Infectious diseases occur and evolve through a dynamic contest between pathogenic qi and the body's healthy qi， with marked stage-dependent progression. This paper constructs a whole-course system of syndrome differentiation and treatment based on the theories of "struggle between pathogenic qi and healthy qi" and "relapse due to overexertion after recovery". The former reveals the intrinsic link between the waxing and waning of pathogenic and healthy qi and the evolution of syndromes， guiding stratified interventions during acute stage by discerning the location and nature of pathogenic factors and determining appropriate strategies for eliminating pathogens and supporting healthy qi according to the dynamics of deficiency and excess syndromes. The latter focuses on the recovery stage after infection and disease relapse， emphasizing harmonizing yin， yang， qi and blood to restore functions of zang-fu （脏腑） organs， and combining unblocking， tonifying， and turbidity-dispelling methods to eliminate both new and lingering pathogens. Throughout the whole-course treatment， attention should be paid to dynamic pathogenesis and stage-to-stage coherence， with emphasis on formula-syndrome correspondence， and integration of modern diagnostic and therapeutic measures， to construct individualized strategies bridging disease stages and integrating prevention with treatment， thereby systematically leveraging the integrative strengths of traditional Chinese medicine in the prevention and treatment of infectious diseases.

Infectious diseases occur and evolve through a dynamic contest between pathogenic qi and the body's healthy qi， with marked stage-dependent progression. This paper constructs a whole-course system of syndrome differentiation and treatment based on the theories of "struggle between pathogenic qi and healthy qi" and "relapse due to overexertion after recovery". The former reveals the intrinsic link between the waxing and waning of pathogenic and healthy qi and the evolution of syndromes， guiding stratified interventions during acute stage by discerning the location and nature of pathogenic factors and determining appropriate strategies for eliminating pathogens and supporting healthy qi according to the dynamics of deficiency and excess syndromes. The latter focuses on the recovery stage after infection and disease relapse， emphasizing harmonizing yin， yang， qi and blood to restore functions of zang-fu （脏腑） organs， and combining unblocking， tonifying， and turbidity-dispelling methods to eliminate both new and lingering pathogens. Throughout the whole-course treatment， attention should be paid to dynamic pathogenesis and stage-to-stage coherence， with emphasis on formula-syndrome correspondence， and integration of modern diagnostic and therapeutic measures， to construct individualized strategies bridging disease stages and integrating prevention with treatment， thereby systematically leveraging the integrative strengths of traditional Chinese medicine in the prevention and treatment of infectious diseases.

Objective To verify the accuracy of Youssef's formula and evaluate whether fetal biacromial diameter(BA)and other fetal biological diameters estimated by ultrasound can be used to predict macrosomia and shoulder dystocia,so as to provide the possibility for clinical prediction of shoulder dystocia.Methods A total of 200 pregnant women with a gestational period of 37-42 weeks were examined with ultrasound within 3 days before delivery for collecting biparietal diameter(BPD),head circumference(HC),abdominal circumference(AC),humerus length(HL),femur length(FL),thoracic transverse diameter and midpoint diameter of upper arm;and the fetal BA was estimated by Youssef's formula.Neonatal BA,body mass and body length were measured within 1 day after delivery.The above data were analyzed for correlation.Newborns were grouped according to their body mass(macrosomia vs non-macrosomia)and whether they had shoulder dystocia or not(shoulder dystocia vs non-shoulder dystocia).Results(1)The fetal BA estimated by Youssef's formula was consistent with neonatal BA(P>0.05),and the estimated BA was positively correlated with BPD,HC,AC and neonatal body mass(P<0.001).(2)The BA,BA/AC and BA/HC in macrosomia group were different from those in non-macrosomia group(P<0.05).ROC curve showed that the sensitivity and specificity were 92.3%and 88.2%for macrosomia prediction when the estimated BA threshold was 16.05 cm,and those were 61.5%and 77.0%when BA/AC threshold was 0.455,and 76.9%and 72.7%when BA/HC threshold was 0.465.(3)Shoulder dystocia group had neonatal weight close to non-shoulder dystocia group(P>0.05),but higher BA/BPD,BA/HC and BA-BPD(P<0.05).ROC curve showed that the sensitivity and specificity were 100.0%and 66.8%for shoulder dystocia when BA threshold was 15.45 cm,100.0%and 80.6%when BA/BPD threshold was 1.695,100.0%and 81.6%when BA/HC threshold was 0.475,and 100.0%and 76.0%when the threshold difference between BA and BPD was 6.35 cm.Conclusion Fetal BA,BA/BPD,BA/HC,BA/AC and BA-BPD may be effective predictors of shoulder dystocia and macrosomia.

Objective To investigate the alterations in skeletal muscle function and mass in an experimental mouse model of high-intensity exercise in a hot and humid environment.Methods Twenty-four male C57BL/6J mice(7～8 weeks old,weighing 21.30±0.67 g)were randomly assigned to a control group(CON group),a normal temperature and humidity exercise group(NE group),and a high temperature and humidity exercise group(HE group),with 8 mice in each group.The HE group was subjected to a high-temperature simulation chamber,maintaining a temperature of 37～39℃and humidity of 70%～80%,for a 60-minute exercise intervention at a 10° incline and 80%of maximum velocity(12 min of exercise followed by 8 min of rest,for 3 cycles).The CON group did not exercise,while the NE group exercised in the same manner in a normal temperature and humidity environment.The overall condition of the mice was evaluated by monitoring their body weight and analyzing their body composition.Their serum creatinine and urea levels were detected using an automated biochemical analyzer.After exercise,skeletal muscle function in the mice of each group was assessed by measuring their grip strength and exhaustion time.The skeletal muscle contractility and resistance to fatigue were evaluated using an in situ/in vivo/ex vivo muscle testing system.HE staining was employed to observe the morphological and structural changes in the skeletal muscles,and the average cross-sectional area and diameter of the muscle fibers were analyzed.Genes related to protein synthesis(Eif4ebp1,p70S6k)and breakdown(Foxo3,Fbxo32,Trim63)and heat stress-related genes(Hsf-1,Hspa1a,Hsp90aa)were quantified using RT-qPCR.Results ① Compared with the CON and NE groups,the HE group exhibited significant decreases in body weight(P<0.01)and lean body mass(P<0.05),an upward trend of creatinine level(P<0.05),and increases in the urea content(P<0.01).② The mice in the HE group had notably reduced grip strength(P<0.001),diminished skeletal muscle contraction,and weakened resistance to fatigue(P<0.05)than the CON and NE groups.③ The HE group demonstrated a reduction in the average cross-sectional area of muscle fibers(P<0.05)and a decrease in average fiber diameter(P<0.05),with particular up-regulation of Fbxo32,Trim63 and Eif4ebp1(P<0.01)and down-regulation of p70S6k(P<0.05)in comparison to the NE and CON groups.④ The expression levels of heat stress-related genes were higher in the HE group than the CON and NE groups(P<0.05).Conclusion High-intensity exercise in a hot and humid environment can lead to a decline in skeletal muscle function and mass in mice,potentially due to the disturbance of skeletal muscle protein synthesis and degradation triggered by excessive heat stress.

Objective To verify the accuracy of Youssef's formula and evaluate whether fetal biacromial diameter(BA)and other fetal biological diameters estimated by ultrasound can be used to predict macrosomia and shoulder dystocia,so as to provide the possibility for clinical prediction of shoulder dystocia.Methods A total of 200 pregnant women with a gestational period of 37-42 weeks were examined with ultrasound within 3 days before delivery for collecting biparietal diameter(BPD),head circumference(HC),abdominal circumference(AC),humerus length(HL),femur length(FL),thoracic transverse diameter and midpoint diameter of upper arm;and the fetal BA was estimated by Youssef's formula.Neonatal BA,body mass and body length were measured within 1 day after delivery.The above data were analyzed for correlation.Newborns were grouped according to their body mass(macrosomia vs non-macrosomia)and whether they had shoulder dystocia or not(shoulder dystocia vs non-shoulder dystocia).Results(1)The fetal BA estimated by Youssef's formula was consistent with neonatal BA(P>0.05),and the estimated BA was positively correlated with BPD,HC,AC and neonatal body mass(P<0.001).(2)The BA,BA/AC and BA/HC in macrosomia group were different from those in non-macrosomia group(P<0.05).ROC curve showed that the sensitivity and specificity were 92.3%and 88.2%for macrosomia prediction when the estimated BA threshold was 16.05 cm,and those were 61.5%and 77.0%when BA/AC threshold was 0.455,and 76.9%and 72.7%when BA/HC threshold was 0.465.(3)Shoulder dystocia group had neonatal weight close to non-shoulder dystocia group(P>0.05),but higher BA/BPD,BA/HC and BA-BPD(P<0.05).ROC curve showed that the sensitivity and specificity were 100.0%and 66.8%for shoulder dystocia when BA threshold was 15.45 cm,100.0%and 80.6%when BA/BPD threshold was 1.695,100.0%and 81.6%when BA/HC threshold was 0.475,and 100.0%and 76.0%when the threshold difference between BA and BPD was 6.35 cm.Conclusion Fetal BA,BA/BPD,BA/HC,BA/AC and BA-BPD may be effective predictors of shoulder dystocia and macrosomia.

Objective To investigate the effect and underlying mechanism of roxadustat on apoptosis and senescence of renal tubular epithelial cell line HK-2 induced by heat stress.Methods After HK-2 cells were treated with different concentrations of roxadustat(10,20,30,40 and 50 μmol/L)for 24 h,CCK-8 assay was used to determine the optimal intervention concentration of roxadustat.HK-2 cells were divided into 4 groups(n=3):control group,roxadustat group(30 μmol/L,24 h),heat-stress group(43 ℃,2 h),and heat-stress+roxadustat group(30 μmol/L roxadustat treatmnet for 24 h followed by heat-stress 2 h).Cell viability was detected by CCK-8 assay.Expression of hypoxia-inducible factor-1α(HIF-1α),Cleaved Caspase-3,p16 and p21 at protein level was detected by Western blotting.Immunofluorescence assay was employed to observe the distribution of HIF-1α.β-galactosidase staining kit was utilized to detect SA-β-Gal activity.TUNEL staining was used to measure cell apoptosis.Results The highest cell viability was observed in the cells after 30 μmol/L roxadustat treatment.Heat stress resulted in a significant decrease in cell viability(P＜0.05),elevated protein levels of HIF-1α,Cleaved Caspase-3,p16 and p21(P＜0.05),enhanced SA-β-Gal activity(P＜0.05)and increased percentage of TUNEL-positive cells(P＜0.05)when compared with the cells in the control group.In comparison with the heat-stress group,the heat-stress+roxadustat group showed significant decrease in the protein levels of Cleaved Caspase-3,p16 and p21(P＜0.05),reduced activity of SA-β-Gal[(65.44±5.00)％vs(77.15±2.61)％,P＜0.05]and decreased percentage of TUNEL-positive cells[(16.73±2.20)％vs(46.40±13.87)％,P＜0.05],but increase in cell viability[(86.33±4.51)％vs(66.33±8.50)％,P＜0.05]as well as HIF-1α protein expression(P＜0.05).Furthermore,immunofluorescence assay showed that HIF-1α was mainly distributed in the nucleus and perinucleus.Conclusion Roxadustat attenuates heat stress-induced apoptosis and senescence of renal tubular epithelial cells by upregulating HIF-1α.

Objective:To evaluate the influence of cytomegalovirus (CMV) infection on T cell senescence and cardiovascular disease (CVD) in maintenance hemodialysis (MHD) patients.Methods:It was a single center cross sectional study. Patients aged over 18 years old and received hemodialysis for at least 6 months at the Blood Purification Centre of the Department of Nephrology of Zhongshan Hospital Affiliated to Fudan University from January 2021 to April 2021 were enrolled. Demographic, hematological, nutritional and inflammatory markers were obtained. Anti-CMV-IgM and IgG antibodies were detected using the Roche Elecsys assay. CD28 - T cell was evaluated by flow cytometry. Mann-Whitney U test or Kruskal-Wallis H test was used for anti-CMV-IgG comparison among groups. Spearman correlation and linear regression were used to assess the relationship between anti-CMV-IgG and CD28 - T cell compartment. Logistic regression was used to assess the relationship between anti-CMV-IgG and CVD. Results:A total of 438 MHD patients (270 men and 168 women) were enrolled in the study. The median age was 62 (51, 70) years. The median time on hemodialysis was 57 (21, 100) months. The primary diseases included chronic glomerulonephritis [213 cases (48.6%)], diabetic nephropathy [82 cases (18.7%)], polycystic kidney disease [34 cases (7.8%)], hypertensive renal disease [34 cases (7.8%)], etc. Of these patients, 430 (98.2%) were seropositive for anti-CMV-IgG, 206 (47.0%) had anti-CMV-IgG titers exceeding the upper limit of 500 U/ml. Patients aged over 70 years old were 100% seropositive for anti-CMV-IgG. Patients on HD for more than 5 years had a higher seropositive rate of 99.1% than those with shorter HD duration, although these results were not statistically significant. Spearman correlation analysis showed that the anti-CMV-IgG titers in MHD patients were positively correlated with the proportion of CD4 + CD28 - T cells and CD8 + CD28 - T cells ( r=0.316, P<0.001; r=0.272, P<0.001). Multiple linear regression analysis showed that after adjusting for age and gender, lg[CD4 + CD28 - T cells(%)] and lg[CD8 + CD28 - T cells(%)] were positively correlated with lg[anti-CMV-IgG titers (U/ml)], respectively ( β=0.455, t=8.315, P<0.001; β=0.412, t=7.282, P<0.001). In analyzing the relationship between anti-CMV-IgG titers and CVD, patients were divided into six groups according to age and anti-CMV-IgG level. Group 1 included young patients with a lower anti-CMV-IgG titers (age ≤55 years old, anti-CMV-IgG <400 U/ml); Group 2 included young patients with a higher anti-CMV-IgG titers (age≤55 years old, anti-CMV-IgG ≥400 U/ml); Group 3 included middle-aged patients with a lower anti-CMV-IgG titers (5565 years old, anti-CMV-IgG<400 U/ml); Group 6 included old aged patients with a higher anti-CMV-IgG titers (age>65 years old, anti-CMV-IgG≥400 U/ml). The incidence of CVD was significantly different among the six groups ( χ2=18.780, P=0.002) and patients aged over 55 years old with higher anti-CMV-IgG level had a higher CVD incidence compared with group 1 ( P<0.05). Multivariate logistic regression analysis showed that increased age ( OR=1.020, 95% CI 1.002-1.038, P=0.033), male ( OR=1.855, 95% CI 1.161-2.965, P=0.010), history of diabetes ( OR=1.867, 95% CI 1.145-3.046, P=0.012), increased lg[NT-proBNP(μg/L)] ( OR=2.848, 95% CI 1.816-4.467, P<0.001) and lg[anti-CMV-IgG (U/ml)] ( OR=3.183, 95% CI 1.582- 6.405, P=0.001) were independent factors associated with CVD in MHD patients. Conclusions:CMV infection is extremely common in MHD patients. Increased anti-CMV-IgG is related to T cell senescence and CVD complications in MHD patients.

OBJECTIVE: To investigate how the National Health Commission of China (NHCC)-recommended Chinese medicines (CMs) modulate the major maladjustments of coronavirus disease 2019 (COVID-19), particularly the clinically observed complications and comorbidities. METHODS: By focusing on the potent targets in common with the conventional medicines, we investigated the mechanisms of 11 NHCC-recommended CMs in the modulation of the major COVID-19 pathophysiology (hyperinflammations, viral replication), complications (pain, headache) and comorbidities (hypertension, obesity, diabetes). The constituent herbs of these CMs and their chemical ingredients were from the Traditional Chinese Medicine Information Database. The experimentally-determined targets and the activity values of the chemical ingredients of these CMs were from the Natural Product Activity and Species Source Database. The approved and clinical trial drugs against these targets were searched from the Therapeutic Target Database and DrugBank Database. Pathways of the targets was obtained from Kyoto Encyclopedia of Genes and Genomes and additional literature search. RESULTS: Overall, 9 CMs modulated 6 targets discovered by the COVID-19 target discovery studies, 8 and 11 CMs modulated 8 and 6 targets of the approved or clinical trial drugs for the treatment of the major COVID-19 complications and comorbidities, respectively. CONCLUSION The coordinated actions of each NHCC-recommended CM against a few targets of the major COVID-19 pathophysiology, complications and comorbidities, partly have common mechanisms with the conventional medicines.
COVID-19/physiopathology* ; Comorbidity ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine ; Medicine, Chinese Traditional ; SARS-CoV-2

Objective:To evaluate the effect of acetaminophen on sepsis-associated encephalopathy (SAE) in mice and the relationship with ferroptosis.Methods:A total of 160 clean-grade healthy adult male C57BL/6J mice, aged 6 weeks, weighing 22-24 g, were divided into 4 groups ( n=40 each) using a random number table method: sham operation group (Sham group), sham operation+ acetaminophen group (Sham+ APAP group), SAE group and SAE+ acetaminophen group (SAE+ APAP group). The model of SAE was established by cecal ligation and puncture in anesthetized mice.Acetaminophen 100 mg/kg was intraperitoneally injected at 1 h before the model was established in group Sham+ APAP and group SAE+ APAP.The postoperative 7-day survival rate was recorded.At 24 h after operation, brain tissues were taken for examination of the pathological changes of neurons in hippocampal CA1 region.At 24 h after establishment of the model, ultrastructure was observed with a transmission electron microscope, the contents of reactive oxygen species (ROS), malondialdehyde (MDA) and glutathione (GSH) in hippocampus were determined by colorimetry, and the expression of glutathione peroxidase (GPX4), cystine/glutamate antiporter (xCT) and 4-hydroxy-2-nonenal (4-HNE) was determined by Western blot. Results:Compared with group Sham, the postoperative 7-day survival rate of mice was significantly decreased, contents of ROS and MDA in hippocampus were increased, GSH content in hippocampus was decreased and expression of GPX4 and xCT was down-regulated in SAE and SAE+ APAP groups, 4-HNE expression was up-regulated in group SAE ( P<0.05), and no significant change was found in the parameters mentioned above in group Sham+ APAP ( P>0.05). Compared with group SAE, the postoperative 7-day survival rate of mice was significantly increased, contents of ROS and MDA in hippocampus were decreased, GSH content in hippocampus was increased, expression of GPX4 and xCT was up-regulated and expression of 4-HNE was down-regulated in group SAE+ APAP ( P<0.05). The pathological changes in hippocampal CA1 region and damage to ultrastructure of hippocampal tissue were significantly attenuated in group SAE+ APAP as compared with group SAE. Conclusion:Acetaminophen can effectively alleviate SAE, and the mechanism is related to inhibiting ferroptosis in mice.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become one major threat to human population health. The RNA-dependent RNA polymerase (RdRp) presents an ideal target of antivirals, whereas nucleoside analogs inhibitor is hindered by the proofreading activity of coronavirus. Herein, we report that corilagin (RAI-S-37) as a non-nucleoside inhibitor of SARS-CoV-2 RdRp, binds directly to RdRp, effectively inhibits the polymerase activity in both cell-free and cell-based assays, fully resists the proofreading activity and potently inhibits SARS-CoV-2 infection with a low 50% effective concentration (EC