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.

As green, sustainable, and environmentally friendly material processing processes using biological cells or enzymes to achieve substance conversion, bioprocesses play an increasingly important role in biomanufacturing. It is difficult to optimize bioprocesses because of the complex relationship at multiple levels and multiple scales. The knowledge of mesoscale behaviors is the key to understanding the dynamics of bioprocesses and to sort out the complex relationships of parameter variations in the spatial-temporal domain. Mesoscale numerical simulation paves a way for understanding these phenomena, and the integration of artificial intelligence (AI) and mesoscale simulation offers new vitality into the optimization of bioprocesses. This article reviews the progress in mesoscale simulation and AI optimization of bioprocesses and discusses the possible development directions, aiming to promote the development of this field.
Artificial Intelligence ; Biotechnology/trends* ; Computer Simulation

Objective To analyze the clinical characteristics of IgG4-related disease (IgG4-RD),guide the selection of therapeutic drugs,and to explore the significance of potential tumor identification for IgG4-RD.Methods A total of 92 patients diagnosed with IgG4-RD and admitted to this hospital from January 1,2017 to December 31,2021were selected as the research subjects by using the Yidu Cloud system.The clinical data conducted the summary analysis. The clinical characteristics of IgG4-RD were summarized.Results The mean age of IgG4-RD was definitely diagnosed in the 92 patients was (58.1±11.3)years old,with 65 male ca-ses (70.7％) and 27 female cases (29.3％).The most commonly affected organ tissues were lymph nodes (37 cases,40.2％),pancreas (33 cases,35.9％) and salivary glands (31 cases,33.7％).In the patients woth the 92 patients,28 cases (30.4％) had involvement of a single organ tissue,while 32 cases (34.8％) had involvement of two or more organs.In the 92 patients,89 cases received steroid therapy,and 71 cases received immunosup-pressive therapy,in which 45 cases (63.4％) used cyclophosphamide.The initial treatment effective rate (72.7％ vs. 55.6％) and one-year non-recurrence rate (38.2％ vs. 20.0％) of the steroid combined immuno-suppressive therapy group were better than those of the single steroid group,but the differences were not sta-tistically significant (P>0.05).The proportion of the patients with tumor comorbidity and IgG4 level>40 g/L (18.2％) was significantly higher than that of the non-tumor comorbidity (1.2％),and the difference was statistically significant (P<0.05).However,there was no statistically significant difference in the proportion of patients with tumor comorbidity compared to the non-tumor comorbidity in other IgG4 level groups (P>0.05).Conclusion IgG4-RD is more common in middle-aged and elderly men,lymph nodes,pancreas and sal-ivary glands are commonly involved,and most patients have the double organs and multiple organs involve-ment. The combination use of hormone and immunosuppressant in treatment is recommended .The IgG4 lev-el>40 g/L in the patients with IgG4-RD may has the suggestive significance for complicating tumor.

As a common clinical disease, fracture is often accompanied by pain, swelling, bleeding as well as other symptoms and has a high disability rate, even threatening life, seriously endangering patients' physical and psychological health and quality of life. Medical practitioners take many strategies for the treatment of fracture healing, including Traditional Chinese Medicine (TCM). In the early stage of fracture healing, the local fracture is often in a state of hypoxia, accompanied by the expression of hypoxia inducible factor-1α (HIF-1α), which is beneficial to wound healing. Through literature mining, we thought that hypoxia, HIF-1α and downstream factors affected the mechanism of fracture healing, as well as dominated this process. Therefore, we reviewed the local characteristics and related signaling pathways involved in the fracture healing process and summarized the intervention of TCM on these mechanisms, in order to inspirit the new strategy for fracture healing, as well as elaborate on the possible principles of TCM in treating fractures based on the HIF molecular mechanism.

Objective To explore the role and efficacy of VEGF and HGF gene adenovirus vector in promoting angiogenesis in ischemic tissue.Methods 84 Kunming mice were randomly divided into sham group,control group,VEGF group,HGF group and VEGF+HGF group,and the left lower limb ischemia model was established.The blood supply of ischemic tissue was observed by rheometer,and the expression levels of VEGF and HGF in each group were detected by Western Blot and ELISA.Immunohistochemical staining was used to detect angiogenesis(CD31,SMA)in ischemic tissues.Safety was assessed by side effects during treatment in mice.Results After the successful modeling,the blood flow velocity of the left lower limb in each group decreased significantly.On the 7th day after operation,the blood flow of the left lower limb in each group was significantly better than that on the 0th day after operation(P<0.05),and the blood flow of the left lower limb in Ad-VEGF-HGF group was significantly better than that in other groups(P<0.05).On the 28th day after operation,the blood flow of the left lower limb in Ad-VEGF-HGF group gradually stabilized,the blood flow in Ad-VEGF-HGF group was significantly better than that in other groups,and both VEGF group and HGF group were significantly better than the control group(P<0.05).On the 7th,14th,and 28th days following surgery,HGF and VEGF protein levels in the Ad-HGF,Ad-VEGF,and Ad-VEGF-HGF groups were substantially greater than those in the control group(P<0.05).The expression level in the Ad-VEGF-HGF group peaked on the 14th day(all P<0.001)and subsequently declined to preoperative levels on the 28th day after operation.Conclusion Ad-VEGF-HGF gene injection can effectively boost VEGF and HGF protein expression and rapidly reach the relative peak level,encour-aging angiogenesis after lower limb ischemia,increasing blood flow,and improving lower limb circulation.

ObjectiveTo carry out an epidemiological analysis on an outbreak of Mycoplasma pneumoniae infection at a welfare institution to provide a theoretical basis for the corresponding prevention and control measures. MethodsUsing the method of field epidemiological investigation， special field treatment was carried out in September 2022. Serum samples from cases and close contacts in the same ward area were collected for detection of nine respiratory tract infection pathogens （Mycoplasma pneumoniae， chlamydia， influenza， human metapneumosis， respiratory syncytial， human boca， parainfluenza type 1‒4 virus， and Middle East respiratory syndrome， severe acute respiratory syndrome coronavirus） by immunofluorescence immunoglobulin M （IgM） antibody test. ResultsA total of 14 Mycoplasma pneumoniae cases were identified， all of whom were residents of the welfare institution. The first case occurred on September 4， while the last case was reported on September 13. The incidence rate of the fifth ward area where the first case reported was 12.82% （10/78）， and it was 3.57% （3/84） in the third ward area and 1.20% （1/83） in the first ward area. There was a significant difference in incidence rates between ward areas （χ²=8.90， P<0.05）， but no significant difference was observed in age distribution and length of hospitalization. Thirty-three samples were collected for detection of nine kinds of IgM antibodies against respiratory pathogens. The results showed that the Mycoplasma pneumoniae IgM antibody was weakly positive in the 14 cases. ConclusionBased on the epidemiological history， clinical symptoms and laboratory tests， it was concluded that it was an outbreak of Mycoplasma pneumoniae infection within the welfare institution. Welfare institutions should continue to control the occurrence and outbreak of infection through effective routine hygiene， ventilation， and disinfection so as to ensure the health and safety of their clients.

Objective:To construct a column-line diagram diagnostic model based on serum and joint fluid inflammatory markers for the diagnosis of periprosthetic joint infections (PJI) after joint arthroplasty and to validate its predictive ability.Methods:The clinical data of 181 patients diagnosed with PJI or aseptic loosening in the Department of Orthopedics of the First Affiliated Hospital of Chongqing Medical University from January 2015 to June 2020 were retrospectively collected as a modeling group. The best indicators for diagnosing PJI were screened by lasso regression, single-factor and multifactor analysis. By comprehensively considering the weights and intrinsic connections of the indicators, a column-line diagram diagnostic model was constructed and used to develop a clinical decision support system (CDSS). Prospectively, the clinical data of patients diagnosed with PJI or aseptic loosening in the Department of Orthopedics of the First Hospital of Chongqing Medical University from July 2020 to December 2022 were collected as a validation group, and the diagnostic performance of the column-line diagram model was externally validated by methods such as receiver operating characteristic curve (ROC).Results:There were 85 cases of PJI in the 181 cases modeling group and 23 cases of PJI in the 49 cases validation group. Among the 27 potential factors analyzed by lasso regression analysis, body mass index (BMI), blood tests including platelet (PLT), absolute lymphocyte value, interferon γ (IFN-γ), ESR, IL-6, C-reactive protein, D-dimer, and joint fluid tests including C-reactive protein, IL-1, IL-4, IL-6, percentage of multinucleated neutrophils (PMN%), and CD64 may be potential indicators for the diagnosis of PJI. Univariate found significant differences between hematologic tests including sedimentation, C-reactive protein, IL-6, D-dimer and joint fluid tests including C-reactive protein, joint fluid CD64 index, C-reactive protein, IL-1, IL-4, IL-6, PMN%( P<0.05). Further multifactorial regression analysis screened serum IL-6, D-dimer, joint fluid CD64 index, C-reactive protein, IL-1, IL-4, IL-6, and percentage of multinucleated neutrophils, and based on that, the column-line graph model and CDSS system were constructed. The area under the ROC in the validation group was 0.978, and the AUC in the internal validation was 0.995; the C-index of the calibration curve was 99.50%, and the C-index of the internal validation was 99.53%, suggesting that the column-line diagram model has a good predictive ability. Conclusions:The column-line diagram for diagnosing PJI based on multiple diagnostic indicators showed good diagnostic performance. The CDSS system constructed by column-line diagrams could assist clinicians in diagnosing PJI and making reasonable strategies in time.

【Objective】 To investigate the expressions of P53 and Ki-67 in prostate cancer (PCa)and to explore their correlation with the clinicopathological characteristics. 【Methods】 The expressions of P53 and Ki-67 in 90 PCa patients were detected with immunohistochemistry. Patients’ age, preoperative prostate-specific antigen (PSA) level, postoperative Gleason score, pathological stage, and invasion of neurovascular cancer embolus of all patients were recorded. The relationship of P53 expression with the above indexes was evaluated. 【Results】 The positive rates of P53 and Ki-67 were 27.8% (25/90) and 46.7% (42/90), respectively. The positive rate of P53 in pT2 and pT3-T4 stage groups were 19.7% (13/66) and 50.0% (12/24) (P=0.005), and the positive rate of Ki-67 were 36.4% (24/66) and 75.0% (18/24) (P=0.001), respectively. The positive rate of Ki-67 in Gleason score ≤6, ≤7 and ≥8 groups were 30.4%, 53.8% and 66.7%, respectively, with statistical difference. Positive expression of P53 was related to Ki-67 expression, but not to patients’ age, preoperative PSA level, postoperative Gleason score and nerve and invasion of neurovascular cancer embolus. 【Conclusion】 P53 expression is related to tumor stage and Ki-67, while Ki-67 expression is associated with tumor stage ang grade.

Objective:To analyze the risk factors and prognosis of endoleak after endovascular aneurysm repair (EVAR) of abdominal aortic aneurysm.Methods:The clinical data of patients with infrarenal abdominal aortic aneurysms treated by endovascular repair at the Department of Vascular Surgery,the First Affiliated Hospital of Guangxi Medical University from Jun 2012 to Nov 2021 were retrospectively analyzed.Results:During the first follow-up CTA after surgery,136 out of 299 patients had endoleak.A total of 186 patients had at least one CTA reexamination after discharge. Statistical analysis showed that excessive neck angulation was an independent risk factor for type Ⅰa endoleak ( t=-6.108, P<0.001), wider common iliac artery diameter (left Z=-2.787, P=0.005, Right Z=-2.381, P=0.017) and iliac aneurysm ( χ2=6.398, P=0.011) were risk factors for type Ⅰb endoleak. The survival time of patients in endoleak group was similar to no endoleak group. Conclusions:Excessive neck angulation is an independent risk factor for type Ⅰa endoleak. Most leaks resolve spontaneously ,the prognosis is fair.

OBJECTIVES: Non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancer, with highmorbidity and mortality rate. Nove drug development for NSCLC is urgently needed.This study aims to investigate the activity of lathyrol derivatives and the mechanism for its inhibitory effect on the growth of NSCLC cells. METHODS: Three lathyrol derivatives were synthesized from lathyrol and their structures were verified by nuclear magnetic resonance. MTT assay was used to detect the effects of the lathyrol derivatives on the proliferation activity of NSCLC cells (A549 and H1299 cells), and the compound with the best activity was selected for subsequent experiments. Colony forming assay, wound-healing assay, and transwell assay were applied to detect in vitro cell proliferation, migration and invasion ability in A549 and H1299 cells, respectively. Quantitative real-time RT-PCR and Western blotting were performed to detect mRNA and protein levels of E-cadherin, N-cadherin, β-catenin, and MMP2 in A549 cells, respectively. RESULTS: Three lathyrol derivatives inhibited the growth of A549 and H1299 cells in a dose-dependent manner, and they showed a weak inhibitory effect on normal cells Beas-2B and 16HBE, indicating that they possessed certain selective toxic effects. Therefore, C-5 benzoylated lathyrol with the best activity was selected as the ideal drug for the subsequent experiments. Compared with the control group, the number and size of cell clusters in the treatment group of A549 and H1299 cells were significantly decreased, the relative mobility were significantly decreased, and the number of invaded cells were significantly decreased (all P<0.05), indicating that the in vitro cell proliferation, migration and invasion ability were decreased. The mRNA levels of integrin α2, integrin β1, MMP2, MMP9, β-catenin, and N-cadherin were decreased, while the expression of E-cadherin was increased (all P<0.05). The protein levels of N-cadherin, β-catenin, MMP2, and integrin αV were decreased, while the expression of E-cadherin was increased (all P<0.05). CONCLUSIONS The lathyrol derivatives synthesized in this study possess good inhibitory activity against NSCLC. Among them, C-5 benzoylated lathyrol significantly inhibits the proliferation, migration, and invasion ability of NSCLC cells in vitro through regulating the process of epithelial-mesenchymal transition.
Cadherins/genetics* ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Epithelial-Mesenchymal Transition ; Humans ; Lung Neoplasms/drug therapy* ; Matrix Metalloproteinase 2/genetics* ; RNA, Messenger ; beta Catenin/genetics*