OBJECTIVE To explore the clinical features， diagnosis， treatment and management measures of multiple immune- related adverse event （irAE） after toripalimab treatment， in order to provide reference for the clinical management of similar cases. METHODS A retrospective analysis was conducted on a post-operative bladder cancer patient who developed various irAEs after toripalimab treatment. The patient’s medical history， laboratory tests， imaging studies， treatment course and outcomes were detailed. The Naranjo scale was used to assess the relationship between the irAEs and toripalimab. RESULTS The patient developed irAEs after receiving toripalimab， such as immune-related myocarditis， liver dysfunction， and myasthenia. According to the Naranjo scale evaluation， it was assessed that these adverse events were related to the administration of toripalimab. After high- dose corticosteroid pulse therapy and immunoglobulin immunomodulation， the patient’s symptoms were effectively relieved， with a improved trend in various physiological indicators and significant improvement in the degree of system/organ damage. CONCLUSIONS Toripalimab may lead to multiple irAEs， including immune-related myocarditis， liver injury， and myasthenia. Early recognition， timely diagnosis， and appropriate treatment of irAE are crucial for improving patient’s prognosis.

Background Coal workers' pneumoconiosis is a serious occupational disease in China. Exhaled volatile organic compounds (VOCs) can serve as the "breath fingerprint" of internal pathological processes, which provides a theoretical basis for exhaled VOCs to be used as potential non-invasive biomarkers for early diagnosis of coal workers' pneumoconiosis. Objective To screen out the characteristic VOCs and important characteristic VOCs of exhaled air in patients with coal workers' pneumoconiosis, and to explore the potential of these VOCs as biomarkers for early non-invasive diagnosis of the disease. Methods In this study, 27 VOCs in the exhaled breath of 22 patients with stage I coal workers' pneumoconiosis, 77 workers exposed to dust, and 92 healthy controls were quantitatively detected by thermal desorption gas chromatography-mass spectrometry (TD-GC-MS). Substances with P<0.05 in univariate analysis and variable importance projection (VIP) >1 in supervised orthogonal partial least squares discriminant analysis (OPLS-DA) model were selected as the characteristic VOCs for early diagnosis of coal workers' pneumoconiosis. Age was included in the LASSO regression model as a covariate to screen out important characteristic VOCs, and the diagnostic performance was evaluated by receiver operating characteristic (ROC) curve. Spearman correlation was further used to explore the correlation between important characteristic VOCs and clinical lung function indicators. Results Through univariate analysis and OPLS-DA modeling, 8 VOCs were selected, including 2-methylpentane, 3-methylpentane, n-hexane, methylcyclopentane, n-heptane, methylcyclohexane, 4-methyl-2-pentanone, and 2-hexanone, in exhaled breath of patients with coal workers' pneumoconiosis. The concentrations of 4 VOCs, including 3-methylpentane, n-hexane, 4-methyl-2-pentanone, and 2-hexanone, showed a decreasing trend with the increase of dust exposure years. By LASSO regression, the important characteristic VOCs of the coal workers' pneumoconiosis group and the dust exposure group were n-hexane, methylcyclohexane and 4-methyl-2-pentanone, and the important characteristic VOCs of the coal workers' pneumoconiosis group and the healthy group were 2-methyl-pentane and 4-methyl-2-pentanone. The ROC analysis showed that the area under the curve (AUC) of n-hexane, methylcyclohexane, and 4-methyl-2-pentanone were 0.969, 0.909, and 0.956, respectively, and the AUC of combined diagnosis was 0.988 and its Youden index was 0.961, suggesting that these results can serve as a valuable reference for further research on early diagnosis. The Correlation analysis found that there was a positive correlation between n-hexane and lung function indicators in the important characteristic VOCs, indicating that it could indirectly reflect the obstruction of lung function ventilation, further proving that important characteristic VOCs have the potential to monitor lung function decline. Conclusion Three important characteristic VOCs selected in this study have the potential to be used as non-invasive biomarkers for early diagnosis and disease monitoring of coal workers' pneumoconiosis, and are worthy of further study and verification.

Background and objective Lung cancer is the cancer with the highest incidence and mortality rates in China,and non-small cell lung cancer(NSCLC)accounts for 80％-85％of all malignant lung tumors.Currently,surgical treat-ment remains the primary treatment modality for lung cancer.In recent years,the effectiveness of immune checkpoint inhibi-tors for NSCLC has become a consensus,and neoadjuvant immunochemotherapy(nICT)has shown promising efficacy and safety in early to intermediate stage NSCLC.However,there are fewer studies related to nICT for locally advanced NSCLC.This study aims to evaluate the efficacy and safety of nICT therapy in locally advanced resectable NSCLC.Methods 85 con-firmed resectable stage ⅢA and ⅢB patients treated in the Department of Thoracic Surgery,Second Hospital of Lanzhou University,from January 2021 to April 2024,were divided into the nICT group(n=32)and the surgery alone group(n=53).Clinical baseline data,perioperative indicators,postoperative complications,imaging response rate,pathological response rate,incidence of adverse events,and quality of life were compared between the two groups.Results There were no statisti-cally significant differences in clinical baseline data between the two groups(P＞0.05).Incidence of choosing thoracotomy was higher in the nICT group than in the surgery alone group(P=0.002).There were no significant differences in surgical time,intraoperative blood loss,number of dissected lymph nodes,duration of chest tube placement,postoperative hospital stay,and R0 resection rate between the two groups(P＞0.05).The overall incidence of postoperative complications was 31.25％in the nICT group and 22.64％in the surgery alone group,with no statistically significant difference(P=0.380).In the nICT group,the objective response rate(ORR)was 84.38％,with 5 cases of complete response(CR)(15.63％),22 cases of partial response(PR)(68.75％),15 cases of pathological response rate(pCR)(46.88％),and 11 cases of major pathological reaponse(MPR)(34.38％).During nICT treatment,12 cases(37.50％)experienced grade 3 treatment-related adverse events,no death induced by adverse events or immune related adverse events.Moreover,the symptoms of the patients were improved after nICT treat-ment.Conclusion Neoadjuvant immunochemotherapy shows promising efficacy in locally advanced resectable NSCLC,with manageable treatment-related adverse events.It is a safe and feasible neoadjuvant treatment modality for locally advanced resectable NSCLC.

Objective To observe the value of feature pyramid network(FPN)for automatic segmentation and semantic feature classification of spontaneous intracerebral hemorrhage(sICH)hematoma showed on non-contrast CT.Methods Non-contrast CT images of 408 sICH patients in hospital A(training set)and 103 sICH patients in hospital B(validation set)were retrospectively analyzed.Deep learning(DL)segmentation model was constructed based on FPN to segment the hematoma region,and its efficacy was assessed using intersection over union(IoU),Dice similarity coefficient(DSC)and accuracy.Then DL classification model was established to identify the semantic features of sICH hematoma.Receiver operating characteristic curves were drawn,and the area under the curves(AUC)were calculated to evaluate the efficacy of DL classification model for recognizing semantic features of sICH hematoma.Results The IoU,DSC and accuracy of DL segmentation model for 95％sICH hematoma in training set was 0.84±0.07,0.91±0.04 and(88.78±8.04)％,respectively,which was 0.83±0.07,0.91±0.05 and(88.59±7.76)％in validation set,respectively.The AUC of DL classification model for recognizing irregular shape,uneven density,satellite sign,mixed sign and vortex sign of sICH hematoma were 0.946-0.993 and 0.714-0.833 in training set and validation set,respectively.Conclusions FPN could accurately,effectively and automatically segment hematoma of sICH,hence having high efficacy for identifying semantic features of sICH hematoma.

Objective To observe the value of 3D Res2Net deep learning model for predicting volume doubling time(VDT)of solid pulmonary nodule.Methods Chest CT data of 734 patients with solid pulmonary nodules were retrospectively analyzed.The patients were divided into progressive group(n=218)and non-progressive group(n=516)according to whether lung nodule volume increased by ≥25％during follow-up or not,also assigned into training set(n=515)and validation set(n=219)at a ratio of 7∶3.Then a clinical model was constructed based on clinical factors being significantly different between groups,CT features model was constructed based on features of nodules on 2D CT images using convolutional neural network,and 3D Res2Net model was constructed based on Res2Net network using 3D CT images as input.Receiver operating characteristic curve was drawn,and the area under the curve(AUC)was calculated.Taken actual VDT as gold standard,the efficacy of the above models for predicting solid pulmonary nodule'VDT≤400 days were evaluated.Results No significant difference of predicting efficacy for solid pulmonary nodule'VDT≤400 days was found among clinical model,CT feature model and 3D Res2Net model,the AUC of which was 0.689,0.698 and 0.734 in training set,0.692,0.714 and 0.721 in validation set,respectively.3D Res2Net model needed 5-7 s to predict VDT of solid pulmonary nodules,with an average time of(5.92±1.08)s.Conclusion 3D Res2Net model could be used to predict VDT of solid pulmonary nodules,which might obviously reduce manual interpreting time.

Objective:To investigate the risk factors of cardiovascular and cerebrovascular diseases in young patients with hyperhomocysteinemia.Methods:A total of 260 patients younger than 45 years old who received treatment at the Department of Emergency, Seventh Medical Center, Chinese PLA General Hospital from January 2018 to January 2019 were included in this study. Among these patients, 126 patients with serum homocysteine levels ≥ 15.0 μmol/L were included in the hyperhomocysteinemia group, and 134 patients with serum homocysteine levels < 15.0 μmol/L were included in the control group. Height, body weight, body mass index, blood pressure, homocysteine, fasting blood glucose, blood uric acid, total cholesterol, triacylglycerol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and N-terminal B-type natriuretic peptide were determined in each group. Changes in risk factors of cardiovascular and cerebrovascular diseases were compared between the hyperhomocysteinemia and control groups.Results:There were significant differences in body mass index [(26.42 ± 3.54) kg/m 2vs. (22.14 ± 3.22) kg/m 2, t = 10.21, P = 0.016], blood uric acid [(308.71 ± 78.44) μmol/L vs. (285.05 ± 92.09) μmol/L, t = 2.22, P = 0.027], the incidence of coronary heart disease (73/126 vs. 61/134, χ2 = 4.00, P = 0.045) and the incidence of stroke (19/126 vs. 6/134, χ2 = 8.39, P = 0.004) between the hyperhomocysteinemia and control groups. There were no significant differences in fasting blood glucose, blood lipid level, N-terminal B-type natriuretic peptide, and the incidences of diabetes mellitus and hypertension between the two groups (all P > 0.05). Conclusion:The related risk factors of cardiovascular and cerebrovascular diseases increase in young patients with hyperhomocysteinemia. The incidences of coronary heart disease and stroke are very high, and therefore timely intervention should be carried out.

OBJECTIVE：To i mprove the transfer rate and purity of oleanolic acid and ursolic acid in total triterpenoids from Ligustrum lucidum ，so as to optimize the purification technology. METHODS ：Oleanolic acid and ursolic acid were used as representative components of total triterpenoids ，and their contents were determined by HPLC. The determination was performed on Thermo BDS Hypersil C 18 column with mobile phase consisted of methanol- 0.02％ ammonium acetate solution （80∶20，V/V）at the flow rate of 1.0 mL/min. The detection wavelength was set at 210 nm，and column temperature was 30 ℃. The sample size was 20 μ L. In single factor tests，using transfer rate of oleanolic acid and ursolic acid as index ，the effects of water precipitation temperature and time ，the amount of redissolved ethanol on the purification technology was investigated ；using transfer rate and purity of two components as indexes ，the effects of the amount of activated carbon and volume fraction of crystallization ethanol were investigated. Based on it ，using the amount of redissolved ethanol and activated carbon ，volume fraction of crystallization ethanol as factors ，Box-Behnken response surface methodology was used to optimize the purification technology ，and validation tests were performed. RESULTS ：The optimal purification technology was adding 4-fold（mL/g，the same below ）water in L. lucidum concentrated solution ，placing for 2 hours at 0 ℃（water precipitation ）；adding 1-fold ethanol to dissolve （redissolution）； adding 4％ activated carbon （edulcoration）；finally adding water to adjust the volume fraction of ethanol to 80％，placing at 4 ℃ for 12 hours（crystallization），centrifuging and drying. The results of 3 times of validation tests showed that the transfer rates of oleanolic acid and ursolic acid in total triterpenoids prepared by optimized technology were 61.11％ and 65.78％，the purities of them were 53.44％ and 19.79％，and RSDs were both lower than 3％. CONCLUSIONS ：The optimized purification technology has high extraction efficiency and simple operation ，which can be used for industrial production of purification of total triterpenoids from L. lucidum and the development of corresponding preparations.

Objective:To investigate the clinicopathological and molecular characteristics of pulmonary enteric adenocarcinoma (PEAC).Methods:The clinical and pathological data of 19 cases of PEAC in the Affiliated Cancer Hospital of Zhengzhou University were retrospectively collected from 2015 to 2019. Immunohistochemistry (IHC) was used to detect the relevant immunophenotypes, amplification refractory mutation system (ARMS) and fluorescence in situ hybridization (FISH) were used to detect the expression of EGFR, KRAS and ALK genes. The patients were followed up, and the relevant literature was reviewed and analyzed.Results:There were 19 cases, including 10 males and 9 females, with a mean age of 58 years (range 33-71 years). Microscopically, the tumors showed moderately to highly differentiated adenoid and/or papillary growth patterns. The tumor cells were highly columnar and sometimes showed pseudostratification. Inflammatory necrosis and scattered nuclear fragmentation were seen in some glandular lumens. IHC showed variable expression of CK7 (19/19), TTF1 (8/19), Napsin A (6/19), villin (17/19), CK20 (16/19) and CDX2 (10/19). Molecular testing showed KRAS mutation in nine cases (9/19), EGFR mutation in one case (1/19), and positive ALK split signal in one case (1/19). In the literature, the reported mutation rate of KRAS in PEAC was much higher than that of EGFR and ALK. All 19 cases underwent surgical resection and 11 cases were subjected to chemotherapy or radiotherapy.Conclusions:PEAC is a rare variant of invasive pulmonary adenocarcinoma, and has similar histological and cytological features to that of colorectal adenocarcinoma. However, detailed medical history, histologic heterogeneity, an IHC combination of CK7 +/villin + and high KRAS mutation rate are the key points of diagnosis. The prognosis needs long-term follow-up and big data statistics.

Objective To indentify the cognitive status of Chinese patients to acne and the influencing factors to theirs' cognitive status,so as to provide solid evidences for the prevention and treatment of acne.Methods A self-designed questionnaire was made to conduct this survey of 16,156 acne patients,who seeked to the treatment in the dermatological departments from 112 hospitals in China.The survey consisted of several parts,including the general status of patients,the patients' cognition of occurrence,development and risk factors of acne,whether the first choice was seeking treatment at the hospital when the patients had acne and the condition of selection of skin care products.The factors were analyzed,which could impact the cognition of the patients' behavior of treatment,how did the patients' cognition to influence their medical behavior and skin care as well as the consistency of assessment of the severity of acne by doctors and patients themselves.Results The acne patients studied had the best knowledge of "acne is a skin disease","it not only occurs in the period of adolescence" and "the disease can be prevented and cured",which accordingly accounted for 80.65％,69.16％ and 65.49％ of the total patients respectively.However,the awareness of acne patients to heredity,high sugar and dairy products as risk factors for acne was insufficient,which accounted for 48.72％,42.40％ and 18.25％ of the total patients,respectively.Gender,age,educational level,occupation and health knowledge were the main factors affecting the cognitive level of patients;the survey also found that men,patient with educational level of junior high or even lower educational condition,occupation of labor workers or farmers and patients were lack of health education with poor knowledge of the genetics and dietary were risk factors for acne;patients with age over 36 years or with mild illness had poor knowledge of dietary risk factors for acne;the difference was statistically significant (P＜0.05).The analysis of the influence of cognitive status on medical treatment behavior and skin care showed that the better the cognition,the higher the probability of patients would choose medical treatment as the first choice as well as choosing functional skin care products;the difference was statistically significant (P＜0.05).The consistency of assessment of the severity of acne by doctors and patients was poor (Kappa value ＜0.4),and the assessment of severity of acne by patients was more serious than doctors' assessment.Conclusions Patient's cognitive status will affect their medical behavior and skin care,and there is also a phenomenon that patients have a more serious assessment of their acne condition.It is suggested that health education for acne patients should be strengthened in clinical medicine so as to improve their knowledge of acne as well as preventing from acne effectively.

Objective: To understand the epidemiologic features of the rabies in Xishuang banna prefecture of Yunnan province, China in 2008-2017 and the viral molecular-evolution characteristics. Methods: The data of rabies case questionnaire were collected. The brain tissue samples from mad dogs, suspicious sick dogs and human brain tissue, saliva and cerebrospinal fluid samples from rabies patients were collected in Xishuangbanna. Coding region of nucleoprotein and glycoprotein genes were amplified by RT-PCR and sequenced. Homology and phylogenetic analysis were performed using the relevant bioinformatics software. Results: A total of 62 cases of human rabies were occurred in 28 districts of the 3 counties, Xishuangbanna prefecture in 2008-2017. Of them, 37 cases in Jinghong county, 15 in Menghai county and 10 in Mengla county. In which 48 cases were bitten by domestic dogs (77.42%), 11 cases were bitten by wild dogs (17.74%). Rabies case was occurred every year in the past decade. The seasonal incidence was not obvious. The majority of patients were aged from 30 to 59 years-old, with the youngest 1 year-old and the eldest 91 year-old. The male to female ratio was 1.70∶1, most cases were farmers. The nucleotide sequences of nucleoprotein gene of 9 virus strains (7 from Jinghong, 1 from Menghai and 1 from Mengla) were obtained from the samples of dogs and patients. Homology and phylogenetic analyses indicated that the 5 strains belonged to clade China-Ⅰ, 3 clade China-Ⅱ and 1 clade China-Ⅵ. The nucleotide sequences of glycoprotein gene of 5 virus strains (3 from Jinghong, 1 from Menghai and 1 from Mengla) were obtained from these positive samples, and all were clade China-Ⅰ, it is same with nucleoprotein genes analysis result from these 5 virus strains. These China-Ⅰ and China-Ⅱ strains from Xishuangbanna have a closer genetic relationship with same clade strains isolated from Pu’er and other prefectures of Yunnan province as well as Sichuan, Guizhou and Guangxi. The China-Ⅵ strain from Xishuangbanna share high homology and genetic relationship with China-Ⅵ strains isolated from southwestern Yunnan and neighbouring countries such as Myanmar, Laos and Vietnam in recent years. Conclusions In Xishuangbanna, rabies mainly occurred in rural area and domestic dog was the main source of transmission. These RABV clades China-Ⅰ, China-Ⅱ and China-Ⅵ were found in this region and the China-Ⅰ was principal clade. The transmission source of China-Ⅰ and China-Ⅱ were from adjacent areas in the province and China-Ⅵ was from Myanmar and Laos.