Objective To explore the anti-inflammatory mechanism of the active ingredients of Gubi Formula in treating osteoarthritis.Methods Normal human chondrocytes were cultured in vitro,and lipopolysaccharide(LPS)stimulated inflammation.The cells were divided into control group(normal culture),model group(10 μg·mL-1 LPS),quercetin group(10 μg·mL-1 LPS+8 μmol·L-1 quercetin),formononetin group(10 μg·mL-1 LPS+50 μmol·L-1 formononetin),naringin group(10 μg·mL-1 LPS+10 μmol·L-1 naringin),asperosaponin Ⅵ group(10 μg·mL-1 LPS+50 pmol·L-1 asperosaponin Ⅵ),β-ecdysterone group(10 μg·mL-1 LPS+50 μmol·L-1β-ecdysterone).Cell counting kit-8(CCK8)was used to detect the viability of chondrocytes.Western blot was used to detect the expression of nuclear factor NF-kappa-B p65 subunit(p65),nuclear factor erythroid 2-related factor 2(Nrf2)nuclear protein.Results The cell viability of control group,model group,quercetin group,formononetin group,naringin group,Dipsacoside Ⅵ group,β-ecdysterone group were(103.10±8.55)％,(62.41±2.35)％,(76.92±1.74)％,(77.01±0.60)％,(80.39±3.06)％,(79.43±0.94)％,(55.20±0.99)％;the relative expression of Nrf2 protein were 1.00±0.00,1.01±0.09,1.30±0.15,0.91±0.15,1.23±0.25,0.71±0.19,1.51±0.13,1.26±0.15;the relative expression of P65 protein were 1.00±0.00,2.24±0.85,0.74±0.33,1.49±0.29,0.97±0.06,1.33±0.07,1.67±0.22,1.52±0.17;the relative expression of inflammatory mediators iNOS were 1.00±0.00,1.52±0.27,1.07±0.24,1.25±0.12,1.01±0.30,1.44±0.12,1.07±0.18,1.11±0.16.The above indexes in quercetin group,formononetin group and naringin group were significantly different from those in model group(P＜0.05,P＜0.01 and P＜0.001).Compared with the model group,there was no significant difference in the above indexes between the Asperosaponin Ⅵ group and theβ-ecdysterone group(all P＞0.05).Conclusion The active components of Gubi Formula,including quercetin,mangiferin,and naringin,can activate Nrf2-HO-1 signaling and inhibit the activation of the Nuclear factor-κB(NF-κB)pathway plays an anti-inflammatory role in alleviating osteoarthritis.

AIM:To investigate the effect of hypericin(Hyp)on the heart of rats with myocardial ischemia-re-perfusion injury(MIRI),and to explore its mechanism.METHODS:Thirty SPF male SD rats were divided into 5 groups:sham group,MIRI group,low-dose Hyp(L-Hyp)group(MIRI+L-Hyp group),high-dose Hyp(H-Hyp)group(MIRI+H-Hyp group),and positive control trimetazidine(TMZ)group(MIRI+TMZ group),with 6 rats in each group.Apart from the sham group,the MIRI model was established by ligating the anterior descending branch of the left coronary artery and then recanalizing it in the remaining four groups of rats.The success of the modeling was determined by monitor-ing the electrocardiogram.We assessed the cardiac function in rats using echocardiography.TTC staining was employed to measure the area of myocardial infarction in rats,and HE staining was utilized to observe the morphological traits of rat myocardium.We assayed the activities of lactate dehydrogenase(LDH)and superoxide dismutase(SOD)and the levels of malondialdehyde(MDA)in rat serum using biochemical kits.ELISA kits were applied to assess the contents of cardiac troponin I(cTnI)and reactive oxygen species(ROS)in rat serum.Western blot analysis was perfomed to measure the pro-tein expression levels of AMPK,p-AMPK,Nrf2,and HO-1 in rat myocardial tissues.RESULTS:The rats in MIRI group exhibited increased myocardial tissue injury,larger myocardial infarction areas,decreased left ventricular ejection fraction(LVEF),and reduced left ventricular fractional shortening(LVFS)compared with sham group,as shown by echo-cardiography.Additionally,there were increases in LDH activity,cTnI,MDA and ROS levels,along with significant de-creases in SOD activity,and p-AMPK,Nrf2 and HO-1 protein levels(P<0.05).Compared with MIRI group,the rats in MIRI+L-Hyp,MIRI+H-Hyp and MIRI+TMZ groups showed decreased myocardial histopathological damage and reduced myocardial tissue infarction area,increased LVEF and LVFS,and lowered serum levels of LDH activity,cTnI,MDA and ROS,while SOD activity,p-AMPK,Nrf2 and HO-1 protein levels were elevated(P<0.05).CONCLUSION:Hypericin attenuates myocardial ischemia-reperfusion injury in rats,possibly by modulating the AMPK/Nrf2/HO-1 signaling path-way.

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

Recent studies revealed the relationship among homologous recombination repair (HRR), androgen receptor (AR), and poly(adenosine diphosphate-ribose) polymerase (PARP); however, the synergy between anti-androgen enzalutamide (ENZ) and PARP inhibitor olaparib (OLA) remains unclear. Here, we showed that the synergistic effect of ENZ and OLA significantly reduced proliferation and induced apoptosis in AR-positive prostate cancer cell lines. Next-generation sequencing followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed the significant effects of ENZ plus OLA on nonhomologous end joining (NHEJ) and apoptosis pathways. ENZ combined with OLA synergistically inhibited the NHEJ pathway by repressing DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and X-ray repair cross complementing 4 (XRCC4). Moreover, our data showed that ENZ could enhance the response of prostate cancer cells to the combination therapy by reversing the anti-apoptotic effect of OLA through the downregulation of anti-apoptotic gene insulin-like growth factor 1 receptor ( IGF1R ) and the upregulation of pro-apoptotic gene death-associated protein kinase 1 ( DAPK1 ). Collectively, our results suggested that ENZ combined with OLA can promote prostate cancer cell apoptosis by multiple pathways other than inducing HRR defects, providing evidence for the combined use of ENZ and OLA in prostate cancer regardless of HRR gene mutation status.
Male ; Humans ; Prostatic Neoplasms, Castration-Resistant/genetics* ; Drug Resistance, Neoplasm/genetics* ; Cell Line, Tumor ; Receptors, Androgen/genetics* ; Nitriles ; Apoptosis

OBJECTIVE: Agar dilution method (ADM) was used as the golden standard to evaluate the consistency of Epsilometer test (E-test) in detecting the sensitivity of Helicobacter pylori (H. pylori) to metronidazole. METHODS: From August 2018 to July 2020, patients with H. pylori infection treated for the first time in Peking University Third Hospital for gastroscopy due to dyspepsia were included in this study. Gastric mucosas were taken from the patients with H. pylori infection. H. pylori culture was performed. Both the ADM and E-test were applied to the antibiotic susceptibility of H. pylori to metro-nidazole, and the consistency and correlation between the two methods were validated. RESULTS: In the study, 105 clinical isolates of H. pylori were successfully cultured, and the minimum inhibitory concentration ≥ 8 mg/L was defined as drug resistance. Both ADM and the E-test showed high resistance rates to metronidazole, 64.8% and 62.9%, respectively. Among them, 66 drug-resistant strains were detected by ADM and E-test, and 37 were sensitive strains, so the consistency rate was 98.1%. Two strains were evaluated as drug resistance by ADM, but sensitive by the E-test, with a very major error rate of 1.9%. There was zero strain sensitive according to ADM but assessed as resistant by the E-test, so the major error rate was 0%. Taking ADM as the gold standard, the sensitivity of E-test in the detection of metronidazole susceptibility was 97.1% (95%CI: 0.888-0.995), and the specificity was 100% (95%CI: 0.883-1.000). Cohen's kappa analysis showed substantial agreement, and kappa coefficient was 0.959 (95%CI: 0.902-1.016, P < 0.001). Spearmans correlation analysis confirmed this correlation was significant (r=0.807, P < 0.001). The consistency evaluation of Bland-Altman method indicated that it was good, and there was no measured value outside the consistency interval. In this study, cost analysis, including materials and labor, showed a 32.2% higher cost per analyte for ADM as compared with the E-test (356.6 yuan vs. 269.8 yuan). CONCLUSION The susceptibility test of H. pylori to metronidazole by E-test presents better agreement with ADM. Because it is less expensive, less labor intensive, and more rapid, it is an easy and reliable method for H. pylori susceptibility testing.
Humans ; Metronidazole/therapeutic use* ; Helicobacter pylori ; Agar/therapeutic use* ; Disk Diffusion Antimicrobial Tests ; Microbial Sensitivity Tests ; Helicobacter Infections/drug therapy* ; Anti-Bacterial Agents/therapeutic use*

Objective: To investigate the diagnostic value of rapid antigen test based on colloidal gold immunochromatographic assay for the detection of SARS-CoV-2 infection in symptomatic patients. Methods: From May 20 to June 5 2022, 76 hospitalized children and their 55 accompanying family members with confirmed SARS-CoV-2 infection in the COVID-19 isolation unit of the Children's Hospital of Fudan University (designated referral hospital for SARS-CoV-2 infection in Shanghai) enrolled. Their nasopharyngeal swab specimens were consecutively collected. The samples were tested for SARS-CoV-2 nucleic acid by real-time quantitative. SARS-CoV-2 antigen was tested by immunochromatography. The correlation between the antigen detection results and the change of the cycle threshold (Ct) values were evaluated, as well as the sensitivity and specificity of SARS-CoV-2 antigen detection at different periods after the onset of the disease. Kappa consistency test was conducted to investigate the consistency between the 2 diagnostic methods. Results: Of the enrolled SARS-CoV-2 symptomatic infections, 76 were children, including 41 males and 35 females, with an age of 5 (2, 9) years; 55 were accompanying families, including 8 males and 47 females, with an age of 38 (32, 41) years. All 478 samples were simultaneously tested for SARS-CoV-2 antigen and nucleic acid. In any period from disease onset to negative conversion of viral nucleic acid, the overall sensitivity of the rapid antigen test was 48.2% (119/247), the specificity was 98.3% (227/231), and antigen test and nucleic acid test showed moderate consistency (κ=0.46, P<0.05). The sensitivity of antigen test was 100% (82/82) when the Ct value was ≤25. And the sensitivity of antigen test was 8/10, 4/15 and 8.3% (3/36) when the Ct value was 26, 30 and 35, respectively. All antigen tests were negative when Ct value was >35. During the period of 1-2 days, 3-5 days, 6-7 days, 8-10 days and >10 days after onset, the sensitivity and specificity of SARS-CoV-2 antigen test were 5/8 and 5/5, 90.2% (37/41) and 5/5, 88.9% (24/27) and 2/5, 45.0% (36/80) and 94.1% (32/34), 18.7% (17/91) and 98.9% (183/185) respectively. The Ct values of nasopharyngeal swabs were<26 during 2 to 7 days after onset, 28.7±5.0 on day 8, 34.5±2.9 on day 13 and > 35 after 14 days, respectively . Conclusion: SARS-CoV-2 antigen test in the patients with SARS-CoV-2 infection shows acceptable sensitivity and specificity within 7 days after onset of disease, and the sensitivity was positively correlated with viral load and negatively correlated with onset time.
Male ; Child ; Female ; Humans ; COVID-19 ; SARS-CoV-2 ; China ; COVID-19 Testing ; Nucleic Acids

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

Aim To investigate the mechanism of eata- pol (CAT) inhibiting differentiation and glyeolysis of Thl7 eel Is through miR-143-3p.Method The peripheral hloorl CD4 ∗ T eells of HA patients were obtained to deteet the expression of miR-143-3p and the mRNA levels of key glycolytic enzymes, ineluding glucose transporter 1 ( Glutl ) , hexokinase 2 ( HK2 ) , pyruvate kinase 2 (PKM2) , laetate dehydrogenase A ( LDHA).The differentiation of Thl7 eells was induced in vitro, and the ShRNA/lentivirus was applied to achieve the overexpression or knockdown of miR- 143-3 p.Un-transfected eells were divided into control group and CAT group (20, 40, 80 mg • L 1 ) , and transfected eells were divided into four groups: negative control group, miR-143-3p inhibitor group, miR- 143-3p mimies group, miR-143-3p inhibitor + CAT group.The percentage of Thl7 eells was deteeted by flow cytometry, and the level of IL-17A was detected by EL1SA.Quantitative real-time PCR was used to detect the mRNA expression of miR-143-3p and key glycolytic enzymes, and the levels of pyruvate and lactate were also detected.Results The mRNA expression of miR-143-3p in RA peripheral blood CD4 ∗ T cells was negatively correlated with disease severity ( DAS28 ) , transcription factor ROR-yt, and the key glycolytic enzymes Glutl/HK2/LDHA.Compared with negative control group, the down-expression of miR-143-3p markedly elevated the mRNA expression of ROR-yt, Glutl, HK2, LDHA, and the levels of IL-17A, pyruvate, lactate.Catalpol groups significantly up-regula- ted the expression of miR-143-3p, decreased the mRNA expression of HK2/LDHA and the levels of pvru- vate/lactate, and inhibited Thl7 cells differentiation.Compared with miR - 1 4 3 - 3 p inhibitor group , catapol could significantly inhibit the abnormal up-regulated of HK2/LDHA mRNA relative expression, pyruvate/lactate levels and the abnormal differentiation of Thl7 eells.Conclusion MiR-143-3p inhibits the differentiation and glycolysis of Thl7 cells.Catalpol could sup-press the glycolysis and differentiation of Thl7 eells by regulating mill-143-3p.

To evaluate the efficacy and safety of Compound Glycyrrhizin Injection(CGI) in improving liver damage in chronic hepatitis B(CHB). PubMed, Web of Science, SinoMed, CNKI, Wanfang and VIP databases were retrieved from their inception to February 10, 2020. The randomized controlled trial(RCT) of CGI in the treatment of CHB was included. Data were independently extracted by two authors, and the methodological quality was evaluated using the Cochrane bias risk assessment tool by other two authors. Statistical analysis was performed using RevMan 5.3 software. A total of 18 two-armed RCTs were included, involving 1 915 participants. The methodological quality of all studies included was generally low. In the comparison between CGI and diammonium glycyrrhizinate, the results showed that CGI was superior to the control group in improving the overall clinical effectiveness, but there was no statistical difference between the two groups in increasing ALT normalization rate, reducing ALT and AST level. In the comparison between CGI and diammonium glycyrrhizinate+other general hepatoprotective drugs, the results showed that CGI was superior to the control group in reducing AST level, while there was no statistical difference between the two groups in reducing ALT level and increasing overall clinical effectiveness. In the comparison between CGI+other commonly used drugs(including energy mixture, glutathione, vitamins, potassium magnesium aspartate) and diammonium glycyrrhizinate+other commonly used drugs, the results showed that CGI combined with other commonly used drugs was better than the control group in reducing ALT and AST level and improving the clinical total effective rate, and there was no statistical difference between the two groups in increasing the rate of ALT normalization. In the comparison between CGI+other commonly used drugs and other commonly used drugs, the results showed that CGI combined with other commonly used drugs was superior to the control group in reducing ALT and AST level and improving the overall clinical effectiveness. In the comparison between CGI+vitamins and diammonium glycyrrhizinate+potassium magnesium aspartate+vitamins, the results showed no statistical difference between the two groups in reducing AST level. A small number of studies included reported that CGI caused mild adverse reactions when used alone or in combination with other drugs. Based on the results, CGI has a certain effect in improving CHB liver damage, but the evidence is not enough to prove that CGI would cause serious adverse events. In the future, more well-designed and strictly-enforced RCT with an adequate sample size are needed to further evaluate the effect CGI in alleviating CHB liver damage.
Drugs, Chinese Herbal/adverse effects* ; Glycyrrhizic Acid ; Hepatitis B, Chronic/drug therapy* ; Humans

OBJECTIVE: To investigate the optimal time of monitoring minimal residual disease (MRD) for predicting survival and prognosis in children with T-cell acute lymphoblastic leukemia (T-ALL) after treated by CCLG-ALL2008 chemotherapy. METHODS: 96 children with T-ALL receiving CCLG-ALL2008 chemotherapy treated in our hospital from January 2015 to January 2020 were retrospectively summarized. The follow-up time was 9.0-65.0 months, with a median of 43.5 months. Kaplan-Meier survival curve was used to detect the overall event-free survival (EFS) and overall survival (OS) of the patients. The clinical data, MRD levels after 15 d, 33 d and 90 d chemotherapy between EFS group and relapse group, as well as OS group and death group were compared by using univariate analysis. Multivariate Logistic regression analysis was used to screen the main risk factors affecting EFS and OS of the patients. The patients were divided into low, moderate and high-risk according to the MRD level after 15 d, 33 d and 90 d, the differences of EFS and OS between each groups were compared again. RESULTS: By the end of follow-up, 50 patients recurred and other 46 patients non-recurred; 40 patients died and 56 patients survived, the EFS was (49.5±6.3)% and OS was (61.5±5.9)%. Univariate analysis showed that the initial WBC count in EFS group (n=46) was significantly lower than that in relapse group (n=50), and MRD levels after 33 d and 90 d were significantly less also (P<0.05). Prednisone response in OS group (n=56) was better than that in death group (n=40), and central nerve invasion rate was lower, MRD level after 33 and 90 d were lower (P<0.05). Logistic regression analysis showed that MRD level after 90 d was the main risk factor affecting EFS of the patients; prednisone reaction, central nerve invasion and MRD level after 90 d were the main risk factors affecting OS of the patients (P<0.05). There were no differences of EFS or OS between the groups according to the MRD levels after 15 and 33 d (P>0.05), however for 90 d, EFS and OS of the patients in high-risk group were significantly lower than those in medium-risk group, and those in medium-risk group were lower than those in low-risk group (P<0.05). CONCLUSION The MRD level after 90 days CCLG-ALL2008 chemotherapy may be the best time to predict the survival and prognosis in T-ALL children.
Child ; Disease-Free Survival ; Humans ; Neoplasm, Residual ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; Retrospective Studies ; Risk Factors ; T-Lymphocytes