1.Construction and validation of pregnancy prediction model of artificial insemination by husband based on endometrial structure and uterine spiral artery blood flow parameters
Guangyu YU ; Jiaqi FAN ; Shibei CHEN ; Leilei GAO ; Qing YU ; Chao ZHOU ; Chunmei YU ; Zhen JIN
Chinese Journal of Tissue Engineering Research 2024;28(19):3061-3068
BACKGROUND:The impact of the endometrium's structure and spiral artery blood flow parameters on the pregnancy rate of artificial insemination by husband remains unclear.This study identified the independent factors and constructed a prediction model with good clinical application efficacy after calibration of other confounding factors. OBJECTIVE:To construct and validate a clinical pregnancy prediction model for artificial insemination by husband based on endometrial structure and uterine spiral artery blood flow parameters. METHODS:A retrospective analysis was conducted on 1 299 patients who underwent artificial insemination by husband treatment at Changzhou Maternal and Child Health Hospital from January 2017 to January 2021.The non-pregnancy group consisted of 1 182 patients,while the pregnancy group included 117 patients.Out of these patients,93 cases were successfully matched between the pregnancy and non-pregnancy groups using a 1∶1 propensity score matching method.Single-factor and multi-factor analyses were used to screen the endometrial structure and uterine spiral artery blood flow parameters to determine their influence on artificial insemination by husband outcomes.The optimal cutoff value was established for each independent influencing factor through receiver operating curve analysis and their risk trend affecting artificial insemination by husband pregnancy outcomes was analyzed using a restricted cubic spline.The clinical efficacy of this combined forecast model was tested by using clinical decision curve and clinical influence curve methods. RESULTS AND CONCLUSION:(1)There was no statistical significance in non-endometrial factors between the pregnancy group and the non-pregnancy group,and the data had a good balance by propensity score matching(P>0.05).(2)Single-factor analysis identified several subendometrial parameters as significant influencing factors of artificial insemination by husband pregnancy outcomes,including vascularization index,flow index,vascular flow index,resistance index,pulsatility index,maximum systolic velocity/end-diastolic velocity,thickness of average junction zone and maximum junction zone from the basal endometrium to the outer myometrium inner layer(P<0.05).(3)Multivariate logistic regression analysis revealed that thickness of average junction zone,pulsatility index,and vascular flow index were independent influencing factors of pregnancy outcomes of artificial insemination by husband,vascular flow index>thickness of average junction zone>pulsatility index.(4)Receiver operating characteristic curve analysis indicated that the area under receiver operating characteristic curve of vascular flow index was 0.704(0.629,0.779),and the optimal cutoff value was 6.26;the area under receiver operating characteristic curve of thickness of average junction zone was 0.660(0.582,0.739),and the optimal cutoff value was 6.38;the area under receiver operating characteristic curve of pulsatility index was 0.642(0.563,0.721),and the optimal cutoff value was 1.18.(5)The restricted cubic spline analysis revealed that artificial insemination by husband pregnancy outcomes were significantly positively affected when the vascular flow index was>6.24 or the thickness of average junction zone was≤6.55 mm,while a negative risk was associated with pulsatility index>1.27.(6)The clinical decision curve and clinical influence curve analyses exhibited that the combined prediction model had the maximum clinical net benefit at the threshold probability value of 0.17-0.93,and the ratio of loss to benefit was consistently less than 1 in the threshold probability range,indicating that the model had good clinical efficacy.(7)It is concluded that after adjusting for other confounding factors outside of the endometrium using propensity score matching and multifactorial logistic regression,the thickness of average junction zone,pulsatility index and vascular flow index were independent factors that influenced pregnancy outcomes of artificial insemination by husband.Through determining their optimal cutoff values and assessing their risk trends,it was confirmed that the combined prediction model had good predictive value and clinical efficacy.
2.Porphyromonas gingivalis persisters induce the immuno-inflammatory responses in macrophages by upregulating the forkhead box1 signaling pathway
Chuan WANG ; Leilei WANG ; Xuan LI ; Lijian JIN ; Zhengguo CAO
Chinese Journal of Stomatology 2024;59(7):672-680
Objective:To investigate the effects of Porphyromonas gingivalis (Pg) persisters (Ps) on immuno-inflammatory responses in macrophages, and to explore the underlying mechanisms. Methods:Pg cells were cultured to the stationary phase (72 h), and subsequently treated by high concentration of metronidazole at 100 mg/L, amoxicillin at 100 mg/L and the combination of them for different time period, named as metronidazole group, amoxicillin group and (metronidazole+amoxicillin) group. Pg cells without treatment were used as Blank control. The survival profile of PgPs cells was measured by colony-forming unit assay. The living state of PgPs was observed by Live/Dead staining. Then, Pg and metronidazole-treated PgPs (M-PgPs) were used to treat macrophages, named as Pg group and M-PgPs group. Transmission electron microscopy (TEM) was used to observe the bacteria in the macrophages. The expression levels of proinflammatory cytokines in macrophages were determined by real-time fluorescence quantitative PCR and enzyme-linked immunosorbent assay. The location of forkhead box transcription factor 1 (FOXO1) was detected by confocal immunofluorescence microscopy. After inhibiting or enhancing the FOXO1 expressions using inhibitors (Fi) or activators (Fa) respectively, the macrophages were treated with Pg and M-PgPs, divided as Blank group, Pg group, M-PgPs group, Fi group, (Fi+Pg) group, (Fi+M-PgPs) group, Fa group, (Fa+Pg) group and (Fa+M-PgPs) group. Then, the expression pattens of proinflammatory cytokines were assessed.Results:Remarkable number of lived PgPs was observed, both in planktonic culture and Pg biofilms either treated with metronidazole, amoxicillin or both, and those persisters could form new colonies. Pg and M-PgPs were able to enter into the macrophages and the protein expression levels of interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor-α (TNF-α) [Pg group: (2 392±188), (162±29), (5 558±661), (789±155) μg/L; M-PgPs group: (2 415±420), (155±3), (5 732±782), (821±176) μg/L] were significantly upregulated than those in Blank group [(485±140), (21±9), (2 332±87), (77±7) μg/L] ( P<0.01). Moreover, Pg and M-PgPs could facilitate the nuclear translocation and accumulation of FOXO1. In addition, the relative mRNA expression levels of FOXO1, B-cell lymphoma 6 and Krüppel-like factor 2 were upregulated when compared to Blank group ( P<0.05). Furthermore, the protein expression levels of IL-1β, IL-6, IL-8 and TNF-α in Fi+Pg group [(1 081±168), (70±8), (1 976±544), (420±47) μg/L] were remarkably lower than Pg group [(4 411±137), (179±6), (5 161±929), (934±24) μg/L] ( P<0.05). Similarly, the protein expression levels of IL-1β, IL-6, IL-8 and TNF-α in Fi+M-PgPs group [(1 032±237), (74±10), (1 861±614), (405±32) μg/L] were remarkably lower than M-PgPs group [(4 342±314), (164±17), (4 438±1 374), (957±25) μg/L] ( P<0.05). On the contrary, the protein expression levels of IL-1β, IL-6, IL-8 and TNF-α in Fa+Pg group [(8 198±1 825), (431±28), (8 919±650), (2 186±301) μg/L] and Fa+M-PgPs group [(8 159±2 627), (475±26), (8 995±653), (2 255±387) μg/L] were significantly higher than Pg group and M-PgPs group, respectively ( P<0.05). Conclusions:PgPs are highly tolerant to metronidazole and amoxicillin. The M-PgPs could enhance the immuno-inflammatory responses in macrophages by upregulating the FOXO1 signaling pathway, while this effect exhibits no significant difference with Pg.
3.The effect of Ba Duan Jin on the balance of community-dwelling older adults: a cluster randomized control trial
Leilei DUAN ; Yubin ZHAO ; Yuliang ER ; Pengpeng YE ; Wei WANG ; Xin GAO ; Xiao DENG ; Ye JIN ; Yuan WANG ; Cuirong JI ; Xinyan MA ; Cong GAO ; Yuhong ZHAO ; Suqiu ZHU ; Shuzhen SU ; Xin'e GUO ; Juanjuan PENG ; Yan YU ; Chen YANG ; Yaya SU ; Ming ZHAO ; Lihua GUO ; Yiping WU ; Yangnu LUO ; Ruilin MENG ; Haofeng XU ; Huazhang LIU ; Huihong RUAN ; Bo XIE ; Huimin ZHANG ; Yuhua LIAO ; Yan CHEN ; Linhong WANG
Chinese Journal of Epidemiology 2024;45(2):250-256
Objective:To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults.Methods:A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test.Results:A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI: 2.23-3.88) points ( P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI: 4.03-5.37) points ( P<0.001). Ba Duan Jin showed significant improvement ( P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions:This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.
4.The status of violence against children in China, 2013-2021
Xin GAO ; Pengpeng YE ; Ye JIN ; Yuan WANG ; Yunning LIU ; Cuirong JI ; Xiang SI ; Xiaolei ZHU ; Yibing YANG ; Leilei DUAN
Chinese Journal of Epidemiology 2024;45(10):1371-1375
Objective:This study aims to obtain the prevalence and features associated with Violence Against Children (VAC) in China and, thus, formulate a prevention strategy.Methods:The mortality-related data of VAC was sourced from the National Disease Surveillance Points System (DSP) during 2013-2021. We analyzed the DSP data regarding children aged 0-17 years old who died from violence. The hospital cases of VAC was sourced from the National Injury Surveillance System (NISS), 2013-2021. We analyzed the data from NISS with the parameter of "intentional injury" caused by VAC in children aged between 0-17 years. Using robust linear regression, we analyze the time trend in the proportion of violence incidence. To understand the variations in the incidence of different types of violence across genders, we apply the chi-square test and adjusted Pearson residuals.Results:The overall trend of death caused by VAC has declined; it was reduced to 0.14/100 000 in 2021 from 0.33/100 000 in 2013. In 2021, male VAC mortality (0.15/100 000) was higher than females (0.13/100 000). The proportion of VAC cases to all injury cases has declined from 3.34% in 2013 to 2.29% in 2021. Among 9 344 VAC cases supervised by hospitals in 2021, the number of males (7 503 cases) was around 4 times that of females (1 841 cases), and the top three modes of violence were blunt tools (64.77%), falls (7.46%) and sharp instruments (6.18%), and 45 cases of sexual violence included 38 girls and 7 boys.Conclusions:The declining death rate due to VAC may be related to the benign development of Chinese society. Prevention strategies targeting training in parenting skills and problem-solving should be prioritized.
5.Discussion on the"simultaneous treatment of liver and intestine"strategy for liver-yang hyperactivity syndrome in hypertension based on the theory of"communication between liver and large intestine"
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2024;31(3):257-261
This paper holds that the main pathogenesis evolution characteristics of the occurrence and development of hypertension is from hyperactivity of live-yang to liver-yang forming wind syndrome,and abnormal ascending and descending of qi movement is its core pathogenesis.The theory of"communication between liver and large intestine"from"Medical Introduction"can be explored and traced back to its origins and development,also analyzing the anatomical and functional correlation between the liver and intestine.Based on this,it is proposed that regulating the movement of liver ascending and intestine descending,and treating the liver and large intestine simultaneously are important strategies for the treatment of hypertension with liver-yang hyperactivity syndrome.
6.Background, design, and preliminary implementation of China prospective multicenter birth cohort
Si ZHOU ; Liping GUAN ; Hanbo ZHANG ; Wenzhi YANG ; Qiaoling GENG ; Niya ZHOU ; Wenrui ZHAO ; Jia LI ; Zhiguang ZHAO ; Xi PU ; Dan ZHENG ; Hua JIN ; Fei HOU ; Jie GAO ; Wendi WANG ; Xiaohua WANG ; Aiju LIU ; Luming SUN ; Jing YI ; Zhang MAO ; Zhixu QIU ; Shuzhen WU ; Dongqun HUANG ; Xiaohang CHEN ; Fengxiang WEI ; Lianshuai ZHENG ; Xiao YANG ; Jianguo ZHANG ; Zhongjun LI ; Qingsong LIU ; Leilei WANG ; Lijian ZHAO ; Hongbo QI
Chinese Journal of Perinatal Medicine 2024;27(9):750-755
China prospective multicenter birth cohort (Prospective Omics Health Atlas birth cohort, POHA birth cohort) study was officially launched in 2022. This study, in collaboration with 12 participating units, aims to establish a high-quality, multidimensional cohort comprising 20 000 naturally conceived families and assisted reproductive families. The study involves long-term follow-up of parents and offspring, with corresponding biological samples collected at key time points. Through multi-omics testing and analysis, the study aims to conduct multi-omics big data research across the entire maternal and infant life cycle. The goal is to identify new biomarkers for maternal and infant diseases and provide scientific evidence for risk prediction related to maternal diseases and neonatal health.
7.Comparison of endoscopic retrograde cholangiopancreatography assisted with colonoscope and enteroscope in patients with history of Roux-en-Y anastomosis (with video)
Leilei ZHAO ; Hangbin JIN ; Jianfeng YANG ; Weigang GU ; Xiaofeng ZHANG
Chinese Journal of Digestive Endoscopy 2023;40(2):121-125
Objective:To compare the efficacy and safety of endoscopic retrograde cholangiopancreatography (ERCP) assisted with colonoscope and enteroscope in patients with history of Roux-en-Y anastomosis.Methods:A retrospective study was performed on the data of 70 patients who underwent ERCP assisted with standard colonoscope or single balloon enteroscope after Roux-en-Y reconstruction in Hangzhou Hospital Affiliated to Nanjing Medical University from January 2017 to December 2020. Patients were divided into the standard colonoscopy group ( n=43) and the single balloon enteroscopy group ( n=27) according to endoscopy. The success rates of insertion, intubation and ERCP, and incidence of complications were compared. Results:A total of 81 ERCP procedures were performed in 70 patients. The insertion success rates of the standard colonoscopy group and the single balloon enteroscopy group were 91.8% (45/49) and 78.1% (25/32), respectively, showing no significant difference ( χ2=2.04, P=0.153). The success rates of primitive papilla intubation in the two groups were 74.1% (20/27) and 1/6, showing significant difference ( P=0.016). The ERCP success rates of the standard colonoscopy group and the single balloon enteroscopy group were 75.5% (37/49) and 59.4% (19/32), showing no significant difference ( χ2=2.36, P=0.124). The post operative complication incidences of the standard colonoscopy group and the single balloon enteroscopy group were 4.1% (2/49) and 9.4% (3/32), showing no significant difference ( χ2=0.25, P=0.620). Conclusion:ERCP assisted with standard colonoscope and single balloon enteroscope is safe and effective in patients after Roux-en-Y anastomosis. Standard colonoscopic ERCP can become an endoscopy solution for patients with biliary tract disease after Roux-en-Y reconstruction.
8.Cost-effectiveness analysis of nucleic acid screening for hepatitis B and C in hospitalized patients in China
Shu SU ; Qi ZHANG ; Peng WANG ; Rong GUI ; Chunhong DU ; Xiying LI ; Xianping LYU ; Rong XIA ; Fenghua LIU ; Li QIN ; Jiameng NIU ; Lili XING ; Leilei ZHANG ; Jinqi MA ; Junhua HU ; Yuan ZHANG ; Juan CAI ; Huifang JIN ; Jun ZHANG ; Rongyi CAO ; Jiwu GONG ; Jiangcun YANG
Chinese Journal of Laboratory Medicine 2023;46(1):38-44
Objective:To compare the cost-effectiveness of hospitalized Chinese patients undergoing nucleic acid screening strategies for hepatitis B and hepatitis C, immunological screening strategy, and no screening strategy under different willingness to pay (WTP). The results might aid to decision-making for the optimal strategy.Methods:In this study, nucleic acid screening, immunological screening and no screening were used as screening strategies, and China′s GDP in 2021 (80 976 yuan) was used as the threshold of WTP to construct a Markov model. After introducing parameters related to the diagnosis and treatment of hepatitis B and C in inpatients, a cohort population of 100 000 inpatients was simulated by TreeAge Pro 2021 software, the total cost, total health effects, incremental cost-effectiveness ratio and average cost-effectiveness ratio of different screening strategies were calculated, and cost-effectiveness analysis was conducted. Univariate and probabilistic sensitivity analysis were used to assess the impact of parameter uncertainty on the final results.Results:Compared with the non-screening strategy, the incremental total cost of the hepatitis B immunological screening strategy for cohort patients was 11 049 536 yuan, and the incremental cost-effectiveness ratio was 24 762 yuan/quality-adjusted life years (QALY), while the total incremental cost of nucleic acid screening was 19 208 059 yuan, and the incremental cost-effectiveness ratio was 29 873 yuan/QALY; the incremental cost-effectiveness ratio of nucleic acid screening and immunological screening was 45 834 yuan/QALY. Compared with the non-screening strategy, the incremental cost-effectiveness ratio of hepatitis C immunological screening strategy was 5 731 yuan/QALY, the incremental cost-effectiveness ratio of nucleic acid screening strategy was 8 722 yuan/QALY, the incremental cost-effectiveness ratio of nucleic acid screening and immunological screening was 45 591 yuan/QALY. The results of probabilistic sensitivity analysis showed that when the cost of nucleic acid testing exceeded 214.53 yuan, it was not cost-effective to perform hepatitis B nucleic acid screening under the WTP as 1 fold GDP. When the cost of nucleic acid testing exceeded 132.18 yuan, it was not cost-effective to conduct hepatitis C screening under the WTP as 1 fold GDP.Conclusions:Nucleic acid screening strategy can achieve more cost-effectiveness and is worthy of vigorous promotion. Compared with no screening, both the nucleic acid and immunological screening strategies are cost-effective, and hepatitis nucleic acid screening is the optimal strategy for hospitalized patients.
9.Effects of hospital-community-family continuous nursing mode in patients with chronic heart failure
Leilei LIU ; Jin WANG ; Yingmei SHI ; Kequn WAN ; Chen XUE ; Aihong PAN
Chinese Journal of Modern Nursing 2023;29(12):1639-1643
Objective:To explore the effects of hospital-community-family continuous nursing mode in patients with chronic heart failure (CHF) .Methods:Totally 140 CHF patients admitted to Hefei First People's Hospital from November 2020 to October 2021 were selected by convenience sampling and divided into the control group and the observation group according to the random number table, with 70 cases in each group. Patients in the control group was given routine cardiovascular care, while patients in the observation group received hospital-community-family continuous care on this basis. The scores of Minnesota Living with Heart Failure Questionnaire (MLHFQ), Self-Care of Heart Failure Index (SCHFI) and Health Promoting Lifestyle Profile-Ⅱ (HPLP-Ⅱ) were compared between the two groups of patients at admission and 3 months after discharge.Result:At admission, there was no significant difference in the scores of MLHFQ, SCHFI and HPLP-Ⅱ between the two groups ( P>0.05) ; 3 months after discharge, the score of MLHFQ in the observation group was lower than that in the control group, and the scores of SCHFI and HPLP-Ⅱ were higher than those in the control group, with statistically significant differences ( P<0.01) . Conclusions:The hospital-community-family continuous nursing model can improve the self-care ability, health behavior and quality of life of CHF patients, which is worth promoting in clinical practice.
10.Repurposing non-oncology small-molecule drugs to improve cancer therapy: Current situation and future directions.
Leilei FU ; Wenke JIN ; Jiahui ZHANG ; Lingjuan ZHU ; Jia LU ; Yongqi ZHEN ; Lan ZHANG ; Liang OUYANG ; Bo LIU ; Haiyang YU
Acta Pharmaceutica Sinica B 2022;12(2):532-557
Drug repurposing or repositioning has been well-known to refer to the therapeutic applications of a drug for another indication other than it was originally approved for. Repurposing non-oncology small-molecule drugs has been increasingly becoming an attractive approach to improve cancer therapy, with potentially lower overall costs and shorter timelines. Several non-oncology drugs approved by FDA have been recently reported to treat different types of human cancers, with the aid of some new emerging technologies, such as omics sequencing and artificial intelligence to overcome the bottleneck of drug repurposing. Therefore, in this review, we focus on summarizing the therapeutic potential of non-oncology drugs, including cardiovascular drugs, microbiological drugs, small-molecule antibiotics, anti-viral drugs, anti-inflammatory drugs, anti-neurodegenerative drugs, antipsychotic drugs, antidepressants, and other drugs in human cancers. We also discuss their novel potential targets and relevant signaling pathways of these old non-oncology drugs in cancer therapies. Taken together, these inspiring findings will shed new light on repurposing more non-oncology small-molecule drugs with their intricate molecular mechanisms for future cancer drug discovery.

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