Objective In order to understand which kind of function genes play an important role for es-timating wound age, the variation of difference genes’ mRNA expression were compared after injury. Methods T he mRNA expression levels of seven candidate genes (ICAM-1, NF-κB, MX2, MT1, MT2, sTnI, and Cox6c) were analyzed in contused rat skeletal muscle at different time points using real-time fluorescent quantitative PC R (R T-qPC R ). T he rawC t values were normalized relative to that of RPL32 mRNA , and converted to standard C t values. A t each time point after injury, the standard deviations (SD ) of the standard C t values were calculated by SPSS. Results T he expression trends of the seven genes were all found to be related to wound age, but there were lower variation coefficients and greater reliability of sTnI and Cox6c when compared with other genes. Conclusion T he genes encoding struc-tural proteins or proteins that performbasic functions can be suitable for wound age estimation.

Obtective The correlation between estrus cycle and the pathological changes of liver and lung in LPS-treated mice and the possible mechanisms were investigted.Methods The pathological lesion in liver and lung、 the content of E_2、P in plasma and the content of TNF-?、EGF in plasma and ovarian supernate were examined in various times after challenge with 12.5 mg/kg LPS in estrus、metestrus and diestrus respectively and the correlation among them was assessed.Results The plasma E_2 and p levels were the lowest in diestrus.When LPS was injected in diestrus,compared with control group,the levels of P and E_2 in plasma were decreased remarkely after ip LPS 10 h(P

Objective To investigate the influencing factors of adverse pregnancy outcomes in patients with preeclampsia and the predictive value of serum trace elements in the second trimester.Methods A total of 98 patients with preeclampsia admitted to Qujing First People's Hospital from January 2019 to June 2022 were enrolled in the study.Patients were divided into poor outcome group and good outcome group according to whether they had adverse pregnancy outcomes.The clinical data of all patients enrolled in the study were col-lected and the serum levels of trace elements calcium,copper,zinc and iron were detected in the second trimes-ter.Univariate analysis and multivariate Logistic regression were used to analyze the influencing factors of ad-verse pregnancy outcomes in patients with preeclampsia.The levels of serum trace elements in the second tri-mester of pregnancy were compared between the poor outcome group and the good outcome group.The re-ceiver operating characteristic(ROC)curve was used to evaluate the predictive value of serum trace elements calcium,copper,zinc and iron for adverse pregnancy outcomes in patients with preeclampsia.Results Univari-ate analysis showed that compared with the good outcome group,the poor outcome group had significantly higher systolic blood pressure,24 h urinary protein quantitation,and D-dimer level(P＜0.05)and significantly less gestational age and platelet count at admission(P＜0.05).Multivariate Logistic regression analysis showed that 24 h urinary protein quantification,D-dimer and platelet count were the influencing factors of ad-verse pregnancy outcomes in patients with preeclampsia(P＜0.05).The levels of serum trace elements calci-um,copper,and zinc in the poor outcome group were significantly lower than those in the good outcome group(P＜0.05),and the level of iron was significantly higher than that in the good outcome group(P＜0.05).ROC curve analysis showed that the areas under the curves(AUCs)of serum calcium,copper,zinc,and iron in the second trimester of pregnancy for predicting adverse pregnancy outcomes in preeclampsia patients were 0.830(95％CI:0.780-0.880),0.855(95％CI:0.805-0.905),0.847(0.797-0.897)and 0.861(95％CI:0.811-0.911),respectively.Conclusion Adverse pregnancy outcomes in patients with preeclampsia are re-lated to 24 h urine protein,D-dimer and platelet count.The levels of serum trace elements calcium,copper,zinc and iron in the second trimester of pregnancy change significantly in patients with adverse pregnancy out-comes,which may become predictive markers of adverse pregnancy outcomes.

Mitochondrial myopathy is a group of multi-system diseases in which mitochondrial DNA(mtDNA)or nuclear DNA(nDNA)defects lead to structural and functional dysfunction of mitochondria.The clinical manifestations of mitochondrial myopathy are complex and varied,and the testing for mtDNA and nDNA is not widely available,so misdiagnosis or missed diagnosis is common.Chronic progressive external ophthalmoplegia(CPEO)is a common type of mitochondrial myopathy,which is characterized by blepharoptosis.Here we report a 38-year-old female with mitochondrial myopathy presented with chronic numbness and weakness of the limbs,accompanied by blepharoptosis that was recently noticed.Laboratory and head magnetic resonance imaging(MRI)examinations showed no obvious abnormalities.Muscle and nerve biopsies showed characteristic ragged red fibers(RRFs)and large aggregates of denatured mitochondria.Testing for mtDNA and nDNA showed a known mutation c.2857C＞T(p.R953C)and a novel variant c.2391G＞C(p.M797I)in the polymerase gamma(POLG)gene,so the patient was diagnosed as mitochondrial myopathy.Clinicians should pay more attention to long-term unexplained skeletal muscle diseases with recent onset blepharoptosis.Histopathologic examination and genetic testing are of great value in the early diagnosis and therapeutic intervention.

Objective: To study the immune regulation function of high expressing interleukin-10 (IL-10) in B cells on CD4⁺T-cells in periodontitis mouse model. Methods: Twenty-four 7-weeks-old female C57BL/6 mice were randomly and equally assigned into 4 groups: the healthy control group (HC group, n=6), the ligation combined Porphyromonasgingivalis (Pg) infection group (P group, n=6), the ligation combined Pg infection with non-stimulated B cell transfer group (P+NSB group, n=6) and the ligation combined Pg infection with stimulated B cell transfer group (P+SB group, n=6). Ligation combined Pg infection of the maxillary second molar was used to induce periodontitis of mice. The exogenous non-stimulated B cells or stimulated B cells were injected into the palate gingivalat the 5th day after ligation, and all mice were sacrificed at the 14th day. HE stain was used to detect the histological of periodontal tissues, toluidine blue stain was used to analysis the alveolar bone loss, immunofluorescence stain was used to detect the expression of CD4⁺T-cell and IL-10, immunohistochemical was used to detect the expression of receptor activator of NF-κB ligand (RANKL) and IL-1β. Results: Results of HE staining showed that more hyperplasia of gingival epithelium and the alveolar bone resorption in P group, P+NSB group and P+SB group compared with HC group. Results of toluidine blue staining showed that the alveolar bone losses in P group [(0.668±0.041) mm²], P+NSB group [(0.750±0.039) mm²] and P+SB group [(0.517±0.038) mm²] were significantly increased compared with that in HC group [(0.336±0.029) mm²](F=146.051, P<0.01), and the alveolar bone resorption was significantly increased in P+NSB group compared with that in P group (F=146.051, P<0.01). However, compared with P+NSB group and P group, the alveolar bone loss in P+SB groupwas significantly decreased (F=146.051, P<0.01). Results of immunofluorescence staining showed that CD4⁺T-cells expressed in P group [(287.5±37.9) cell/mm²], P+NSB group [(314.6±53.3) cell/mm²] and P+SB group [(185.4±42.9) cell/mm²] were higher than that in HC group [(12.5±13.7) cell/mm²)(F=71.284, P<0.01). Compared with P group and P+NSB group, CD4⁺T-cells expression in group P+SB was decreased (F=71.284, P<0.01). IL-10 levels were increased in P group [(111.7±20.4) cell/mm²], P+NSB group [(126.7±15.1) cell/mm²] and P+SB group [(191.0±22.6) cell/mm²] compared with that in HC group [(22.7±4.3) cell/mm²] (F=98.516, P<0.01), and the IL-10 expressed in P+SB group was significantly higher than those in P+NSB group and P group. Results of immunohistochemical tests showed that RANKL expressions in gingival tissues among P group [(674.0±71.5) cell/mm²], P+NSB group [(831.0±97.5) cell/mm²] and P+SB group [(420.1±40.8) cell/mm²] were significantly higher than that in HC group [(69.3±29.1) cell/mm²] (F=154.886, P<0.01). However, it dramatically decreased in P+SB group compared with those in P group and P+NSB group.The IL-1βexpression in P group [(447.8±40.8) cell/mm²], P+NSB group [(512.5±38.2) cell/mm²] and P+SB group [(281.6±32.4) cell/mm²] were significantly higher than that in HC group [(50.8±20.9) cell/mm²], and it also higher in P+NSB group compared with in P group. However, it decreased in P+SB group compared with those in P group and P+NSB group (F=221.185, P<0.01). Conclusions High expression IL-10 in B cell smight inhibit alveolar bone loss, RANKL and IL-1β expressions and CD4⁺T-cell infiltration through IL-10.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins