyroid mass and ¹³¹I dose. All the patients were and followed up for one year to analyze the treatment efficacy. The ROI ratios after the treatment were analyzed in the two groups using ROC curves. RESULTS: There was a significant positive correlation between the ROI ratio and 24 h RAUI in the no peak forward group (Y=58.13 + 0.2X, R²=0.118, P < 0.05), and the formula for calculating ¹³¹I dose was converted into: ¹³¹I dose=thyroid mass× planned amount/(58.13+0.2×ROI ratio)%. Before the treatment, therapeutic ¹³¹I dose, thyroid hormone levels, TRAb, 3 h and 24 h RAIU, thyroid area, thyroid mass, and ROI ratio all differed significantly between the two groups (P < 0.05). At 3 months after treatment, thyroid hormone levels, TRAb, TPOAb, thyroid area, thyroid mass, ROI ratio, response rate, hypothyroidism rate, cure rate, remission rate, and nonresponse rate were similar between two groups (P>0.05). At the 1-year follow-up, the composition ratios of hyperthyroidism, hypothyroidism and cured cases remained similar between two groups (P>0.05). ROC curve analysis showed that at 3 months after treatment, the optimal cutoff values of ROI ratio for predicting hyperthyroid recurrence and hypothyroidism were 15.79 and 6.33, respectively. CONCLUSION Thyroid ^99mTcO₄^- imaging ROI ratio can be used for calculating ¹³¹I dose in individualized treatment of hyperthyroidism and for prognostic evaluation of the patients.
Humans ; Iodine Radioisotopes/therapeutic use* ; Retrospective Studies ; Thyroid Neoplasms ; Hypothyroidism

Objective:To explore the data of patients with inoperable stage Ⅲ non-small cell lung cancer (NSCLC) after radiotherapy from the Surveillance, Epidemiology, and End Results (SEER) database, and to evaluate the effect of age on prognosis.Methods:The data of patients with inoperable stage Ⅲ A and Ⅲ B NSCLC according to the 7th edition of the American Joint Committee on Cancer (AJCC) staging standard who had been treated with radiotherapy from 2010 to 2016 were collected in the SEER database. A total of 17 117 cases were included in the analysis. According to the maximally selected test, the best cut-off value of age was 72 years old. According to the best cut-off value of age, patients were divided into the young group (< 72 years old, 11 008 cases) and the elderly group (≥ 72 years old, 6 109 cases). The basic clinical characteristics were compared between the two groups. Kaplan-Meier method was used to analyze the overall survival (OS) and log-rank test was performed. The multivariate Cox proportional hazards regression model was used to analyze the influencing factors for OS. The cumulative incidence function (CIF) was used to calculate the lung cancer-specific death rate and death rate from other causes in the different age groups, and the difference between the two groups was compared by Fine-Gray competing risk model, and the influencing factors of lung cancer-specific death were analyzed. Results:The proportion of squamous cell carcinoma in the elderly group was higher than that in the young group [51.1% (3 123/6 109) vs. 46.8% (5 154/11 008), P < 0.01], and the proportion of stage Ⅲ A was also higher than that in the young group [67.4% (4 120/6 109) vs. 60.1% (6 615/11 008), P < 0.01]; the proportion of patients receiving chemotherapy in the elderly group was lower than that in the young group [69.2% (4 226/6 109) vs. 88.6% (9 748/11 008), P < 0.01]. The 2-year and 5-year OS rates of the young group were 39.2% and 18.0%, and the elderly group were 32.4% and 12.5% (both P < 0.01). The multivariate Cox regression analysis showed that age, gender, race, year of diagnosis, pathological type, T stage, N stage, reason for non-operation and chemotherapy were independent influencing factors for patients' OS after radiotherapy, and among them, HR of age (≥ 72 years old vs. < 72 years old) was 1.13 (95% CI 1.09-1.18) ( P <0.01). The 2-year and 5-year cumulative incidence rate of lung cancer-specific death in the elderly group were 60.3% and 75.7%, which were higher than the corresponding values of 55.9% and 74.0% in the young group, and the difference of cumulative incidence rate of lung cancer-specific death between the two groups was statistically significant ( P < 0.01). The 2-year and 5-year cumulative incidence rate of death from other causes in the elderly group were 7.3% and 11.8%, which were higher than the corresponding values of 4.9% and 8.0% in the young group, and the difference of death from other causes between the two groups was statistically significant ( P < 0.01). The competing risk model analysis showed that age, gender, race, year of diagnosis, pathological type, T stage, N stage, and with or without chemotherapy were independent influencing factors for lung cancer-specific death in patients with inoperable stage Ⅲ NSCLC after radiotherapy, and among them, HR of age (≥ 72 years old vs. < 72 years old) was 1.07 (95% CI 1.02-1.12) ( P =0.002). Conclusions:Age is an independent prognostic factor for patients with inoperable stage Ⅲ NSCLC after radiotherapy. The prognosis of elderly patients is poor, and they have high risks of lung cancer-specific death and death from other causes.

【Objective】 To investigate the feasibility of using the indirect labeling method to label small molecular peptide cNGQGEQc with ¹⁸⁸Re and to observe the inhibitory effect of ¹⁸⁸Re-cNGQGEQc on lung adenocarcinoma cell line A549 in vitro. 【Methods】 ¹⁸⁸Re-cNGQGEQc and ¹⁸⁸Re-cNAQAEQc(negative polypeptide radiolabeled with 188Re) were prepared by indirect labeling method with ethylene dicysteine(EC) as the bifunctional chelating agent. The labeling rate, specific activity, radiochemical purity(RCP) and octanol-water partition coefficient were determined, and the stability in normal human serum was evaluated. CCK-8 assay was used to detect the inhibitory effects of ¹⁸⁸Re-cNGQGEQc, ¹⁸⁸RecNAQAEQc and free ¹⁸⁸ReO4^- with different radioactive doses on A549 lung cancer cell proliferation. Then the relative inhibitory rates and 50% inhibiting concentration(IC50) of the three peptides were calculated and compared. 【Results】 The labeling rate, specific activity and log P value of ¹⁸⁸Re-cNGQGEQc were(90.24±1.58) %, (4.07±0.14) TBq·mmol/L^-1 and(-2.90±0.03), respectively. The RCP of ¹⁸⁸Re-cNGQGEQc purified by using a Sep-Pak C18 column and after being placed in normal serum for 24 h at 37 ℃ were(98.42±0.32) % and(89.08±0.94) %, respectively. CCK-8 assay results revealed that ¹⁸⁸Re-cNGQGEQc significantly inhibited the proliferation of A549 lung cancer cells in a dose-dependent and positively-correlated manner. IC50 value of ¹⁸⁸Re-cNGQGEQc was 44.88×10⁷ Bq/L, significantly lower than 93.45× 10⁷ Bq/L for ¹⁸⁸Re-cNAQAEQc and 99.60×10⁷ Bq/L for ¹⁸⁸ReO4^- (P<0.01) . 【Conclusion】 It is feasible to use EC as the bifunctional chelating agent to label small molecular peptide with ¹⁸⁸Re and this labeling method has high labeling rate and good in vitro stability. The in vitro experiment confirms that ¹⁸⁸Re-cNGQGEQc can effectively inhibit the proliferation of lung adenocarcinoma cell line A549. These results provide the experimental basis for further in vivo application of small molecular peptides for the targeted therapy of lung cancer.

The model of drug-induced liver injury (DILI) induced by acetaminophen (APAP) in mice was established to investigate the anti-oxidation and anti-ferroptosis mechanisms of Fuzheng Yanggan Mixture on DILI. C57BL/6 mice were randomly divided into five groups: control group, model group, positive group, and low and high-dose Fuzheng Yanggan Mixture groups (0.12, 0.24 g·kg⁻¹). Mice were intragastrically administration with Fuzheng Yanggan Mixture (0.12, 0.24 g·kg⁻¹) once per day for 21 consecutive days, and at the same time, mice were weighted every day. The mice were injected intraperitoneally with 600 mg·kg⁻¹ of APAP to establish a mouse model of acute DILI after 16 h from the last administration of Fuzheng Yanggan Mixture. After 6 h from APAP challenge, the experimental animals were weighted and sacrificed to collect blood and liver tissue samples. And then, the effect of Fuzheng Yanggan Mixture on liver weight and the liver weight ratio of mice were examined; the content of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum and the level of malondialdehyde (MDA), glutathione (GSH) and nicotinamide adenine dinucleotide phosphate (NADPH) in the liver tissue were measured. Prostaglandinendoperoxide synthase 2(ptgs2) mRNA level in liver tissues was detected by Q-PCR, and protein expression levels of SLC7A11 and GPX4 in liver tissues were detected by Western blot. Moreover, HE staining, immunohistochemical assay and TUNEL staining were used to observe pathological changes of the liver tissue sections. It is found that Fuzheng Yanggan Mixture could relieve APAP-induced liver enlargement and inhibit hepatic weight ratio increase. Compared with model group, the mice in Fuzheng Yanggan Mixture groups showed decreases in the content of ALT, AST and MDA, and increases in the content of GSH and NADPH. What is more, Fuzheng Yanggan Mixture could down-regulate ptgs2 mRNA level and up-regulate SLC7A11 and GPX4 protein levels. All of the results lead to a conclusion that Fuzheng Yanggan Mixture plays a protective effect on DILI in mice, which may be associated with the inhibition of ferroptosis.
Acetaminophen ; Alanine Transaminase ; Animals ; Aspartate Aminotransferases ; Chemical and Drug Induced Liver Injury ; Glutathione ; Liver ; Mice ; Mice, Inbred C57BL ; Oxidative Stress