In recent decades, the prevalence of hyperuricemia and gout has increased dramatically due to lifestyle changes. The drugs currently recommended for hyperuricemia are associated with adverse reactions that limit their clinical use. In this study, we report that berberine (BBR) is an effective drug candidate for the treatment of hyperuricemia, with its mechanism potentially involving the modulation of gut microbiota and its metabolite, succinic acid. BBR has demonstrated good therapeutic effects in both acute and chronic animal models of hyperuricemia. In a clinical trial, oral administration of BBR for 6 months reduced blood uric acid levels in 22 participants by modulating the gut microbiota, which led to an increase in the abundance of Bacteroides and a decrease in Clostridium sensu stricto_1. Furthermore, Bacteroides fragilis was transplanted into ICR mice, and the results showed that Bacteroides fragilis exerted a therapeutic effect on uric acid similar to that of BBR. Notably, succinic acid, a metabolite of Bacteroides, significantly reduced uric acid levels. Subsequent cell and animal experiments revealed that the intestinal metabolite, succinic acid, regulated the upstream uric acid synthesis pathway in the liver by inhibiting adenosine monophosphate deaminase 2 (AMPD2), an enzyme responsible for converting adenosine monophosphate (AMP) to inosine monophosphate (IMP). This inhibition resulted in a decrease in IMP levels and an increase in phosphate levels. The reduction in IMP led to a decreased downstream production of hypoxanthine, xanthine, and uric acid. BBR also demonstrated excellent renoprotective effects, improving nephropathy associated with hyperuricemia. In summary, BBR has the potential to be an effective treatment for hyperuricemia through the gut-liver axis.

Genetic risk factors have been shown to contribute to the development of sexual dysfunction. However, the role of methylenetetrahydrofolate reductase (MTHFR) gene variants in the risk of erectile dysfunction (ED) remains unclear. In this study, we recruited 1254 participants who underwent ED assessed by the International Index of Erectile Function-5. The MTHFR c.677C>T variant was also measured by fluorescence polymerase chain reaction (PCR). No significant difference in the genotypic frequency of the MTHFR C677T polymorphism (CC, CT, and TT) was observed between men from the ED and non-ED groups. In addition, on binary logistic regression analysis, both crude and adjusted models showed that the risk of ED was not significantly associated with the C677T polymorphism. Interestingly, a significantly higher frequency of the 677TT polymorphism was found in severe and moderate ED (P = 0.02). The positive correlation between the MTHFR 677TT polymorphism and severe ED was confirmed by logistic regression analysis, even after adjusting for potential confounders (odds ratio [OR] = 2.46, 95% confidence interval [CI]: 1.15-5.50, P = 0.02). These findings suggest a positive correlation between the MTHFR 677TT polymorphism and the risk of severe ED. Identification of MTHFR gene polymorphisms may provide complementary information for ED patients during routine clinical diagnosis.

OBJECTIVE: To observe the occurrence time of neuralgia and the expression of purinergic ligand-gated ion channel 7 receptor (P2X7R) in the dorsal horn of the spinal cord after intraperitoneal injection of streptozotocin (STZ) in diabetic rats, and to explore the effect of electroacupuncture (EA) and pretreatment of EA on the heat pain threshold and expression of P2X7R in the spinal dorsal horn in rats with diabetic neuropathic pain (DNP), and to explore the possible mechanism of EA for DNP. METHODS: PartⅠ: Thirty male SD rats were randomly selected from 64 male SD rats as the control group; the remaining rats were given intraperitoneal injection of STZ (10 mg/mL) at a dose of 65 mg/kg to establish the diabetes model, and 30 rats were successfully modeled as the model group. The control group and the model group were divided into three subgroups respectively at 7, 14 and 21 days, with 10 rats in each subgroup. Body mass, fasting blood glucose (FBG) and thermal pain threshold were recorded at 7, 14 and 21 days after injection; the expression of P2X7R in spinal dorsal horn was detected by Western blot. PartⅡ: Eight SD rats were randomly selected from 35 male SD rats as the blank group, and the remaining 27 rats were given intraperitoneal injection of STZ (10 mg/mL) at a dose of 65 mg/kg to establish the diabetes model. The 24 rats with successful diabetes model were randomly divided into a DNP group, an EA group and a pre-EA group, 8 rats in each group. Fifteen to 21 days after STZ injection, the EA group received EA at "Zusanli" (ST 36) and "Kunlun" (BL 60), continuous wave, frequency of 2 Hz, 30 min each time, once a day; the intervention method in the pre-EA group was the same as that in the EA group. The intervention time was 8 to 14 days after STZ injection. The body mass, FBG and thermal pain threshold were recorded before STZ injection and 7, 14 and 21 days after STZ injection; the expression of P2X7R in spinal dorsal horn was detected by Western blot 21 days after injection. RESULTS: PartⅠ: Compared with the control group, in the model group, the body mass was decreased and FBG was increased 7, 14 and 21 days after STZ injection (P<0.01), and the thermal pain threshold was decreased 14 and 21 days after STZ injection (P<0.05), and the expression of P2X7R in spinal dorsal horn was increased 7, 14 and 21 days after STZ injection (P<0.05, P<0.01). PartⅡ: Compared with the blank group, in the DNP group, the body mass was decreased and fasting blood glucose were increased 7, 14 and 21 days after STZ injection (P<0.01). Compared with the DNP group, in the pre-EA group, the heat pain threshold was increased 14 and 21 days after STZ injection (P<0.05), while in the EA group, the heat pain threshold was increased 21 days after STZ injection (P<0.01), and the expression of P2X7R in the dorsal horn in the EA group and the pre-EA group was decreased (P<0.01). CONCLUSION The diabetic neuropathic pain is observed 14 days after STZ injection. EA could not only treat but also prevent the occurrence of DNP, and its mechanism may be related to down-regulation of P2X7R expression in the dorsal horn of the spinal cord.
Animals ; Diabetes Mellitus, Experimental/therapy* ; Electroacupuncture ; Male ; Neuralgia/therapy* ; Rats ; Rats, Sprague-Dawley ; Spinal Cord ; Spinal Cord Dorsal Horn

In this study, we employed Q Exactive to determine the main differential metabolites of Magnoliae Officinalis Cortex du-ring the "sweating" process. Further, we quantified the color parameters and determined the activities of polyphenol oxidase(PPO), peroxidase(POD), and tyrosinase of Magnoliae Officinalis Cortex during the "sweating" process. Gray correlation analysis was performed for the color, chemical composition, and enzyme activity to reveal the effect of enzymatic reaction on the color of Magnoliae Officinalis Cortex during the "sweating" process. Magnoliae Officinalis Cortex sweating in different manners showed similar metabolite changes. The primary metabolites that changed significantly included amino acids, nucleotides, and sugars, and the secondary metabolites with significant changes were phenols and phenylpropanoids. Despite the different sweating methods, eleven compounds were commonly up-regulated, including L-glutamic acid, acetylarginine, hypoxanthine, and xanthine; six compounds were commonly down-re-gulated, including L-arginine, L-aspartic acid, and phenylalanine. The brightness value(L~*), red-green value(a~*), and yellow-blue value(b~*) of Magnoliae Officinalis Cortex kept decreasing during the "sweating" process. The changes in the activities of PPO and POD during sweating were consistent with those in the color parameter values. The gray correlation analysis demonstrated that the main differential metabolites such as amino acids and phenols were closely related to the color parameters L~*, a~* and b~*; POD was correlated with amino acids and phenols; PPO had strong correlation with phenols. The results indicated that the color change of Magnoliae Officinalis Cortex during "sweating" was closely related to the reactions of enzymes dominated by PPO and POD. The study analyzed the correlations among the main differential metabolites, color parameters, and enzyme activities of Magnoliae Officinalis Cortex in the "sweating" process. It reveals the common law of material changes and ascertains the relationship between color changes and enzymatic reactions of Magnoliae Officinalis Cortex during "sweating". Therefore, this study provides a reference for studying the "sweating" mechanism of Magnoliae Officinalis Cortex and is of great significance to guarantee the quality of Magnoliae Officinalis Cortex.
Magnolia/chemistry* ; Quality Control ; Sweating

BACKGROUND: It has been a global trend that increasing complications related to pelvic floor surgeries have been reported over time. The current study aimed to outline the development of Chinese pelvic floor surgeries related to pelvic organ prolapse (POP) over the past 14 years and investigate the potential influence of enhanced monitoring conducted by the Chinese Association of Urogynecology since 2011. METHODS: A total of 44,594 women with POP who underwent pelvic floor surgeries between October 1, 2004 and September 30, 2018 were included from 22 tertiary academic medical centers. The data were reported voluntarily and obtained from a database. We compared the proportion of each procedure in the 7 years before and 7 years after September 30, 2011. The data were analyzed by performing Z test (one-sided). RESULTS: The number of different procedures during October 1, 2011-September 30, 2018 was more than twice that during October 1, 2004-September 30, 2011. Regarding pelvic floor surgeries related to POP, the rate of synthetic mesh procedures increased from 38.1% (5298/13,906) during October 1, 2004-September 30, 2011 to 46.0% (14,107/30,688) during October 1, 2011-September 30, 2018, whereas the rate of non-mesh procedures decreased from 61.9% (8608/13,906) to 54.0% (16,581/30,688) (Z = 15.53, P < 0.001). Regarding synthetic mesh surgeries related to POP, the rates of transvaginal placement of surgical mesh (TVM) procedures decreased from 94.1% (4983/5298) to 82.2% (11,603/14,107) (Z = 20.79, P < 0.001), but the rate of laparoscopic sacrocolpopexy (LSC) procedures increased from 5.9% (315/5298) to 17.8% (2504/14,107). CONCLUSIONS: The rate of synthetic mesh procedures increased while that of non-mesh procedures decreased significantly. The rate of TVM procedures decreased while the rate of LSC procedures increased significantly. TRIAL REGISTRATION NUMBER NCT03620565, https://register.clinicaltrials.gov.
China ; Female ; Gynecologic Surgical Procedures/adverse effects* ; Humans ; Pelvic Floor/surgery* ; Pelvic Organ Prolapse/surgery* ; Surgical Mesh/adverse effects* ; Treatment Outcome ; Vagina

Background:The Food and Drug Administration recently announced that the use of morcellation may cause fibroids or pelvic dissemination and metastasis of uterine sarcoma;therefore,the use of morcellation is limited in the USA.A large sample study is necessary to assess the proportion of uterine malignant tumors found in patients with laparoscopic myomectomy.Methods:A national multicenter study was performed in China.From 2002 to 2014,33,723 cases were retrospectively selected.We calculated the prevalence and recorded the clinical characteristics of the patients with malignancy after morcellation application.A total of 62 cases were finally pathologically confirmed as malignant postoperatively.Additionally,the medical records of the 62 patients were analyzed in details.Results:The proportion of postoperative malignancy after morcellation application was 0.18％ (62/33,723) for patients who underwent laparoscopic myomectomy.Nearly 62.9％ (39/62) of patients had demonstrated blood flow signals in the uterine fibroids before surgery.And,23 (37.1％) patients showed rapid growth at the final preoperative ultrasound.With respect to the pathological types,38 (61.3％) patients had detectable endometrial stromal sarcoma,13 (21.0％) had detectable uterine leiomyosarcoma,only 3 (3.2％) had detectable carcinosarcoma,and 5 (8.1％) patients with leiomyoma had an undetermined malignant potential.Conclusions:The proportion of malignancy is low after using morcellation in patients who undergo laparoscopic myomectomy.Patients with fast-growing uterine fibroids and abnormal ultrasonic tumor blood flow should be considered for malignant potential,and morcellation should be avoided.

BACKGROUND: Acute liver failure (ALF) caused by viral and non-viral hepatitis is often accompanied with severe metabolic disorders, the accumulation of toxic substances and continuous release and accumulation of a large number of endogenous toxins and inflammatory mediators. The present study aimed to investigate the effects of various combined non-biological artificial liver treatments for patients with acute liver failure (ALF) complicated by multiple organ dysfunction syndrome (MODS). METHODS: Thirty-one patients with mid- or late-stage liver failure complicated by MODS (score 4) were randomly divided into three treatment groups: plasmapheresis (PE) combined with hemoperfusion (HP) and continuous venovenous hemodiafiltration (CVVHDF), PE+CVVHDF, and HP+CVVHDF, respectively. Heart rate (HR) before and after treatment, mean arterial pressure (MAP), respiratory index (PaO2/FiO2), hepatic function, platelet count, and blood coagulation were determined. RESULTS: Signifi cant improvement was observed in HR, MAP, PaO2/FiO2, total bilirubin (TBIL) and alanine aminotransferase (ALT) levels after treatment (P<0.05). TBIL and ALT decreased more signifi cantly after treatment in the PE+CVVHDF and PE+HP+CVVHDF groups (P<0.01). Prothrombin time (PT) and albumin were signifi cantly improved only in the PE+CVVHDF and PE+HP+CVVHDF groups (P<0.05). TBIL decreased more significantly in the PE+HP+CVVHDF group than in the HP+CVVHDF and PE+CVVHDF groups (P<0.05). The survival rate of the patients was 58.1％ (18/31), viral survival rate 36.4％ (4/11), and non-viral survival rate 70％ (14/20). CONCLUSION: Liver function was relatively improved after treatment, but PE+HP+CVVHDF was more efficient for the removal of toxic metabolites, especially bilirubin. The survival rate was significantly higher in the patients with non-viral liver failure than in those with viral liver failure.

In this study,the current status for breast diseases in a region with high-incidence of cervical cancer were epidemiologically investigated.From March to August,2009,17618 women,from Wufeng area of Hubei province,China,were recruited to screen breast diseases by using breast infrared diagnostic apparatus.Other diagnostic methods,such as B-mode ultrasound,X-ray mammography,needle biopsy and pathological examination were,if necessary,used to further confirm the diagnosis.The screening showed that 5990 of 17618 cases (34.00％) had breast diseases,5843 (33.16％) had mammary gland hyperplasia,48 (0.27％) had breast fibroadenoma,ll (0.06％) had breast carcinoma,and 88 (0.50％) had other breast diseases.The peak morbidity of breast cancer was found in the women aged 50-0 ages.The morbidity of breast cancer was significantly increased in women elder than or equal to 50 years old (n=8,0.157％) in comparison with that in the subjects younger than 50 years old (n=3,0.024％) (u=2.327,P＜0.05).It was shown that the occurrence of breast diseases was concentrated in women aged 20-40 years,while the total morbidity reached its peak at the age of 30 years and then decreased sharply after age of 40.Compared with the patients elder than or equal to 40 years old (n=3289,27.46％),the morbidity rate of breast diseases was significantly increased in women less than 40 years old (2648 cases,47.18％; P＜0.001).However,there was no significant difference in the morbidity of breast diseases between the age group of 20-29 years and that of 30-39 years (P=0.453),and both of them were high.There was no significant association between the morbidity of breast diseases and cervical cancer.Since the morbidity of breast diseases was higher among young women,more attention should be paid to the screening of breast diseases among young women for early diagnosis.

Objective To explore effects of kurarinol combined with Diammonium Glycyrrhizinate on specific cellular immunity of patients with chronic hepatitis B ( CHB ).Methods Sixty-three CHB patients were randomly divided into two groups,32 cases in group of kurarinol combined with Diammonium Glycyrrhizinate group (combined therapy group )were treated with 600 mg kurarinol glucose injection intravenously,once a day for one month,then 200 mg kurarinol capsule was used orally,three times a day for two months.150 mg Diammonium Glycyrrhizinate for Injection was added to 250 ml 10％ glucose injection for intravenous drip,once a day for one month,then 150 mg Diammonium Glycyrrhizinate capsule was used orally,three times a day for two months;31 case in kurarinol group( single drug group)only used kurarinol,methods and dosage were the same as those of treatment group.HBV specific CTL,T cell subgroups,change of Th1 and Th2 leveI,HBV-DNA and HBeAg negative rate of the two groups were compared.Results Three months after treatment,HBV specific CTL,CD4 + and Th1 of combined therapy group were higher than those before treatment,and higher than those of single drug group after treatment ( P ＜ 0.01 ).Conclusion HBV-DNA and HBeAg negative rate between the two groups had no statistic significance ( P ＞ 0.05 ).Conclusion Kurarinol combined with Diammonium Glycyrrhizinate can further increase HBV specific CTL,CD4 + and Th1 level of CHB patients.

Objective To modify the methods of operation and establishment of cerebral ischemia rat models made by thread occlusion. Method We randomly divided 120 male SD rats into a common group (n = 50), an improvement group (n = 60) and a sham-operated group (n - 10). Rats in the common and improvement groups were made into models using the common and improvement methods separately. All models were evaluated on the basis of physical sign indices and 2,3,5-triphenyltetrazolium chloride (TTC) staining. The TTC staining results were taken as gold standards. Then, we compared the achievement ratios of the two groups, and computed the sensitivity and specificity of every physical sign index based on these standards. The χ~2 or correction χ~2 test was used to compare the ratios. Results (1) The achievement ratio in the improvement group was significantly higher than that in the common group (71.67% vs. 52.00%, P = 0.034). (2) The sensitivity of evaluation for both common and improvement methods was 98.55%. However, the specificity of evaluation for the improvement method was significantly higher than that for the common method (100.00% vs. 40.00%, P =0.000). Conclusions The establishment achievement ratio and evaluation correctness of models are obviously elevated by modification of the operation and establishment methods.