Extensive studies have identified potential adverse effects on semen quality of obesity, based on body mass index, but the association between body fat distribution, a more relevant indicator for obesity, and semen quality remains less clear. We conducted a longitudinal study of 4304 sperm donors from the Guangdong Provincial Human Sperm Bank (Guangzhou, China) during 2017-2021. A body composition analyzer was used to measure total and local body fat percentage for each participant. Generalized estimating equations were employed to assess the association between body fat percentage and sperm count, motility, and morphology. We estimated that each 10% increase in total body fat percentage (estimated change [95% confidence interval, 95% CI]) was significantly associated with a 0.18 × 10 6 (0.09 × 10 6 -0.27 × 10 6 ) ml and 12.21 × 10 6 (4.52 × 10 6 -19.91 × 10 6 ) reduction in semen volume and total sperm count, respectively. Categorical analyses and exposure-response curves showed that the association of body fat distribution with semen volume and total sperm count was stronger at higher body fat percentages. In addition, the association still held among normal weight and overweight participants. We observed similar associations for upper limb, trunk, and lower limb body fact distributions. In conclusion, we found that a higher body fat distribution was significantly associated with lower semen quality (especially semen volume) even in men with a normal weight. These findings provide useful clues in exploring body fat as a risk factor for semen quality decline and add to evidence for improving semen quality for those who are expected to conceive.
Humans ; Male ; Adult ; Semen Analysis ; China ; Body Fat Distribution ; Longitudinal Studies ; Sperm Count ; Sperm Motility ; Body Mass Index ; Tissue Donors ; Obesity/complications* ; Spermatozoa ; Young Adult ; Middle Aged ; East Asian People

OBJECTIVE: To construct a longitudinal trajectory model of arterial oxygen tension (PaO₂) within 24 hours after cardiac arrest (CA). METHODS: A retrospective cohort study was conducted. CA patients admitted to the ICU from 2014 to 2015 were selected from the eICU Collaborative Research Database (eICU-CRD). Data about patients' demographic characteristics, history of comorbidities, laboratory test indicators within 24 hours of intensive care unit (ICU) admission [including all PaO₂ data and arterial carbon dioxide tension (PaCO₂)], vasopressor use, and clinical outcomes were extracted from the database. The primary outcome variable was all-cause in-hospital mortality. Group-based trajectory model (GBTM) were built based on the changes in PaO₂ within 24 hours of ICU admission, and patients were grouped according to their initial static PaO₂ values upon ICU admission. Multivariable adjusted Poisson regression analysis was used to compare the in-hospital mortality risk among patients in different PaO₂ dynamic trajectory groups. Sensitivity analyses were performed using multivariable logistic regression and multivariable adjusted Poisson regression without imputation of missing values. RESULTS: A total of 3 866 CA patients were included. Three GBTM trajectory groups were identified based on PaO₂ changes within 24 hours of ICU admission: Group-1 (low level first increased then decreased, 148 cases), Group-2 (sustained low level, 3 040 cases), and Group-3 (first high level then decreased, 678 cases). Significant differences were found among the three groups in age, body weight, maximum serum potassium, maximum PaCO₂, minimum hemoglobin (Hb), vasopressor use, total hospitalization time, ICU stay, and hospital mortality. After incorporating variables with significant differences into the multivariable adjusted Poisson regression model, results showed that compared to Group-2 patients, patients in Group-1 and Group-3 had an increased risk of all-cause in-hospital mortality [Group-1 adjusted relative risk (aRR) = 1.20, 95% confidence interval (95%CI) was 1.02-1.41; Group-3 aRR = 1.11, 95%CI was 1.01-1.24]. Based on initial static PaO₂ values at ICU admission, patients were divided into four groups: PaO₂ < 100 mmHg (1 mmHg = 0.133 kPa; 1 217 cases), PaO₂ 100-200 mmHg (569 cases), PaO₂ 201-300 mmHg (547 cases), and PaO₂ > 300 mmHg (1 082 cases). Multivariable adjusted Poisson regression analysis indicated a significant upward trend in aRR for the latter three groups compared to the PaO₂ < 100 mmHg group. Sensitivity analyses revealed that compared to Group-2, patients in Group-1 and Group-3 had a significantly increased risk of all-cause in-hospital mortality (both P < 0.05). CONCLUSIONS Within 24 hours after return of spontaneous circulation in CA patients, PaO₂ exhibits different dynamic trajectories, and patients with hyperoxia have an increased risk of in-hospital mortality.
Humans ; Retrospective Studies ; Hospital Mortality ; Heart Arrest/blood* ; Prognosis ; Oxygen/blood* ; Intensive Care Units ; Cardiopulmonary Resuscitation ; Male ; Female ; Middle Aged

Objective:To evaluate the safety and efficacy of sequential consolidation thoracic radiotherapy after first-line chemotherapy combined with immunotherapy for extensive-stage small cell lung cancer (SCLC).Methods:A retrospective analysis of patients with extensive-stage SCLC admitted to Jiangsu Cancer Hospital from January 2019 to September 2022 was conducted. Patients who achieved effective chemotherapy combined with immunotherapy received sequential consolidation thoracic radiotherapy. The safety was evaluated according to the common terminology criteria for adverse events (CTCAE) 5.0 standard, and the overall survival (OS) and progression-free survival (PFS) were analyzed by Kaplan-Meier method.Results:A total of 33 patients were enrolled, with a median age of 66 years (range, 50-79 years). The median follow-up time was 20 months (range, 3-33 months). Fifteen patients (46%) had disease progression, and 12 patients (36%) died. The toxicities mainly included leukopenia, thrombocytopenia, radiation esophagitis, anorexia, and fatigue, etc. Six patients (18%) had grade 4 hematological toxicity, mainly leukopenia. One patient (3%) had grade 3 radiation pneumonitis, and 3 patients (9%) had grade 1-2 radiation pneumonitis. No grade 5 toxicity was observed in all patient groups. The median PFS was 12 months (95% CI=3.9-20.1). The 6-month, 1-year, and 2-year PFS rates were 78%, 49.6%, and 35.6%, respectively. The median OS was 23 months (95% CI=15.98-30.01). The 6-month, 1-year, and 2-year OS rates were 86.2%, 74.5%, and 47.2%, respectively. Conclusions:Sequential consolidation thoracic radiotherapy after first-line chemotherapy combined with immunotherapy is a safe protocol for extensive-stage SCLC. It brings survival benefits to patients by increasing PFS and OS rates.

Objective:To evaluate the safety and efficacy of tumor-treating fields (TTFields) and chemoradiation in patients with high-grade glioblastoma.Methods:Clinical data of 38 patients admitted to the Jiangsu Cancer Hospital from September 2021 to May 2023 who were diagnosed with high-grade glioblastoma (36 cases of World Health Organization grade Ⅳ and 2 cases of grade Ⅲ) were retrospectively analyzed. All patients received TTFields combined with concurrent chemoradiation after surgery. Response assessment in neuro-oncology (RANO) criteria was used to evaluate the glioma responses as tumor remission, stable or progression. Common terminology criteria for adverse events v5.0 and TTFields related skin adverse reaction (dAE) criteria were used to evaluate the adverse events. Treatment compliance was assessed by data on the NovoTTF-200A therapeutic device, calculated as a percentage of daily TTFields usage time. Survival analysis was estimated by the Kaplan-Meier method and compared by the log-rank test.Results:The median duration of treatment with TTFields in 38 patients was 20 h (rang: 2.4-22.6 h), and the median treatment compliance was 83% (range: 10%-94%). After 42 days of TTFields combined with concurrent chemoradiation, 12 patients who underwent complete tumor resection were assessed as stable according to RANO criteria. Among the 26 patients who underwent partial tumor resection, 23 (88%) were evaluated as disease remission according to RANO criteria. The 7-, 10-, 13-month progression-free survival rate was 81.0%、64.0%、49.5%, repectively. The common adverse events included grade 1 (45%) and grade 2 (8%) dAE, without grade 3-4 dAE. Typical presentations included contact dermatitis, blisters, lesions or ulcers, and abscesses. The median follow-up time was 10.0 months (range: 1.6-21.3 months). At follow-up as of July 2023, 26 of the 38 patients were stable and 12 had disease progression (8 died).Conclusion:The preliminary results show that TTFields combined with chemoradiation is effective, safe and reliable treatment for high-grade glioblastoma.

Objective To explore the difference in efficacy of metoprolol versus ivabradine in the treatment of postural orthostatic tachycardia syndrome(POTS)in the elderly after COVID-19 infection.Methods A total of 110 patients diagnosed with POTS at our department from Decem-ber 1,2022 to January 31,2023 were included.According to their drug regimen,they were divided into metoprolol group(62 patients)and ivabradine group(48 patients).On the 28th day of out-patient follow-up,the resting heart rate,heart rate of 10 min of standing,symptom disappearance rate,hospitalization rate,and mortality rate were compared between the two groups.Results On the 28th day of treatment,the resting heart rate and postural heart rate for 10 min were decreased in both groups when compared with the levels at initial diagnosis(P＜0.01).And there were no significant differences in the two types of heart rate between the two groups on the 28th day(71.0±7.0 vs 72.1±7.0,P=0.401;76.5±7.2 vs 77.4±7.6,P=0.573).No obvious differences were observed between the two groups in symptom disappearance rate,hospitalization rate,or mortality rate(88.7％vs 89.6％,3.2％vs2.1％,0％vs 0％,P＞0.05).Conclusion Metoprolol and ivabradine can effectively treat POTS in the elderly patients after COVID-19 infection.

Objective: To understand the current situation and related factors of tobacco use among high school students in Shannan City, so as to provide reference for tobacco control strategies for high school students. Methods: A self administered questionnaire survey was conducted among 10 052 high school students from 6 high schools in Shannan City, Tibetan Autonomous Region by census methods from April to July in 2023. The comparison of rates was conducted by using Chi square test, and the influencing factors of tobacco use among high school students were analyzed using binomial classification Logistic regression. Results: The rate of high school students in Shannan City trying cigarettes was 17.63%, and the current smoking rate was 10.07%, both of which were higher in boys than girls, and higher in urban areas than in rural areas ( χ 2 gender = 1 262.35 , 869.79; χ 2 area =35.90, 29.16, P <0.01). The smoking rate of students with parents and good friends smoking was higher than that of students with parents and good friends not smoking( χ 2= 190.50 ,1 741.44), and the current smoking rate showed an upward trend with age and age ( χ 2 trend =74.87, 122.86)( P <0.01). The tobacco dependence rate was 41.80%; 75.30% wanted to quit smoking, 83.99% had received smoking cessation assistance, but had received less professional smoking cessation assistance ( 13.41 %). Logistic regression analysis showed that vocational high school students, senior students (second and third grade), parents smoking (both smoking, mother smoking), and good friends smoking (some smoking, most smoking, all smoking) were positively correlated with smoking cigarettes among high school students ( OR=1.51, 1.54, 2.17, 2.22, 1.69, 5.30, 13.28, 8.59, P <0.05). Conclusions The smoking rate of high school students in Shannan City is high and second hand smoke exposure is common. Vocational high schools are the key to prevention and control. Effective cooperation between families, schools, and society should be strengthened to create a smoke free environment and protect students from tobacco hazards.

We designed and synthesized eighteen lycorine derivatives with five different structural types, and evaluated their antiviral activities on a HCoV-OC43-infected H460 cell model. Structure-activity relationships suggested that the introduction of appropriate substituents on the 6N atom of lycorine was beneficial to activity. Compound 6a gave a good activity with the half effective concentration (EC₅₀) and selectivity index (SI) values of 2.36 μmol·L^-1 and 16.52, respectively. Surface plasmon resonance (SPR) result indicated that 6a might target the non-structural protein 12 (NSP12) subunit in RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 with the dissociation constant (K_D) value of 1.36 μmol·L^-1. Molecular docking indicated that 6a might act on nidovirus RdRp-associated nucleotidyltransferase (NiRAN) catalytic center of NSP12, distinct from the mechanism of nucleoside-like drugs such as remdesivir. This study provides scientific data for the development of lycorine derivatives into a new class of anti-SARS-CoV-2 small molecule inhibitors.

In this study, we designed and synthesized 12 novel aloperine derivatives with different core structures. Among them, compound 3 with a ten-membered ring core was obtained through a special ring expansion reaction after γ-H Huffman elimination of quaternary ammonium salt, and the structure was verified by X-single crystal diffraction. Furthermore, their antiviral activity against human β-coronavirus HCoV-OC43 was evaluated by CCK-8 assay. Quaternary ammonium salt 2a and 3 had a good inhibitory effect against HCoV-OC43, and 2a had the highest anti-HCoV-OC43 activity with an EC₅₀ values of 3.77 μmol·L^-1 and a SI value of over 53.1. Schrӧdinger molecular docking results showed that both 2a and 3 might display their anti-HCoV-OC43 activity by directly acting on host TMPRSS2 and SR-B1. The results expanded the structural types of endocyclic aloperine and the function against coronavirus, and provided useful scientific data for the development of pharmaceutical applications of these compounds.

Objective:To explore the clinical characteristics,molecular characteristics,treatment and prognosis of pediatric Philadelphia chromosome-like acute lymphoblastic leukemia(Ph-like ALL)with a therapeutic target.Methods:A total of 27 patients of Ph-like ALL with targeted drug target were initially diagnosed in Children's Hospital of Soochow University from December 2017 to June 2021.The data of age,gender,white blood cell(WBC)count at initial diagnosis,genetic characteristics,molecular biological changes,chemotherapy regimen,different targeted drugs were given,and minimal residual disease(MRD)on day 19,MRD on day 46,whether hematopoietic stem cell transplantation(HSCT)were retrospective analyed,and the clinical characteristics and treatment effect were summarized.Survival analysis was performed by Kaplan-Meier method.Results:The intensity of chemotherapy was adjusted according to the MRD level during induced remission therapy in 27 patients,10 patients were treated with targeted drugs during treatment,and 3 patients were bridged with HSCT,1 patient died and 2 patients survived.Among the 24 patients who did not receive HSCT,1 patient developed relapse,and achieved complete remission(CR)after treatment with chimeric antigen receptors T cells(CAR-T).The 3-year overall survival,3-year relapse-free survival and 3-year event-free survival rate of 27 patients were(95.5±4.4)％,(95.0±4.9)％and(90.7±6.3)％respectively.Conclusion:Risk stratification chemotherapy based on MRD monitoring can improve the prognosis of Ph-like ALL in children,combined with targeted drugs can achieve complete remission as soon as possible in children whose chemotherapy response is poor,and sequential CAR-T and HSCT can significantly improve the therapeutic effect of Ph-like ALL in children whose MRD is continuously positive during induced remission therapy.

Aim To investigate the mechanism of treatment of hepatolenticular degeneration with Garde-nia and Rhubarb decoction based on network pharma-cology and animal experiments.Methods The chemi-cal components and target sites of Gardenia and Rhu-barb decoction were retrieved using the Traditional Chi-nese Medicine System Pharmacology Analysis Platform(TCMSP).The disease targets were obtained by searching the databases of DisGeNET,GeneCards.The PPI network of active compound target sites was constructed using the STRING database.GO function and KEGG pathway enrichment analysis were per-formed using the DAVID database to predict the action pathway.A copper-loaded WD rat model was estab-lished by intragastric administration of copper sulfate pentahydrate.A total of 36 rats were randomly divided into the normal group,model group,penicillamine group and the low,medium and high dose groups of gardenia rhubarb.The relevant indicators and patho-logical changes of liver tissue were detected in WD rats.Results Network pharmacology screening identi-fied 68 potential active components of Gardenia and Rhubarb Decoction,30 intersection targets of diseases and drugs,involving key targets such as TNF,IL10,IGF1,IL1B,TP53,CASP3,PPARG,IL6,CXCL8,IL1A,TGFB1,mainly related to signal pathways such as MAPK,AGE-RAGE signaling pathway in diabetic complications.In the animal experiments,compared with the normal group,the urine copper,liver copper,blood copper,liver coefficient,serum and liver ALT,AST,TNF-α,CASP3,P53 levels in the model group rats significantly increased(P＜0.05);hepatocyte swelling,cytoplasm loose reticular appearance,feath-er-like degeneration and reticular necrosis were ob-served in liver tissue pathology;compared with the model group,the urine copper,liver copper,blood copper,liver coefficient,serum and liver ALT,AST,TNF-α,CASP3,P53 levels in the penicillamine group and Gardenia and Rhubarb decoction groups were sig-nificantly reduced(P＜0.05),and the degree of re-ticular necrosis in the rat liver cells in the penicilla-mine group and the Gardenia and Rhubarb decoction group was significantly reduced.Conclusions Garde-nia and Rhubarb decoction has the effect of regulating copper metabolism and reducing liver injury.The mechanism of action may be related to reversing apop-tosis and downregulating protein expression of TNF-α,CASP3,P53 in MAPK signaling pathway.