This study explores the therapeutic differences and mechanisms of salt-processed Phellodendri Chinensis Cortex in improving insulin resistance(IR) based on network pharmacology, molecular docking, and cellular experiments. The components and intersection targets of Phellodendri Chinensis Cortex in improving IR were collected from databases, and a "drug-component-target-disease" network and protein-protein interaction(PPI) network were constructed to screen core components and targets. A total of 29 active components and 240 intersection targets were identified, of which 13 were core targets. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were used to identify key signaling pathways, and molecular docking was performed to validate the binding activity between core components and targets. An IR model in HepG2 cells was induced using insulin combined with high glucose, and the effects of Phellodendri Chinensis Cortex before and after salt-processing on cell glucose consumption were evaluated. The expression of proteins related to the mitogen-activated protein kinase(MAPK) and phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT) signaling pathways was detected by Western blot. The cellular experimental results showed that, compared with the model group, glucose consumption in the drug-treated groups was significantly increased(P<0.01), the phosphorylation level of extracellular regulated protein kinase(ERK) was decreased(P<0.05), the phosphorylation levels of PI3K and AKT were increased, and the expression of glucose transporter 4(GLUT4) was also upregulated(P<0.05). Furthermore, the effect of salt-processed Phellodendri Chinensis Cortex was better than that of raw Phellodendri Chinensis Cortex. The study demonstrates that Phellodendri Chinensis Cortex, both before and after salt-processing, improves IR by regulating the expression of related proteins in the MAPK and PI3K-AKT signaling pathways, with enhanced effects after salt-processing.
Humans ; Network Pharmacology ; Phellodendron/chemistry* ; Insulin Resistance ; Drugs, Chinese Herbal/chemistry* ; Hep G2 Cells ; Signal Transduction/drug effects* ; Molecular Docking Simulation ; Protein Interaction Maps/drug effects* ; Proto-Oncogene Proteins c-akt/genetics* ; Phosphatidylinositol 3-Kinases/genetics* ; Glucose/metabolism*

Objective： The aim of this study is to explore the predictive value of biparametric magnetic resonance imaging(bpMRI)for pelvic lymph node metastasis in prostate cancer patients with PSA≤20 μg/L and establish a nomogram. Methods： The imaging data and clinical data of 363 patients undergoing radical prostatectomy and pelvic lymph node dissection in the First Affiliated Hospital of Nanjing Medical University from July 2018 to December 2023 were retrospectively analyzed. Univariate analysis and multivariate logistic regression were used to screen independent risk factors for pelvic lymph node metastasis in prostate cancer, and a nomogram of the clinical prediction model was established. Calibration curves were drawn to evaluate the accuracy of the model. Results： Multivariate logistic regression analysis showed extrocapusular extension (OR=8.08,95%CI=2.62－24.97, P<0.01), enlargement of pelvic lymph nodes (OR=4.45,95%CI=1.16－17.11,P=0.030), and biopsy ISUP grade(OR=1.97,95%CI=1.12－3.46, P=0.018)were independent risk factors for pelvic lymph node metastasis. The C-index of the prediction model was 0.834, which indicated that the model had a good prediction ability. The actual value of the model calibration curve and the prediction probability of the model fitted well, indicating that the model had a good accuracy. Further analysis of DCA curve showed that the model had good clinical application value when the risk threshold ranged from 0.05 to 0.70.Conclusion： For prostate cancer patients with PSA≤20 μg/L, bpMRI has a good predictive value for the pelvic lymph node metastasis of prostate cancer with extrocapusular extension, enlargement of pelvic lymph nodes and ISUP grade≥4.
Humans ; Male ; Prostatic Neoplasms/diagnostic imaging* ; Lymphatic Metastasis ; Retrospective Studies ; Nomograms ; Prostate-Specific Antigen/blood* ; Lymph Nodes/pathology* ; Pelvis ; Predictive Value of Tests ; Prostatectomy ; Lymph Node Excision ; Risk Factors ; Magnetic Resonance Imaging ; Logistic Models ; Middle Aged ; Aged

OBJECTIVE: This study aimed to investigate possible serum 25-hydroxyvitamin D [25(OH)D] cutoffs for the associations between 25(OH)D and Bone turnover markers (BTMs), and how GC gene variation influences such cutoffs in Chinese women of childbearing age. METHODS: In total, 1,505 non-pregnant or non-lactating women (18-45 years) were recruited from the 2015 Chinese Adult Chronic Disease and Nutrition Surveillance. Serum 25(OH)D, osteocalcin (OC), procollagen type 1 N-terminal propeptide (P1NP), β-CrossLaps of type 1 collagen containing cross-linked C-telopeptide (β-CTX), and single nucleotide polymorphisms were determined. Locally weighted regression and smoothing scatterplot and segmented regression were performed to estimate the 25(OH)D thresholds. RESULTS: The median serum 25(OH)D was 16.63 (11.96-22.55) ng/mL and the prevalence of low serum 25(OH)D (< 12 ng/mL) was 25.2%. Women with the lowest 25(OH)D had the highest β-CTX. After adjustment for the confounders, 25(OH)D cutoffs for OC [14.04 (12.84-15.23) ng/mL], β-CTX [13.94 (12.49-15.39) ng/mL], and P1NP [13.87 (12.37-15.37) ng/mL] in the whole population, cutoffs for OC [12.30 (10.68-13.91) ng/mL], β-CTX [12.23 (10.22-14.23) ng/mL], and P1NP [11.85 (10.40-13.31) ng/mL] in women with the GC rs2282679 G allele, and cutoffs for OC [12.75 (11.81-13.68) ng/mL], β-CTX [13.05 (11.78-14.32) ng/mL], and P1NP [12.81 (11.57-14.06) ng/mL] in women with the GC rs2282679 T allele, were observed. Below these cutoffs, BTMs were negatively associated with 25(OH)D, while above these cutoffs, BTMs plateaued. CONCLUSION In Chinese women of childbearing age, there were thresholds effect of serum 25(OH)D concentrations on BTMs. The results indicated that serum 25(OH)D concentrations < 13.87 ng/mL in this population had adverse influences on maintaining bone remodeling. BTMs were suppressed at a relatively lower serum 25(OH)D in women with the GC rs2282679 G allele compared with those with the T allele.
Humans ; Female ; Vitamin D/blood* ; Adult ; Middle Aged ; Polymorphism, Single Nucleotide ; Adolescent ; Young Adult ; China ; Biomarkers/blood* ; Bone Remodeling/genetics* ; Vitamin D-Binding Protein/genetics* ; Procollagen/blood* ; Osteocalcin/blood* ; Peptide Fragments/blood* ; East Asian People

Objective: To assess the impact of long-term antiretroviral therapy (ART) on human immunodeficiency virus (HIV) blood screening outcomes in post-exposure prophylaxis (PEP) failure cases through a longitudinal analysis of blood screening results over a 7-year period in a patient with HIV PEP failure. Methods: This study conducted 13 follow-up assessments for a high-risk individual who initiated ART shortly after exposure. The effectiveness of various blood screening methods, including immunological assays and nucleic acid testing (NAT), was analyzed. Blood samples were also tested with HIV RNA quantification testing, Western blot (WB) confirmation testing, chemiluminescence immunoassay (CLIA), and HIV rapid tests utilizing gold and selenium labels. A comprehensive analysis was performed to evaluate the changes in diagnostic capabilities of different testing methods for HIV biomarkers over an extended period following PEP failure. Results: The patient had two high-risk exposures: one day before ART initiation (BA1) and seven days preceding treatment (BA7). On the first day after the ART treatment (AA1), the HIV RNA concentration (viral load) was 9.07×10 copies/mL; by day five (AA5), the viral load decreased to 1.04×10 copies/mL. At day eleven (AA11), NAT and ELISA tests were both positive, with the WB result remaining indeterminate (gp160+). At day 48 (AA48), the S/CO value of the fourth generation ELISA reagent was 1.07, while results from a 6-sample pool and quantitative NAT were negative. However, a single sample NAT returned a positive result and WB tests indicated positivity for p17, p24, and gp160. At AA74, the quantitative NAT rebounded to 2.83×10 copies/mL, with positive NAT results for single and 6-sample pool NAT tests. The S/CO values of the imported and domestic ELISA reagents were 3.39 and 23.44, respectively. At AA201, 6-sample pool and quantitative NAT were negative again, while single sample NAT remained positive. From AA319 to AA2221, all NAT results have remained consistently below the minimum detection limit. At AA2221, S/CO values of the imported and domestic ELISA reagents were 3.47 and 23.44, respectively. Conclusion: The findings indicate that patients experiencing PEP failure after high-risk HIV exposure are at a higher risk of being missed by mixed-sample NAT pools and individual serological tests. Nonetheless, anti-HIV antibody levels are sustained at elevated values for an extended duration, underscoring antibody testing as an effective measure for blood screening.

Objective To observe the effect of modified Banxia Xiexin Decoction on inflammatory factors in patients with polycystic ovary syndrome(PCOS)of stomach heat and spleen deficiency type through the regulatory mechanism of intestinal flora.Methods A total of 86 patients with PCOS of stomach heat and spleen deficiency type were randomly divided into control group(45 cases)and observation group(41 cases).The control group was treated with conventional western medicine,and the observation group was treated with modified Banxia Xiexin Decoction on the basis of treatment for the control group.One menstrual cycle constituted a course of treatment,and the treatment lasted for three continuous menstrual cycles.The two groups were observed in the changes of traditional Chinese medicine(TCM)syndrome score,endometrial thickness,serum inflammatory factors of tumor necrosis factor α(TNF-α),C-reactive protein(CRP)and interleukin-6(IL-6),sex hormone levels of luteinizing hormone(LH),estradiol(E2),follicle stimulating hormone(FSH)and LH/FSH,as well as the intestinal flora before and after treatment.The clinical efficacy and pregnancy rate of the two groups were compared after treatment.Results(1)After 3 menstrual cycles of treatment,the total effective rate of the observation group was 87.80%(36/41),and that of the control group was 68.89%(31/45).The intergroup comparison(tested by chi-square test)showed that the clinical efficacy of the observation group was significantly superior to that of the control group(P<0.05).(2)After treatment,the scores of TCM syndromes in the two groups were decreased when compared with those before treatment(P<0.05),and the decrease in the observation group was more significant than that in the control group(P<0.01).(3)After treatment,the endometrial thickness in the two groups was increased when compared with that before treatment(P<0.05),and the increase in the observation group was superior to that in the control group(P<0.01).(4)The pregnancy rate of the observation group was 92.68%(38/41),which was significantly higher than 73.33%(33/45)of the control group,and the difference was statistically significant(P<0.05).(5)After treatment,the levels of serum E2,LH and LH/FSH in the two groups were decreased when compared with those before treatment(P<0.05),but there was no significant change in the level of serum FSH before and after treatment(P>0.05).The comparison between the two groups showed that the decrease of serum E2,LH and LH/FSH levels in the observation group was significantly superior to that in the control group(P<0.01).(6)After tieatment,the levels of serum CRP,IL-6,TNF-α in patients of the two groups were decreased compared with those before treatment(P<0.05),and the decrease in the observation group was superior to that in the control group(P<0.01).(7)After treatment,the levels of Bifidobacteria and Lactobacilli in the intestinal flora of the two groups were higher than those before treatment(P<0.05),and the levels of Enterococcus faecalis and Bacteroides were lower than those before treatment(P<0.05),while the levels of Enterobacter did not change significantly before and after treatment(P>0.05).The comparison between the two groups showed that the increase of the levels of Bifidobacteria and Lactobacilli and the decrease of the levels of Enterococcus faecalis and Bacteroides in the observation group were significantly superior to those in the control group(P<0.05 or P<0.01).Conclusion Modified Banxia Xiexin Decoction has a significant clinical effect in the treatment of PCOS of stomach heat and spleen deficiency type.The decoction is effective on improving the clinical symptoms and inflammatory factor levels of patients by regulating intestinal flora.

Background: Genetic defects in the human thyroid-stimulating hormone (TSH) receptor (TSHR) gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype–phenotype relationships for most TSHR variants associated with CH remain unexplored. We aimed to identify TSHR variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between TSHR genotypes and clinical phenotypes. Methods: In total, 367 patients with CH were recruited for TSHR variant screening using whole-exome sequencing. The effects of the variants were evaluated by in-silico programs such as SIFT and polyphen2. Furthermore, these variants were transfected into 293T cells to detect their Gs/cyclic AMP and Gq/11 signaling activity. Results: Among the 367 patients with CH, 17 TSHR variants, including three novel variants, were identified in 45 patients, and 18 patients carried biallelic TSHR variants. In vitro experiments showed that 10 variants were associated with Gs/cyclic AMP and Gq/11 signaling pathway impairment to varying degrees. Patients with TSHR biallelic variants had lower serum TSH levels and higher free triiodothyronine and thyroxine levels at diagnosis than those with DUOX2 biallelic variants. Conclusions We found a high frequency of TSHR variants in Chinese patients with CH (12.3%), and 4.9% of cases were caused by TSHR biallelic variants. Ten variants were identified as loss-of-function variants. The data suggest that the clinical phenotype of CH patients caused by TSHR biallelic variants is relatively mild. Our study expands the TSHR variant spectrum and provides further evidence for the elucidation of the genetic etiology of CH.

We aimed to identify the infectious source of a case of melioidosis,to provide evidence for the prevention and control of melioidosis in Shanxi Province,China.The patient developed repeated fever,fatigue,diarrhea,and other symptoms after being caught in the rain while traveling in Hainan Province.The blood culture was positive,and the bacterial strain was i-dentified as Burkholderia thayensis and sent to the provincial Center for Disease Control and Prevention for further evaluation.MALDI-TOF MS and biochemical identification were used to identify the strain,whole genome sequencing was performed after nucleic acid extraction,MLST type and drug-resistance genes were analyzed,and a phylogenetic tree was constructed.The iso-lated strain was identified as Burkholderia pseudomallei by MALDI-TOF MS and biochemistry,and the MLST type was 366.The whole gene sequencing analysis indicated a close evolutionary relationship with the three isolates in Hainan Province,with high homology.This case of melioidosis was indeed imported from Hainan Province,according to molecular tracing analysis and epidemiological investigation,thus suggesting that medical institutions and disease control departments should strengthen understanding of melioidosis,and improve the diagnosis and treatment ability.

Objective To observe the clinical efficacy of acupuncture combined with acupoint catgut embedding therapy on back-shu and front-mu points and external application on shenque(RN8)point for premature ovarian failure(POF).Methods A total of 62 patients with POF were randomly divided into the observation group and the control group,with 31 patients in each group.The observation group was treated with acupuncture combined with acupoint catgut embedding therapy on back-shu and front-mu points and external application on shenque point,and the control group was treated with hormone replacement therapy.After three months of treatment,the clinical efficacy of the two groups was evaluated,and the changes in the traditional Chinese medicine(TCM)syndrome scores,as well as the ovarian volume,number of antral follicle,and antral follicle diameter of the patients in the two groups before and after treatment were observed.The changes of serum follicle stimulating hormone(FSH),luteinizing hormone(LH)and estradiol(E2)levels before and after treatment were compared between the two groups.Results(1)The total effective rate was 93.55%(29/31)in the observation group and 80.64%(25/31)in the control group.The efficacy of the observation group was significantly superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the serum FSH,LH and E2 levels of patients in the two groups were significantly improved(P＜0.05),and the improvement in the observation group was significantly superior to that in the control group,with statistically significant differences(P＜0.05).(3)After treatment,ovarian volume,number of antral follicle,and antral follicle diameter were significantly improved in the two groups(P＜0.05),and the improvement in the observation group was significantly superior to that in the control group,and the difference was statistically significant(P＜0.05).Conclusion The treatment of POF with acupuncture combined with acupoint catgut embedding therapy on back-shu and front-mu points and external application on shenque point can significantly improve the clinical symptoms of the patients,conducive to the recovery of ovarian function,and significantly improve the sex hormone levels of the patients,with precise clinical efficacy.

Objective To assess the effect of different postoperative body positions on respiratory func-tion of patients undergoing shoulder arthroscopy under general anesthesia with interscalene brachial plex-us block.Methods Seventy patients undergoing arthroscopic repair of the supraspinatus tendon were ran-domly allocated to a supine position group and a group with a 30° head elevation.Patients in both groups were in a horizontal position before anesthesia,and diaphragm movement was measured under B-ultrasound as baseline.Promptly after removal of the endotracheal tube upon arrival at the anesthe-sia recovery room,the supine group was conducted blood gas analysis,and monitored heart rate,res-piration,non-invasive arterial blood pressure and blood oxygen saturation,wearing a mask for oxygen supplementation,while the group with a 30° head elevation was given identical nursing procedures af-ter the bed's head was elevated 30°.Then right after entering the anesthesia recovery room,as well as 5 and 15 minutes after deoxygenation,the oxygen partial pressure(PaO2),carbon dioxide partial pressure(PaCO2)and percutaneous oxygen saturation(SpO2)were recorded and compared between the two groups.Moreover,the diaphragmatic movements during deep breathing before nerve block and pri-or to discharge from the anesthesia recovery room were measured,and such adverse reactions as hypox-emia,labored breathing and glossoptosis were observed.Results Compared with the supine position group,a significant increase in the average PaO2 and SpO2 15 minutes after deoxygenation,diaphrag-matic movement during deep breathing and comfort was observed in the group with a 30° head eleva-tion,but a significant decrease in the incidence of postoperative laboured breathing and glossoptosis.However,no significant differences were found between the two groups in the incidence of hypoxemia and the average PaO2,PaCO2 and SpO2 immediately after entering the anesthesia recovery room and 5 minutes after deoxygenation.Conclusion Elevating the head of the bed by 30° enhances respiratory function in patients undergoing shoulder surgery with general anesthesia intubation and intermuscular groove brachial plexus block,compared to the supine position.Although no significant reduction in hy-poxemia incidence is observed,there is a notable relief of adverse reactions such as laboured breath-ing and glossoptosis,which makes patients feel more comfortable.Therefore,such posture care is wor-thy of application in clinical practice.