ObjectiveTo study the effect and mechanism of Shentong Zhuyutang in treating intervertebral disc degeneration （IDD） in rats. MethodsIn the cell experiment， male rats were administrated with normal saline or low-， medium-， and high-dose （3.38， 6.75，13.5 g·kg^-1， respectively） Shentong Zhuyutang by gavage， respectively， and serum samples were collected after 7 days of continuous administration. Another 10 male rats were selected for the isolation of nucleus pulposus cells. The cell model of IDD was established by treatment with interleukin （IL）-1β. The modeled cells were then treated with Shentong Zhuyutang-containing serum and the ferroptosis inhibitor ferrostatin-1 （Fer-1）， respectively， to investigate the effects of Shentong Zhuyutang-containing serum on the proliferation and ferroptosis of nucleus pulposus cells. To study the role of silent information regulator 1 （SIRT1）/nuclear factor erythroid 2-related factor 2 （Nrf2） in the regulation of ferroptosis in nucleus pulposus cells by Shentong Zhuyutang-containing serum， this study treated the cells with the SIRT1 inhibitor Ex 527 and the Nrf2 inhibitor ML385， respectively， in addition to the treatment with IL-1β and high-dose Shentong Zhuyutang-containing serum. The cell-counting kit-8 （CCK-8） assay and EdU staining were employed to measure the cell viability and proliferation， respectively. The Fe²⁺， glutathione （GSH）， and malondiadehyde （MDA） levels were measured by colorimetric assay. Western blot was employed to determine the protein levels of glutathione peroxidase 4 （GPX4）， acyl-CoA synthetase long-chain family 4 （ACSL4）， Collagen Ⅱ， Aggrecan， SIRT1， and Nrf2. Immunofluorescence was used detect SIRT1 expression. In the animal experiment， male rats were treated with anulus puncture for the modeling of IDD. Rats were randomly assigned into sham operation， model， Shentong Zhuyutang-containing serum （13.5 g·kg^-1）， and positive control （nimesulide dispersible tablets， 0.18 mg·kg^-1） groups. Rats in the drug intervention groups were administrated with corresponding agents at 1 mL·kg^-1， and those in the sham operation and model groups were administrated with equal volumes of normal saline， once daily for 28 consecutive days. At the end of the last administration， the histopathological changes in the intervertebral discs of rats were observed by hematoxylin-eosin staining and scored by the Masuda method. Western blot was employed to determine the protein levels of SIRT1， Nrf2， GPX4， and Collagen Ⅱ in the nucleus pulposus tissue. ResultsCompared with the control group， the IL-1β group of nucleus pulposus cells showed elevated levels of Fe²⁺， MDA， and ACSL4 （P<0.05）， decreased cell viability， lowered GSH level， and down-regulated protein levels of GPX4， Collagen Ⅱ， and Aggrecan （P<0.05）. Shentong Zhuyutang-containing serum and Fer-1 reversed the effects of IL-1β on the viability and ferroptosis of nucleus pulposus cells and up-regulated the protein levels of Collagen Ⅱ and Aggrecan in nucleus pulposus cells （P<0.05）. Compared with the control group， the IL-1β group showcased down-regulated expression of Sirt1 and Nrf2 in nucleus pulposus cells （P<0.05）. Compared with the IL-1β group， the high-dose Shentong Zhuyutang-containing serum+IL-1β group showed up-regulated expression of SIRT1 and Nrf2 in nucleus pulposus cells （P<0.05）. Compared with the high-dose Shentong Zhuyutang-containing serum+IL-1β group， the ML385 group showed down-regulated protein levels of Nrf2 and GPX4， lowered GSH level， and elevated Fe²⁺ and MDA levels （P<0.05）. In addition， the Ex 527 group showed down-regulated protein levels of SIRT1， Nrf2， and GPX4 （P<0.05）. The results of the animal experiment showed that compared with the sham operation group， the model group had severe degeneration of the intervertebral disc tissue with increased pathological score， up-regulated protein level of ACSL4 （P<0.05）， and down-regulated protein levels of SIRT1， Nrf2， GPX4， and Collagen Ⅱ （P<0.05）. Compared with the model group， the Shentong Zhuyutang group showed alleviated IDD with declined pathological score， down-regulated protein level of ACSL4 （P<0.05）， and up-regulated protein levels of SIRT1， Nrf2， GPX4， and Collagen Ⅱ （P<0.05）. ConclusionShentong Zhuyutang may activate the SIRT1/Nrf2 signaling pathway to inhibit the ferroptosis of nucleus pulposus cells， thereby delaying the process of IDD in rats.

Objective To investigate the regulatory effect of small interfering RNA(siRNA)silencing zinc finger protein A20 on pyroptosis of rheumatoid arthritis(RA)fibroblast-like synoviocytes(HFLS-RA).Methods Hu-man FLS-RA cell line MH7A cells were cultivated,A20 siRNA silencing group was synthesized for knocking down the human A20 gene,and then specific A20 gene siRNA and siRNA-NC(negative control)were transfected into MH7A cells using liposome method.RT-qPCR was applied to detect the expression of NLRP3 and Caspase-1 mRNA in cells.The protein expression of NLRP3 and Caspase-1 was detected by Western blot,and IL-1β and IL-18 in cell culture medium were detected by ELISA method.Transmission electron microscopy(TEM)was used to detect pyroptosis.Results After A20 knockdown,the mRNA and expression of NLRP3 and Caspase-1 in MH7A cells in the siRNA-A20 group were significantly increased as compared with the siRNA-NC group(P＜0.01).The concentration of IL-1β and IL-18 in the cell culture supernatant of the siRNA-A20 group was sig-nificantly increased compared with the siRNA-NC group(P＜0.01).Compared with the siRNA-NC group,some cells in the siRNA-A20 group showed swollen and ruptured.The integrity of the cell membrane was also lost,and a large area of edema was present in the cell.In addition,a blurred depression of the local nuclear membrane was noted,while an increase in heterochromatin pyknosis was accompanied by their uneven distribution as well as their aggregation around the nuclear membrane.Conclusions Silencing of A20 gene with siRNA might promote NLRP3/Caspase-1 mediated pyroptosis in HFLS-RA,which lays an experimental foundation for new clinical treatment meth-ods of RA.

Rheumatoid arthritis(RA)is an autoimmune disease with an early clinical manifestation of symmetric small joint pain,which gradually worsens and often involves multiple joints,ultimately result ing in arthritic deformities and loss of labor capacity.Molecular signaling pathways have been a focus of research regarding the prevention and treatment of RA,and the progression of RA has been shown to be closely related to various signaling pathways,including the Janus kinase-signal transducer and activator of transcription,mitogen-activated protein kinase,NOD-like receptor protein 3,Toll-like receptor,Wnt,Notch,hypoxia-inducible factor 1-α and vascular endothelial growth factor,programmed death factor 1 and ligand 1,and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathways.Increasing recent studies have investigated the external treatment of RA using traditional Chinese medicines based on the above signaling pathways.In this paper,we review the relevant data and reports to explain the relationship between the above pathways and the pathogenesis and prevention of RA.We also summarize the research result regarding the modulation of these signaling pathways by external treatment with traditional Chinese medicines aimed at preventing and treating rheumatoid joints,with a view to providing a scientific basis for the clinical selection of these treatments.

Objective: To analyze the base incidence, distribution characteristics, survival status and social security of occupational pneumoconiosis (hereinafter referred to as "pneumoconiosis") in Zibo City. Methods: The new pneumoconiosis patients in Zibo City from 1949 to 2021 were selected as the research subjects using a cross-sectional survey. Household survey or telephone follow-up were carried out, and the distribution characteristics, living conditions and social security situation were retrospectively analyzed. Results: A total of 8 910 patients with pneumoconiosis were investigated, and 96.0% of them were male. The stage Ⅰ pneumoconiosis patients accounted for 91.3%. From 1949 to 2021, the number of pneumoconiosis patients showed a stepwise upward trend with time. Most of the patients suffered from coal worker pneumoconiosis and silicosis, which accounted for 48.7% and 38.9%, respectively. The average age of onset was (52.7±11.4) years, and the average length of service exposed to dust was (21.1±9.4) years. The patients were concentrated in Zichuan District, Boshan District and Zhangdian District, that accounted for 87.8%. The industry distribution was mostly mining industry and manufacturing industry, accounting for 61.1% and 31.6% respectively. Among the 8 910 cases of pneumoconiosis, 543 cases were lost in follow-up. A total of 8 367 patients were followed-up, with a follow-up rate of 93.9%. The mortality rate of patients who completed follow-up was 50.5%, and the mortality rate decreased with the increase of the stage of pneumoconiosis (P<0.01). The rate of adoring social security in the 4 138 surviving patients was 98.4%. Conclusion: The situation of prevention and treatment of pneumoconiosis in Zibo City is challenging. It is necessary to strengthen the special control of dust hazards in mining and manufacturing industries in key areas such as Zichuan District, Boshan District and Zhangdian District.

Objective:To observe the expression characteristics of eukaryotic translation initiation factor 2α(eIF2α), and analyze its proliferation regulation effect on fibroblasts of rheumatoid arthritis synovium.Methods:The synovial tissues were collected in patients with rheumatoid arthritis(RA)(40 cases) and osteoarthritis(OA)(40 cases). EIF2α and proliferating cell nuclear antigen(PCNA) were detected by immunohistochemistry method. Fibroblast cell line of rheumatoid arthritis synovium(MH7A) were cultured to establish si-eIF2α group(siRNA-eIF2α plasmid transfection), vector transfection group and blank control group in vitro. PCNA was detected by Western blot method, cell proliferation activity was detected by CCK-8 method. χ2 test was performed on count data, two-sample t-test was performed on quantitative data, one-way analysis of variance (ANOVA) was performed to compare the means of more than two groups, regression equation was calculated by correlation regression analysis. Results:The positive rate of eIF2α was significantly higher in RA synovial fibroblasts than that of OA [52.5%(21/4) vs 20.00%(8/20), χ2=9.14, P=0.003]. Positive correlation was found between eIF2α and PCNA in RA ( Y=0.366 X+2.220, P=0.001) . Compared with blank control group and vector transfection group, cell proliferation activity decreased significantly in si-eIF2α group of MH7A cell line at 72 h [(0.65±0.08) vs (0.96±0.12) vs (1.09±0.06), F=4.52, P=0.022] and 96 h [(1.13±0.14) vs (1.42±0.97) vs (1.56±0.12), F=9.87, P=0.001) , PCNA expression decreased significantly [(0.84±0.15) vs (1.32±0.18) vs (1.28±0.14), F=5.22, P=0.012) . Conclusion:High expression of eIF2α can promote the proliferation of fibroblasts of RA synovium.

Currently, radiotherapy has been found to induce lymphopenia in multiple solid tumors, which has been proven to be associated with poor prognosis. Radiation-induced lymphopenia (RIL) is associated with age, baseline lymphocyte count, tumor size and location and radiotherapy regimens (radiation fractionation, field size and technique), etc. In addition, several drugs and cytokines may help restore lymphocytes. Exploration of effective strategies to prevent or treat RIL may be an important future direction to improve prognosis of cancer patients.

The fall armyworm (FAW), Spodoptera frugiperda, is a destructive pest native to America and has recently become an invasive insect pest in China. Because of its rapid spread and great risks in China, understanding of FAW genetic background and pesticide resistance is urgent and essential to develop effective management strategies. Here, we assembled a chromosome-level genome of a male FAW (SFynMstLFR) and compared re-sequencing results of the populations from America, Africa, and China. Strain identification of 163 individuals collected from America, Africa and China showed that both C and R strains were found in the American populations, while only C strain was found in the Chinese and African populations. Moreover, population genomics analysis showed that populations from Africa and China have close relationship with significantly genetic differentiation from American populations. Taken together, FAWs invaded into China were most likely originated from Africa. Comparative genomics analysis displayed that the cytochrome p450 gene family is extremely expanded to 425 members in FAW, of which 283 genes are specific to FAW. Treatments of Chinese populations with twenty-three pesticides showed the variant patterns of transcriptome profiles, and several detoxification genes such as AOX, UGT and GST specially responded to the pesticides. These findings will be useful in developing effective strategies for management of FAW in China and other invaded areas.
Animals ; China ; Genomics ; Humans ; Male ; Pesticides ; Spodoptera/genetics* ; Transcriptome

Objective:To analyze the efficacy of chest wall boost radiotherapy in stage T 4 breast cancer patients after modified radical mastectomy. Methods:A retrospective analysis was performed on the data of 148 stage T 4 breast cancer patients who were admitted from 2000 to 2016 and received radiotherapy after modified radical mastectomy. There were 57 cases in the chest wall boost radiotherapy group and 91 cases in the conventional dose group. Radiotherapy was performed by conventional+ chest wall electron beam, three-dimensional conformal+ chest wall electron beam, intensity modulated radiotherapy+ chest wall electron beam irradiation. EQD 2 at the boost group was >50Gy. All patients received neoadjuvant chemotherapy. Kaplan-Meier method was used to analyze survival; Logrank was used to test differences; and Cox model was used to do multivariate prognostic analysis. Results:The median follow-up time was 67.2 months. The 5-year rates of chest wall recurrence (CWR), locoregional recurrence (LRR), disease-free survival (DFS), and overall survival (OS) were 9.9%, 16.2%, 58.0%, and 71.4%, respectively. The 5-year rates of CWR, LRR, DFS, and OS with and without chest wall boost radiotherapy were 14% vs. 7%, 18% vs. 15%, 57% vs. 58%, 82% vs. 65%( P>0.05), respectively. Multivariate analysis showed that chest wall boost radiotherapy had no significant effect on prognosis ( P>0.05). Among 45 patients in the recurrent high-risk group, boost radiotherapy seemed to have higher OS rate ( P=0.058), DFS rate ( P=0.084), and lower LRR rate ( P=0.059). Conclusions:Stage T 4 breast cancer patients had strong heterogeneity. Chest wall boost radiotherapy did not apparently benefit all patients. For patients with 2-3 high risk factors including positive vascular tumor embolus, pN 2-N 3, and hormone receptor negative, chest wall boost radiotherapy showed a trend of improving efficacy.

Objective:To evaluate the methods and effects of mini-invasive treatment of non-dilated common bile duct stones.Methods:From Oct 2015 to Dec 2018, clinical data of 230 cases of cholecystolithiasis combined with non-dilated common bile duct stones (choledochal diameter ≤8 mm) at our hospital were analyzed. The treatment methods included endoscopic retrograde cholangiopancreatography (ERCP)+ synchronous LC, ERCP+ nonsynchronous LC, laparoscopic transcyctic duct common bile duct exploration(LTCBDE).Results:In 69 out of 70 patients in the ERCP+ synchronous LC group stones were successfully extracted. In 118(118/120) cases out of the ERCP+ nonsynchronous LC group common bile duct stones were successfully removed, LTCBDE was performed in 38(38/40) cases and stones were successfully removed. There was no significant difference in the success rate among the three methods ( P>0.05), while patients in LTCBDE group had the shortest mean postoperative hospitalization time ( F=243.22, P=0.000) , the least average hospitalization cost ( F=300.40, P=0.000) and with lower incidence of complications (10.00%, P<0.05). Conclusions:It is of great importance to adopt the appropriate procedures for the mini-invasive treatment of non-dilated extrahepatic common bile duct stones. LTCBDE is the most suitable procedures for this purpose.

Objective: To analyze the failure patterns of locoregional recurrence (LRR) and investigate the range of radiotherapy in T_1-2N₁ breast cancer patients undergoing modified radical mastectomy. Methods: From September 1997 to April 2015, 2472 women with T_1-2N₁ breast cancer after modified radical mastectomy without neoadjuvant systemic therapy were treated in our hospital. 1898 patients who did not undergo adjuvant radiotherapy were included in this study. The distribution of accumulated LRR was analyzed. The LR and RR rates were estimated by the Kaplan-Meier method, and the prognostic factors were identified in univariate analyses with Log-rank test. Multivariate analysis was performed using Cox logistic regression analysis. Results: With a median follow-up of 71.3 months (range 1.1-194.6), 164 patients had LRR, including supraclavicular/infraclavicular lymph nodes in 106(65%), chest wall in 69(42%), axilla in 39(24%) and internal mammary lymph nodes (IMNs) in 19 patients (12%). In multivariate analysis, age (>45 years vs.≤45 years), tumor location (other quadrants vs. inner quadrant), T stage (T₁ vs. T₂), the number of positive axillary lymph nodes (1 vs. 2-3), hormone receptor status (positive vs. negative) were significant prognostic factors for both LR and RR. Conclusions In patients with T_1-2N₁ breast cancer after modified radical mastectomy, the most common LRR site is supraclavicular/infraclavicular nodal region, followed by chest wall. The axillary or IMN recurrence is rare. The prognostic factors for LR and RR are similar, which indicates that supraclavicular/infraclavicular and chest wall irradiation should be considered for postmastectomy radiotherapy.