This paper summarizes Professor HAN Mingxiang's clinical experience in the use of Zeqi （Euphorbia HelioscopiaL.）. It is believed that Zeqi （Euphorbia HelioscopiaL.） has the effects of promoting qi， relieving water retention and swelling， resolving phlegm， stopping cough， dissipating masses， activating blood， removing stasis， and detoxifying. In clinical practice， Zeqi （Euphorbia HelioscopiaL.） is flexibly applied in the treatment of skin diseases， respiratory diseases， tumors， etc. For instance， in treating psoriasis with the pathogenesis of damp-heat toxin， a compound prescription of Zeqi Decoction （泽漆汤） is formulated. For bronchial asthma with kidney deficiency and water retention， Zeqi Decoction is commonly combined with Wuling Powder （五苓散） in adjusted doses. For lung nodules with a combination of deficiency， phlegm， stasis， and toxin， a Lung Nodule Prescription is proposed. For advanced lung cancer with both qi and yin deficiency and toxin accumulation， Qiyu Sanlong Decoction （芪玉三龙汤） is suggested， and for cancer-related ascites with qi deficiency and water retention， Wuling Powder combined with Zeqi （Euphorbia HelioscopiaL.）is chosen.

BACKGROUND:Deferoxamine mesylate is a potential anti-osteoporosis drug with iron chelation,vascular regeneration,and antioxidant effects.Recent studies have shown that the application of deferoxamine mesylate can be extended to the field of tissue regeneration engineering. OBJECTIVE:To investigate whether deferoxamine mesylate can promote the repair effect of iron overload osteoporotic rats after bone grafting for mandibular bone defects by simulating the state of iron accumulation in patients with postmenopausal osteoporosis with high iron intervention in osteoporotic rats. METHODS:An iron accumulation ovariectomized osteoporosis model was firstly constructed.The model group underwent bilateral ovariectomy,and the intraperitoneal injection of ferric ammonium citrate(90 mg/kg,twice a week,for 11 weeks)was started in the 2nd week,while the sham-operated group had some fat around the ovaries removed and was given an equal amount of saline for 11 weeks.After the successful modeling,the experimental rats were divided into sham-operated group(n=6),high iron ovariectomtized group(n=6)and high iron ovariectomized deferoxamine mesylate treatment group(deferoxamine mesylate group,n=6).Bone defects of 5 mm in diameter were established in the rat's bilateral mandibles and implanted with Bio-Oss bone powder.Intraperitoneal injection of deferoxamine mesylate(100 mg/kg,3 times a week)was started on postoperative day 4 in the deferoxamine mesylate group,and equal volume of saline was given in the sham-operated and high iron ovariectomized groups.The bone samples of the mandible,liver and blood were taken at 2 and 12 weeks after bone grafting for Prussian blue staining of the jaw and liver and ELISA detection of serum ferritin to detect iron levels in various body tissues;hematoxylin-eosin staining and Masson staining were performed to observe inflammatory cell infiltration and early osteogenesis in the bone defect area;tartrate resistant acid phosphatase staining was performed to observe osteoclast differentiation;ELISA was performed to detect serum calcitonin and type I collagen C-terminal peptide levels;and Micro-CT and hematoxylin-eosin staining were performed to observe osteogenesis in the middle and late stages. RESULTS AND CONCLUSION:The number of tibial trabeculae was reduced and the trabeculae were sparsely arranged in the high iron ovariectomized group.Iron levels in the liver,jaw bone and serum were significantly higher in the high iron ovariectomized group than the sham-operated group at 2 weeks after bone grafting,while the iron levels were significantly decreased after deferoxamine mesylate intervention(P＜0.05).In the early stage of bone defect repair,more inflammatory cell infiltration,less new bone matrix and less type I collagen fiber production were observed in the high iron ovariectomized group than in the sham-operated group(P＜0.05);after deferoxamine mesylate treatment,inflammatory cell infiltration was reduced,a small amount of new bone matrix was produced and collagen fibers increased significantly(P＜0.05).In the middle and late stages of bone defect repair,Micro-CT results showed a reduction in new bone production in the high iron ovariectomized group compared with the sham-operated group and increased new bone matrix after deferoxamine mesylate treatment(P＜0.05).Compared with the sham-operated group,the osteoclast number,serum calcitonin level,and serum type I collagen C-terminal peptide level were increased in the high-iron ovariectomized group,while the osteoclast number was decreased and bone metabolic indexes were improved after treatment with deferoxamine mesylate.To conclude,in ovariectomized rats with high iron intervention,elevated iron levels can be seen in multiple tissues,accompanied by reduced new bone production in the mandibular bone defect area.Deferoxamine mesylate can improve bone metabolism and inhibit osteoclast activity by removing iron deposits in tissues,improve bone formation in iron-accumulated osteoporotic rats,and promote bone healing in the mandibular bone defect area.

BACKGROUND:Interleukin-4 can promote the osteogenic effect of bone substitute materials,but its molecular mechanism is not yet clear.Further elucidating the mechanism of interleukin-4 promoting osteogenic effect can help find safe,economical,and effective methods for the regeneration treatment of alveolar bone defects in patients. OBJECTIVE:To explore the effect of interleukin-4 intervention on polarization transformation of macrophages and osteogenic differentiation of bone marrow mesenchymal stem cells and its possible mechanism. METHODS:RAW264.7 cells in the M1 group were induced with interferon gamma + lipopolysaccharide for 24 hours.RAW264.7 cells in the interleukin-4+M1 group were induced with interferon gamma + lipopolysaccharide for 24 hours and then interleukin-4 was added for 24 hours.RAW264.7 cells in the interleukin-4+AG+M1 group were induced with interferon gamma + lipopolysaccharide for 24 hours,and then interleukin-4 and AG-490,a JAK/STAT pathway inhibitor,were added for 24 hours.After intervention,immunofluorescence staining was used to analyze the expression of inducible nitric oxide synthase and CD206,the phenotypic marker protein of macrophages.ELISA kit was used to detect the expression of interleukin-10 and tumor necrosis factor-α in the supernatant of cell culture.The gene expressions of nodular receptor protein-3(NLRP3),interleukin-1β,and caspase-1 were detected by RT-qPCR.The expression levels of tyrosine protein kinase 1(JAK1)/phosphorylated tyrosine protein kinase 1(p-JAK1),signal transduction and transcription activator 6(STAT6)/phosphorylated signal transduction and transcription activator 6(p-STAT6),NLRP3,pro-interleukin-1β and pro-caspase-1 were detected by western blot assay.Then,RAW264.7 cells in the above four groups were indirectly co-cultured with bone marrow mesenchymal stem cells by transwell for 24 hours,followed by alkaline phosphatase staining and alizarin red staining.The mRNA expressions of alkaline phosphatase,collagen type I,and osteocalcin were detected by RT-qPCR. RESULTS AND CONCLUSION:(1)Immunofluorescence and ELISA results showed that interleukin-4 intervention could promote the expression of CD206 and interleukin-10 in M2 macrophages,and inhibit the secretion of inducible nitric oxide synthase and tumor necrosis factor-α.(2)RT-qPCR results showed that interleukin-4 could suppress the expression of NLRP3,interleukin-1β,and caspase-1 mRNAs.(3)Western blot assay showed that interleukin-4 could promote the expression of JAK1/p-JAK1,STAT6/p-STAT6 and NLRP3 proteins.(4)The alkaline phosphatase staining and alizarin red staining of bone marrow mesenchymal stem cells co-cultured with the interleukin-4+M1 group were significantly enhanced,and the mRNA expressions of alkaline phosphatase,collagen type I,and osteocalcin were significantly increased.It is concluded that interleukin-4 may inhibit the activation of NLRP3 by up-regulating JAK1/STAT6 pathway,thus promoting the transformation of macrophages from M1 polarization to M2 polarization,and finally enhancing the osteogenic differentiation ability of bone marrow mesenchymal stem cells.

OBJECTIVE To evaluate the effictiveness and safety of recombinant human endostatin combined with afatinib and teggio in the treatment of advanced lung squamous cell carcinoma. METHODS A total of 25 patients with driver-negative advanced lung squamous cell carcinoma were included in this single-arm prospective study, and the enrolled patients were treated with recombinant human endostatin combined with afatinib and teggio as scheduled. Progression-free survival(PFS), overall survival(OS), disease control rate(DCR), objective response rate(ORR), and adverse reactions(AR) were observed and analyzed. RESULTS The 25 enrolled patients received at least 2 cycles of second-line treatment, and were followed up as of March 31, 2023. Among them, 4 patients had partial remission, 17 patients had stable disease, and 4 patients experienced progressive disease. The ORR confirmed by the researchers was 16%(95%CI, 4.5%−36.1%), DCR was 84%(95%CI, 63.9%−95.5%), and median PFS was 5.3 months(95%CI, 3.5−6.9 months). The median OS had not yet been achieved. The entire group of patients had good treatment tolerance, and the most common level Ⅲ or Ⅳ adverse events related to treatment were leukopenia(20%) and rash(12%), with no reported treatment-related deaths. CONCLUSION Recombinant human endostatin combined with afatinib and teggio in the second line treatment of advanced lung squamous cell carcinoma can prolong the progression free survival period of patients and is relatively safe, which is worth further exploration and promotion.

ObjectiveTo explore the impact of overtime work on work-related musculoskeletal disorders in male employees in the automobile manufacturing industry. Methods A total of 1 731 male employees with more than one year of working experience from an automobile manufacturing industry were selected as the research subjects using judgment sampling method. The Musculoskeletal Disorder Questionnaire was used to investigate the prevalence of musculoskeletal disorder. Employees were divided into control group and overtime group, and a 1∶1 matching was performed using propensity score matching method, and 573 pairs were successfully matched. The prevalence of WMSDs in various body parts was compared between the two groups. Results The overtime working rate of the research subjects was 34.2%, and the prevalence of WMSDs was 57.1%. Overtime work increased the risk of WMSDs in the neck, shoulders, upper back, lower back, ankle/feet, and overall body of the workers (all P<0.05), with the odd ratio and 95% confidence interval of 1.43 (1.10-1.85), 1.38 (1.06-1.80), 1.42 (1.07-1.89), 1.28 (1.01-1.62), 1.37 (1.01-1.87), and 1.49 (1.17-1.89), respectively. However, there was no association between overtime work and the risk of WMSDs in the elbows, hands/wrists, hips, and knees of the subjects (all P>0.05). Conclusion Overtime work increases the risk of WMSDs in the neck, shoulders, upper back, lower back, ankles/feet, and overall body of male employees in the automobile manufacturing industry. Enterprises should improve labor organization, reduce overtime work, and protect the health of workers.

Objective To investigate the influence of individual factors and labor organization factors on work-related musculoskeletal disorders (WMSDs) in automobile manufacturing workers, and to provide a scientific basis for the prevention and treatment of WMSDs in automobile manufacturing workers. Methods In April 2020, 5564 workers in an automobile factory were selected by cluster sampling method. The prevalence of WMSDs was investigated by using the Musculoskeletal Disorders Questionnaire, and the influence of individual factors and labor organization factors on WMSDs was investigated by using generalized estimation equation. Results The prevalence rate of WMSDs was 79.00% (4396/5564), and the prevalence rate of multisite WMSDs was 67.95% (3781/5564). The analysis of generalized estimation equation showed that doing the same job every day (OR= 1.478, P < 0.05), age ≥40 years (OR=1.416, P< 0.05), personnel shortage (OR= 1.356, P < 0.05), and work length of 6～10 years and 11～15 years (OR= 1.349, P< 0.05) were the main risk factors for WMSDs in automobile manufacturing workers. Shift work and working time > 40 hours per week increased the risk of WMSDs (P< 0.05). Male and adequate rest time were protective factors for WMSDs. The job correlation matrix showed that WMSDs in most parts had a positive correlation. Conclusions The prevalence of multisite WMSDs of workers in automobile manufacturing industry is high, and unreasonable labor organization is the main risk factor of WMSDs. Appropriate work breaks can effectively reduce the risk of WMSDs, and effective intervention measures should be carried out to prevent the occurrence of WMSDs in workers in automobile manufacturing industry. The generalized estimation equation can better analyze the influencing factors of WMSDs.

Objective:To explore the risk factors of neck work-related musculoskeletal disorders (WMSDs) among automobile manufacturing enterprise workers, and construct the risk prediction model.Methods:In May 2022, a cluster convenience sampling method was used to selet all front-line workers from an automobile manufacturing factory in Xiangyang City as the research objects. And a questionnaire survey was conducted using the modified Musculoskeletal Disorders Questionnaire to analyze the occurrence and exposure to risk factors of neck WMSDs. Logistic regression was used to analyze the influencing factors of workers' neck WMSDs symptoms, and Nomogram column charts was used to construct the risk prediction model. The accuracy of the model was evaluated by the receiver operating characteristic (ROC) curve, the Bootstrap resampling method was used to verify the model, Hosmer-Lemeshow goodness of fit test was used to evaluate the model, and the Calibration curve was drawn.Results:A total of 1783 workers were surveyed, and the incidence of neck WMSDs symptoms was 24.8% (442/1783). Univariate logistic regression showed that age, female, smoking, working in uncomfortable postures, repetitive head movement, feeling constantly stressed at work, and completing conflicting tasks in work could increase the risk of neck WMSDs symptoms in automobile manufacturing enterprise workers ( OR=1.37, 95% CI: 1.16-1.62; OR=2.85, 95% CI: 1.56-5.20; OR=1.50, 95% CI: 1.18-1.91; OR=1.18, 95% CI: 1.02-1.37; OR=1.34, 95% CI: 1.04-1.72; OR=1.62, 95% CI: 1.21-2.17; OR=1.48, 95% CI: 1.13-1.92; P<0.05). While adequate rest time could reduce the risk of neck WMSDs symptoms ( OR=0.56, 95% CI: 0.52-0.86, P<0.05). The risk prediction model of neck WMSDs of workers in automobile manutacturing factory had good prediction efficiency, and the area under the ROC curve was 0.72 (95% CI: 0.70-0.75, P<0.001) . Conclusion:The occurrence of neck WMSDs symptoms of workers in automobile manufacturing factory is relatively high. The risk prediction model constructed in this study can play a certain auxiliary role in predicting neck WMSDs symptoms of workers in automobile manufacturing enterprise workers.

Objective To study the syndrome-drug association rule and the medication law of cough medical cases treated by Xin'an doctors using the data mining method;To provide reference for the treatment of cough.Methods The medical records of Xin'an doctors were collected and summarized.The frequency analysis,topology analysis and Louvain clustering analysis were used to conduct data mining research on syndrome types and prescriptions,and the relationship between syndrome types and prescriptions in cough treatment medical records and the law of drug composition in prescriptions were discussed.Results A total of 525 medical cases were included,and 26 kinds of syndromes were obtained,such as wind-heat invading lung,phlegm-dampness holding lung,lung qi deficiency.There were 243 kinds of Chinese materia medica involved,and 18 kinds of Chinese materia medica were with more than 70 times in frequency.The main properties were cold,warm and mild,and the main tastes were sweet,bitter and pungent,mainly in lung meridian,or the main properties were mild and warm and the main taste was sweet,mainly in spleen and stomach meridian.There were 25 categories in efficacy,which were mainly tonics and heat-clearing medicine.30 core medicines and core medicinal networks were obtained,such as Glycyrrhizae Radix et Rhizoma,Poria and Armeniacae Semen Amarum.The core drug combination of main syndromes of exogenous cough and excess syndrome and deficient syndrome of endogenous cough were obtained by syndrome-drug clustering analysis.Conclusion Xin'an doctors have distinctive characteristics in the diagnosis and treatment of cough diseases,and pay attention to the use of the methods of"strengthening the basic and promoting original qi","nourishing yin and protecting yin","cultivating the soil and promoting gold"and the inheritance of the prescriptions on the basis of cough relieving,phlegm resolving,and syndrome-based treatment.

Objective To investigate the effects of Shenqi Tiaoshen Formula(SQTSF)for alleviating airway inflammation in rats with both chronic obstructive pulmonary disease(COPD)and lung-kidney qi deficiency syndrome and explore its therapeutic mechanism.Methods Forty-eight SD rats were randomly divided into control group,model group,low-,medium-,and high-dose SQTSF groups,and aminophylline(APL)group.In all but the control group,rat models of COPD with lung-kidney qi deficiency syndrome were established and treated with saline,SQTSF or APL via daily gavage as indicated(starting from day 30).The rats were observed for changes in body weight,grip strength,lung function,lung pathology,inflammatory cytokines in bronchoalveolar lavage fluid(BALF),oxidative stress levels,iron ion metabolism,cellular and mitochondrial ultrastructural changes in the lung tissue,and expressions of Nrf2/SLC7A11/GPX4 signaling pathway and ferroptosis-related proteins.Results The rats in the model group exhibited obvious symptoms of lung-kidney qi deficiency syndrome with significantly decreased body weight,grip strength,and lung function parameters.Examination of the lung tissue revealed showed significant inflammatory cell infiltration and emphysema with obvious bronchial,perivascular,and alveolar inflammation and alveolar destruction,significantly increased IL-1β,TNF-α,IL-6,and IL-13 levels in BALF,and elevated pulmonary oxidative stress levels and Fe2+and total iron ion concentrations.The rat models also showed characteristic ultrastructural changes of ferroptosis in the lung tissue cells under transmission electron microscope and significantly decreased Nrf2,GPX4,and SLC7A11 and increased ACSL4 expressions in the lung tissue.Treatment with SQTSF significantly improved these pathological changes in the rat models with a better effect than APL.Conclusion SQTSF can effectively improve airway inflammation and oxidative stress in COPD rats with lung-kidney qi deficiency possibly by inhibiting ferroptosis via regulating the Nrf2/SLC7A11/GPX4 signaling pathway.

Objective To explore the therapeutic mechanism of Liuwei Buqi(LWBQ)Formula for chronic obstructive pulmonary disease(COPD)in rat models.Methods SD rat models of COPD established by cigarette smoking combined with intratracheal lipopolysaccharide(LPS)instillation and hormone injection were treated with LWBQ Formula by gavage with or without intraperitoneal injection of MCC950 for 3 weeks,starting at the 5th week of modeling.After the treatments,the rats were examined for lung pathologies,lung function,total cell count and white blood cell count in bronchoalveolar lavage fluid(BALF),and serum levels of IL-6,TNF-α,IL-18 and NO.The mRNA expressions of NLRP3,ASC,caspase-1,GSDMD-N,IL-1β,and IL-18 in the lung tissue were detected with qRT-PCR.Results Compared with the normal control rats,the COPD rat models had severe lung pathologies and showed significantly decreased lung function,increased total cell and leukocyte subset counts in BALF,and increased serum levels of IL-6,TNF-α,IL-18 and NO and mRNA expressions of pyroptosis-related proteins in the lung tissue.Treatment of the rat models with LWBQ Formula significantly improved lung pathology and lung function,reduced total cell and leukocyte counts in BALF,and decreased serum levels of the inflammatory factors and expressions of pyroptosis-related proteins in the lung tissue.The combined treatment with MCC950 further improved lung pathology and function in spite of a significant difference,but BALF cell counts,serum inflammatory factor levels and pulmonary expressions of pyroptosis-related proteins were all significantly reduced following the treatment.Conclusion LWBQ Formula can delay the progression of COPD in rats possibly by inhibiting lung tissue pyroptosis via regulating the NLRP3/caspase-1/GSDMD pathway to reduce inflammatory response and lung damage.