Premature ejaculation refers to a sexual dysfunction in which men experience a short intravaginal ejaculation latency and a lack of control over ejaculation during sexual activity. The onset of this condition is often accompanied by anxiety and depression, which can seriously affect the quality of the patient′s sexual life and the relationship between partners. Based on the "integration of body and spirit" theory in traditional Chinese medicine, our team believes that this condition is a comorbidity of physical and spiritual factors. We propose that the core pathogenesis of this disease lies in the "loss of form and essence, impairment of spirit, and depression of the mind, "while the primary treatment principle involves "nourishing form and regulating spirit." As a result, a new diagnosis and treatment approach of "four-dimensional integration" is summarized in this study. The disease is treated through the four dimensions of shape, body, spirit, and emotion. Traditional Chinese medicine is used to adjust the shape in cases where the physical form is damaged. For individuals with depression of heart and liver qi, the treatment focuses on soothing the heart and smoothing liver qi, and the modified Wangyou Powder and Xuanzhi Decoction is used. In cases where the heart and kidney function are compromised, the treatment involves nourishing both the heart and kidney while restoring interaction between the heart and the kidney, and modified Jihuo Yansi Elixir is used. To reduce the sensitivity of the glans penis, the patient′s body is washed with a traditional Chinese medicine formula, and a delicate fumigation formula is decocted for external washing. For those who are not in tune with their god, psychological counseling can be used to regulate their spirit and advocate "self-partner" and psychotherapy. If there are issues with intimacy, partners should focus on cooperating during foreplay, sexual intercourse, and post-coital interactions. Overall, the treatment aims to harmonize the body and spirit, addressing both physical and psychological factors through a comprehensive, multi-dimensional approach. This method provides new perspectives and ideas for the clinical diagnosis and treatment of this condition.

BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

Through a comprehensive analysis combining network pharmacology prediction and transcriptomics, this study systematically explained the multi-target mechanism of Cyanotis arachnoidea(CA) Gel in improving melasma. A melasma model was induced in female SD rats by progesterone injection combined with ultraviolet B(UVB) irradiation for 40 consecutive days, while the blank control group was only fed routinely. After successful model establishment, the rats were randomly divided into five groups and administered different doses of CA ethanol extract gel(high, medium, and low doses) or arbutin Gel(positive control), which were applied once daily for 28 consecutive days. Subsequently, the levels of superoxide dismutase(SOD), malondialdehyde(MDA), and tyrosinase(TYR) in the skin, serum, and liver tissues were measured. Hematoxylin-eosin(HE) staining and Masson-Fontana staining were used to observe the pathological changes in the tissues. Network pharmacology combined with transcriptomics was employed to identify core targets and pathways, and the differential gene expression was validated by quantitative real-time PCR(qPCR). Pharmacodynamic experiments showed that CA Gel significantly increased SOD activity and decreased MDA and TYR levels in the skin, serum, and liver of model rats. It also improved epidermal thickening, inflammatory infiltration, collagen loss, and melanin deposition. Network pharmacology analysis showed that CA mainly regulated core targets such as signal transducer and activator of transcription 3(STAT3), epidermal growth factor receptor(EGFR), and interleukin-6(IL-6), and modulated the phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT) and interleukin-17(IL-17) signaling pathways. Transcriptomic analysis showed that CA Gel significantly downregulated the gene expression of heat shock protein 90β family member 1(Hsp90b1), heat shock protein 90α family member 1(Hsp90aa1), and the key steroid synthesis enzyme cytochrome P450 family 17 subfamily A member 1(Cyp17a1), while upregulating thioredoxin 1(Txn1). qPCR results confirmed that CA Gel regulated oxidative stress and inflammatory response by inhibiting the IL-17 signaling pathway and steroid hormone synthesis. This study, for the first time, reveals the molecular mechanism of CA Gel in improving melasma through multi-target synergistic regulation of oxidative stress, inflammatory response, and hormone metabolism pathways, providing a scientific basis for the treatment of pigmentation diseases with traditional Chinese medicine.
Animals ; Rats ; Female ; Rats, Sprague-Dawley ; Network Pharmacology ; Drugs, Chinese Herbal/administration & dosage* ; Melanosis/metabolism* ; Transcriptome/drug effects* ; Humans ; Superoxide Dismutase/genetics* ; Signal Transduction/drug effects* ; Malondialdehyde/metabolism*

OBJECTIVE: To explore the neuroprotective effects of Xuefu Zhuyu Decoction (XFZYD) based on in vivo and metabolomics experiments. METHODS: Traumatic brain injury (TBI) was induced via a controlled cortical impact (CCI) method. Thirty rats were randomly divided into 3 groups (10 for each): sham, CCI and XFZYD groups (9 g/kg). The administration was performed by intragastric administration for 3 days. Neurological functions tests, histology staining, coagulation and haemorheology assays, and Western blot were examined. Untargeted metabolomics was employed to identify metabolites. The key metabolite was validated by enzyme-linked immunosorbent assay and immunofluorescence. RESULTS: XFZYD significantly alleviated neurological dysfunction in CCI model rats (P<0.01) but had no impact on coagulation function. As evidenced by Evans blue and IgG staining, XFZYD effectively prevented blood-brain barrier (BBB) disruption (P<0.05, P<0.01). Moreover, XFZYD not only increased the expression of collagen IV, occludin and zona occludens 1 but also decreased matrix metalloproteinase-9 (MMP-9) and cyclooxygenase-2 (COX-2), which protected BBB integrity (all P<0.05). Nine potential metabolites were identified, and all of them were reversed by XFZYD. Adenosine was the most significantly altered metabolite related to BBB repair. XFZYD significantly reduced the level of equilibrative nucleoside transporter 2 (ENT2) and increased adenosine (P<0.01), which may improve BBB integrity. CONCLUSIONS XFZYD ameliorates BBB disruption after TBI by decreasing the levels of MMP-9 and COX-2. Through further exploration via metabolomics, we found that XFZYD may exert a protective effect on BBB by regulating adenosine metabolism via ENT2.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Blood-Brain Barrier/metabolism* ; Brain Injuries, Traumatic/metabolism* ; Adenosine/metabolism* ; Male ; Rats, Sprague-Dawley ; Rats

OBJECTIVE: Peritoneal fibrosis (PF) is an adverse event that occurs during long-term peritoneal dialysis, significantly impairing treatment efficiency and adversely affecting patient outcomes. Astragaloside IV (AS-IV), a principal active component derived from Astragalus membranaceus (Fisch.) Bunge, has exhibited anti-inflammatory and antifibrotic effects in various settings. This study aims to investigate the potential therapeutic efficacy and mechanism of AS-IV in the treatment of PF. METHODS: The PF mouse model was established by intraperitoneal injection of 4.25% peritoneal dialysis fluid (100 mL/kg). The epithelial-mesenchymal transition (EMT) of HMrSV5 cells was induced by the addition of 10 ng/mL transforming growth factor β (TGF-β). The differentially expressed genes in HMrSV5 cells treated with AS-IV were screened using transcriptome sequencing analysis. The potential targets of AS-IV were screened using network pharmacology and analyzed using molecular docking and molecular dynamics simulations. RESULTS: Administration of AS-IV at doses of 20, 40, or 80 mg/kg effectively mitigated the increase in peritoneal thickness and the development of fibrosis in mice with PF. The expression of the fibrosis marker α-smooth muscle actin in the peritoneum was significantly decreased in AS-IV-treated mice. The treatment of AS-IV (10, 20, and 40 μmol/L) significantly delayed the EMT of HMrSV5 cells induced by TGF-β, as demonstrated by the decreased number of 5-ethynyl-2'-deoxyuridine-positive cells, reduced migrated area, and decreased expression of fibrosis markers. A total of 460 differentially expressed genes were detected in AS-IV-treated HMrSV5 cells through transcriptome sequencing, with notable enrichment in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-AKT serine/threonine kinase 1 (AKT) signaling pathway. The reduced levels of phosphorylated PI3K (p-PI3K) and p-AKT were detected in HMrSV5 cells with AS-IV treatment. Epidermal growth factor receptor (EGFR) was predicted as a direct target of AS-IV, exhibiting strong hydrogen bond interactions. The activation of the PI3K-AKT pathway by the compound 740Y-P, and the activation of the EGFR pathway by NSC 228155 each partially counteracted the inhibitory effect of AS-IV on the EMT of HMrSV5 cells. CONCLUSION AS-IV delayed the EMT process in peritoneal mesothelial cells and slowed the progression of PF, potentially serving as a therapeutic agent for the early prevention and treatment of PF. Please cite this article as: Huang Y, Chu CL, Qiu WH, Chen JY, Cao LX, Ji SY, Zhu B, Wang GK, Shen QQ. Astragaloside IV delayed the epithelial-mesenchymal transition in peritoneal fibrosis by inhibiting the activation of EGFR and PI3K-AKT pathways. J Integr Med. 2025; 23(6):694-705.
Epithelial-Mesenchymal Transition/drug effects* ; Animals ; Saponins/pharmacology* ; Triterpenes/pharmacology* ; Mice ; Peritoneal Fibrosis/pathology* ; Proto-Oncogene Proteins c-akt/metabolism* ; ErbB Receptors/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Signal Transduction/drug effects* ; Male ; Humans ; Molecular Docking Simulation ; Cell Line ; Mice, Inbred C57BL

Objective To review the occurrence of allergic reactions during therapeutic plasma exchange(TPE)and to explore the risk factors of TPE allergic reactions.Methods The clinical data of 929 patients treated with TPE using plasma components by the Department of Transfusion Medicine in our medical center from 2018 to 2023 were collected.The influen-cing factors of allergic reactions were analyzed by univariate analysis,and the independent risk factors of allergic reactions were analyzed by logistic multivariate regression analysis.Results A total of 4 071 TPEs were performed in 929 patients.A-mong them,198 patients(21.31%)experienced 349 times(8.57%)of allergic reactions,with the incidence of gradeⅠ,Ⅱ and Ⅲ allergic reactions of 16.33%,81.38%and 2.29%,respectively,and no deaths.The univariate analysis showed that the patient′s age,allergy history,diagnosis of immune-related diseases,ICU admission,plasma consumption,total blood volume,maximum blood flow rate and combined use of albumin were related to the occurrence of allergic reactions(P＜0.05).Multivariate regression analysis showed that young patients,a history of allergy,immune-related diseases and non-ICU patients were prone to allergic reactions in TPE,but the treatment options of TPE such as substitute fluid category,plasma consumption and blood flow rate were not related to the occurrence of allergic reactions.Conclusion There are sig-nificant individual differences in the occurrence of allergic reactions for TPE,and young age,history of allergies,immune-related diseases and non-ICU patients are risk factors for allergic reactions in TPE.Identifying patients with risk factors be-fore TPE treatment and giving corresponding preventive measures can reduce the incidence of allergic reactions.

Objective:To investigate the effect of the number of positive preoperative serological tumor markers on the surgical approach and prognosis of patients with intrahepatic cholangiocarcinoma.Methods:This is a retrospective case-series study. Data from 548 patients with intrahepatic cholangiocarcinoma after radical resection from October 2010 to April 2019 were retrospectively collected in 10 hospitals of China. There were 277 males and 271 females with an age of (57.8±10.2)years(range:23 to 84 years). Four hundred and twenty-six patients(77.7%) had at least one positive preoperative serum tumor marker. The data collection included the results of 4 preoperative serological tumor markers,other preoperative indicators(5 prodromal symptoms, 6 medical history,8 preoperative serological indicators,5 preoperative imaging indicators,and 14 preoperative pathological examination indicators),baseline data (gender and age),surgical methods,and prognostic follow-up data. Four preoperative results of serologic tumor marker and surgical procedure were converted into categorical variables. The number of positive preoperative serum tumor markers was used as the treatment variable,the surgical method was used as the mediating variable,and the survival time was used as the outcome variable. Univariate and multivariate analysis were used to screen for other preoperative indicators which were independent factors that influenced the surgical procedure and the prognosis of patients as covariates to analyze the mediating effect.Results:Of the 548 patients included in the study, 176 patients (32.1%) underwent partial hepatectomy,151 patients(27.5%) underwent hemihepatectomy, and 221 patients(40.3%) underwent partial hepatectomy or hemihepatectomy combined with other treatments. The results of the univariate and multivariate analysis showed that the number of positive serum tumor markers,intrahepatic bile duct dilatation,portal vein invasion,pathological differentiation,pathological type,vascular invasion,T stage,N stage and maximum tumor diameter were independent factors influencing the surgical procedure(all P<0.05). Intrahepatic bile duct dilatation,pathological differentiation and T stage were independent prognostic factors for patients with intrahepatic cholangiocarcinoma(all P<0.05). Intrahepatic bile duct dilatation,differentiation and T stage were included as covariates in the mediation effect model. The results showed that the number of positive serum tumor markers before surgery had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.092, P=0.039),and had a positive predictive effect on the surgical method ( β=0.244, P<0.01). The number of positive serum tumor markers had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.151, P=0.002). Direct and indirect effects accounted for 71.3% and 28.7% of total effects,respectively. Conclusions:The higher the positive number of preoperative tumor markers,the worse the prognosis of patients with intrahepatic cholangiocarcinoma. The number of positive cells not only directly affects the prognosis of patients,but also indirectly affects the prognosis of patients by affecting the surgical method.

Objective:To investigate the effect of the number of positive preoperative serological tumor markers on the surgical approach and prognosis of patients with intrahepatic cholangiocarcinoma.Methods:This is a retrospective case-series study. Data from 548 patients with intrahepatic cholangiocarcinoma after radical resection from October 2010 to April 2019 were retrospectively collected in 10 hospitals of China. There were 277 males and 271 females with an age of (57.8±10.2)years(range:23 to 84 years). Four hundred and twenty-six patients(77.7%) had at least one positive preoperative serum tumor marker. The data collection included the results of 4 preoperative serological tumor markers,other preoperative indicators(5 prodromal symptoms, 6 medical history,8 preoperative serological indicators,5 preoperative imaging indicators,and 14 preoperative pathological examination indicators),baseline data (gender and age),surgical methods,and prognostic follow-up data. Four preoperative results of serologic tumor marker and surgical procedure were converted into categorical variables. The number of positive preoperative serum tumor markers was used as the treatment variable,the surgical method was used as the mediating variable,and the survival time was used as the outcome variable. Univariate and multivariate analysis were used to screen for other preoperative indicators which were independent factors that influenced the surgical procedure and the prognosis of patients as covariates to analyze the mediating effect.Results:Of the 548 patients included in the study, 176 patients (32.1%) underwent partial hepatectomy,151 patients(27.5%) underwent hemihepatectomy, and 221 patients(40.3%) underwent partial hepatectomy or hemihepatectomy combined with other treatments. The results of the univariate and multivariate analysis showed that the number of positive serum tumor markers,intrahepatic bile duct dilatation,portal vein invasion,pathological differentiation,pathological type,vascular invasion,T stage,N stage and maximum tumor diameter were independent factors influencing the surgical procedure(all P<0.05). Intrahepatic bile duct dilatation,pathological differentiation and T stage were independent prognostic factors for patients with intrahepatic cholangiocarcinoma(all P<0.05). Intrahepatic bile duct dilatation,differentiation and T stage were included as covariates in the mediation effect model. The results showed that the number of positive serum tumor markers before surgery had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.092, P=0.039),and had a positive predictive effect on the surgical method ( β=0.244, P<0.01). The number of positive serum tumor markers had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.151, P=0.002). Direct and indirect effects accounted for 71.3% and 28.7% of total effects,respectively. Conclusions:The higher the positive number of preoperative tumor markers,the worse the prognosis of patients with intrahepatic cholangiocarcinoma. The number of positive cells not only directly affects the prognosis of patients,but also indirectly affects the prognosis of patients by affecting the surgical method.

AIM To optimize the extraction process for uracil,hypoxanthine,xanthine,uridine,thymine,inosine,guanosine and 2'-deoxyguanosine from Pheretima guillelmi(Michaelsen),and to determine their contents.METHODS With solid-liquid ratio,ultrasonic time and ultrasonic temperature as influencing factors,contents of hypoxanthine and total nucleosides as evaluation indices,the extraction process was optimized by orthogonal test.HPLC was adopted in the content determination of varioud nucleosides,the analysis was performed on a 30℃thermostatic Agilent C18 column(4.6 mm×250 mm,5 μm),with the mobile phase comprising of methanol-water flowing at 1 mL/min in a gradient elution manner,and the detection wavelength was set at 260 nm.RESULTS The optimal conditions were determined to be 1∶250 for solid-liquid ratio,60 min for ultrasonic time,and 60℃for ultrasonic temperature.Eight nucleosides showed good linear relationships within their own ranges(R2＞0.999 0),whose average recoveries were 99.11%-103.27%with the RSDs of 0.85%-2.89%.CONCLUSION This stable and reliable method can be used for the extraction and content determination of nucleosides from P.guillelmi.

The purpose of this study was to investigate the regulatory effects of biofilm associated non-coding small RNA(sRNA)00085 on the survival and environmental fitness of Listeria monocytogenes.Homologous recombination technology was used to construct a deletion mutant strain(△sRNA 00085)and a complementary strain(C △sRNA 00085)of the sRNA00085 target gene.The differences in biological characteristics were compared among the standard strain,△sRNA 00085,and C△sRNA 00085.The deletion of sRNA00085 led to a significant decrease in biofilm formation capacity and sensitivity to several antibiotics,including penicillin,piperacillin,doxycycline,tetracycline,vancomycin,and cotrimoxazole.However,only the minimum inhibitory concentration(MIC)of tetracycline exhibited a significant decrease in △sRNA00085.Meanwhile,the decreased biofilm formation and antibiotic resistance of the sRNA00085 mutant were restored in the C△sRNA00085 strain.Furthermore,we investigated the transcription levels of tetracycline resistance-related genes in L.monocytogenes.Down-regu-lated transcription of the tetS gene but no significant difference in transcription of the tetA gene were observed in △sRNA 00085 compared with the standard strain and C△sRNA00085.Moreover,the elimination of sRNA00085 did not affect bacterial growth ability or sensitivity to disinfectants.These findings highlight that sRNA00085 plays an important role in the environ-mental adaptability of L.monocytogenes by affecting bacterial biofilm formation and resistance.