Immune checkpoint inhibitors （ICIs） can activate anti-tumour-related immunity in the treatment of malignant tumours， but at the same time， they can also cause non-specific immune activation， leading to the occurrence of immune-related adverse reactions （irAEs）. It is believed that under physiological conditions， ICIs can be classified as tonic agents in traditional Chinese medicine， exerting the effect of warming yang and benefiting qi， but when the immune response become over-excited， ICIs evolve into pathogen of exuberant fire， which is destructive to the body. Combining the different periods of immunotherapy and the degree of symptoms， irAEs are divided into two phases： symptom onset phase （exuberant fire consuming qi and essence） and intermittent phase （latent fire dispersing healthy qi in critical condition）， in which yang movement is excess fire leading to toxicity of the skin and oral mucous membranes， qi constraint transforming into fire leading to toxicity of gastrointestinal tract， qi block generating fire leading to cardiotoxicity， and qi and yin deficiencies leading to fire manifesting as ICIs-related diabetes. The general principle of “simultaneous treatment of qi and fire” is proposed to guide the treatment of irAEs. During the onset phase， draining fire， directing qi downward， and dispelling drug toxicity are used to remove excess fire； raising yang， dispersing fire， and dispelling drug toxicity are used to disperse fire constraint； promoting the flow of yang and qi and dispelling drug toxicity are used to close fire and smoothen the flow； cultivating qi， clearing fire， and dispelling drug toxicity are used to disperse the deficiency fire， so as to achieve the goal of clearing exuberant fire， eliminating drug toxicity， and alleviating acute symptoms. During the intermittent phase， the aim is to generate fire slightly to warm yang qi， block latent fire， and prevent recurrence， and ultimately restore the balance of qi and yang in human physiology to prevent and treat irAEs and improve the quality of life of patients.

OBJECTIVE To study the effects of Zigui yichong formula on premature ovarian insufficiency （POI） in mice through glycolysis metabolic pathway. METHODS Eighty SPF C57BL/6N female mice were divided into normal group， model group， Zigui yichong formula group （14.175 g/kg）， Zigui yichong formula+2-deoxy-D-arabino-hexose （2-DG） group （Zigui yichong formula 14.175 g/kg + glycolysis inhibitor 2-DG 100 mg/kg）， with 20 mice in each group. Except for the normal group， POI model mice were induced by intraperitoneal administration of cyclophosphamide in the other groups. After the model was successfully established， each group was given corresponding drugs. HE staining was employed to observe the pathomorphological changes in ovarian tissue and to count follicles at all developmental stages； radioimmunoassay was conducted to measure the serum levels of estradiol （E2）， anti-Müllerian hormone （AMH）， and follicle-stimulating hormone （FSH）； TUNEL assay was employed to detect apoptosis in ovarian granulosa cells of mice； the activities of hexokinase （HK）， pyruvate kinase （PK） and lactate dehydrogenase （LDH） were detected by colorimetry； Western blot and real-time fluorescence quantitative PCR were employed to analyze the protein and mRNA expressions of B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， caspase-3， HK2， pyruvate kinase M2 （PKM2）， and lactate dehydrogenase A （LDHA）. RESULTS Compared with model group， the number of primordial follicles， growing follicles， antral follicles and granulosa cells were increased significantly（P＜0.05）， and granulosa cells arranged neatly， but the number of atretic follicles and granulosa cells apoptosis were decreased significantly in Zigui yichong formula group （P＜0.05）； the serum levels of E2 and AMH， the activities of HK， PK and LDH， protein and mRNA expressions of Bcl-2， HK2， PKM2 and LDHA were increased significantly （P＜0.05）； the serum levels of FSH， the protein and mRNA expressions of Bax and caspase-3， Bax/Bcl-2 ratio were decreased significantly （P＜0.05）. 2-DG could reverse the improvement effects of Zigui yichong formula on the above indexes of POI model mice. CONCLUSIONS Zigui yichong formula may inhibit the apoptosis of ovarian granulosa cells， reduce follicle atresia and improve ovarian reserve function by promoting glycolysis levels in POI model mice.

Objective To investigate the current situation and health effects of indoor microbial pollution in Xi'an, to analyze the purification effect of air purifiers on indoor microbial pollution, and to provide reference for improving the indoor environment. Methods Through stratified random sampling, 20 families from rural areas and 20 families from upwind and downwind urban areas respectively were selected from Xi'an. Data was collected by questionnaire surveys and on-site environmental sampling. Non-parametric analysis and correlation analysis were used for statistical analysis. Results Overall, the standard-exceeding rate of total count of bacteria was 5.00%. The medians of the total count of bacteria and fungi were 312.50 cfu/m3 and 260.00 cfu/m³, respectively. In terms of health effects, the correlation between rhinitis and cold with total bacterial count was statistically significant (P<0.05), with the correlation coefficients of 0.182 and 0.223, respectively. Purification effect of air purifiers on microbial pollution was statistically significant (P<0.05). After opening for 2 hours, the total numbers of bacteria and fungi decreased significantly. Conclusion The occurrence risk of colds and rhinitis is increased by indoor microbial pollution. Air purifiers have a certain effect on decreasing the total number of bacteria and fungi. It is recommended to use air purifiers with high CADR of particulate matter, double-layer filter and sterilization and dehumidification function, and replace the filters regularly to reduce indoor microbiological contamination.

Objective To observe the value of intratumoral and peritumoral CT radiomics for evaluating KRAS gene status in patients with colorectal adenocarcinoma.Methods Totally 245 patients with colorectal adenocarcinoma were retrospectively enrolled and divided into mutant group(n=139)and wild group(n=106)according to KRAS gene status,also divided into training set(n=171)and test set(n=74)at a ratio of 7∶3.Clinical data were compared between groups,and clinical factors were screened with logistic regression analysis to establish a clinical model.Based on enhanced venous phase CT images,intratumoral volume of interest(VOI),peritumoral VOI,and intratumoral+peritumoral VOI were delineated,radiomics features were extracted,and radiomics models were constructed.The combination model was constructed based on the best radiomics model combined with clinical factors.The value of each model for evaluating KRAS gene status in patients with colorectal adenocarcinoma was analyzed.Results Significant differences of patients’gender and carcinoembryonic antigen(CEA)were found between mutant group and wild group(both P＜0.05),which were independent impact factors of KRAS gene status in patients with colorectal adenocarcinoma(both P＜0.05).The area under the curve(AUC)of clinical model for evaluating KRAS gene status in patients with colorectal adenocarcinoma in training set and test set was 0.633 and 0.658,respectively.Intratumoral+peritumoral 3 mm model was the best radiomics model,with AUC of 0.921 and 0.894 in training set and test set,respectively.AUC of the combination model in training set and test set was 0.949 and 0.956,respectively.In training set,significant differences of AUC were found between clinical model and intratumoral+peritumoral 3 mm model,also between clinical model and combination model(both P＜0.001),while in test set,significant differences of AUC were found between each two models(all P＜0.05).Conclusion Intratumoral+peritumoral 3 mm radiomics based on enhanced venous phase CT could help to evaluate KRAS gene status in patients with colorectal adenocarcinoma.Combining with patients’gender and CEA could further improve efficacy of this model.

Objective To observe the value of contrast-enhanced CT radiomics combined with clinical and hematology indicators for predicting lymph node(LN)metastasis(LNM)of esophageal squamous cell carcinoma(ESCC).Methods Totally 218 ESCC patients were retrospectively enrolled.Stage pN1 and pN2 were clustering as LNM(n=90),while stage pN0 were taken as non-LNM(n=128).The patients were divided into training set(n=174)and test set(n=44)at the ratio of 8∶2.In training set,clinical and LN imaging features which could be used to independently judge LNM were screened and a clinical-imaging model was constructed.The hematological indicators that might be associated with ESCC LNM were screened,and a hematological model was constructed.Radiomics features in LN ROI and ESCC volume of interest(VOI)were extracted based on venous-phase contrast-enhanced CT images,and those might be associated with LNM were screened,and a radiomics model was constructed.Finally a combined model was constructed based on all the above features.The efficacy of each model for diagnosing LNM was evaluated with the area under the curve(AUC)of receiver operating characteristic curves,and the clinical net benefit was evaluated using decision curve analysis(DCA).Results Body mass index(BMI)and internal necrosis of target LN were both independent judging factors for ESCC LNM(both P＜0.05),and AUC of clinical-imaging model for diagnosing LNM in training and test sets was 0.747 and 0.687,respectively.Seven hematological indicators were included in hematological model,and AUC in training and test sets was 0.623 and 0.583,respectively.Ten LN radiomics features and 15 ESCC radiomics features were included in radiomics model,and AUC in training and test sets was 0.769 and 0.745,respectively.AUC of the combined model for diagnosing LNM in training and test sets was 0.822 and 0.739,respectively,better than other models in training set(all P＜0.05),but no significantly different in test set(all P＞0.05).DCA showed that combined model had higher net gain than the other models in 0.55-0.80 threshold probability interval.Conclusion Combined model based on venous-phase contrast-enhanced CT radiomics and clinical and hematology indicators could relatively effectively evaluate ESCC LNM,which might bring some promotions in clinical benefit.

Objective:To evaluate the clinical efficacy of intermediate frequency pulse electrical stimulation combined with TCM directional drug penetration therapy in the treatment of patients with lumbar spinal stenosis.Methods:Randomized controlled trial. Totally 90 patients with lumbar spinal stenosis who were treated between July 2018 and December 2021 in the hospital were selected according to randomized controlled trial design, and they were divided into the two groups through the random number table method, with 45 cases in each group. The control group was given non-steroidal anti-inflammatory drugs+conventional intermittent traction + intermediate frequency pulse electrical stimulation, and the combined group was treated with TCM directional drug penetration therapy on the basis of the control group. Both groups were continuously treated for 1 month. The TCM syndromes were scored before and after treatment, and Visual Analogue Scale (VAS) was used to evaluate the pain degree. Japanese Orthopedic Association (JOA) and Oswestry Disability Index (ODI) were applied to assess the dysfunction degree and quality of life, and the clinical efficacy was assessed.Results:The total effective rate was 95.56% (43/45) in combined group and was 82.22% (37/45) in control group, with statistical significance ( χ2=4.05, P=0.044). The scores of lumbago pain, articular soreness, knee soreness and weakness and impaired activity and total score in combined group after treatment were lower than those in the control group ( t=18.40, 15.81, 15.40, 26.50, 59.575, P<0.01), and the JOA score was higher than that of the control group ( t=5.62, P<0.01), while the ODI score was lower than that of the control group ( t=9.43, P<0.01). The time-point effect and between-group effect of VAS score in combined group were lower than those in the control group with the extension of time ( F=240.00, 17.19, P<0.01), and there was an interaction effect between decrease and treatment method ( F=6.66, P<0.01). Conclusion:Intermediate frequency pulse electrical stimulation combined with TCM directional drug penetration therapy is helpful to relieve the pain, improve the lumbar dysfunction degree and enhance the quality of life and clinical efficacy in patients with lumbar spinal stenosis.

Objective To explore the relationship between the outpatient visits for adult asthma and air pollution in a tertiary hospital in Hefei. Methods The number of outpatient visits for asthma in a tertiary hospital in Hefei from 2014 to 2020 was collected. The air pollutant data was obtained through the Hefei Air Monitoring Station, and the meteorological indicators of the same period were collected through the China Meteorological Network. The R statistical software was used to establish a generalized additive model to analyze the lag effect of air pollution on the number of outpatient visits for asthma. Results From 2014 to 2020, there were 7 220 asthma outpatients in the tertiary hospital in Hefei, including 3104 males and 4 116 females, 3 798 patients in warm season, and 3 422 patients in cold season. During the period, the average concentrations of SO₂, NO₂, CO, O₃, PM₁₀, and PM_2.5 were 11.9μg/m³, 40.1μg/m³, 0.9 mg/m³, 87.3μg/m³, 81.3μg/m³, and 55.7μg/m³, respectively. The results of the single-pollutant model showed that every 10μg/m³ increase in SO₂ concentration increased the risk of asthma by 0.74% (95%CI: 0.22%-1.29%), and the effect was the greatest on Lag2 day. NO2 increased the risk of asthma by 0.31% (95%CI: 0.13%-0.49%), with the greatest effect on Lag0 day. The analysis of the dual pollutant model found that whereas the effect of SO₂ decreased after the incorporation of NO₂, the effect increased after the incorporation of CO, O₃, PM₁₀, or PM_2.5, respectively. The effect of NO₂ on asthma decreased after the incorporation of SO₂, whereas the effect on asthma increased after the inclusion of CO, PM₁₀, or PM_2.5. Stratified analysis of cold and warm seasons showed that the effect of NO₂ on asthma was the greatest in lag0 in cold season. The effect of SO₂ was higher in cold season than in warm season, and it was the highest in lag2. The gender stratification analysis showed that the effects of SO₂ and NO₂ on male asthma were higher than those on females. Conclusion From 2014 to 2020, the increase of SO₂ and NO₂ concentrations in Hefei is positively correlated with the risk of asthma in the outpatient department of a tertiary hospital. The effect has a certain lag. It is of great significance to formulate relevant preventive measures for the occurrence and attack of asthma.

With the acceleration of aging process and the increase of average life in China, the number of disabled elderly in China is also growing rapidly, which undoubtedly brings a heavy care burden and pressure to families and society.Facing the great challenges brought by aging, the increasing evidences show that only by reducing the incidence of disease and disability from the source, improving the health level of the elderly, prolonging their healthy life and realizing healthy aging, we can fundamentally alleviate the great pressure brought by the aging society.The concept of motor function maintenance and health promotion of the elderly has become an important link and breakthrough to realize healthy aging and active health.Facing the requirements of active health medicine and the development trend of science and technology in the future, it is imperative to deeply study the motion characteristics and function maintenance of the elderly, and promote the development of sports medicine with innovative technologies such as internet, big data and artificial intelligence.In the future, we will continue to improve the assessment and maintenance system for motor function of the elderly, develop and optimize functional maintenance products that meet the exercise needs of the elderly, and actively build an elderly-friendly sports environment support system, thereby promoting the healthy China strategy and realize healthy aging to the greatest extent.

Although DNA 5-hydroxymethylcytosine (5hmC) is recognized as an important epige-netic mark in cancer, its precise role in lymph node metastasis remains elusive. In this study, we investigated how 5hmC associates with lymph node metastasis in breast cancer. Accompanying with high expression of TET1 and TET2 proteins, large numbers of genes in the metastasis-positive pri-mary tumors exhibit higher 5hmC levels than those in the metastasis-negative primary tumors. In contrast, the TET protein expression and DNA 5hmC decrease significantly within the metastatic lesions in the lymph nodes compared to those in their matched primary tumors. Through genome-wide analysis of 8 sets of primary tumors, we identified 100 high-confidence metastasis-associated 5hmC signatures, and it is found that increased levels of DNA 5hmC and gene expression of MAP7D1 associate with high risk of lymph node metastasis. Furthermore, we demonstrate that MAP7D1, regulated by TET1, promotes tumor growth and metastasis. In conclusion, the dynamic 5hmC profiles during lymph node metastasis suggest a link between DNA 5hmC and lymph node metastasis. Meanwhile, the role of MAP7D1 in breast cancer progression suggests that the metastasis-associated 5hmC signatures are potential biomarkers to predict the risk for lymph node metastasis, which may serve as diagnostic and therapeutic targets for metastatic breast cancer.

Purpose: C-X-C motif chemokine receptor 4 (CXCR4) and integrin αvβ6 play important roles in the malignant progression of multiple cancers. However, it remains unclear whether the expression of one or both proteins in breast cancer (BC) is of clinical significance. In this study, we investigated the expression of CXCR4 and integrin αvβ6 in BC tissues and their correlation with clinicopathological characteristics, including survival. Methods: CXCR4 and αvβ6 expression in 111 BC tissues was examined by immunocytochemistry. Correlations between the expression of the 2 proteins and patient clinicopathological characteristic were investigated using the Kaplan–Meier method and the Cox proportional hazards model. Results: CXCR4 and αvβ6 were overexpressed in BC tissue compared with normal breast tissue. Overexpression of both molecules was related to lymph node status (p = 0.013 and p = 0.022, respectively). αvβ6 overexpression was also associated with tumor size (p = 0.044). A positive correlation was detected between the expression of CXCR4 and αvβ6 (r = 0.649, p = 0.001), and co-overexpression of both molecules was associated with tumor size (p = 0.018) and lymph node metastasis (p = 0.015). Kaplan–Meier analysis revealed that overexpression of CXCR4, αvβ6, or both molecules was associated with short overall survival (OS; p < 0.001, p < 0.001, and p = 0.009, respectively) and disease-free survival (DFS; p < 0.001, p = 0.005, and p = 0.019, respectively). Multivariate analysis indicated that lymph node metastasis was an independent prognostic factor for unfavorable OS and DFS (p = 0.002 and p = 0.005, respectively), whereas co-overexpression of CXCR4 and αvβ6 was an independent prognostic factor only for OS (p = 0.043). Conclusion CXCR4 and αvβ6 may play synergistic roles in the progression of BC, and co-targeting of CXCR4 and αvβ6 could be a potential strategy for the prevention and treatment of BC.