This paper aimed to investigate the therapeutic effect and mechanism of action of the Yiqi Fumai Formula(YQFM), a kind of traditional Chinese medicine(TCM), on mice with experimental heart failure based on the "heart-gut axis" theory. Based on the network pharmacology integrated with the group collaboration algorithm, the active ingredients were screened, a "component-target-disease" network was constructed, and the potential pathways regulated by the formula were predicted and analyzed. Next, the model of experimental heart failure was established by intraperitoneal injection of adriamycin at a single high dose(15 mg·kg~(-1)) in BALB/c mice. After intraperitoneal injection of YQFM(lyophilized) at 7.90, 15.80, and 31.55 mg·d~(-1) for 7 d, the protective effects of the formula on cardiac function were evaluated using indicators such as ultrasonic electrocardiography and myocardial injury markers. Combined with inflammatory factors in the cardiac and colorectal tissue, as well as targeted assays, the relevant indicators of potential pathways were verified. Meanwhile, 16S rDNA sequencing was performed on mouse fecal samples using the Illumina platform to detect changes in gut flora and analyze differential metabolic pathways. The results show that the administration of injectable YQFM(lyophilized) for 7 d significantly increased the left ventricular end-systolic internal diameter, fractional shortening, and ejection fraction of cardiac tissue of mice with experimental heart failure(P<0.05). Moreover, markers of myocardial injury were significantly decreased(P<0.05), indicating improved cardiac function, along with significantly suppressed inflammatory responses in cardiac and intestinal tissue(P<0.05). Additionally, the species of causative organisms was decreased, and the homeostasis of gut flora was improved, involving a modulatory effect on PI3K-Akt signaling pathway-related inflammation in cardiac and colorectal tissue. In conclusion, YQFM can affect the "heart-gut axis" immunity through the homeostasis of the gut flora, thereby exerting a therapeutic effect on heart failure. This finding provides a reference for the combination of TCM and western medicine to prevent and treat heart failure based on the "heart-gut axis" theory.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Heart Failure/microbiology* ; Mice ; Mice, Inbred BALB C ; Male ; Disease Models, Animal ; Gastrointestinal Microbiome/drug effects* ; Heart/physiopathology* ; Humans ; Signal Transduction/drug effects*

This study primarily aimed to investigate the prevalence of human papillomavirus (HPV) and other common pathogens of sexually transmitted infections (STIs) in spermatozoa of infertile men and their effects on semen parameters. These pathogens included Ureaplasma urealyticum, Ureaplasma parvum, Chlamydia trachomatis, Mycoplasma genitalium , herpes simplex virus 2, Neisseria gonorrhoeae, Enterococcus faecalis, Streptococcus agalactiae, Pseudomonas aeruginosa , and Staphylococcus aureus . A total of 1951 men of infertile couples were recruited between 23 March 2023, and 17 May 2023, at the Department of Reproductive Medicine of The First People's Hospital of Yunnan Province (Kunming, China). Multiplex polymerase chain reaction and capillary electrophoresis were used for HPV genotyping. Polymerase chain reaction and electrophoresis were also used to detect the presence of other STIs. The overall prevalence of HPV infection was 12.4%. The top five prevalent HPV subtypes were types 56, 52, 43, 16, and 53 among those tested positive for HPV. Other common infections with high prevalence rates were Ureaplasma urealyticum (28.3%), Ureaplasma parvum (20.4%), and Enterococcus faecalis (9.5%). The prevalence rates of HPV coinfection with Ureaplasma urealyticum, Ureaplasma parvum, Chlamydia trachomatis, Mycoplasma genitalium , herpes simplex virus 2, Neisseria gonorrhoeae, Enterococcus faecalis, Streptococcus agalactiae , and Staphylococcus aureus were 24.8%, 25.4%, 10.6%, 6.4%, 2.4%, 7.9%, 5.9%, 0.9%, and 1.3%, respectively. The semen volume and total sperm count were greatly decreased by HPV infection alone. Coinfection with HPV and Ureaplasma urealyticum significantly reduced sperm motility and viability. Our study shows that coinfection with STIs is highly prevalent in the semen of infertile men and that coinfection with pathogens can seriously affect semen parameters, emphasizing the necessity of semen screening for STIs.
Humans ; Male ; Infertility, Male/epidemiology* ; Coinfection/microbiology* ; Papillomavirus Infections/virology* ; Adult ; Sexually Transmitted Diseases/complications* ; China/epidemiology* ; Staphylococcus aureus/isolation & purification* ; Chlamydia trachomatis/isolation & purification* ; Prevalence ; Mycoplasma genitalium/isolation & purification* ; Ureaplasma urealyticum/isolation & purification* ; Neisseria gonorrhoeae/isolation & purification* ; Enterococcus faecalis/isolation & purification* ; Streptococcus agalactiae/isolation & purification* ; Herpesvirus 2, Human/genetics* ; Pseudomonas aeruginosa/isolation & purification* ; Semen/virology* ; Sperm Motility ; Spermatozoa/microbiology* ; Human Papillomavirus Viruses

OBJECTIVES: To evaluate the safety and efficacy of thiotepa (TT)-containing conditioning regimens for allogeneic hematopoietic stem cell transplantation (HSCT) in children with inborn errors of immunity (IEI). METHODS: Clinical data of 22 children with IEI who underwent HSCT were retrospectively reviewed. Survival after HSCT was estimated using the Kaplan-Meier method. RESULTS: Nine patients received a traditional conditioning regimen (fludarabine + busulfan + cyclophosphamide/etoposide) and underwent peripheral blood stem cell transplantation (PBSCT). Thirteen patients received a TT-containing modified conditioning regimen (TT + fludarabine + busulfan + cyclophosphamide), including seven PBSCT and six umbilical cord blood transplantation (UCBT) cases. Successful engraftment with complete donor chimerism was achieved in all patients. Acute graft-versus-host disease occurred in 12 patients (one with grade III and the remaining with grade I-II). Chronic graft-versus-host disease occurred in one patient. The incidence of EB viremia in UCBT patients was lower than that in PBSCT patients (P<0.05). Over a median follow-up of 36.0 months, one death occurred. The 3-year overall survival (OS) rate was 100% for the modified regimen and 88.9% ± 10.5% for the traditional regimen (P=0.229). When comparing transplantation types, the 3-year OS rates were 100% for UCBT and 93.8% ± 6.1% for PBSCT (P>0.05), and the 3-year event-free survival rates were 100% and 87.1% ± 8.6%, respectively (P>0.05). CONCLUSIONS TT-containing conditioning for allogeneic HSCT in children with IEI is safe and effective. Both UCBT and PBSCT may achieve high success rates.
Humans ; Retrospective Studies ; Transplantation Conditioning/methods* ; Thiotepa/therapeutic use* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child, Preschool ; Infant ; Child ; Transplantation, Homologous ; Graft vs Host Disease ; Adolescent

OBJECTIVE: To investigate the influencing factors of pathological positive surgical margins (PSM) after radical resection of prostate cancer. METHODS: The clinical data of 407 patients who underwent radical resection of prostate cancer in our hospital from 2011 to 2020 were retrospectively analyzed. And the patients were divided into two groups according to postoperative pathological results. Single factor analysis was used to evaluate the differences in postoperative Gleason score, preoperative total prostate-specific antigen (tPSA), preoperative serum free prostate-specific antigen to preoperative tPSA ratio (fPSA/ tPSA), clinical stage, postoperative pathological stage, operation method, age, body mass index (BMI), diameter and volume of prostate tumor. Multivariate logistic regression was used to determine the independent risk factor of PSM. RESULTS: Among 407 patients with prostate cancer, 179 cases (43.98%) were positive. Univariate analysis showed that there were significant differences in postoperative Gleason score, preoperative tPSA, clinical stage and postoperative pathological stage between the two groups (P<0.05). And Gleason score, preoperative tPSA and pathologic stage were independent risk factors for PSM. CONCLUSION There are relationships between PSM and postoperative Gleason score, tPSA, clinical T stage, postoperative pathologic pT stage. Among them, postoperative Gleason score (Gleason=7 points, Gleason≥8 points), preoperative total prostate-specific antigen (tPSA > 20 μg/L), and postoperative pathologic pT stage (pT3a, pT3b) were independent risk factors for positive pathological margins of prostate cancer.
Margins of Excision ; Prostatic Neoplasms/surgery* ; Prostatectomy/statistics & numerical data* ; Prostate/surgery* ; Retrospective Studies ; Neoplasm Grading/statistics & numerical data* ; Prostate-Specific Antigen/blood* ; Neoplasm Staging/statistics & numerical data* ; Postoperative Period ; Risk Factors ; Humans ; Male

Objective To analyze the influence of midazolam and propofol on sedation effect and blood gas indicators in elderly patients undergoing mechanical ventilation after cardiopulmonary bypass(CPB)cardiac surgery.Methods The elderly patients with mechanical ventilation after CPB cardiac surgery were grouped according to cohort method,including midazolam group(group M),propofol group(group P)and midazolam-propofol combined administration group(group M-P).Group M was treated with midazolam(intravenous injection of 0.05-0.10 mg kg-1 midazolam for sedation induction,and then continuously intravenous injection of 0.05-0.15 mg·kg-1·h-1 midazolam by micropump),and group P was treated with propofol(intravenous injection of 0.5 mg·kg-1 propofol for sedation induction,and then continuously intravenous injection of 0.5-2.0 mg·kg-1·h-1 propofol by micropump),and group M-P was given combined administration of midazolam and propofol(intravenous injection of 0.02-0.05 mg·kg-1 midazolam and 0.2-0.5 mg·kg-1 propofol for sedation induction and then continuously intravenous pump of 0.05-0.1 mg·kg-1 midazolam and 0.5-0.8 mg·kg·h-1 propofol).The sedation effect,blood gas indicators,hemodynamic indicators,extubation time,intensive care unit(ICU)stay time and treatment cost were compared among the three groups,and the adverse drug reactions during sedation therapy were recorded.Results There were 43 cases in group M,44 cases in group P,39 cases in group M-P.The drug onset times in groups M,P and M-P were(77.94±12.05),(18.18±5.20)and(21.25±9.36)s;the times to achieve satisfactory sedation effect were(42.57±11.41),(22.63±8.17)and(23.98±10.25)min;the recovery times after withdrawal were(59.30±14.86),(19.83±5.44)and(22.16±6.29)min;the extubation times were(1.61±0.20),(1.45±0.22)and(1.37±0.15)d;the ICU stay times were(2.17±0.29),(1.91±0.36)and(1.84±0.25)d;the treatment costs were(186.59±60.83),(922.97±164.34)and(375.03±71.16)thousand yuan;and the total incidence rates of adverse drug reactions were 34.88％,4.55％and 7.69％respectively,all with significant difference(all P＜0.05).There were no statistically significant differences in mean arterial pressure(MAP),heart rate(HR),oxygen saturation(SpO2),partial pressure of oxygen(PaO2),partial pressure of carbon dioxide(PaCO2)at T0,T1,T2,T3 and T4 among the three groups(all P＞0.05).Conclusion Combined administration of midazolam and propofol in elderly patients underwent mechanical ventilation after CPB cardiac surgery has a significant sedation effect,and it is conducive to reducing the dosages of sedative drugs,and it has small impact on blood gas indicators and hemodynamic indicators of patients.Compared with midazolam alone,it is more beneficial to shortening the extubation time and ICU stay and reducing the total incidence rate of adverse drug reactions,and compared with propofol alone,it is more beneficial to reducing treatment cost,and is a more ideal sedation administration model.

The abuse of novel phenylcyclohexylpyridine drugs poses a significant threat to societal safety. The novel psychoactive substance 2-methyl-deschloroketamine (2-MDCK), belonging to the phenylcyclohexylpyridine class, has recently surfaced as a new compound. However, there is a lack of understanding regarding its metabolic pathways and the identification of suitable biomarkers. In this study, a human liver microsomal model was established, and ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) technology was applied to investigate the in vitro metabolism and products of 2-MDCK. The results indicate that 2-MDCK undergoes various metabolic reactions, including dehydrogenation, deamination, hydroxylation, and demethylation, leading to the formation of eight metabolites. By conducting actual testing on hair samples from 2-MDCK abusers, the existence of six metabolites was confirmed. Comparing the metabolic products in the liver microsomal in vitro model, M3.1 and M4.1 were identified as biomarkers for 2-MDCK consumption. Five samples of abusers of 2-methyl-dechloroketamine were provided by the Anti-Drug Brigade of the Hangzhou Public Security Bureau. Negative hair samples were provided by laboratory volunteers, and all samples were obtained with the informed consent of the volunteers. These findings provide a scientific basis for the detection and identification of 2-MDCK and its metabolites, as well as crucial support for the study of the metabolic mechanisms of similar novel psychoactive substances in the phenylcyclohexylpyridine class. This research holds significant importance in addressing the issue of abuse of new psychoactive substances.

Objective To compare the short- to mid-term outcomes of aortic valve plasty (AVP) and Ross surgery in children with severe aortic valve disease. Methods The patients (aged<18 years) with severe aortic valve disease who underwent AVP (an AVP group) or Ross surgery (a Ross group) at the Department of Cardiovascular Surgery, West China Hospital from January 2019 to September 2023 were retrospectively included. We compared perioperative and follow-up data between the groups. Results A total of 48 pediatric patients were included, including 28 males and 20 females, with an average age of (9.3±4.5) years. There were 25 patients in the AVP group, and 23 in the Ross group. Leaflet thinning (15/25, 60.0%) and leaflet extension (10/25, 40.0%) were the most common strategies used in the AVP group, while root replacement technique (12/23, 52.2%) and subcoronary technique (10/23, 43.5%) were the most frequently used strategies in the Ross group. There was no in-hospital death. The median follow-up time was 16.0 (7.0, 30.0) months. Peak flow velocity of the aortic valve was higher in the AVP group [2.0 (1.4, 2.9) m/s vs. 1.2 (1.0, 1.5) m/s, P<0.001], while there was no statistical difference in the postoperative aortic valve regurgitation severity between the two groups (P=0.127). During follow-up, the overall reoperation rate and aortic valve reoperation rate were similar between the AVP group and the Ross group (8.0% vs. 13.0%, P=0.922; 8.0% vs. 0.0%, P=0.266). The rate of recurrent aortic valve disease was higher in the AVP group (52.0% vs. 4.3%, P<0.001), while further analysis failed to recognize any risk factors. Conclusion AVP and Ross procedure show similar perioperative safety, survival and reoperation rate. The rate of recurrent aortic valve disease is higher in the AVP group, but further investigations are needed to confirm the causes.

DRG payment reform is an important means to control the unreasonable growth of medical expenses, improve the quality of medical services and achieve a win-win situation among three sides of hospitals, medical insurance and patients. This study adopted the Smith policy implementation process model to analyze the difficulties in the DRG policy implementation process from four aspects(idealized policies, policy implementation institutions, target groups, and policy environment), including the deviation between policy connotations and actual needs; the interest objectives of all parties were not completely aligned, the target group lacked a sense of identity, and the social impact and technological support needed to be improved. It was suggested that optimization should be carried out from four dimensions: policy supply coordination and precision, performance evaluation and personnel literacy, target group cognitive level and participation willingness, and policy implementation environment and atmosphere, in order to synergistically promote the effective implementation of DRG policies.

Objective:To explore the clinical manifestations,diagnosis,pathological features and treatment of small-cell carci-noma of the prostate(SCCP).Methods:We conducted a retrospective analysis of the clinical and pathological data of 2 cases of confirmed SCCP treated from November 2017 to March 2018,and reviewed relevant literature.Results:Both the patients had the symptoms of frequent,urgent and difficult urination,with an elevated level of PSA and grades Ⅱ-Ⅲ enlargement of the prostate at palpation.One underwent prostate puncture biopsy and the other received transurethral 1470 laser vaporization resection of the tumor.Postoperative pathology indicated prostate adenocarcinoma accompanied by SCCP in both of the cases.One of them was treated by eto-poside-platinum(EP)chemotherapy and died of systemic multiple organ failure 20 months after diagnosis,while the other underwent endocrine therapy and has lived with tumor up to the present day.Conclusion:The incidence rate of SCCP is low,its malignancy is high,and its prognosis is poor.The average survival of the patient is about 7 to 10 months after diagnosis.Currently there is no effec-tive management of the dissease,except by relying on the experience of the treatment of small-cell lung cancer,with chemotherapy as the main option.

Objective To investigate the prevalence of tension-type headache(TTH)in children and adolescents aged 0-19 years globally in 1990-2021,and to provide a basis for the prevention and treatment of TTH.Methods Based on the Global Burden of Disease Study data,the age-standardized prevalence distribution of TTH and its changing trend were analyzed among the children and adolescents aged 0-19 years,with different sexes,age groups,sociodemographic index(SDI)regions and countries/territories.Results The age-standardized prevalence rate(ASPR)of TTH in children and adolescents aged 0-19 globally in 2021 was 17 339.89/100 000,which was increased by 1.73%since 1990.The ASPR in females was slightly higher than that in males(1990:17 707.65/100 000 vs 16 403.78/100 000;2021:17 946.29/100 000 vs 16 763.09/100 000).The ASPR in adolescence was significantly higher than that in school-aged and preschool periods(1990:27 672.04/100 000 vs 10 134.16/100 000;2021:28 239.04/100 000 vs 10 059.39/100 000).Regions with high SDI exhibited a higher ASPR than the other regions,with significant differences in prevalence rates across different countries.From 1990 to 2021,there was a slight increase in global ASPR,with an average annual percentage change(AAPC)of 0.06%.Females experienced a smaller increase than males based on AAPC(0.04%vs 0.07%).There was reduction in ASPR in preschool and school-aged groups,with an AAPC of-0.02%,while there was a significant increase in ASPR in adolescence,with an AAPC of 0.07%.ASPR decreased in regions with low-middle and low levels of SDI,with an AAPC of-0.02%and-0.04%,respectively,while it increased in regions with middle SDI,with an AAPC of 0.24%.Conclusions There is a consistent increase in the ASPR of TTH in children and adolescents aged 0-19 years globally,with significant differences across sexes,age groups,SDI regions and countries/territories.