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.

Objective To analyze the epidemiological characteristics of occupational hand-arm vibration disease (OHAVD) in Guangdong Province from 2006 to 2022. Methods The data of newly reported OHAVD cases and suspected occupational disease cases in Guangdong Province from 2006 to 2022 was collected from the Report Card of Occupational Diseases and Report Card of Suspected Occupational Diseases using Occupational Diseases and Health Hazard Factors Monitoring Information System under China Disease Prevention and Control Information System. Epidemiological characteristics of the newly reported OHAVD cases and related suspected occupational disease reports were analyzed. Results A total of 660 newly reported OHAVD cases were reported in Guangdong Province from 2006 to 2022. The number of cases showed a periodic fluctuating trend over the years. Males accounted for 98.64% of the newly reported OHAVD cases with a median age of 38 years and a median hand-transmitted vibration exposure period of 8.7 years. These cases were predominantly distributed in the Pearl River Delta region, including Zhongshan City, Dongguan City, Guangzhou City, Shenzhen City and Foshan City, accounting for 99.25%. The manufacturing enterprises had 98.79% of the cases, investment enterprises of Hong Kong, Macao and Taiwan merchants of China had 83.18% of the cases, and large- and medium-sized enterprises had 92.73% of the cases. The 660 cases were distributed in 440 enterprises, but there were some characteristics of group outbreaks. There were 20 enterprises (4.55% of the total number of enterprises) had more than three cases involving 219 cases (33.18%). There were five enterprises which had more than 10 cases and the cases number ranged from 12 to 56. Among 382 newly reported OHAVD cases from 2014 to 2022, 44.24% were identified as suspected occupational diseases before diagnosis, of which 59.76% (101/169) were determined by occupational health inspection institutions. Conclusion Newly reported OHAVD cases in Guangdong Province were aggregated in terms of regional distribution, industry, enterprise ownership, and enterprise scale, with a risk of group outbreaks. It is suggested to enhance the OHAVD prevention and control in male workers exposed to hand-transmitted vibrations in the Pearl River Delta's manufacturing enterprises.

A case of IgG4-related hypertrophic pachymeningitis was reported. The patient was an elderly female, with the course of disease more than 8 years. Clinical manifestations included recurrent headache, vision and hearing loss, exophthalmos and thyroid dysfunction. Finally, she was diagnosed as IgG4-related disease and IgG4-related hypertrophic pachymeningitis by PET-CT and dural biopsy. After treatment with methylprednisolone and mycophenolate mofetil, the patient′s clinical symptoms improved.

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.

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.

Liver cholesterol metabolism disorder plays an important role in the development of non-alcoholic fatty liver disease (NAFLD).In order to reveal the molecular mechanism of cholesterol homeostasis imbalance induced by saturated fatty acids, HepG2 cells were stimulated with palmitic acid (PA).Lipids accumulation was analyzed by Oil Red O staining, intracellular triglyceride and cholesterol quantification.The level of genes and proteins related to cholesterol homeostasis was measured by RT-qPCR and western blotting.Additionally, intracellular bile acids and mitochondrial oxysterols were detected by LC-MS/MS.The results demonstrated that intracellular lipids such as TG and TC were significantly increased in the model with PA stimulation.Although no significant difference was detected in genes related to cholesterol synthesis and uptake, the protein expression of ABCG5 and LXRα were significantly down-regulated, indicating a decrease in cholesterol efflux.Meanwhile, the gene expression of STARD1 and CYP7B1, which are responsible for bile acid alternative synthesis, were markedly enhanced, along with a significant increase of cholesterol and 27-OHC in mitochondria and CDCA in cells.These results suggested that PA overload may disrupt cholesterol homeostasis by inhibiting cholesterol efflux and promoting bile acids synthesis.

OBJECTIVE: To explore an objective evaluation mode for emergency response capacity on sudden poisoning incidents. METHODS: Based on the health emergency drills and blind design,22 teams in Guangdong Province were recruited to participate in the first round of evaluation,including blind sample analysis,theoretical examination( poisoning medical rescue,detection and investigation) and skills assessment( poisoning medical care,poisoning investigation,personal protection,poisoning detection and emergency decision-making). Then,the top 10 teams in the first round of evaluation were proceeded to desktop exercise in the second round of evaluation. The evaluation results were compared with the local gross domestic product( GDP) from 2011 to 2015 by Spearman rank correlation analysis. RESULTS: The median scores of the 4 sections were as follows: blind sample analysis was 71. 0,theoretical examination was 61. 4,skills assessment was 76. 5,and the desktop exercise was 55. 0. The rates of excellent for assessment of blind sample analysis,theoretical examination and skills assessment were 22. 7%,4. 5% and 0. 0%,while the failure rates were 31. 8%,45. 5% and 4. 5%,respectively. The rates of failure in medical rescue and investigation in theoretical examination were63. 6% and 50. 0%,the rates of failure in medical rescue and investigation in skills assessment were 40. 9% and 31. 8%,respectively. The middle-grade and passing rates of the top 10 teams in the desktop exercise were 10. 0%,and the failure rate was 80. 0%. There was a moderate positive correlation between the emergency response capacity for emergent poisoning and local GDP( Spearman rank correlation coefficient > 0. 700,P < 0. 05). CONCLUSION: The evaluation mode of emergency response capability assessment combined with actual combat and desktop emergency drill is established successfully. It can objectively test the assessment of emergency response capabilities.

Objective To observe the learning and memory ability of rats after injection of Aβ25-35 protein in different concentrations into the lateral ventricle assessed by Morris water maze test, and to explore the optimal concentration of Aβ25-35 in the preparation of AD model rats.Methods Male SD rats were randomly divided into sham operated group and model group.The rats of model group received Aβ25-35 injection in concentrations of 2 μg/μL, 4 μg/μL and 8 μg/μL, respectively.According to the Rat Brain Stereotaxic Atlas, 5 μL of aggregation of Aβ25-35 was injected into the right lateral ventricle to establish the AD rat model.7 days after successful modeling, Morris water maze was used to test thechanges of learning and memory ability of the rats.Results There was no significant difference in the average swimming speed between the two groups (P > 0.05).The escape latency time of rats in the model group was significantly increasedcompared with the sham group (P < 0.05).In the model group, the escape latency time of rats treated with 4 μg/μL and 8 μg/μL Aβ25-35 was significantly increased compared with the rats injected with 2 μg/μL (P < 0.05), while there was no significant difference between rats treated with 4 μg/μL and 8 μg/μL Aβ25-35 (P > 0.05).The activity time and distance of target quadrant of the rats injected with different concentration of Aβ25-35in the model group were significantly reduced compared with the sham group (P < 0.05), but no significant difference amongthe rats treated with different Aβ25-35 concentrations (P > 0.05).Compared with the sham-operated group, the number of platform-crossing of rats injected with different doses of Aβ25-35in the model group were significantly reduced (P < 0.05).In the model group, the rats treated with 4 μg/μL and 8 μg/μL was significantly reduced compared with the group with 2 μg/μL injection (P < 0.05).There was no significant difference between the rats injected with 4 μg/μL and 8 μg/μL (P > 0.05).Conclusions The recommended dose and concentration of Aβ25-35 to be injected into the unilateral ventricle to establisha rat model of Alzheimer's disease is 4 μg/μL in a volume of 5 μL.

Objective:To investigate the clinical application of cognitive behavioral therapy (CBT) and the reasons of the choosing CBT.Method:Totally 14 psychotherapists accepted a semi-structured interview,including their backgrounds of CBT training,the application of CBT in psychotherapy,their attitude toward consultative relations,their opinion on comparing other schools with CBT,and their reasons for choosing CBT.Results:The main reasons for choosing CBT included the influence of important others,the characters of CBT and personal factors.In clinical practice,the most commonly used behavioral techniques included exposure therapy,roll play,relaxation Waining and so on.The most commonly used cognitive techniques included Socratic questioning,cognitive restructuring and challenge unreasonable cognition.Conclusion:Cognitive behavioral therapy (CBT) is suitable for those who are sensible and preferring structural therapy.Nevertheless,the trend in therapy is the integration of different psychotherapy schools.

Discoidin domain receptor 1(DDR1)is a kind of receptor tyrosine kinases(RTKs),which is expressed abnormally in many tumors. It is involved in the development,invasion and metastasis process of tumors and may become a potential target of tumor therapy. This article reviewed the expression and significance of DDR1 in tumors of digestive system.