Rectal microbiomes and serum metabolomics reveal the improved effect of Artemisia ordosica crude polysaccharides on the lactation performance, antioxidant and immune responses of lactating donkeys.

This study is aimed at investigating the effects of dietary supplementation with Artemisia ordosica crude polysaccharides (AOCP) on lactation performance, antioxidant status, and immune status of lactating donkeys and analyzing rectal microbiomes and serum metabolomes. Fourteen lactating Dezhou donkeys with similar age (6.16 ± 0.67 years of BW ± SD), weight (250.06 ± 25.18 kg), days in milk (39.11 ± 7.42 d), and averaged parity of 3 were randomly allocated into 2 treatments: a control group (CON, basal diet) and an AOCP group (AOCP, basal diet with 1.0 g/kg DM AOCP). Ten weeks were allotted for the experiment, 2 weeks for adaptation, and 8 weeks for collecting data and samples. The results showed that supplementation of donkey diets with AOCP increased lactation performance, including dry matter intake, milking yield, estimated milk yield, solids-corrected milk, energy-corrected milk, milk fat yield, milk protein yield, milk lactose yield, milk total solids yield, and milk solid not fat yield. The digestibility of dry matter, crude protein, acid detergent fiber, and neutral detergent fiber was increased in the AOCP group compared with the CON group. The AOCP group increased the concentrations of immunoglobulin A, immunoglobulin G, and immunoglobulin M, the activities of the superoxide dismutase, catalase and total antioxidant capacity in the serum. AOCP decreased the concentrations of tumor necrosis factor-α, nitric oxide, reactive oxygen species, and malondialdehyde in the serum. Compared with the CON group, AOCP increased propionate, butyrate, isovalerate, and total VFA concentrations in rectal feces (P < 0.05). The addition of AOCP to increased diversity (Shannon index) and altered structure of the rectal microflora. As a result of AOCP supplementation, there has been a significant improvement in the colonization of beneficial bacteria, including Lactobacillus, Unclassified_f_Prevotellacea, Ruminococcus, and Fibrobacter genera. In contrast, a decrease in the colonization of the Clostridium_sensu_stricto_1 bacterial genus and other pathogenic bacteria was observed. Meanwhile, metabolomics analysis found that AOCP supplementation upregulated metabolites L-tyrosine content while downregulating 9(S)-HODE, choline, sucrose, LysoPC (18:0), LysoPC (18:1(9Z), and LysoPC (20:2(11Z,14Z)) concentrations. These altered metabolites were involved in the PPAR signaling pathway, prolactin signaling pathway, glycerophospholipid metabolism, carbohydrate digestion and absorption, and tyrosine metabolism pathways, which were mainly related to antioxidant capacity, immune responses, and protein metabolism in the lactating donkeys. As a consequence of feeding AOCP diets, beneficial bacteria were abundant, and antioxidant and protein metabolism-related pathways were enriched, which may enhance lactation performance in donkeys. Therefore, supplementing AOCP diets is a desirable dietary strategy to improve donkey health and lactation performance.

[Metformin ameliorates PM2.5-induced functional impairment of placental trophoblasts by inhibiting ferroptosis].

OBJECTIVE: To investigate the protective effect of metformin against PM2.5-induced functional impairment of placental trophoblasts and explore the underlying mechanism. METHODS: Sixteen pregnant Kunming mice were randomly assigned into two groups (n=8) for intratracheal instillation of PBS or PM2.5 suspension at 1.5, 7.5, and 12.5 days of gestation. The pregnancy outcome of the mice was observed, and placental zonal structure and vascular density of the labyrinth area were examined with HE staining, followed by detection of ferroptosis-related indexes in the placenta. In cultured human trophoblasts (HTR8/SVneo cells), the effects of PM2.5 exposure and treatment with metformin on cell viability, proliferation, migration, invasion, and tube formation ability were evaluated using CCK8 assay, EDU staining, wound healing assay, Transwell experiment, and tube formation experiment; the cellular expressions of ferroptosis-related proteins were analyzed using ELISA and Western blotting. RESULTS: M2.5 exposure of the mice during pregnancy resulted in significantly decreased weight and number of the fetuses and increased fetal mortality with a reduced placental weight (all P<0.001). PM2.5 exposure also caused obvious impairment of the placental structure and trophoblast ferroptosis. In cultured HTR8/SVneo cells, PM2.5 significantly inhibited proliferation, migration, invasion, and angiogenesis of the cells by causing ferroptosis. Metformin treatment obviously attenuated PM2.5-induced inhibition of proliferation, migration, invasion, and angiogenesis of the cells, and effectively reversed PM2.5-induced ferroptosis in the trophoblasts as shown by significantly increased intracellular GSH level and SOD activity, reduced MDA and Fe2+ levels, and upregulated GPX4 and SLC7A11 protein expression (P<0.05 or 0.01). CONCLUSION: PM2.5 exposure during pregnancy causes adverse pregnancy outcomes and ferroptosis and functional impairment of placental trophoblasts in mice, and metformin can effectively alleviate PM2.5-induced trophoblast impairment.

[High-quality acceleration of the Chinese national schistosomiasis elimination programme to advance the building of Healthy China].

The goal of achieving elimination of schistosomiasis across all endemic counties in China by 2030 was proposed in the Outline of the Healthy China 2030 Plan. On June 16, 2023, the Action Plan to Accelerate the Elimination of Schistosomiasis in China (2023-2030) was jointly issued by National Disease Control and Prevention Administration and other 10 ministries, which deployed the targets and key tasks of the national schistosomiasis elimination programme in China. This article describes the progress of the national schistosomiasis control programme, analyzes the opportunities to eliminate schistosomiasis, and proposes targeted recommendations to tackle the challenges of schistosomiasis elimination, so as to accelerate the process towards schistosomiasis elimination and facilitate the building of a healthy China.

[Interpretation of the Action Plan to Accelerate the Elimination of Schistosomiasis in China (2023-2030)].

On June 16, 2023, National Disease Control and Prevention Administration of the People's Republic of China, in collaboration with other ministries, formulated and issued the Action Plan to Accelerate the Elimination of Schistosomiasis in China (2023-2030). The implementation of this plan provides an important basis for achieving the targets set in the "Healthy China 2030" action plan and the implementation of the rural revitalization strategy. This paper describes the background, principles, targets, control strategies, safeguard measures and effectiveness evaluation of the plan, in order to guide the scientific and standardized implementation of actions for schistosomiasis elimination at the grassroots level, and facilitate the progress towards elimination of schistosomiasis in China with a high quality.

[Capacity building in schistosomiasis control institutions in China: a cross-sectional study].

OBJECTIVE: To understand the current status of capacity building in schistosomiasis control institutes in schistosomiasis-endemic provinces (municipality, autonomous region) of China. METHODS: The responsibilities and construction requirements of various schistosomiasis control institutions were surveyed by expert discussions, and field interviews and visits during the period between May and June, 2023, and the questionnaire for capacity maintenance and consolidation in schistosomiasis control institutions was designed. An online questionnaire survey was conducted in county-, municipal-, and provincial-level institutions that undertook schistosomiasis control and surveillance activities through the Wenjuanxing program. The distribution of schistosomiasis control institutions, the status of institutions, departments and staff undertaking schistosomiasis control activities and the translation of scientific researches on schistosomiasis control in China were analyzed. The laboratories accredited by China National Accreditation Service for Conformity Assessment (CNAS) were considered to be capable for testing associated with schistosomiasis control, and the testing capability of schistosomiasis control institutions was analyzed. RESULTS: A total of 486 valid questionnaires were recovered from 486 schistosomiasis control institutions in 12 endemic provinces (municipality, autonomous region) of China, including 12 provincial-level institutions (2.5%), 77 municipal-level institutions (15.8%) and 397 county-level institutions (81.7%). Of all schistosomiasis control institutions, 376 (77.4%) were centers for disease control and prevention or public health centers, 102 (21.0%) were institutions for schistosomiasis, endemic disease and parasitic disease control, and 8 (1.6%) were hospitals, healthcare centers or others. There were 37 713 active employees in the 486 schistosomiasis control institutions, including 5 675 employees related to schistosomiasis control, and the proportions of employees associated with schistosomiasis control among all active employees were 5.9% (231/3 897), 5.5% (566/10 134), and 20.6% (4 878/23 682) in provincial-, municipal-, and county-level institutions, respectively. There were 3 826 full-time employees working in schistosomiasis control activities, with 30.5% (1 166/3 826), 34.6% (1 324) and 34.9% (1 336/3 826) at ages of 40 years and below, 41 to 50 years and over 50 years, and there were 1 571 (41.0%) full-time schistosomiasis control employees with duration of schistosomiasis control activities for over 25 years, and 1 358 (35.5%) employees with junior professional titles and 1 290 with intermediate professional titles (35.5%), while 712 (18.6%) full-time employees working in schistosomiasis control activities had no professional titles. The three core schistosomiasis control activities included snail control (26.3%, 374/1 420), epidemics surveillance and management (25.4%, 361/1 420) and health education (18.8%, 267/1 420) in schistosomiasis control institutions. The Kato-Katz method, miracidium hatching test with nylon gauzes, and indirect haemagglutination assay (IHA) were the most commonly used techniques for detection of schistosomiasis, and there were less than 50% laboratories that had capabilities or experimental conditions for performing enzyme-linked immunosorbent assay (ELISA), dipstick dye immunoassay (DDIA), dot immunogold filtration assay (DIG-FA), loop-mediated isothermal amplification (LAMP) and polymerase chain reaction (PCR) assays. During the period from 2018 to 2022, schistosomiasis control institutions had undertaken a total of 211 research projects for schistosomiasis control, with a total funding of 18.596 million RMB, published 619 articles, participated in formulation of 13 schistosomiasis control-related criteria, and applied for 113 schistosomiasis control-related patents, including 101 that were granted, and commercialized 4 scientific research outcomes. CONCLUSIONS: The proportion of independent specialized schistosomiasis control institutions is low in schistosomiasis control institutions in China, which suffers from problems of unsatisfactory laboratory testing capabilities, aging of staff and a high proportion of low-level professional titles. More investment into and intensified schistosomiasis control activities and improved capability building and talent cultivation in schistosomiasis control institutions are recommended to provide a powerful support for high-quality elimination of schistosomiasis in China.

[Short-term substitution of calcineurin inhibitors (CNI) with recombinant humanized anti-CD25 monoclonal antibody (Basiliximab) as aGVHD prophylaxis in CNI intolerant patients after allogeneic hematopoietic stem cell transplantation].

Objectives: To investigate the efficacy of short-term substitution of recombinant humanized anti-CD25 monoclonal antibody (Basiliximab) as acute GVHD (aGVHD) prophylaxis in calcineurin inhibitors (CNI) intolerant patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: This study included 17 patients with refractory malignant hematological disorders who underwent salvage allo-HSCT at the Bone Marrow Transplantation Department of Shanghai Zhaxin Traditional Chinese and Western Medicine Hospital from August 2021 to August 2022 and were treated with Baliximab to prevent aGVHD due to severe adverse reactions to CNI. There were seven men and ten women, with a median age of 43 years (18-67). Following the discontinuation of CNI, Basiliximab was administered at a dose of 1 mg/kg once weekly until CNI or mTOR inhibitors were resumed. Results: Basiliximab was started at an average of 5 (1-32) days after HSCT. The median duration of substitution was 20 (7-120) days. All had neutrophil engraftment within a median of 12 (10-17) days. Thirteen patients had platelet engraftment after a median of 13 (11-20) days. Four patients did not develop stable platelet engraftment. Eight patients (47.1% ) developed Grade Ⅱ-Ⅳ aGVHD, while four (23.6% ) developed Grade Ⅲ/Ⅳ aGVHD. Only one patient died from aGVHD. Before the end of the followup period, seven of 17 patients died. The longest followup period of the survivors was 347 days, and the median survival rate was not met. The overall survival (OS) rate at six months was 62.6%. Among the 17 patients, 13 (76.4% ) experienced cytomegalovirus reactivation, 7 (41.2% ) experienced EB virus activation, and no cytomegalovirus disease was observed. Conclusions: When CNI intolerance occurs during allo-HSCT, short-term replacement with Baliximab can be used as an alternative to prevent aGVHD.

[Current status of pubertal sexual characteristics development of 2 704 girls aged 6-18 years in Tongzhou District of Beijing].

Objective: To understand the current status of pubertal sexual characteristics development of girls aged 6-18 years in Tongzhou District of Beijing and to compare the differences in sexual characteristics development among girls characterized as thin, normal, overweight, and obese. Methods: A cross-sectional survey was conducted among 2 844 girls aged 6-18 years in Tongzhou District of Beijing from September 2022 to July 2023. The developmental stages of breast and pubic hair were assessed on site, and menarche status was inquired. Weight and height were measured. The girls were subsequently characterized into thin, normal, overweight and obese groups. Basic information (including family and personal history) was obtained through questionnaires. Probit probability unit regression was applied to calculate the age of each Tanner stage of sexual characteristics development and the age of menarche. The χ2 test was applied to compare the counting data between two or multiple groups. Results: A total of 2 844 girls were surveyed and 2 704 girls met the inclusion criteria, resulting in a valid response rate of 95.1%. Among these girls, 1 105 (40.9%) were aged 6-9 years, 1 053 (38.9%) were aged 10-13 years, and 546 (20.2%) were aged 14-18 years. The of height-for-age Z-score (HAZ), weight-for-age Z-score (WAZ), and body mass index-for-age Z-score (BAZ) were 0.46(-0.23,1.16), 0.69(-0.16,1.67), and 0.67(-0.27,1.73) respectively. The prevalences of thin, overweight, and obesity were respectively 1.7% (45/2 704), 17.3% (467/2 704), and 19.9% (538/2 704), respectively. There were 45 girls in the thin group, 1 654 girls in the normal weight group, 1 005 girls in the overweight and obesity group. The age of Tanner stage breast 2 (B2), Tanner stage pubic hair 2 (P2), and menarche was 9.0 (95%CI 8.9-9.1), 10.5 (95%CI 10.4-10.6), and 11.4 (95%CI 11.3-1.5) years, respectively. The current status of breast and pubic hair maturity in girls with pubertal development shows that 64.6% (1 211/1 874) of these girls had breast development preceding pubic hair development, 32.4% (607/1 874) had concurrent breast and pubic hair development, and 3.0% (56/1 874) had pubic hairs development preceding breast development. The interval age between B2 and B5 was 4.7 (95%CI 4.6-4.8) years, between P2 and P5 was 4.5 (95%CI 4.4-4.6) years, and between B2 and menarche was 2.4 (95%CI 2.3-2.5) years. The ages of sexual characteristics development in overweight and obese groups were earlier than that in normal and thin groups. The ages of B2 in thin, normal, overweight, and obese groups were 10.0 (95%CI 9.5-10.6), 9.3 (95%CI 9.2-9.4), and 8.6 (95%CI 8.4-8.7) years, respectively. The age of menarche in thin, normal, overweight, and obese groups were 13.1 (95%CI 12.4-13.7), 11.6 (95%CI 11.4-11.7), and 11.1 (95%CI 11.0-11.2) years, respectively. The interval ages between B2 and B5 and between P2 and P5 was 4.5 and 4.1 years, respectively in the overweight and obese groups, and those in normal group and thin group was 4.7 and 4.5 years, 4.6 and 4.7 years, respectively. Conclusions: The ages of sexual characteristics development and menarche tend in Tongzhou District of Beijing to be earlier than that being reported of Beijing's survey 20 years ago. Girls characterized as overweight and obese not only start puberty at an earlier age than girls of normal weight, but also have a shorter developmental process.

[Mid-term analysis of prospective cohort study of rivaroxaban in preventing CRT in breast cancer].

Objective: To explore the efficacy and safety of Rivaroxaban in preventing catheter related thrombosis (CRT) in patients with breast cancer who are undergoing central venous catheter chemotherapy, and provide basis for making standardized prevention and treatment strategies. Methods: In this research, a prospective cohort study was adopted, and breast cancer patients who received central venous catheter chemotherapy in Sanhuan Cancer Hospital during September 2020 to March 2022 were selected as a treatment group to take the rivaroxaban anticoagulation therapy with 10 mg.po.qd for one month. The control group got no preventive anticoagulation therapy. Vascular ultrasound examination was taken to confirm the occurrence of CRT, and a chi-square test was done for comparison the disparity between the groups. Logistic regression was applied to analyze the univariate and multivariate factors for the formation of CRT. Results: In the research, a total of 235 patients were selected, and there were a total of 19 035 days of catheterization with 81 days of catheterization on average. While in the control group, the incidence of CRT was 28.0% (33/118), the incidence of CRT in the treatment group was 20.5% (24/117), the difference was no significant (P=0.183). Subgroup analysis results showed that the peripherally inserted central catheter (PICC) was performed in 165 cases with the CRT incidence of 18.2% (30/165) and thrombosis was mostly seen around axillary vein, accounting for 63.3%. Subclavian vein catheterization was performed in 63 cases with the CRT incidence of 39.7% (25/63), and thrombosis was mostly seen around subclavian vein, accounting for 88.0% (22/25). Implantable venous access port was implanted in 7 cases around subclavian vein and internal jugular vein with the CRT incidence of 28.6% (2/7). The patients who developed CRT within 30 days after catheterization accounted for 54.4% (31/57), 22.8% (13/57) in a period during 30 days and 60 days) and 22.8% (13/57) in a period during 60 days and 180 days). The diagnosed CRT patients had been treated with rivaroxaban 15 mg.bid.po for 3 months. During the 3 months, 100.0% of the thrombosis waned, 71.9% (41/57) of the thrombosis waned within 30 days, 19.3% (11/57) in a period during 30 and 60days and 8.8% (5/57) in a period during 60 days and 90 days. Univariate and multivariate analysis indicated that the risk of CRT in subclavian vein catheterization was higher than that in PICC, respectively (OR=2.898, 95% CI:1.386-6.056 P=0.005), and the type of catheterization was an independent factor for the formation of thrombosis. Safety analysis result showed that in the prevention of CRT, rivaroxaban treatment did not induce drug-related bleeding, liver function damage, bone marrow suppression or any other side effects. While CRT diagnosed patients were treated with anticoagulation, they kept the central venous catheter, and the infusion was smooth. These patients all finished the anti-tumor treatment as planned, and no abnormalities like new thrombosis or pulmonary embolism were observed. Conclusions: In the mid-term analysis, the proportion of Rivaroxaban in preventing anticoagulant CRT decreases, but it don't reach statistical significance. The sample size should be further increased for observation. Rivaroxaban is proved effective and very safe in the treatment of CRT, and does not affect the concurrent chemotherapy. Medical personnel should carry out the policy of "early prevention, early detection and early treatment" for CRT so as to improve the patients' quality of life.

[The diagnostic value of genetic testing in familial hypercholesterolemia in patients with premature myocardial infarction].

Objective: To evaluate the diagnostic value of gene testing in familial hypercholesterolemia (FH) in patients with premature myocardial infarction(PMI). Methods: This study was a single center cross-sectional study. A retrospective analysis was made on PMI patients who visited the People's Hospital of Peking University from May 1, 2015 to March 31, 2017. Clinical data of patients was collected and gene testing of FH related genes low density lipoprotein receptor (LDLR), proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein B(APOB) and low density lipoprotein receptor adaptor protein 1(LDLRAP1) was carried out. Clinical diagnosis of FH patients was performed using Simon Broome criteria, DLCN criteria, and FH Chinese expert consensus. Results: There were 188 males (83.6%) among 225 PMI patients, and the age of the first myocardial infarction was (46.6±7.2) years old. Ten patients carried FH pathogenic or possibly pathogenic mutations (4.4%). Compared with Simon Broome standard, DLCN standard and FH Chinese expert consensus, gene testing increased the diagnostic rate of FH by 53.3%, 33.3% and 42.1% respectively. Conclusion: Gene testing is helpful to improve the diagnosis of FH, and it is important to start the standard treatment of FH as early as possible in patients with premature myocardial infarction.

Clinical and cardiac MRI characteristics: prognosis in patients with alcoholic cardiomyopathy.

AIMS: Alcoholic cardiomyopathy (ACM) is recognized as a type of non-ischemic dilated cardiomyopathy (DCM). To date, the clinical prognosis of ACM remains a topic of debate in previous studies and there are limited studies on its cardiac MRI characteristics. The aim of this study was to summarize the clinical and MRI features of ACM patients and to identify the predictors of adverse prognosis based on clinical characteristics and MRI imaging findings. MATERIALS AND METHODS: Adult patients who were clinically diagnosed with ACM and underwent enhanced CMR between September 2015 and August 2022 were retrospectively enrolled. The primary endpoints were major adverse cardiovascular events, including cardiac-related death, heart transplantation, hospitalization for heart failure and life-threatening ventricular arrhythmias (sustained ventricular tachycardia, ventricular fibrillation, or ICD shock). The risk factors associated with these primary end points were identified using multivariable Cox analysis. RESULTS: A total of 62 ACM patients (50 ± 9 years, 62 men) were included. The majority of patients presented with symptoms of heart failure. Over a median follow-up period of 30.3 months (IQR 12.2-57.7 months), 24 patients reached the primary endpoints. For clinical variables, multivariable analysis showed that drinking duration (HR=1.05; 95%CI:1.01, 1.11; p=0.03) and persistent drinking (HR=3.71; 95%CI:1.46, 9.44; p=0.01) were associated with MACE. For CMR variables, late gadolinium enhancement (LGE) percent (HR = 1.09; 95% CI: 1.03, 1.14; p<0.001) stood out as an independent predictor for MACE. CONCLUSIONS: In ACM patients, persistent drinking and cardiac MRI-defined myocardial scar were associated with adverse outcomes such as cardiac death, heart transplantation, hospitalization for heart failure or life-threatening ventricular arrhythmias.

[Influences and mechanism of extracellular vesicles from dermal papilla cells of mice on human hypertrophic scar fibroblasts].

Objective: To investigate the influences and mechanism of extracellular vesicles from dermal papilla cells (DPC-EVs) of mice on human hypertrophic scar fibroblasts (HSFs). Methods: The study was an experimental research. The primary dermal papilla cells (DPCs) of whiskers were extracted from 10 6-week-old male C57BL/6J mice and identified successfully. The DPC-EVs were extracted from the 3rd to 5th passage DPCs by ultracentrifugation, and the morphology was observed through transmission electron microscope and the particle diameter was detected by nanoparticle tracking analyzer (n=3) at 24 h after culture. The 3rd passage of HSFs were divided into DPC-EV group and phosphate buffer solution (PBS) group, which were cultured with DPC-EVs and PBS, respectively. The cell scratch test was performed and cell migration rate at 24 h after scratching was calculated (n=5). The cell proliferation levels at 0 (after 12 h of starvation treatment and before adding DPC-EVs or PBS), 24, 48, 72, and 96 h after culture were detected by using cell counting kit 8 (n=4). The protein expressions of α-smooth muscle actin (α-SMA) and collagen typeⅠ (ColⅠ) in cells at 24 h after culture were detected by immunofluorescence method and Western blotting, and the protein expression of Krüppel-like factor 4 (KLF4) in cells at 24 h after culture was detected by Western blotting. After the 3rd passage of HSFs were cultured with DPC-EVs for 24 h, the cells were divided into blank control group, KLF4 knockdown group, and KLF4 overexpression group according to the random number table. The cells in blank control group were only routinely cultured for 48 h. The cells in KLF4 knockdown group and KLF4 overexpression group were incubated with KLF4 knockdown virus for 24 h, then the cells in KLF4 knockdown group were routinely cultured for 24 h while the cells in KLF4 overexpression group were incubated with KLF4 overexpression virus for 24 h. The protein expressions of KLF4, α-SMA, and ColⅠ in cells were detected by Western blotting at 48 h after culture. Results: At 24 h after culture, the extracted DPC-EVs showed vesicular structure with an average particle diameter of 108.8 nm. At 24 h after scratching, the migration rate of HSFs in PBS group was (54±10)%, which was significantly higher than (29±8)% in DPC-EV group (t=4.37, P<0.05). At 48, 72, and 96 h after culture, the proliferation levels of HSFs in DPC-EV group were significantly lower than those in PBS group (with t values of 4.06, 5.76, and 6.41, respectively, P<0.05). At 24 h after culture, the protein expressions of α-SMA and ColⅠ of HSFs in DPC-EV group were significantly lower than those in PBS group, while the protein expression of KLF4 was significantly higher than that in PBS group. At 48 h after culture, compared with those in blank control group, the protein expression of KLF4 of HSFs in KLF4 knockdown group was down-regulated, while the protein expressions of α-SMA and ColⅠ were both up-regulated; compared with those in KLF4 knockdown group, the protein expression of KLF4 of HSFs in KLF4 overexpression group was up-regulated, while the protein expressions of ColⅠ and α-SMA were down-regulated. Conclusions: The DPC-EVs of mice can inhibit the proliferation and migration of human HSFs and significantly inhibit the expressions of fibrosis markers α-SMA and ColⅠ in human HSFs by activating KLF4.

Sodium-glucose cotransporter 2 inhibitors and cancer: a systematic review and meta-analysis.

BACKGROUND: The effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on cancer has yet to be fully elucidated. OBJECTIVE: This systematic review and meta-analysis investigated the effects of SGLT2 inhibitors on cancer. METHODS: We searched the PubMed and ClinicalTrials.gov databases up to July 15, 2023, to identify eligible randomized, double-blind, placebo-controlled trials that lasted at least ≥24 weeks. The primary outcome was the overall cancer incidence, and the secondary outcomes were the incidences of various types of cancer. We used the Mantel-Haenszel method, fixed effects model, risk ratio (RR) and 95% confidence interval (CI) to analyze dichotomous variables. Subgroup analysis was performed based on the SGLT2 inhibitor type, baseline conditions, and follow-up duration. All meta-analyses were performed using RevMan5.4.1 and Stata MP 16.0. RESULTS: A total of 58 publications (59 trials) were included, comprising 113,909 participants with type 2 diabetes mellitus and/or chronic kidney disease and/or high cardiovascular risk and/or heart failure (SGLT2 inhibitor group, 63864; placebo group, 50045). Compared to the placebo SGLT2 inhibitors did not significantly increase the overall incidence of cancer (RR 1.01; 95% CI 0.94-1.08; p = 0.82). However, ertugliflozin did significantly increase the overall incidence of cancer (RR 1.29; 95% CI 1.01-1.64; p = 0.04). SGLT2 inhibitors did not increase the risks of bladder or breast cancer. However, dapagliflozin did significantly reduce the risk of bladder cancer by 47% (RR 0.53; 95% CI 0.35-0.81; p = 0.003). SGLT2 inhibitors had no significant effect on the risks of gastrointestinal, thyroid, skin, respiratory, prostate, uterine/endometrial, hepatic and pancreatic cancers. Dapagliflozin reduced the risk of respiratory cancer by 26% (RR 0.74; 95% CI 0.55-1.00; p = 0.05). SGLT2 inhibitors (particularly mediated by dapagliflozin and ertugliflozin but not statistically significant) were associated with a greater risk of renal cancer than the placebo (RR 1.39; 95% CI 1.04-1.87; p = 0.03). CONCLUSION: SGLT2 inhibitors did not significantly increase the overall risk of cancer or the risks of bladder and breast cancers. However, the higher risk of renal cancer associated with SGLT2 inhibitors warrants concern.

Component Patterns and Survival Outcomes in Patients with Mixed Malignant Ovarian Germ Cell Tumors: A Retrospective Cohort Study.

AIMS: To evaluate the component patterns and risk stratification in patients with mixed malignant ovarian germ cell tumors (mMOGCT). METHODS: A retrospective study of 70 mMOGCT patients treated in our hospital between 2000 and 2022 was conducted. The recurrence-free survival (RFS), disease-specific survival (DSS), and risk stratification systems based on scoring the identified prognostic factors were assessed. RESULTS: Yolk sac tumor component was the most common type (80%), followed by dysgerminoma (50%), immature teratoma (40%), embryonic carcinoma (27.1%), and chorionic carcinoma (15.7%). The 5-year RFS and DSS rates were 77.9% and 87.9%, respectively. International federation of gynecology and obstetrics (FIGO) stage III-IV (RR 3.253, P = 0.029) and normalization of tumor marker (TM) ≤ 3 cycles of chemotherapy (RR 6.249, P = 0.017) were risk factors for RFS and DSS, respectively. Significant DSS (RR 8.268, P = 0.006) was also noted between patients who had normalized TM ≤ 4 and ≥5 cycles of chemotherapy. FIGO stages I-II and stages III-IV were scored as 0 and 2, respectively. AFP normalization ≤3, 4, and ≥5 cycles of chemotherapy were scored as 0, 1, and 4, respectively. A total score of 0, 1-2, and ≥3 stratified patients into low-risk (43 patients), intermediate-risk (13 patients), and high-risk groups (14 patients), respectively. Patients in three risk stratifications manifested significant differences in DSS (P = 0.010) but not in RFS (P > 0.05). CONCLUSION: Distinct different component patterns existed among mMOGCT patients, and predicting survival outcomes in a universal model was challenging.

[Studies on clinicopathological features of duodenal-type follicular lymphoma of 18 patients].

To investigate the clinical and pathological characteristics of duodenal-type follicular lymphoma (D-FL), and to deepen the understanding of Duodenal-type follicular lymphoma. The clinical symptoms, endoscopic features, pathologic features, immunophenotype, molecular pathological features and treatment follow-up of 18 D-FL patients diagnosed in Department of Pathology, Beijing Tiantan Hospital affiliated to Capital Medical University between January 2020 and July 2023 were summarized. A total of 18 patients with D-FL were included, including 10 males and 8 females. The median age was 49 (32-69) years respectively. Most of the patients were found during gastroenteroscopy or presented with the common gastrointestinal symptoms of stomach pain, acid reflux, vomiting and diarrhea. Most endoscopic findings were multiple small gray and white polyposis. In the pathological morphology, the mucous layer and submucous layer showed lymphoid follicular structures with full and strained follicles. The immunophenotype showed that the tumor cells strongly expressed CD20 and BCL2 and had low proliferation activity. Immunoglobulin clonal analysis of 1 case showed IgK monoclonal rearrangement (1/1). FISH showed 1 case of BCL2 gene rearrangement (1/3). All patients did not receive targeted chemotherapy and adopted a wait-and-see strategy. Median follow-up was 12 (2-34) months. This study shows that D-FL is an indolent lymphoma, which tends to occur in the duodenum and has a good prognosis.

[Safety and efficacy of donor-derived chimeric antigen receptor T-cell therapy in patients with relapsed B-cell acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation].

Objective: To investigated the safety and efficacy of donor-derived CD19+ or sequential CD19+ CD22+ chimeric antigen receptor T-cell (CAR-T) therapy in patients with B-cell acute lymphoblastic leukemia (B-ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: The data of 22 patients with B-ALL who relapsed after allo-HSCT and who underwent donor-derived CAR-T therapy at the Zhujiang Hospital of Southern Medical University and the 920th Hospital of Joint Logistics Support Force of the People's Liberation Army of China from September 2015 to December 2022 were retrospectively analyzed. The primary endpoint was overall survival (OS), and the secondary endpoints were event-free survival (EFS), complete remission (CR) rate, and Grade 3-4 adverse events. Results: A total of 81.82% (n=18) of the 22 patients achieved minimal residual disease-negative CR after CAR-T infusion. The median follow-up time was 1037 (95% CI 546-1509) days, and the median OS and EFS were 287 (95% CI 132-441) days and 212 (95% CI 120-303) days, respectively. The 6-month OS and EFS rates were 67.90% (95% CI 48.30%-84.50%) and 58.70% (95% CI 37.92%-79.48%), respectively, and the 1-year OS and EFS rates were 41.10% (95% CI 19.15%-63.05%) and 34.30% (95% CI 13.92%-54.68%), respectively. Grade 1-2 cytokine release syndrome occurred in 36.36% (n=8) of the patients, and grade 3-4 occurred in 13.64% of the patients (n=3). Grade 2 and 4 graft-versus-host disease occurred in two patients. Conclusion: Donor-derived CAR-T therapy is safe and effective in patients with relapsed B-ALL after allo-HSCT.

[Advances in the co-signal molecular function of Mtb-specific T lymphocytes].

Costimulatory and co-inhibitory receptors on T lymphocytes play an essential role in the immune response. There is increasing evidence that the expression of co-signal molecules on T cells is altered in infection, tumor, autoimmunity, and other diseases, and that intervention of co-signal molecules can be used in the immunotherapy. This paper reviewed the costimulatory and coinhibitory receptors on Mtb-specific T lymphocytes and further explained the mechanism of co-signal molecules in the progression of tuberculosis, to provide a reference for future research and clinical application.

Influence of intracranial hemorrhage on clinical outcome in acute vertebrobasilar artery occlusion undergoing endovascular treatment.

BACKGROUND AND PURPOSE: The effect of intracranial hemorrhage (ICH) on the outcome of patients with large-vessel occlusion undergoing endovascular treatment (EVT) has mainly focused on the anterior circulation. Knowledge of the relationship between ICH and outcomes in patients with acute vertebrobasilar artery occlusion (VBAO) receiving EVT is limited. We aimed to assess whether ICH is a prognostic marker for acute VBAO following EVT. METHODS: Patients who underwent EVT for acute VBAO in the acute posterior circulation ischemic stroke (PERSIST) registry were included. All patients were classified as having no or any-ICH. Any-ICH was subdivided into asymptomatic and symptomatic ICH. A multivariate regression analysis was performed to evaluate the association between ICH and functional outcomes in patients with acute VBAO after receiving EVT. RESULTS: Five hundred and forty-seven patients, including 107 patients with ICH (19.6%): 38 (7.0%) and 69 (12.6%) with symptomatic and asymptomatic ICH, respectively. After adjustment for potential confounders, any-ICH was independently associated with reduced chance of favorable outcome (OR 0.39, 95% CI 0.21-0.72, P=0.003), functional independence (OR 0.24, 95% CI 0.16-0.52, P<0.001), and excellent outcome (OR 0.34, 95% CI 0.15-0.75, P=0.008), and increased mortality risk (OR 2.14, 95% CI 1.30-3.51, P=0.003). Symptomatic ICH had a similar association. Moreover, asymptomatic ICH was a negative predictor of functional independence (OR 0.39, 95% CI 0.17-0.88, P=0.024). CONCLUSION: Any- and symptomatic ICH were strongly associated with worse clinical outcomes and increased mortality in patients with acute VBAO who underwent EVT. Asymptomatic ICH was an inverse predictor of functional independence.

[Feasibility and efficacy of pre-management of superior laryngeal artery in endoscopic surgery for hypopharyngeal cancer].

Objective: To explore the feasibility and efficacy for the dissection and ligation of the superior laryngeal artery in endoscopic surgery for hypopharyngeal cancer. Methods: Eight cadaveric heads were selected, and the laryngopharynxes were harvested. The positions of the superior laryngeal arteries entering the larynxes were dissected and observed under endoscopic vision, and their anatomical characteristics were summarized. Twenty-nine patients (all were male, aged 39-74 years old) with hypopharyngeal cancer who underwent transoral endoscopic surgery at the Department of Otorhinolaryngology Head and Neck Surgery of the Second Xiangya Hospital, Central South University from January 2018 to December 2019 were selected, and the patients were randomly divided into two groups by drawing lots, namely, the superior laryngeal artery was actively dissected and occluded during surgery in observation group (n=15) or not in control group (n=14). The differences in surgical time, bleeding volume, postoperative complications, and postoperative disease-free survival rate were compared between the two groups. Statistical analysis was conducted using SPSS 25.0 software. Results: The entry point of the superior laryngeal artery into the larynx was approximately at the level of the superior edge of the thyroid cartilage, and entered the larynx at the posterior one-third of the lateral wall of the pyriform fossa. The superior laryngeal artery might be determined through endoscopic exploration in all patients of observation group. The endoscopic surgery time [(40.00±7.56) minutes] and intraoperative bleeding volume [(24.00±8.28) ml] in the observation group were respectively less than those [(48.57±14.06) minutes and (42.86±15.41) ml] in the control group, and the differences were statistically significant (t=-2.064, P=0.049; t=-4.064, P=0.001). There was no case with postoperative bleeding in the observation group, but with one case of postoperative bleeding in the control group. Total disease free survival rate was 86.2% and there was no significant difference in disease free survival rates between the two groups during a follow-up period of at least 36 months (P=0.986). Conclusion: Dissection of the superior laryngeal artery during endoscopic surgery for hypopharyngeal cancer is feasible, and pre-management and occlusion of the superior laryngeal artery can effectively reduce intraoperative bleeding.