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.

Echinocandin B (ECB) is a key precursor of the antifungal drug anidulafungin. It is a secondary metabolite of Aspergillus nidulans, and its titer in fermentation is significantly affected by the ECB synthesis pathway and cell morphology. In this study, the key genes related to the transcription activation, hydroxylation, and cell morphology during ECB biosynthesis were investigated to increase the fermentation titer of ECB and to change the cell morphology of Aspergillus nidulans to reduce the viscosity of the fermentation broth. The results indicated that after overexpression of ecdB and ecdK, the ECB titer increased by 25.8% and 23.7%, respectively, compared with that of the wild-type strain, reaching (2 030.5±99.2) mg/L and (1 996.4±151.4) mg/L. However, the deletion of fksA associated with cell wall synthesis resulted in damage to the cell wall, affecting strain growth and product synthesis. The engineered strain overexpressing ecdB was fermented in a 50-L bioreactor, in which the ECB titer reached 2 234.5 mg/L. The findings laid a research foundation for the subsequent metabolic engineering of this strain.
Fermentation ; Aspergillus nidulans/genetics* ; Echinocandins/genetics* ; Bioreactors/microbiology* ; Fungal Proteins/biosynthesis* ; Metabolic Engineering

At present, clinical interventions for chronic kidney disease are very limited, and most patients rely on dialysis to sustain their lives for a long time. However, studies on the gut-kidney axis have shown that the gut microbiota is a potentially effective target for correcting or controlling chronic kidney disease. This study showed that berberine, a natural drug with low oral availability, significantly ameliorated chronic kidney disease by altering the composition of the gut microbiota and inhibiting the production of gut-derived uremic toxins, including p-cresol. Furthermore, berberine reduced the content of p-cresol sulfate in plasma mainly by lowering the abundance of g_Clostridium_sensu_stricto_1 and inhibiting the tyrosine-p-cresol pathway of the intestinal flora. Meanwhile, berberine increased the butyric acid producing bacteria and the butyric acid content in feces, while decreased the renal toxic trimethylamine N-oxide. These findings suggest that berberine may be a therapeutic drug with significant potential to ameliorate chronic kidney disease through the gut-kidney axis.

Specnuezhenide(SNZ)is among the main components of Fructus Ligustri Lucidi,which has anti-inflammation,anti-oxidation,and anti-tumor effect.The low bioavailability makes it difficult to explain the mechanism of pharmacological effect of SNZ.In this study,the role of the gut microbiota in the metabolism and pharmacokinetics characteristics of SNZ as well as the pharmacological meaning were explored.SNZ can be rapidly metabolized by the gut microbiome,and two intestinal bacterial metabolites of SNZ,salidroside and tyrosol,were discovered.In addition,carboxylesterase may be the main intestinal bacterial enzyme that mediates its metabolism.At the same time,no metabolism was found in the incubation system of SNZ with liver microsomes or liver homogenate,indicating that the gut microbiota is the main part involved in the metabolism of SNZ.In addition,pharmacokinetic studies showed that salidroside and tyrosol can be detected in plasma in the presence of gut microbiota.Interestingly,tumor development was inhibited in a colorectal tumor mice model administered orally with SNZ,which indicated that SNZ exhibited potential to inhibit tumor growth,and tissue distribution studies showed that salidroside and tyrosol could be distributed in tumor tissues.At the same time,SNZ modulated the structure of gut microbiota and fungal group,which may be the mechanism governing the antitumoral activity of SNZ.Furthermore,SNZ stimulates the secretion of short-chain fatty acids by intestinal flora in vitro and in vivo.In the future,targeting gut microbes and the interaction between natural products and gut microbes could lead to the discovery and development of new drugs.

Objective:To analyze and summarize the epidemiological and molecular characteristics of SARS-CoV-2 Delta variant, a variant of concern (VOC), in Henan Province in 2021 in order to provide a basis for epidemic prevention and control.Methods:According to the feedback of sequencing results from Chinese Center for Disease Control and Prevention, 111 patients infected with SARS-CoV-2 Delta VOC were selected from the Henan imported and local cases in 2021. Basic patient information was obtained from the pandemic website. The differences in age, gender, vaccination history, the number of vaccine doses and different clinical types were analyzed. Moreover, the differences in RT-qPCR results of ORF1 ab gene and N gene Ct values between cases of different genders and symptoms were analyzed statistically. Sequencing results of the nucleotide and S protein mutation sites were analyzed. Results:There was no significant difference in the gender distribution of 111 cases between different age groups (χ 2=2.217, P=0.529). There was also no significant difference in clinical types between patients with different vaccination history (χ 2=12.074, P=0.209). The Ct values of most SARS-CoV-2 nucleic acid-positive specimens were distributed in the lower range and the viral loads were higher. The difference in the Ct value of ORF1 ab gene between different gender groups was not statistically significant (χ 2=1.646, P=0.439), but were significantly different among asymptomatic, mild, normal, and severe cases (χ 2=13.257, P=0.039). There was no significant difference in N gene Ct value among cases of different genders or different symptoms (all P>0.05). The 111 patients in this study were mainly found through close-contact screening and full-staff nucleic acid screening and accounted for 62.2% (69 cases) of the total. The sequencing length coverage was basically greater than 99% (accounting for 90.1%, 100/111); the total number of nucleotide mutation sites was mostly in the range of 46-50 (86.4%, 89/103); the total number of S protein mutation sites was mostly 12 (82.5%, 85/103). The 103 Delta mutants all contained nine mutation sites, which were T19R, R158G, L452R, T478K, D614G, P681R, D950N, E156del and F157del, with a mutation rate of 100%. Conclusions:People were highly susceptible to the SARS-CoV-2 Delta in Henan Province in 2021. High viral load and increase in the ORF1 ab gene load would aggravate the clinical symptoms.

Objective:To analyze the pathogenic bacteria and epidemiological characteristics in children with respiratory tract infection in Tianjin area.Methods:Retrospective case analysis was performed on 2 392 hospitalized children in the wards of respiratory diseases, intensive care unit and special care ward of Tianjin Children′s Hospital from June 2018 to May 2019. Thirteen pathogenic bacteria in deep sputum and bronchoalveolar lavage fluid samples were detected by loop-mediated isothermal amplification. The laboratory data and clinical characteristics of the infected children were analyzed, and the comparison between groups was performed by t test or χ 2 test. Results:Among 2 392 cases, 1 407 were males and 985 females. There was no significant difference in the detection rate between males and females (72.5% (1 020/1 407) vs.74.2% (731/985), χ 2=0.87, P=0.35). A total of 1 751 strains and 12 kinds of positive respiratory pathogens were detected, with a detection rate of 73.2%. Among them, 913 (38.2%) strains were Mycoplasma pneumoniae (MP), 514 (21.5%) were Streptococcus pneumoniae (Sp), 381 (15.9%) were Methicillin-resistant Staphylococcus aureus (MRSA) and 279 (11.7%) were Hemophilus influenzae (Hi). There was significant difference in the detection rate of pathogens among different age groups (χ2=83.67, P<0.01). The positive rate of alveolar lavage fluid group was higher than that of deep sputum fluid group [81.6% (614/752) vs. 69.3% (1 137/1 640), χ 2=39.89, P<0.01]. The length of hospital stay of children infected with different pathogens was significantly different (all P<0.01). There was significant difference in duration of fever among children infected with different pathogens (χ2=228.69,103.56, 3.96, 27.38,24.50,41.66, all P<0.05). There were 63 (7.7%) cases of atelectasis, 260 (31.9%) cases of pleurisy and 120 (14.7%) cases of pleural effusion in MP children. Children with Sma were most likely to involve the heart system (2/9), and children with Eco infection had a higher incidence of complications such as those of blood (3/19), urinary (2/19), digestive systems(4/19), systemic inflammatory response syndrome and sepsis (1/19). Conclusions:The main bacterial pathogens of respiratory tract infection in children in Tianjin were MP, Sp, MRSA and Hi. It is suggested that clinicians should not only pay attention to the respiratory symptoms of children, but also pay attention to the complications caused by bacterial pathogen infection, so as to prevent the deterioration of the disease and improve the prognosis.

Objective To investigate the efficacy of calf self weight traction reduction combined with locking plate fixation for the treatment of intertrochanteric fractures in the elderly.Methods A retrospective case series study was conducted on the clinical records of 174 elderly patients with the modified Evans Ⅰ-Ⅲ types of fresh intertrochanteric fractures treated with locking plate from January 2012 to December 2015.According to treatment method,the patients were assigned to traction bed reduction with locking plate fixation (Group A,62 patients) and calf self weight traction reduction with locking plate fixation (Group B,112 patients).Group A comprised 32 males and 30 females,with age range of 65-91 years [(72.47 ± 6.35) years].Group B comprised 68 males and 44 females,with age range of 65-95 years [(73.23 ± 6.05) years].The time of reduction,operation time,incision length,intraoperative blood loss,frequency of fluoroscopy,postoperative drainage volume,hospital stay,postoperative weightbearing standing time or walking time (ambulation time),surgical complications,and fracture healing were recorded.Harris and modified Barthel index score in Chinese (MBI-C) were used to evaluate the functional recovery of hip joint.Results All patients were followed up for 5-61 months (mean,15 months),and noted with fracture healing.The time of reduction in Group A was (13.27 ± 3.03) minutes,longer than that in Group B (0 minute) (P ＜0.05).The operation time in Group A was (63.63 ± 13.90)minutes,longer than that in Group B [(59.62 ± 8.38) minutes] (P ＜ 0.05).Fluoroscopy in Group A was (5.35 ± 2.36) times,more than (4.28 ± 3.11) times in Group B (P ＜ 0.05).There were no significant differences in the incision length,intraoperative blood loss,postoperative drainage volume,ambulation time,fracture healing time,Harris score,and MBI-C index between the two groups (P ＞0.05).There were no significant differences in the postoperative complications such as deep venous thrombosis,pulmonary infection,incisional infection,urinary tract infection,delirium,bed sores,cardiac insufficiency,electrolyte disturbance,and postoperative plate rupture between the two groups (P＞0.05).The incidence of deep vein thrombosis was 9.7％ (6/62) in Group A,and 4.5％ (5/112) in Group B (P ＞0.05).No screw fracture,nail and plate combination failure,bone nonunion,or screw cut out of the femoral head were observed in both groups.Conclusions For the modified Evans Ⅰ-Ⅲ types of intertrochanteric fractures,both traction bed reduction and calf weight reduction with locking plate have equivalent efficacy.However,the latter method has advantages of shorter reduction and operation time and less intraoperative X-ray exposure,and hence is worthy of clinical application.

Objective To systematically evaluate the postoperative complications following open reduction and internal fixation combined with vascularized bone flap graft versus only reduction and internal fixation for femoral neck fractures.Methods CNKI,Wan Fang Chinese database,Pubmed,EMBASE and Google Scholar English database were searched for the randomized controlled trials from January 1,2000 through October 31,2017 which compared open reduction and internal fixation combined with vascularized bone flap graft (combined surgery group) with only reduction and internal fixation (simple surgery group) for femoral neck fractures.The data concerning postoperative nonunion and avascular necrosis of the femoral head were extracted.The 2 surgical treatments of the patients with femoral neck fracture were compared in terms of the 2 complications.Statistical analyses were conducted using software Stata 12 by relative risk (RR) and corresponding 95％ confidence intervals (95％ CI).Results According to our inclusion and exclusion criteria,a total of 23 studies were included,involving 2,162 cases (1,048 cases receiving combined surgery and 1,114 cases simple surgery).The Meta analyses showed that the fracture nonunion rate for the combined surgery group was significantly lower than that for the simple surgery group [RR =0.27,95％ CI(0.19,0.38),P ＜ 0.001] and the rate of avascular necrosis was also significantly lower for the former than for the latter [RR =0.31,95 ％ CI(0.24,0.42),P ＜ 0.001].Conclusion In the treatment of femoral neck fractures,open reduction and internal fixation combined with vascularied bone graft may lead to lower rates of nonunion and avascular necrosis of the femoral head than simple open reduction and internal fixation.

Objective To study the clinical effect of drug intervention on the treatment of peptic ulcer with blood clots in the Department of internal medicine.Methods From 62 cases of peptic ulcer adherent blood clot were randomly divided into study group and control group according to the random number table,31 cases in each group,in each group.The control group was treated with esomeprazole infusion and subsequent oral treatment.The study group was given endoscopic hemostasis and subsequent oral esomeprazole treatment.Compare the two groups of curative effect,treatment profile and treatment before and after the study of the changes in the situation.Results The total effective rate of the study group was 90.32％,which was significantly better than that of the control group(P<0.05),which was significantly better than that of the control group 70.97％.Research group of rebleeding rate and transfer rate of surgery was significantly lower than that of control group(P<0.05),the study group,the time of hemostasis,the time of hospitalization significantly faster than that of the control group(P<0.05),study group medical expenses are significantly less than the control group(P<0.05).The two groups before treatment Blatchford score,Rockall score,SF-36 score no significant difference,after treatment in the two groups of the three scores were compared with those before treatment significantly optimized(P<0.05)study group the score optimization was significantly better than the control group(P<0.05).Conclusion Peptic ulcer adhesion blood clot give endoscopic therapy can greatly enhance the efficacy,reduce bleeding and transfer the risk of surgery,more effectively improve the acute upper digestive tract bleeding symptoms and signs,improve the life quality of the patients.

Objective To study the imaging characteristics of the ligaments in craniocervical junction (CCJ), and to optimize the examination methods and scanning sequences of the ligaments in this region. Methods Two groups of 51 healthy volunteers in each were selected to undergo CT and MRI examination respectively. The CT and MRI features of the ligaments in CCJ were assessed. Two senior imaging doctors compared the results of showing the ligaments in CCJ by several MRI sequences, including T1 WI ,T2 WI, proton density weighted imaging (PDWI), T2 * WI and short time inversion recovery (STIR) ,and proton density fat saturate (PDFSAT). Standard normal rank transformation was done according to the primary data,and then analysis of variance of repeated measurement was applied. Results CT and MRI could both demonstrate the ligaments (except the anterior atlantooccipital membrane only seen on MRI) and their adjoins in CCJ, while MRI had more advantages than CT. The display ratio of the anterior atlantooccipital membrane was 100% (51/51) by MRI. The display ratio of the apical ligament was 29.4%(15/51) by CT and 43.1% (22/51) by MRI. The posterior atlantooccipital membrane-dura complex,tectorial ligament-dura complex, transverse ligament, and alar ligament could be demonstrated clearly by CT and MRI, the display ratio was 100% respectively (51/51). The results of PDWi scored by two doctors were both 5.0, there were no significant differences between them (F = 0.000, P > 0.05), which were significantly higher than T, WI (M = 3.0), T2Wi (M = 3.0), T2 * WI (M = 1.0), STIR (M = 1.0), and PDFSAT(M = 3.0)(P < 0.01). Conclusion MRI was superior to CT in demonstrating the ligaments in CCJ. PDWI was the optimal MRI sequence. Imaging research of normal ligamentous structures in CCJ could provide valuable diagnostic and therapeutic information for evaluating the ligamentous diseases.