Nitazoxanide is an FDA-approved antiprotozoal drug. Our previous study found that oral administration of nitazoxanide inhibited Western diet (WD)-induced hepatic steatosis in ApoE^-/- mice. However, the specific mechanism remains to be elucidated. In the present study, we performed an untargeted metabolomics approach to reveal the effect of nitazoxanide on the liver metabolic profiles in WD-fed ApoE^-/- mice, and carried out the cellular experiments to elucidate the underlying mechanisms. UPLC-MS-based untargeted metabolomics analysis was used to investigate the effect of nitazoxanide on global metabolite changes in liver tissues. The differential metabolites were screened for enrichment analysis and pathway analysis. Hepatocytes were treated with tizoxanide, the metabolite of nitazoxanide, to investigate the underlying mechanism based on the findings in metabolomics study. The improvement of liver lipid metabolism disorders by nitazoxanide treatment in WD-fed ApoE^-/- mice was mainly through regulating glycerophospholipid metabolism, D-glutamine and glutamate metabolism, glutathione metabolism, and arginine biosynthesis metabolism. Tizoxanide, the active metabolite of nitazoxanide, increased glutathione (GSH) contents and glutamate-cysteine ligase catalytic subunit (Gcl-c) and glutathione reductase (Gsr) mRNA expressions in HepG2 cells. Tizoxanide increased cystathionine β-synthase (CBS) and phosphatidylethanolamine N-methyltransferase (PEMT) protein levels, inhibited lipid accumulation in hepatocytes induced by free fatty acid (FFA). Tizoxanide increased S-adenosyl-L-homocysteine hydrolase (SAHH) protein levels in HepG2 cells and mouse primary liver cells stimulated with free fatty acid (FFA). Tizoxanide increased N-acetyl glutamate synthase (Nags) and carbamoylphosphate synthetase 1 (Cps1) mRNA expressions in HepG2 cells. In conclusion, nitazoxanide improves WD-induced hepatic steatosis in ApoE^-/- mice and the underlying mechanisms include increasing CBS expression, GSH content, PEMT protein expression, Nags and Cps1 mRNA expression in hepatocytes.

AIM To evaluate the quality of Beidougen Formula Granules.METHODS Fifteen batches of standard decoctions and three batches of formula granules were prepared,after which paste rate and contents,transfer rates of magnoflorine,daurisoline,dauricine were determined.HPLC specific chromatograms were established,and cluster analysis was adopted in chemical pattern recognition.RESULTS For three batches of formula granules,the paste rates were 15.1%-16.6%,the contents of magnoflorine,daurisoline,dauricine were 18.93-19.39,9.42-9.60,6.79-6.85 mg/g with the transfer rates of 34.42%-35.25%,43.81%-44.65%,27.27%-27.51%from decoction pieces to formula granules,respectively,and there were seven characteristic peaks in the specific chromatograms with the similarities of more than 0.95,which demonstrated good consistence with those of standard decoctions and accorded with related limit requirements.Fifteen batches of standard decoctions were clustered into two types,and the medicinal materials produced from Jilin,Hebei,Shangdong could be used for the preparation of formula granules.CONCLUSION This reasonable and reliable method can provide references for the quality control and clinical application of Beidougen Formula Granules.

AIM To investigate the consistency of chemical constituents between formula granules and standard decoction of Coptidis Rhizoma.METHODS Eighteen batches of standard decoctions were prepared,after which the extraction rate and contents,transfer rates of magnolflorine,jatrorrhizine,columbamine,epiberberine,coptisine,palmatine,berberin were determined,HPLC characteristic chromatograms were established.RESULTS There were 11 common peaks in the characteristic chromatograms of 18 batches of standard decoctions and 24 batches of formula granules with the similarities of 0.861-1.000,which were clusterd into two categories.The formula granules and standard decoction demonstrated approximated extraction rate and contents,transfer rates of index constituents.CONCLUSION The chemical constituents between formula granules and standard decoction of Coptidis Rhizoma display good consistency,which can provide references for the quality control,process research and clinical application of the former.

Insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) is a recognition protein for N⁶-methyladenosine (m⁶A), mediating the stability of downstream mRNA, and is a promising anti-tumor target. Based on the lead compound 1g from previous screening, this study designed and synthesized 52 IGF2BP2 small molecule inhibitors using thiazole hydrazone as the parent nucleus. Among them, 9g, 10g, 37g, 47g and 52g showed good inhibitory activities. This work represents an initial exploration in the development of small molecule inhibitors targeting IGF2BP2, using thiazolehydrazone as the core structure. It lays a foundation for subsequent related research.

Abstract: Objective　To further investigate the underreporting of mortality surveillance data among permanent residents in Hainan Province in 2020, and to explore the application of Application of the Analysis of National Causes of Death for Action (ANACONDA) in the quality analysis of mortality surveillance. Methods　The data were collected from the Death Information Monitoring and Management System of Hainan Center for Disease Control and Prevention, and mainly included 33 418 deaths reported from 19 cities and counties in Hainan Province from January 1, 2020 to December 31, 2020. All the data were analyzed by the application of ANACONDA, and the causes of death were classified by the International Classification of Diseases, 10th Revision (ICD-10). Results　A total of 33 418 deaths were reported in Hainan Province in 2020, with a crude mortality rate of 3.6‰. The proportion of deaths in males under 85 years old was higher than that in females, while the proportion of deaths in 85 years old and above was opposite. The quality analysis of cause of death surveillance showed that there was under-reporting of death surveillance in Hainan Province in 2020, with an under-reporting rate of 30.1%. There were differences in the age composition and GBD regional composition ratio of deaths of the three major categories of diseases, and the misreporting of causes of death in the middle and high age groups was more significant. The Vital Statistics Performance Index (VSPI) score of death data in Hainan Province in 2020 was 52.8, the score of cause of death reporting quality was 85.5, and the score of specific cause of death level that could be used was 88.4. The completeness of death reports in the priority action areas for improving cause of death data quality accounted for the largest share, followed by the quality of cause of death reports. There was a difference in the proportion of specific causes of death between males and females after the survey, but the change in order was not obvious. Conclusions　The data integrity of cause-of-death surveillance is low in Hainan Province in 2020. It is suggested to improve the completeness of reporting data, strengthen the training of cause-of-death surveillance system, and regularly evaluate and supervise the system.

OBJECTIVE: To observe the short-term efficacy, long-term efficacy and safety of acupuncture for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: Forty-two patients with CP/CPPS were randomly divided into an acupuncture group (21 cases, 1 case dropped off) and a sham acupuncture group (21 cases). The patients in the acupuncture group were treated with acupuncture at bilateral Zhongliao (BL 33), Huiyang (BL 35), Shenshu (BL 23) and Sanyinjiao (SP 6); the needling depth of Zhongliao (BL 33) and Huiyang (BL 35) was 60 to 80 mm, while Shenshu (BL 23) and Sanyinjiao (SP 6) was directly punctured of 30 mm. The patients in the sham acupuncture group were treated with acupuncture at non-acupoints, including points 2 cm next to Shenshu (BL 23), Zhongliao (BL 33) and Huiyang (BL 35), and the midpoint of the connecting line between the spleen meridian and the kidney meridian. All the non-acupoints were treated with directly puncture of 2 to 3 mm. The needles were left for 30 min in both groups, once every other day in the first four weeks, three times a week, and twice a week in the next four weeks, totally 20 treatments. Before treatment, after treatment and in follow-up of 24 weeks after treatment completion, the National Institutes of Health-chronic prostatitis symptom index (NIH-CPSI) score and urinary flow rate were observed in both groups; the clinical efficacy and safety were evaluated. RESULTS: Compared with those before treatment, the pain and discomfort scores, urination symptoms scores, quality of life scores and total scores of NIH-CPSI in both groups were reduced after treatment in the two groups (P<0.01), while each item score and total score of NIH-CPSI in the acupuncture group were reduced in follow-up (P<0.01, P<0.05). After treatment and in follow-up, each item score and total score of NIH-CPSI in the acupuncture group were lower than those in the sham acupuncture group (P<0.05, P<0.01). After treatment, the maximum and average urinary flow rates in the acupuncture group were higher than those before treatment (P<0.05), and the average urinary flow rate in the acupuncture group was higher than that in the sham acupuncture group (P<0.05). The total effective rate was 75.0% (15/20) in the acupuncture group, which was higher than 42.9% (9/21) in the sham acupuncture group (P<0.05). No significant adverse reactions were observed in the two groups, and there was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). CONCLUSION Acupuncture could effectively alleviate the clinical symptoms, improve quality of life, and has a sustained, safe and reliable therapeutic effect in patients with CP/CPPS.
United States ; Male ; Humans ; Prostatitis/therapy* ; Quality of Life ; Acupuncture Therapy ; Punctures ; Meridians

Humans ; Male ; Semen ; Sperm Motility ; Mediation Analysis ; East Asian People ; Microcystins/toxicity* ; Spermatozoa ; Sperm Count ; Infertility, Male

OBJECTIVE: To investigate whether Omicron BA.1 breakthrough infection after receiving the SARS-CoV-2 vaccine could create a strong immunity barrier. METHODS: Blood samples were collected at two different time points from 124 Omicron BA.1 breakthrough infected patients and 124 controls matched for age, gender, and vaccination profile. Live virus-neutralizing antibodies against five SARS-CoV-2 variants, including WT, Gamma, Beta, Delta, and Omicron BA.1, and T-lymphocyte lymphocyte counts in both groups were measured and statistically analyzed. RESULTS: The neutralizing antibody titers against five different variants of SARS-CoV-2 were significantly increased in the vaccinated population infected with the Omicron BA.1 variant at 3 months after infection, but mainly increased the antibody level against the WT strain, and the antibody against the Omicron strain was the lowest. The neutralizing antibody level decreased rapidly 6 months after infection. The T-lymphocyte cell counts of patients with mild and moderate disease recovered at 3 months and completely returned to the normal state at 6 months. CONCLUSION Omicron BA.1 breakthrough infection mainly evoked humoral immune memory in the original strain after vaccination and hardly produced neutralizing antibodies specific to Omicron BA.1. Neutralizing antibodies against the different strains declined rapidly and showed features similar to those of influenza. Thus, T-lymphocytes may play an important role in recovery.
Humans ; Antibodies, Neutralizing ; Prospective Studies ; SARS-CoV-2 ; Breakthrough Infections ; COVID-19 Vaccines ; COVID-19 ; T-Lymphocytes ; China/epidemiology* ; Antibodies, Viral

This study aimed to characterize and identify the non-volatile components in Pogostemonis Herba by using ultra-perfor-mance liquid chromatography-quadrupole-time of flight-mass spectrometry(UPLC-Q-TOF-MS) combined with UNIFI and an in-house library. The chemical components in 50% methanol extract of Pogostemonis Herba were detected by UPLC-Q-TOF-MS in both positive and negative MS~E continuum modes. Then, the MS data were processed in UNIFI combined with an in-house library to automatically characterize the metabolites. Based on the multiple adduct ions, exact mass, diagnostic fragment ions, and peak intensity of compounds and the fragmentation pathways and retention behaviors of reference substances, the structures identified by UNIFI were further verified and those of the unidentified compounds were tentatively elucidated. A total of 120 compound structures were identified or tentatively identified, including flavonoids, phenylpropanoids, phenolic acids, terpenes, fatty acids, alkaloids, and phenylethanoid glycosides. Sixteen of them were accurately identified by comparison with reference substances, and 53 compounds were reported the first time for Pogostemonis Herba. This study systematically characterized and identified the non-volatile compounds in Pogostemonis Herba for the first time. The findings provide a scientific basis for revealing the pharmacodynamic material basis, establishing a quality control system, and developing products of Pogostemonis Herba.

Objective: To investigate the clinical value of plasma scaffold protein SEC16A level and related models in the diagnosis of hepatitis B virus-related liver cirrhosis (HBV-LC) and hepatocellular carcinoma (HBV-HCC). Methods: Patients with HBV-LC and HBV-HCC and a healthy control group diagnosed by clinical, laboratory examination, imaging, and liver histopathology at the Third Hospital of Hebei Medical University between June 2017 and October 2021 were selected. Plasma SEC16A level was detected using an enzyme-linked immunosorbent assay (ELISA). Serum alpha-fetoprotein (AFP) was detected using an electrochemiluminescence instrument. SPSS 26.0 and MedCalc 15.0 statistical software were used to analyze the relationship between plasma SEC16A levels and the occurrence and development of liver cirrhosis and liver cancer. A sequential logistic regression model was used to analyze relevant factors. SEC16A was established through a joint diagnostic model. Receiver operating characteristic curve was used to evaluate the clinical efficacy of the model for liver cirrhosis and hepatocellular carcinoma diagnosis. Pearson correlation analysis was used to identify the influencing factors of novel diagnostic biomarkers. Results: A total of 60 cases of healthy controls, 60 cases of HBV-LC, and 52 cases of HBV-HCC were included. The average levels of plasma SEC16A were (7.41 ± 1.66) ng/ml, (10.26 ± 1.86) ng/ml, (12.79 ± 1.49) ng /ml, respectively, with P < 0.001. The sensitivity and specificity of SEC16A in the diagnosis of liver cirrhosis and hepatocellular carcinoma were 69.44% and 71.05%, and 89.36% and 88.89%, respectively. SEC16A, age, and AFP were independent risk factors for the occurrence of HBV-LC and HCC. SAA diagnostic cut-off values, sensitivity, and specificity were 26.21 and 31.46, 77.78% and 81.58%, and 87.23% and 97.22%, respectively. The sensitivity and specificity for HBV-HCC early diagnosis were 80.95% and 97.22%, respectively. Pearson correlation analysis showed that AFP level was positively correlated with alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), and γ-glutamyltransferase (GGT) with P < 0.01, while the serum SEC16A level was only slightly positively correlated with ALT and AST in the liver cirrhosis group (r = 0.268 and 0.260, respectively, P < 0.05). Conclusion: Plasma SEC16A can be used as a diagnostic marker for hepatitis B-related liver cirrhosis and hepatocellular carcinoma. SEC16A, combined with age and the AFP diagnostic model with SAA, can significantly improve the rate of HBV-LC and HBV-HCC early diagnosis. Additionally, its application is helpful for the diagnosis and differential diagnosis of the progression of HBV-related diseases.
Humans ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; alpha-Fetoproteins/metabolism* ; Endoplasmic Reticulum/metabolism* ; Golgi Apparatus/metabolism* ; Vesicular Transport Proteins ; Liver Cirrhosis/complications* ; Hepatitis B/complications* ; ROC Curve ; Hepatitis B virus/metabolism* ; Biomarkers, Tumor