BACKGROUND:Rev-erbα is involved in the regulation of inflammation,but pharmacological activation of Rev-erbα increases the risk for cardiovascular diseases.To reduce the relevant risk,an exploration on SR9009,a Rev-erbα agonist,combined with other drugs to relieve inflammation in skeletal myoblasts was conducted,laying the theoretical foundation for the treatment of inflammation-associated skeletal muscle atrophy. OBJECTIVE:To investigate the relationship of SR9009,indolepropionic acid and nuclear factor-κB signaling pathways in lipopolysaccharide-induced C2C12 myoblasts. METHODS:(1)C2C12 myoblasts were induced to differentiate in the presence of lipopolysaccharide(1 μg/mL).RNA-seq and KEGG pathway analysis were used to study signaling pathways.(2)C2C12 myoblast viability was assessed using the cell counting kit-8 assay to determine optimal concentrations of indolepropionic acid.Subsequently,cells were categorized into control group,lipopolysaccharide(1 μg/mL)group,SR9009(10 μmol/L)+lipopolysaccharide group,indolepropionic acid(80μmol/L)+lipopolysaccharide group,and SR9009+indolepropionic acid+lipopolysaccharide group.ELISA was employed to measure protein expression levels of interleukin-6 in the cultured supernatant.Real-time quantitative PCR were employed to measure mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Western blot assay were employed to measure protein expression levels of NF-κB p65 and p-NF-κB p65.(3)After Rev-erbα was knocked down by siRNA,knockdown efficiency was assessed by RT-qPCR.And mRNA levels of interleukin-6 and tumor necrosis factor α were also measured. RESULTS AND CONCLUSION:Compared with the blank control group,lipopolysaccharide time-dependently inhibited myofibroblast fusion to form myotubes,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were elevated,and the level of interleukin-6 in the cell supernatant was significantly increased.The results of KEGG pathway showed that the nuclear factor-κB signaling pathway was activated by lipopolysaccharide.Indolepropionic acid exhibited significant suppression of C2C12 myoblasts viability when its concentration exceeded 80 μmol/L.Indolepropionic acid and SR9009 inhibited the activation of NF-κB signaling pathway,thereby played an anti-inflammatory role,and suppressed the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Compared with the lipopolysaccharide group,the ratio of p-NF-κB p65/NF-κB p65 protein expression were downregulated.SR9009 combined with indolepropionic acid notably reduced lipopolysaccharide-induced inflammation,further downregulated the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.The ratio of p-NF-κB p65/NF-κB p65 protein expression was significantly lower than that in the SR9009+lipopolysaccharide group or indolepropionic acid+lipopolysaccharide group.Rev-erbα increases time-dependently with lipopolysaccharide induction.The knockdown efficiency of Rev-erbα by siRNA reached over 58%,and lipopolysaccharide was added after Rev-erbα was successfully knocked down.Compared with the lipopolysaccharide group,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were significantly up-regulated.These results conclude that Rev-erbα may act as a promising pharmacological target to reduce inflammation.SR9009 targeted activation of Rev-erbα combined with indolepropionic acid significantly inhibits the nuclear factor-κB signaling pathway and attenuates the inflammatory response of C2C12 myofibroblasts.Moreover,the combined anti-inflammatory effect is superior to that of the intervention alone.

Objective:To evaluate the immunogenicity, safety, and immune persistence of the sequential booster with the recombinant protein-based COVID-19 vaccine (CHO cell) in healthy people aged 18-84 years.Methods:An open-label, multi-center trial was conducted in October 2021. The eligible healthy individuals, aged 18-84 years who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, were recruited from Shangyu district of Shaoxing and Kaihua county of Quzhou, Zhejiang province. All participants were divided into three groups based on the differences in prime-boost intervals: Group A (3-4 months), Group B (5-6 months) and Group C (7-9 months), with 320 persons per group. All participants received the recombinant COVID-19 vaccine (CHO cell). Blood samples were collected before the vaccination and after receiving the booster at 14 days, 30 days, and 180 days for analysis of GMTs, antibody positivity rates, and seroconversion rates. All adverse events were collected within one month and serious adverse events were collected within six months. The incidences of adverse reactions were analyzed after the booster.Results:The age of 960 participants was (52.3±11.5) years old, and 47.4% were males (455). The GMTs of Groups B and C were 65.26 (54.51-78.12) and 60.97 (50.61-73.45) at 14 days after the booster, both higher than Group A′s 44.79 (36.94-54.30) ( P value<0.05). The GMTs of Groups B and C were 23.95 (20.18-28.42) and 27.98 (23.45-33.39) at 30 days after the booster, both higher than Group A′s 15.71 (13.24-18.63) ( P value <0.05). At 14 days after the booster, the antibody positivity rates in Groups A, B, and C were 91.69% (276/301), 94.38% (302/320), and 93.95% (295/314), respectively. The seroconversion rates in the three groups were 90.37% (272/301), 93.75% (300/320), and 93.31% (293/314), respectively. There was no significant difference among these rates in the three groups (all P values >0.05). At 30 days after the booster, antibody positivity rates in Groups A, B, and C were 79.60% (238/299), 87.74% (279/318), and 90.48% (285/315), respectively. The seroconversion rates in the three groups were 76.92% (230/299), 85.85% (273/318), and 88.25% (278/315), respectively. There was a significant difference among these rates in the three groups (all P values <0.001). During the sequential booster immunization, the incidence of adverse events in 960 participants was 15.31% (147/960), with rates of about 14.38% (46/320), 17.50% (56/320), and 14.06% (45/320) in Groups A, B, and C, respectively. The incidence of adverse reactions was 8.02% (77/960), with rates of about 7.50% (24/320), 6.88% (22/320), and 9.69% (31/320) in Groups A, B, and C, respectively. No serious adverse events related to the booster were reported. Conclusion:Healthy individuals aged 18-84 years, who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, have good immunogenicity and safety profiles following the sequential booster with the recombinant COVID-19 vaccine (CHO cell).

Objective:To explore the cortical abnormalities in brain regions in adolescent with self-injury and the correlation between cortical structural changes and clinical emotional manifestations.Methods:From April 2023 to June 2024, totally 38 adolescents with self-injury(self-injury group) from psychological outpatient department of First People’s Hospital of Changzhou and 41 healthy volunteers (HC group) matched with age, gender and years of education were selected.T1-weighted magnetic resonance imaging and clinical data of all participants were collected. All of them were investigated by the 17-item Hamilton depression scale (HAMD-17) and Hamilton anxiety scale (HAMA). Image preprocessing and surface-based morphometry analysis were performed by the DPABISurf software. Cortical parameters from regions showing significant differences were extracted, which were then evaluated the correlation with the emotional scores based on Spearman correlation analysis by SPSS 29.0 software.Results:Compared with HC group, self-injury group showed reduced thickness in areas primarily involving the left somatosensory and motor cortex, left paracentral lobular and mid cingulate cortex, left posterior cingulate cortex and premotor cortex(MNI: cluster 1: x=-17.73, y=-32.81, z=43.87, cluster 2: x=-35.97, y=-8.72, z=52.01, cluster 3: x=-18.94, y=-41.39, z=65.94)(all P<0.05). Lower sulcal depth in the left orbital and polar frontal cortex (MNI: x=-39.9, y=47.92, z=-5.42) ( P<0.05) and higher mean curvature in the right superior parietal cortex (MNI: x=21.89, y=-61.89, z=50.55) ( P<0.05) were found in the self-injury group. In the self-injury group, Spearman correlation analysis revealed negative correlations between cortical thickness in the regions of interest and clinical emotional scores (HAMD-17: r=-0.385, -0.332, P<0.05; HAMA: r=-0.395, -0.481, P<0.05), primarily involving the left supplementary motor area, left premotor cortex and the left somatosensory and motor cortex. Conclusion:The perception and execution cortex of adolescents with self-injury shows surface morphological abnormalities, which may be relevant to clinical emotional manifestations.

Objective To investigate the therapeutic effect and prognostic significance of lateral lymph node dissection (LPLND) in patients with lateral lymph node (LPLN) metastasis. Methods The clinicopathological data of rectal cancer patients who underwent total mesorectal excision (TME) combined with LPLND and pathologically confirmed as LPLN metastasis after operation were retrospectively analyzed. The clinicopathological characteristics and metastasis rules of patients with LPLN metastasis were discussed, and the survival prognosis after LPLND was analyzed. Results A total of 102 rectal cancer patients with pathologically confirmed LPLN metastasis were included. The common sites of LPLN metastasis were internal iliac vessels lymph nodes (n=68, 66.7%), followed by obturator lymph nodes (n=44, 43.1%), and common iliac vessels or external iliac vessels lymph nodes (n=12, 11.8%). There were 10 patients (9.8%) with bilateral LPLN metastases, and the mean number of LPLN metastases was 2.2±2.4, among which 16 patients (15.7%) had LPLN metastases number≥2. The 3-year OS (66.8% vs. 7.7%, P < 0.001) and DFS (39.1% vs. 10.5%, P=0.012) of patients with LPLN metastases to the external iliac or common iliac lymph node were significantly lower than those with metastases to the internal iliac or obturator lymph node. The multivariate analysis showed that LPLN metastasis to external iliac or common iliac lymph node was an independent risk factor both for OS (HR=3.53; 95%CI: 1.50-8.31; P=0.004) and DFS (HR=2.40; 95%CI: 1.05-5.47; P=0.037). Conclusion LPLN mainly metastasizes to the internal iliac or obturator lymph node areas. The survival of patients with metastasis to the external iliac or common iliac lymph node cannot be improved by LPLND, and thus systemic comprehensive treatment is often the optimal treatment option.

It is a common problem for all mentors to cultivate the capacity for scientific research of master degree candidates in plastic surgery under the current training program of "double-track in one" and "four-certificate in one". This study introduces the "COME" training mode that includes clinical study, off-hour, multiple modalities, and efficient feedback. This study elaborates the composition and method of this training mode, and compares the number and quality of published papers and thesis before and after its implementation. Results show that the "COME" training mode can significantly improve the capacity for scientific research of master degree candidates in plastic surgery.

Objective:To use metagenomic sequencing to compare the differences in intestinal microbiota species and metabolic pathways in patients with hepatitis B cirrhosis with or without ascites and further explore the correlation between the differential microbiota and clinical indicators and metabolic pathways.Methods:20 hepatitis B cirrhosis cases [10 without ascites (HBLC-WOA), 10 with ascites (HBLC-WA), and 5 healthy controls (HC)] were selected from the previously studied 16S rRNA samples. Metagenome sequencing was performed on the intestinal microbiota samples. The Kruskal-Wallis rank sum test and Spearman test were used to identify and analyse differential intestinal microbiota populations, metabolic pathways, and their correlations.Results:(1) The overall structure of the intestinal microbiota differed significantly among the three groups ( R = 0.19, P = 0.018). The HC group had the largest abundance of Firmicutes and the lowest abundance of Proteobacteria at the genus level. Firmicutes abundance was significantly decreased ( Pfdr < 0.01), while Proteobacteria abundance was significantly increased ( Pfdr < 0.01) in patients with cirrhosis accompanied by ascites; (2) LEfSe analysis revealed that 29 intestinal microbiota (18 in the HBLC-WA group and 11 in the HBLC-WOA group) played a significant role in the disease group. The unclassified Enterobacteriaceae and Klebsiella species in the HBLC-WA group and Enterobacteriaceae in the HBLC-WOA group were positively correlated with the Child-Turcotte-Pugh (CTP) score, prothrombin time, and international normalized ratio score and negatively correlated with albumin and hemoglobin levels ( P < 0.05). Escherichia and Shigella in the HBLC-WA group were positively correlated with CTP scores ( P < 0.05); (3) The correlation analysis results between the KEGG pathway and 29 specific intestinal microbiota revealed that Enterobacteriaceae and arachidonic acid, α-linolenic acid, glycerolipid metabolism, and fatty acid degradation were positively correlated in the lipid metabolism pathway, while most Enterobacteriaceae were positively correlated with branched-chain amino acid degradation and negatively correlated with aromatic amino acid biosynthesis in the amino acid metabolic pathway. Conclusion:A significant increment of Enterobacteriaceae in the intestines of HBLC-WA patients influenced hepatic reserve function and was associated with amino acid and lipid metabolic pathways. Therefore, attention should be paid to controlling the intestinal microbiota to prevent complications and improve the prognosis in patients with hepatitis B cirrhosis, especially in those with ascites.

It is a common problem for all mentors to cultivate the capacity for scientific research of master degree candidates in plastic surgery under the current training program of "double-track in one" and "four-certificate in one". This study introduces the "COME" training mode that includes clinical study, off-hour, multiple modalities, and efficient feedback. This study elaborates the composition and method of this training mode, and compares the number and quality of published papers and thesis before and after its implementation. Results show that the "COME" training mode can significantly improve the capacity for scientific research of master degree candidates in plastic surgery.

Tripterygium wilfordii Hook. F. (TWF) belongs to celastraceae under Tripterygium family. It is a traditional Chinese medicine with a variety of pharmacological effects such as anti- inflammatory, analgesic, anti- tumor, immunomodulation and so on, which is applied for many diseases because of its significant effects. However, its toxic and side effects frequently occur, especially liver injury, affecting its safety in clinical practice. In this paper, the clinical characteristics of liver injury of TWF were preliminarily explored by combining with literature analysis and single center clinical epidemiological investigation. Furthermore, the main toxic constituents and mechanism of TWF are reviewed. Finally, the key issues have been raised and analyzed on clinical diagnosis, clinical characteristics and toxicological mechanism of liver injury of TWF, and brought forward the future research directions.

This study chiefly aimed at investigating the effects of Dan Zhi Jiang Tang Capsule (DJC) on myocardial Toll-like receptor 4 (TLR4),tumor necrosis factor α (TNFα) and interleukin-8 (IL-8) and the cardiopathologic changes in diabetic rats.Fifty male rats,excluding 8 rats in the control group,had been administered with high fat forage for 4 weeks,which established the diabetic rat model combined with the intraperitoneal injection of streptozotocin (STZ) at 35 mg· kg-1.The established model rats were randomly divided into the model group,the DJC high-dose group,the DJC low-dose group and the pioglitazone group.The rats in the model group and the control group were intragastrically administered with DJC at 1.08 and 0.54 g· kg-1 each day,while those of the pioglitazone group were treated with pioglitazone at 10 mg· kg-1 each day,and those of the model group and control group with saline of the same volume.The administrations lasted 8 weeks with the continues high-fat diet.The levels of TLR4,TNFα and IL-8 protein in myocardium of the rats were determined,and so were the blood glucose,HbA1c and blood lipids.Compared with the control group,the expressions of myocardial TLR4,TNFα and IL-8 in the model group were significantly increased (P＜ 0.01).The expressions of TLR4,TNFα and IL-8 in the DJC high-dose and low-dose groups were significantly decreased (P＜0.05 or P＜0.01).The cardiopathological report showed severe myocardial lesion in the model group.However,myocardial lesion in the DJC high-dose group was significantly mitigated,which presented better therapeutic effects than the DJC low-dose group and the pioglitazone group.The levels of blood glucose,HbA1c,TG,TC,LDL-C in the model group were significantly higher than those in the control group (P＜0.05 or P＜0.01).The levels of blood glucose,HbA1c,TG,TC and LDL-C were significantly decreased in the DJC high-dose and low-dose groups in comparison with the model group (P＜ 0.05 or P＜ 0.01).In conclusion,DJC down-regulated the expressions of TLR4,TNFα and IL-8 and improved the degree of myocardial lesion in the diabetic rats,showing favorable hypoglycemic and lipid-lowering effects.

Objective To observe the effect of Danzhi Jiangtang Capsules(DJC) on serum interleukin-18 (IL-18),cystatin C (CysC) and relative biochemical indexes in patients with early diabetic kidney disease(DKD),and to explore its protective action on the kidney.Methods Sixty-two hospitalized patients with early diabetic nephropathy (period 11-Ⅲ) in Endocrinology Department of the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine were divided into western medicine group and DJC group,31 cases in each group.The patients in western medicine group received conventional hypoglycemic drugs,and DJC group received DJC based on the treatment for the western medicine group.Before and after treatment,we observed the levels of serum IL-18,CysC,fasting plasma glucose (FPG),2-hour postprandial glucose (2hPG),glycosylated hemoglobin (HbA1c),serum creatinine (SCr),blood urea nitrogen (BUN),microalbumin (mAlb),urinary albumin /creatinine ratio (UACR),and estimated glomerular filtration rate (eGFR).Results The total effective rate was 90.0％ in DJC group and 76.7％ in the western medicine group,there being significant difference between the two groups(P ＜ 0.05).After treatment,the main traditional Chinese medical syndrome scores of DJC group were significantly lower than those before treatment,and the improvement was better than that of the western medicine group (P ＜ 0.05 or P ＜ 0.01).After treatment,the serum levels of IL-18,CysC,2hPG,SCr,BUN,mAlb,UACR in the two groups were significantly lower than those before treatment (P ＜ 0.05 or P ＜ 0.01),while eGFR level was higher than that before treatment (P ＜ 0.05 or P ＜ 0.01),and the improvement effect (except for BUN) in the DJC group was superior to that in the western medicine group(P ＜ 0.01).DJC had an effect on lowering the FPG and HbA1c (P ＜ 0.05 or P ＜ 0.01 compared with those before treatment),and the western medicine had no obvious effect on the two indexes (P ＞ 0.05).The results of Spearman correlation analysis showed that IL-18 was correlated with CysC,IL-18 and CysC were correlated with HbA1c,mALB and uACR.Conclusion DJC can protect renal function of patients with early diabetic nephropathy.