OBJECTIVE To conduct a comprehensive clinical evaluation of four nucleoside （acid） analogues that have been approved and marketed in China， such as entecavir， tenofovir disoproxil fumarate， tenofovir alafenamide fumarate， and tenofovir amibufenamide. METHODS According to the Guideline for the Administration of Clinical Comprehensive Evaluation of Drugs （2021 edition， trial implementation）， a comprehensive search was conducted across databases including CNKI， Wanfang Data， VIP， PubMed， the Cochrane Library， Embase， as well as relevant official websites. Drug package inserts， guidelines， consensus statements， and relevant literature for the four drugs were collected and subjected to a comprehensive evaluation across six dimensions： safety， efficacy， cost-effectiveness， innovativeness， suitability， and accessibility. RESULTS The scores for entecavir in terms of safety， efficacy， cost-effectiveness， innovativeness， suitability， and accessibility-along with its comprehensive score-were 13， 14， 13， 10， 18， and 6， totaling 74 points. For tenofovir disoproxil fumarate， the respective scores were 13， 17， 18， 8， 18， and 7， totaling 81 points. For tenofovir alafenamide fumarate， the scores were 14， 20， 12， 8， 18， and 5， totaling 77 points. Finally， for tenofovir amibufenamide， the scores were 10.5， 17， 10， 6， 15， and 4， totaling 62.5 points. CONCLUSIONS Tenofovir disoproxil fumarate， with the highest score， is recommended as the first-line option， suitable for adults， children， and pregnant women. However， caution is warranted for potential renal impairment. Tenofovir alafenamide fumarate is recommended as a second-line alternative， particularly for individuals at high risk for bone and renal damage. Entecavir has a score similar to tenofovir alafenamide fumarate but requires dosing on an empty stomach and dose adjustment based on renal function of patients. Tenofovir amibufenamide received the lowest score and is considered a weak recommendation. The clinical application of these nucleoside （acid） analogues should be individualized based on the patient’s age， physiological status， and risk factors.

Objective To elucidate the mechanism by which the BANCR/miR-145-5p axis regulates the AKT-GLUT1/HK2 pathway through downstream targets Reg3A/DMBT1 to facilitate the Warburg effect in gastric cancer. Methods Expression levels of BANCR, miR-145-5p, Reg3A, and DMBT1 were detected by RT-qPCR and Western blot in gastric cancer tissues and cell lines. Dual-luciferase reporter assays confirmed targeted relationships. Glycolytic capacity was assessed via glucose uptake. Immunohistochemistry analyzed molecular expression in 60 paired clinical samples. The prognostic values of key molecules in the BANCR/miR-145-5p-Reg3A/DMBT1 axis were evaluated by Kaplan-Meier survival analysis and Cox proportional hazards regression model. Results BANCR was significantly upregulated, whereas miR-145-5p was downregulated in gastric cancer tissues, correlating with advanced TNM stage, lymph node metastasis, and poor differentiation. Reg3A and DMBT1 were identified as direct targets of miR-145-5p. Knockdown of BANCR or overexpression of miR-145-5p significantly suppressed Reg3A/DMBT1 expression, reduced AKT phosphorylation and GLUT1/HK2 levels, and inhibited glycolysis. Clinical analysis revealed positive correlations between Reg3A/DMBT1 expression and glycolytic markers, with both serving as independent risk factors for poor prognosis. Conclusion The BANCR/miR-145-5p axis activates the AKT pathway by targeting Reg3A/DMBT1, thereby promoting GLUT1/HK2/LDHA-mediated glycolysis and facilitating the Warburg effect in gastric cancer. This regulatory axis represents a potential therapeutic target and prognostic biomarker.

Objective To investigate the prevalence of Clonorchis sinensis human infections in Congjiang County, Guizhou Province in 2023, so as to provide insights into formulation of the clonorchiasis control strategy. Methods Congjiang County was divided into eastern, western, southern, northern and central areas according to the geographical locations, and one township was randomly sampled from each area. Then, each administrative village was randomly sampled from each township, and 200 permanent residents over 3 years of age were randomly sampled from each village. Participants’ stool samples were collected for detection of C. sinensis eggs with the Kato-Katz technique (two slides for each stool sample), and the prevalence and intensity of C. sinensis infections were calculated. In addition, the risk factors of clonorchiasis were identified among participants using a questionnaire survey. Results A total of 1 001 residents were included, and the prevalence of C. sinensis infections was 16.28% (163/1 001), with mild infections as the predominant category of infection intensity [73.01% (119/163)]. The prevalence rates of C. sinensis human infections were 30.50% (61/200), 1.50% (3/200), 30.35% (61/201), 12.50% (25/200), and 6.50% (13/200) at five survey sites, respectively (χ² = 107.03, P < 0.05), and there was a significant difference in the prevalence of C. sinensis infections between men [22.44% (112/499)] and women [10.16% (51/502)] (χ² = 27.71, P < 0.05). The prevalence of C. sinensis infections was relatively high among participants at ages of 60 to 70 years [26.14% (23/88)], public servants [46.15% (6/13)], and Han ethnic participants [33.33% (5/15)]. The prevalence of C. sinensis infections was higher among participants with a habit of consuming raw or un-dercooked freshwater fish and shrimp [22.06% (90/408)] than among those without the habit [12.31% (73/593)] (χ² = 16.85, P < 0.05), and there was no significant difference in the prevalence of C. sinensis infections between participants with [13.99% (41/293)] and without separation of raw and cooked chopping boards [17.23% (122/708)] (χ² = 1.59, P > 0.05). In addition, the prevalence of C. sinensis infections was 8.70% (2/23) and 16.46% (161/978) among participants with and without fever complicated by discomfort in the right upper abdomen during the past half year (χ² = 0.99, P > 0.05). Conclusions The prevalence of C. sinensis human infections was high in Congjiang County, Guizhou Province in 2023, and infections predominantly occurred among young and middle-aged men. Intensified health education among high-risk residents and alteration of dietary habits of consuming raw or undercooked freshwater fish or shrimp are recommended to reduce the prevalence of C. sinensis human infections.

Objective:To analyze the human immunodeficiency virus (HIV) screening status and the resulting residual risk (RR) among blood donors across 17 provincial blood centers in China.Methods:This study used a cross-sectional study. Data on HIV infection markers per 100 000 first-time donors (FD) and repeat donors (RD) from January 2015 to December 2024 were extracted from the National Blood Establishment Performance Comparison Information Management System. Questionnaires were used to collect each center′s HIV screening strategy, algorithm, serological test (ST) kit manufacturers, gray-zone setting for ST, and nucleic acid test (NAT) modality, method, and platform. The incidence-window-period model was used to calculate the residual risk for first-time donors (RR FD), repeat donors (RR RD), and total donors (RR TD) at each center. Horizontal and vertical analysis of RR FD, RR RD, and RR TD across centers and years were performed. Results:All 17 centers applied the same HIV screening strategy which was two rounds of ST followed by one round of NAT. Eight of them operated a single screening algorithm, six employed two algorithms and three used three. Eleven centers used both imported and domestic ST kits, five relied on domestic ST kits only, and one used imported ST kits only, while four centers never set a grey zone for ST throughout the decade. For NAT modalities, eight centers adopted both individual nucleic acid test (ID-NAT) and minipool nucleic acid test (MP-NAT), eight used MP-NAT only and one used ID-NAT only. Seven centers combined transcription mediated amplification (TMA) and polymerase chain reaction (PCR), nine used PCR only and one used TMA only, and fourteen centers ran both imported and domestic NAT systems, two used imported systems only and one used a domestic system only. Over the ten-year period, the mean RR FD across the centers ranged from 2.22 to 12.33 per 10 6 person-years, RR RD from 0.83 to 3.29 per 10 6 person-years and RR TD from 1.59 to 9.29 per 10 6 person-years, with center Z4 consistently showing the lowest values for all three metrics and center U4 recording the highest RR FD and RR TD, while center D2 had the highest RR RD. In 2024 compared with 2015, eleven centers achieved a lower RR FD and ten centers achieved lower RR RD and RR TD. The RR FD and RR TD of centers W2 and U4 displayed pronounced fluctuations and an upward trend in recent years. Conclusions:The 17 provincial blood centers maintain consistent HIV screening strategies, while demonstrating variations in screening algorithm, ST kit manufacturers, NAT modalities, methods, and platform. And the RR FD, RR RD, and RR TD differ across centers. Although most centers show declining trend in RR over the ten-year period, some centers exhibite data fluctuations with a rising trend, suggesting potential for further optimization of HIV screening protocols.

AIM To study the chemical constituents from ethyl acetate fraction of Balanophora harlandii Hook.f.and their tyrosinase inhibitory activity.METHODS Separation and purification were performed using silica gel,MCI,ODS,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The monophenolase inhibitory activity was determined by the tyrosinase-catalyzed oxidation of L-tyrosine.RESULTS Twenty-four compounds were isolated and identified as sesamin(1),methyl caffeate(2),quercetin(3),5,7-dihydroxychromanone(4),methyl 3,4-dihydroxybenzoate(5),esculetin(6),kaempferol(7),naringenin(8),pyrogallic acid(9),pinosylvin(10),methyl propionate(11),caffeic acid(12),saccharinol(13),ferulic acid(14),trans-p-hydroxycinnamic acid(15),cinnamic acid(16),vanillic acid(17),vanillin(18),4-hydroxyacetophenone(19),4-hydroxybenzaldehyde(20),apigenin(21),(-)-isolariciresinol(22),(-)-secoisolariciresinol(23)and meso-2,3-di(3′,4′-methylenedioxybenzyl)butane-1,4-diol(24).The IC50 values of compounds 3,5,7,8,19,and 20 ranged from(0.246 5±0.028 3)to(1.278 2±0.021 3)mmol/L.CONCLUSION Compounds 1-9、11、15、17-21、24 are isolated from this plant for the first time,and 1,6,9,17-19,24 are first isolated from genus Balanophora.Compounds 3、5、7、8、19 and 20 have tyrosinase inhibitory activity.

Objective To investigate the prevalence of human soil-transmitted nematode infections in Congjiang County, Guizhou Province in 2023, so as to provide insights into soil-transmitted nematodiasis prevention and control in the county. Methods Congjiang County was divided into 5 areas according to geographical locations, and one township was randomly sampled from each area, followed by one administrative village randomly sampled from each township as the survey site. Two hundred permanent residents without deworming during the past three months were randomly sampled from each survey site using the random cluster sampling method. Participants’ fecal samples were collected, soil-transmitted nematode eggs were detected using the KatoKatz technique and the prevalence of human soil-transmitted nematode infections was compared among participants. Mild, moderate and severe soil-transmitted nematode infections were classified according to eggs per gram (EPG), and the proportions of mild, moderate and severe infections were estimated. In addition, participants’ family status and household sanitary toilets construction were investigated using questionnaires. Results A total of 1 001 participants were included at 5 survey sites in Congjiang County, and the overall prevalence of soil-transmitted nematode infections was 19.08% (191/1 001). The prevalence rates of Ascaris lumbricoides and hookworm infections were 2.30% (23/1 001) and 1.90% (19/1 001), with all egg-positives identified as mild infections, and the prevalence of Enterobius vermicularis infections was 0.10% (1/1 001). The prevalence of Trichuris trichiura infections was 15.78% (158/1 001) among participants, and there was a significant difference in the prevalence among survey villages (χ² = 123.345, P < 0.001), with the highest prevalence detected in Liujia Village (39.00%), followed by in Longjiang Village (18.00%). There was an age-specific prevalence rate of T. trichiura infections among participants (χ² = 166.050, P < 0.001), and the highest prevalence was detected among participants at ages of 10 to 19 years (48.19%), followed by at ages of over 70 years (14.53%) and 50 to 59 years (13.04%). There was an occupation-specific prevalence rate of T. trichiura infections among participants (χ² = 74.134, P < 0.001), and the highest prevalence was detected among students (32.32%), followed by among workers/migrant workers (10.34%) and farmers (10.12%). There was an educational level-specific prevalence rate of T. trichiura infections among participants (χ² = 28.761, P < 0.001), and the highest prevalence was detected among participants with an educational level of primary school (21.60%), followed by among illiterate participants (12.03%). There was an ethnicity-specific prevalence rate of T. trichiura infections among participants (χ² = 42.193, P < 0.001). The proportions of mild, moderate and severe T. trichiura infections were 76.58% (121/158), 14.56% (23/158) and 3.16% (5/158), and all severe infections were identified among primary school students. T. trichiura infections were detected in 123 families, and there were 27 families (21.95%) in which two and more family members were identified with T. trichiura infections. A total of 1 001 valid questionnaires were recovered, and the prevalence rates of T. trichiura infections were 14.69% (139/964) and 34.55% (19/55) in families with and without sanitary toilets (χ² = 15.410, P < 0.001). Conclusions The prevalence of soil-transmitted nematode infections was relatively high in Congjiang County, Guizhou Province in 2023, and the T. trichiura infections was notably serious. Intensified soil-transmitted nematodiasis control measures are recommended targeting primary school students, middle-aged and elderly farmers and migrant workers.

BACKGROUND: The sirtuin family is well recognized for its crucial involvement in various cellular processes. Nevertheless, studies on its role in the human endometrium are limited. This study aimed to explore the expression and localization of the sirtuin family in the human endometrium, focusing on sirtuin 3 (SIRT3) and its potential role in the oxidative imbalance of the endometrium in polycystic ovary syndrome (PCOS). METHODS: Endometrial specimens were collected from both patients with PCOS and controls undergoing hysteroscopy at the Center for Reproductive Medicine, Peking University Third Hospital, from July to August 2015 and used for cell culture. The protective effects of SIRT3 were investigated, and the mechanism of SIRT3 in improving endometrial receptivity of patients with PCOS was determined using various techniques, including cellular bioenergetic analysis, small interfering ribonucleic acid (siRNA) silencing, real-time quantitative polymerase chain reaction, Western blot, immunofluorescence, immunohistochemistry, and flow cytometry analysis. RESULTS: The sirtuin family was widely expressed in the human endometrium, with SIRT3 showing a significant increase in expression in patients with PCOS compared with controls ( P <0.05), as confirmed by protein and gene assays. Concurrently, endometrial antioxidant levels were elevated, while mitochondrial respiratory capacity was reduced, in patients with PCOS ( P <0.05). An endometrial oxidative stress (OS) model revealed that the downregulation of SIRT3 impaired the growth and proliferation status of endometrial cells and reduced their receptivity to day 4 mouse embryos. The results suggested that SIRT3 might be crucial in maintaining normal cellular state by regulating antioxidants, cell proliferation, and apoptosis, thereby contributing to enhanced endometrial receptivity. CONCLUSIONS Our findings proposed a significant role of SIRT3 in improving endometrial receptivity in patients with PCOS by alleviating OS and regulating the balance between cell proliferation and apoptosis. Therefore, SIRT3 could be a promising target for predicting and improving endometrial receptivity in this patient population.
Humans ; Female ; Polycystic Ovary Syndrome/metabolism* ; Endometrium/metabolism* ; Sirtuin 3/genetics* ; Oxidative Stress/genetics* ; Adult ; Animals ; Mice ; Apoptosis/physiology* ; Immunohistochemistry ; Cell Proliferation/physiology*

BACKGROUND: The main cause of restenosis after percutaneous transluminal angioplasty (PTA) is the excessive proliferation and migration of vascular smooth muscle cells (VSMCs). Lin28a has been reported to play critical regulatory roles in this process. However, whether CCAAT/enhancer-binding proteins β (C/EBPβ) binds to the Lin28a promoter and drives the progression of restenosis has not been clarified. Therefore, in the present study, we aim to clarify the role of C/EBPβ-Lin28a axis in restenosis. METHODS: Restenosis and atherosclerosis rat models of type 2 diabetes ( n   =  20, for each group) were established by subjecting to PTA. Subsequently, the difference in DNA methylation status and expression of C/EBPβ between the two groups were assessed. EdU, Transwell, and rescue assays were performed to assess the effect of C/EBPβ on the proliferation and migration of VSMCs. DNA methylation status was further assessed using Methyltarget sequencing. The interaction between Lin28a and ten-eleven translocation 1 (TET1) was analysed using co-immunoprecipitation (Co-IP) assay. Student's t -test and one-way analysis of variance were used for statistical analysis. RESULTS: C/EBPβ expression was upregulated and accompanied by hypomethylation of its promoter in restenosis when compared with atherosclerosis. In vitroC/EBPβ overexpression facilitated the proliferation and migration of VSMCs and was associated with increased Lin28a expression. Conversely, C/EBPβ knockdown resulted in the opposite effects. Chromatin immunoprecipitation assays further demonstrated that C/EBPβ could directly bind to Lin28a promoter. Increased C/EBPβ expression and enhanced proliferation and migration of VSMCs were observed after decitabine treatment. Further, mechanical stretch promoted C/EBPβ and Lin28a expression accompanied by C/EBPβ hypomethylation. Additionally, Lin28a overexpression reduced C/EBPβ methylation via recruiting TET1 and enhanced C/EBPβ-mediated proliferation and migration of VSMCs. The opposite was noted in Lin28a knockdown cells. CONCLUSION Our findings suggest that the C/EBPβ-Lin28a axis is a driver of restenosis progression, and presents a promising therapeutic target for restenosis.
Animals ; Cell Proliferation/genetics* ; Cell Movement/genetics* ; Muscle, Smooth, Vascular/metabolism* ; Rats ; DNA Methylation/physiology* ; CCAAT-Enhancer-Binding Protein-beta/genetics* ; Male ; Myocytes, Smooth Muscle/cytology* ; Rats, Sprague-Dawley ; RNA-Binding Proteins/genetics* ; Cells, Cultured ; Coronary Restenosis/metabolism*