Objective To explore the possible mechanism of emodin in inhibiting proliferation,migration,and invasion of AGS cells and in suppressing the expressions of YAP1 and FOXD1.Methods Normal gastric cell GES-1 and gastric cancer cell AGS were cultured with different concentrations of emodin.CCK8 test,scratch test and Transwell assay were used to verify changes in the biological phenotype of AGS cells.TCGA database was applied to analyze expressions of HK2,YAP1 and FOXD1 in gastric cancer tissues and normal gastric tissues.Western blotting method was used to detect the impacts of emodin on HK2,YAP1 and FOXD1 proteins in AGS cells.Exogenous pyruvic acid was added to verify the changes in YAP1 and FOXD1.Results The IC50 of emodin was significantly higher in GES-1 cells than in AGS cells(P<0.05).CCK8 proliferation test,scratch test,and Transwell assay showed that emodin significantly inhibited the biological abilities of AGS(P<0.05 for comparisons).Analysis on the TCGA bioinformatics database found that the expression of key enzymes HK2 in the glycolysis pathway and oncogenes YAP1 and FOXD1 was significantly higher in gastric cancer tissues than in normal gastric tissues(P<0.05 for comparisons).Emodin significantly inhibited the protein expressions of key glycolytic enzymes HK2 and oncogenes YAP1 and FOXD1(P<0.05 for comparisons).With supplement of exogenous glycolytic metabolite pyruvate,the protein expressions of oncogenes YAP1 and FOXD1 significantly increased(P<0.05 for comparisons).Conclusions Emodin has a significant pharmacological inhibitory effect on gastric cancer AGS cells,markedly suppressing their biological phenotype.Emodin not only significantly inhibits the key enzyme HK2 in glycolysis metabolism,but also the protein expressions of oncogenes YAP1 and FOXD1.With the addition of exogenous pyruvate to enhance the glycolytic metabolic pathway,the protein expressions of oncogenes YAP1 and FOXD1 significantly increased.The above results suggest a close association of YAP1 and FOXD1 with glycolytic metabolism.Emodin may inhibit oncogenes YAP1 and FOXD1 through the glycolytic metabolism of gastric cancer AGS cells.

Objective To observe the analgesic effects of mild moxibustion on primary dysmenorrhea(PD)rats with cold and dampness stagnation syndrome and its effect on BDNF/TrkB signaling pathway in hypothalamus;To explore its mechanism for the treatment of PD.Methods A total of 32 Wistar non-pregnant female rats were randomly divided into blank group,model group,Western medicine group and mild moxibustion group,with 8 rats in each group.Except for the blank group,the other groups received estradiol benzoate intraperitoneal injection combined with ice bath treatment + oxytocin intraperitoneal injection to establish PD with cold and dampness stagnation syndrome model.The mild moxibustion group received treatment at"Shenque"and"Guanyuan"from the eighth day of modeling for 10 min,and the Western medicine group was given ibuprofen solution intragastically for 4 days.The latency period of rats twisting was observed and the twisting score was calculated,Western blot and PCR were used to detect the expressions of c-fos,BDNF,TrkB protein and mRNA in hypothalamic tissue.Results Compared with the blank group,the model group showed a shortened latency period and an increased twisting score(P<0.01),the expressions of c-fos,BDNF,TrkB protein and mRNA in hypothalamic tissue increased(P<0.01,P<0.05).Compared with the model group,the mild moxibustion group had a longer latency period and lower twisting score(P<0.01),while the expressions of c-fos,BDNF,TrkB protein and mRNA in hypothalamic tissue increased(P<0.01,P<0.05).Conclusion Mild moxibustion may effectively improve the pain state of PD rats with cold and dampness stagnation syndrome.This mechanism may be related to downregulating c-fos expression,inhibiting BDNF/TrkB signaling pathway activation,thereby inhibiting pain signal transmission,regulating pain occurrence and maintenance.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective To investigate the effects and complications of mitral valve membrane replacement surgery with preservation of mitral valve subvalvular structure on cardiac and valve function.Methods A total of 84 patients receiving mitral valve membrane replacement surgery with preserved mitral valve subvalvular structure in the First Affiliated Hospital of Soochow University from August 2019 to July 2022 were selected as the observa-tion group,and 68 patients receiving mitral valve membrane replacement surgery without preservingmitral valve subvalvular structure were selected as the control group.The surgical indicators,comorbidities,preoperative and postoperative cardiac function,and mitral valve hemodynamic parameters were compared between the two groups.Results There was no statistically significant difference between the observation group and the control group in terms of surgical history,extracorporeal circulation time,aortic occlusion time,postoperative mechanical ventilation time,ICU retention time,and postoperative hospitalization time(P>0.05).At 1,3,and 6 months after surgery,the left ventricular end systolic diameter(LVESD)and left ventricular end diastolic diameter(LVEDD)in the observation group were significantly lower than those in the control group(P<0.05),while the left ventricular short axis shortening rate(LVFS)was significantly higher than that in the control group(P<0.05).There was no statistically significant difference in left ventricular ejection fraction(LVEF)between the observation group and the control group at 1,3,and 6 months after surgery(P>0.05).There was no statistically significant difference(P>0.05)in the peak mitral valve velocity(Vmax),maximum pressure gradient difference(PGmax),and mean pressure gradi-ent difference(PGmean)between the observation group and the control group at 1,3,and 6 months after surgery.There was no statistically significant difference in creatine kinase isoenzyme(CK-MB)and N-terminal precursor brain natriuretic peptide(NT-proBNP)between the observation group and the control group at 1,3,and 6 months after surgery(P>0.05).There was no statistically significant difference in the incidence of postoperative complica-tions between the observation group and the control group(P>0.05).Conclusion The preservation of the mitral valve subvalvular structure and mitral membrane replacement surgery improved patient cardiac function,while there was no significant difference in mitral valve orifice blood flow parameters and complications compared with surgery without preservation of the mitral valve subvalvular structure.

Objective:In order to explore the impact of corona virus disease 2019(COVID-19)on the hospitalization of children with bronchiolitis and to improve clinicians′ understanding of the characteristics of bronchiolitis during the COVID-19 epidemic.Methods:This was a multicenter clinical study, and the data have been collected from 23 children′s medical centers in China.All the clinical data were retrospectively collected from children with bronchiolitis who were hospitalized at each study center from January 1, 2019 to December 31, 2021.The results included gender, age at hospitalization, length of stay, respiratory syncytial virus(RSV) test results, severity rating, ICU treatment, and the total number of children hospitalized with respiratory tract infection during the same period.The clinical data of children with bronchiolitis in 2019 before COVID-19 epidemic and in 2020、2021 during COVID-19 epidemic were statistically analyzed and compared.Results:According to a summary of data provided by 23 children′s medical centers, there were 4 909 cases of bronchiolitis in 2019, 2 654 cases in 2020, and 3 500 cases in 2021.Compared with 2019, the number of bronchiolitis cases decreased by 45.94% in 2020 and 28.70% in 2021.In 2019, 2020 and 2021, there were no significant differences in gender ratio, age, and duration of hospitalization.Compared with 2019, the ratio of bronchiolitis to the total number of hospitalizations for respiratory tract infection decreased significantly in 2020 and 2021( χ2=12.762, P<0.05; χ2=84.845, P<0.05).The proportion of moderate to severe bronchiolitis cases in both 2020 and 2021 was lower than that in 2019, and the difference was statistically significant ( χ2=4.054, P<0.05; χ2=8.109, P<0.05).There was no statistically significant difference in the proportion of bronchiolitis cases requiring ICU treatment between 2019, 2020, and 2021 ( χ2=1.914, P>0.05).In 2019, a total of 52.60%(2 582/4 909) of children with bronchiolitis underwent RSV pathogen testing, and among them, there were 708 cases with RSV positive, accounting for 28.00%.In 2020, 54.14%(1 437/2 654) of children with bronchiolitis underwent RSV pathogen testing, and there were 403 cases with RSV positive, accounting for 28.04%.In 2021, 66.80%(2 238/3 500) of children with bronchiolitis underwent RSV pathogen testing, and there were 935 cases with RSV positive, accounting for 41.78%.Compared with 2019 and 2020, the RSV positive rate in 2021 showed a significant increase( χ2=99.673, P<0.05; χ2=71.292, P<0.05). Conclusion:During the COVID-19 epidemic, the implementation of epidemic prevention and control measures reduced the hospitalization rate and severity of bronchiolitis, but did not reduce the positive rate of RSV detection.

Astragali Radix(AR)is a clinically used herbal medicine with multiple immunomodulatory activities that can strengthen the activity and cytotoxicity of natural killer(NK)cells.However,owing to the complexity of its composition,the specific active ingredients in AR that act on NK cells are not clear yet.Cell membrane chromatography(CMC)is mainly used to screen the active ingredients in a complex system of herbal medicines.In this study,a new comprehensive two-dimensional(2D)NK-92MI CMC/C18 column/time-of-flight mass spectrometry(TOFMS)system was established to screen for potential NK cell acti-vators.To obtain a higher column efficiency,3-mercaptopropyltrimethoxysilane-modified silica was synthesized to prepare the NK-92MI CMC column.In total,nine components in AR were screened from this system,which could be washed out from the NK-92MI/CMC column after 10 min,and they showed good affinity for NK-92MI/CMC column.Two representative active compounds of AR,isoastragaloside Ⅰ and astragaloside Ⅳ,promoted the killing effect of NK cells on K562 cells in a dose-dependent manner.It can thus suggest that isoastragaloside Ⅰ and astragaloside Ⅳ are the main immunomodulatory compo-nents of AR.This comprehensive 2D NK-92MI CMC analytical system is a practical method for screening immune cell activators from other herbal medicines with immunomodulatory effects.

Objective:To investigate the relationship between calf circumference and appendicular skeletal muscle mass (ASM) index, handgrip strength and gait speed in the elderly in Shanghai, and to explore the optimal cut-off point of calf circumference as a simple proxy marker of skeletal muscle mass, strength and function.Methods:A total of 2 294 participants were recruited from physical examination centers in Huadong Hospital Affiliated to Fudan University and 4 communities (954 males and 1 340 females) with an average age of (71.6±8.7) years. Appendicular skeletal muscle mass (ASM), Upper (UMM) and lower (LMM) limbs skeletal muscle mass were measured by bioelectrical impedance analysis (BIA). The ASM index (ASM/height 2) were calculated.Gait speed was measured.Muscle strength was measured by handgrip strength using an electronic hand dynamometer.Height, weight, right calf circumference and waist circumference were measured. Results:The age, body mass index (BMI), waist circumference and gait speed were not statistically different (all P>0.05) between both genders. Height, weight, ASM, ASM/height 2, UMM, LMM, handgrip strength, calf circumference were significantly higher in men than in women (all P<0.05). The calf circumference of the elderly with age ≥ 80 was significantly lower than that of the 70-79 age group and 60-69 age group ( P<0.05). The calf circumference of older women (age≥80) was significantly lower than that of the elderly women in the 70-79 age group and 60-69 age group ( P<0.05). Calf circumference was correlated negatively with age( P<0.01) and positively with ASM/height 2, height, weight, BMI, handgrip strength, UMM and LMM( P<0.01). There was no correlation between calf circumference and gait speed ( P>0.05). In the receiver operating characteristic curve (ROC), the cut-off value of calf circumference for low muscle mass was 35.1 cm for male(specificity, 0.721; sensitivity, 0.803, ROC, 0.809) and 33.6 cm for female(specificity, 0.774; sensitivity, 0.778; ROC, 0.827). Conclusions:Calf circumference decreases with ageing in the elderly. The optimal cut-off value of calf circumference for low muscle mass is 35.1 cm for males and 33.6 cm for females. We should pay attention to the importance of calf circumference in evaluation and diagnosis of sarcopenia.

Objective To describe the evaluation method of uncertainty in measurement of depth individual dose equivalent.Methods Based on the performance of the personal dosimeter,GUM method was used to evaluate the uncertainty of Hp(10) measurement by using a personal dosimeter.Results The relative extended uncertainty was 28％ when the measurement result was corrected by nonlinear response and energy response,as well as 33％ when not corrected in the same way.Conclusions This method can be used to effectively evaluate the uncertainty arising from personal dose equivalent Hp(10) measurement in routine monitoring.

Objective To study the changes in protein expression levels of 8 oxide of guanine in the temporal and frontal lobes in SAMP8 (senescence accelerated mice)mice versus SAMR1 (control mice).Methods In the study,we collected 12 SAMP8 mice and 12 SAMR1 mice at different month stage(1m,4m,8m,12m)(n=6,each group).After anesthesia,mice were sacrificed.The temporal and frontal lobe tissues of mice were labeled according to the stereotactic anatomical map of mouse brain and taken up for study.After paraffin sections were made,the expression level of 8 oxide of guanine in brain tissues was detected by immunohistochemical method.Results In the same age group at 1 month in the same temporal lobe,the average optical density of 8-oxodG was slightly higher in SAMP8 mice(0.086)than in SAMR1 mice(0.061,t =1.541,P＞0.05).There were significant differences in the mean optical density of 8-oxodG in temporal lobe in 4,8 and 12 months groups between SAMP8 and SAMR1 group(0.101 vs.0.081,0.147 vs.0.109 and 0.176 vs.0.120,t =2.405,2.612 and 5.019,respectively,P ＜0.05).There was no significant difference in the average optical density levels of 8-oxodG in frontal lobe in 1 and 4 months groups between SAMP8 and SAMR1 mice (0.044 vs.0.030,0.062 vs.0.046,t =1.843 and 1.163,respectively,P ＞ 0.05),while the average optical density levels of 8-oxodG in 8 and 12 months groups(0.090 and 0.138)were higher than those of SAMR1 mice in the same age group(0.049 and 0.063)(t =5.327 and 4.88,P＜0.01).There was no significant difference in the average optical density of 8-oxoG in temporal lobe in 1 month group between SAMP8 and SAMR1 mice(0.099 vs.0.066,t =1.956,P ＞0.05).There were significant differences in the average optical density levels of 8-oxoG in temporal lobe in 4,8 and 12 months groups between SAMP8 and SAMR1 mice(0.119 vs.0.076,0.148 vs.0.094 and 0.173 vs.0.101,t =4.033,3.042 and 5.328,respectively,P＜0.01).There was no significant difference in the average optical density levels of 8-oxoG in frontal lobe in 1 month and 4 months groups between SAMP8 and SAMR1 mice(0.049 vs.0.039,0.058 vs.0.056,t =0.713 and 0.172,respectively,P ＞0.05).The average optical density of 8-oxoG in frontal lobe in 8 months and 12 months groups had significant differences between SAMP8 and SAMR1 mice(0.087 vs.0.058,0.12 vs.0.063,t =2.261 and 4.185,P ＜0.05).In addition,we also found that the average optical density of 8 oxide of guanine in same SAMP8 mice at the same age was higher in temporal lobe than in frontal lobe.Conclusions The protein levels of 8-oxodG and 8-oxoG are increased with age,and the damage caused by nucleic acid oxidation is more severe in temporal lobe than in frontal lobe in SAMP8 mice.

Objective To investigate the influence mechanism of Cordyceps sinensis (CS) on β-glycerophosphate-induced vascular smooth muscle cell (VSMC) calcification.Methods The effect of CS on VSMC cell viability was detected by CCK-8.The cellular models of rat VSMC calcification were established by treating with β-glycerophosphate (β-GP,10 mmol/L);then CS (10 mg/L),autophagy inhibitor 3-methyladenine (3-MA,5 mmol/L),and AMPK inhibitor compound C (CC,10 μmol/L) were added to the cell cultures.There were a total of 5 experiment groups:VSMC cultured in normal medium (Control),VSMC treated with β-GP,VSMC treated with β-GP and CS,VSMC treated with 3-MA,β-GP and CS,and VSMC treated with CC,β-GP and CS.The calcium nodules and calcium content were examined with alizarin red S staining and the O-cresolphthaleincomplexone method,respectively.The autophagosomes within the VSMC were observed using transmission electron microscope (TEM).Immunofluorescence showed the accumulation of microtubule-associated protein 1 light chain 3 (LC3) puncta.In addition,levels of osteogenic related proteins,autophagy related proteins,and AMPK/mTOR pathway related proteins were evaluated by Western blotting.Results CS increased the number of autophagosomes and the accumulation of LC3 puncta within VSMC.It also upregulated the protein levels of LC3 Ⅱ/LC3 Ⅰ,beclin1,α-SMA,and p-AMPK;whereas,the protein levels of Runx2 and p-mTOR,as well as calcium nodules and calcium content were reduced (all P ＜ 0.01).When the cells were pretreated with 3-MA before treating with β-GP and CS,the autophagosomes,accumulation of LC3 puncta,and protein levels of LC3 Ⅱ/LC3 Ⅰ,beclinl,and α-SMA were decreased (all P ＜ 0.01);however,the protein level of Runx2,and the calcium nodules and calcium content were increased (all P ＜ 0.01).Nevertheless,when the cells were pretreated with CC before giving β-GP and CS,the autophagosomes,the accumulation of LC3 puncta,and the expression levels of p-AMPK,LC3 Ⅱ/LC3 Ⅰ,beclin1,and α-SMA were significantly down-regulated (all P ＜ 0.01);whereas,the expression levels of Runx2 and p-mTOR,as well as calcium nodules and calcium content were increased (all P ＜ 0.01).Conclusions CS can effectively alleviate β-GP-induced VSMC calcification,which may be due to the activation of autophagy by AMPK/mTOR signaling pathway.