Objective At present, the grading evaluation of patients with disorders of consciousness (DOC) is still a focus and difficulty in related fields. Electroencephalogram (EEG) can directly read and continuously reflect scalp electrical activity generated by brain tissue structure, with high temporal resolution. Auditory stimulation is easy to operate and has broad application prospects in clinical detection of DOC. The causal network can intuitively reflect the direction of information transmission through the causal relationship between time series, helping us better understand the information interaction between different regions of the brain of patients. This paper combines EEG and causal networks to explore the differences in brain functional connectivity between patients with unresponsive arousal syndrome (VS) and those with minimum state of consciousness (MCS) under auditory stimulation. MethodsA total of 23 DOC patients were included, including 11 MCS patients and 12 VS patients. Based on the Oddball paradigm, auditory naming stimulation was performed on DOC patients and EEG signals of DOC patients were synchronously collected. The brain functional networks were constructed using multivariate Granger causality method, and the differences in node degree, clustering coefficient, global efficiency, and causal flow of the brain networks between MCS patients and VS patients were calculated. The differences in network characteristics of patients with different levels of consciousness under auditory stimulation were compared from the perspective of cooperation between brain regions. ResultsThe causal connectivity between most brain regions in MCS patients was stronger than that in VS patients, and MCS patients had more brain network connectivity edges than VS patients. The average degree (P<0.05), average clustering coefficient, and global efficiency (P<0.05) of MCS patients under naming stimulation were higher than those of VS patients. The difference in out-degree between each node of VS patients was larger, and the difference in in-degree between each node of MCS patients was smaller. The difference in in-degree of MCS patients was more significant than that of VS patients, and the inflow and outflow of information in the brain functional network of MCS patients were stronger than those of VS patients. MCS and VS patients had differences of causal flow in the frontal and temporal lobes, the direction of information transmission in the parietal lobe and central region was not the same, and MCS patients had more electrodes as causal sources than VS patients. ConclusionThe information transmission ability of MCS patients is stronger than that of VS patients under auditory naming stimulation. Compared with VS patients, MCS patients have an increase in the number of electrode channels as the causal source, an increase in information output to other brain regions, and also an increase in the information output within brain regions, which may indicate a better state of consciousness in patients. MCS patients have more electrode channels for information output in the frontal lobe than VS patients, and the number of electrode channels for changing the direction of information transmission in the frontal lobe is the highest. The frontal lobe is closely related to the level of consciousness in patients with consciousness disorders. This study can provide a theoretical basis for the grading evaluation of consciousness levels in DOC patients.

Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.
Medicine, Chinese Traditional ; Nonprescription Drugs ; Consensus ; China ; Reference Standards ; Drugs, Chinese Herbal

Objective: To investigate the clinical characteristics of hospitalized children infected with the Omicron variant in Kunming after the withdrawal of non-pharmaceutical interventions (NPI) and analyze the risk factors of severe cases. Methods: Clinical data was retrospectively collected from 1 145 children with SARS-CoV-2 Omicron infection who were hospitalized in six tertiary grade A hospitals in Kunming from December 10^th, 2022 to January 9^th, 2023. According to clinical severity, these patients were divided into the general and severe SARS-CoV-2 groups, and their clinical and laboratory data were compared. Between-group comparison was performed using t-test, chi-square test and Mann-Whitney U test. Spearman correlation test and multivariate Logistic regression analysis were used to determine the risk factors of severe illness. Results: A total of 1 145 hospitalized patients were included, of whom 677 were male and 468 female. The age of these patients at visit was 1.7 (0.5, 4.1) years. Specifically, there were 758 patients (66.2%) aged ≤3 years at visit and 387 patients (33.8%) aged >3 years. Of these children, 89 cases (7.8%) had underline diseases and the remaining 1 056 cases (92.2%) had no combined diseases. Additionally, of all the patients, 319 cases (27.9%) were vaccinated with one or two doses of SARS-CoV-2 vaccine, 748 cases (65.3%) had acute upper respiratory tract infection (AURTI), and six cases died (0.5%). A total of 1 051 cases (91.8%) were grouped into general SARS-CoV-2 group and 94 cases (8.2%) were grouped into severe SARS-CoV-2 group. Compared with the general cases, the severe cases showed a lower rate of SARS-CoV-2 vaccination and younger median age, lower lymphocyte count, as well as proportions of CD8⁺T lymphocyte (36 cases (38.3%) vs. 283 cases (26.9%), 0.5 (2.6, 8.0) vs. 1.6 (0.5, 3.9) years, 1.3 (1.0, 2.7) ×10⁹ vs. 2.7 (1.3,4.4)×10⁹/L, 0.17 (0.12, 0.24) vs. 0.21 (0.15, 0.16), respectively, χ²=4.88, Z=-2.21,-5.03,-2.53, all P<0.05). On the other hand, the length of hospital stay, proportion of underline diseases, ALT, AST, creatine kinase isoenzyme, and troponin T were higher in the severe group compared to those in the general group ((11.6±5.9) vs. (5.3±1.8) d, 41 cases (43.6%) vs. 48 cases (4.6%), 67 (26,120) vs. 20 (15, 32) U/L, 51 (33, 123) vs. 44 (34, 58) U/L、56.9 (23.0, 219.3) vs. 3.6 (1.9, 17.9) U/L, 12.0 (4.9, 56.5) vs. 3.0 (3.0, 7.0) ×10^-3 pg/L,respectively, t=-20.43, χ²=183.52, Z=-9.14,-3.12,-6.38,-3.81, all P<0.05). Multivariate regression analysis indicated that increased leukocyte count (OR=1.88, 95%CI 1.18-2.97, P<0.01), CRP (OR=1.18, 95%CI 1.06-1.31, P<0.01), ferritin (OR=1.01, 95%CI 1.00-1.00, P<0.01), interleukin (IL)-6 (OR=1.05, 95%CI 1.01-1.08, P=0.012), D-dimer (OR=2.56, 95%CI 1.44-4.56, P<0.01) and decreased CD4⁺T lymphocyte (OR=0.84, 95%CI 0.73-0.98, P=0.030) were independently associated with the risk of severe SARS-CoV-2 in hospitalized children with Omicron infection. Conclusions: After the withdrawal of NPI, the pediatric inpatients with Omicron infection in Kunming were predominantly children younger than 3 years of age, and mainly manifested as AURTI with relatively low rate of severe SARS-CoV-2 infection and mortality. Elevated leukocyte counts, CRP, ferritin, IL-6, D-dimer, and decreased CD4⁺T lymphocytes are significant risk factors for developing severe SARS-CoV-2 infection.
Humans ; Child ; Female ; Male ; COVID-19 ; COVID-19 Vaccines ; Retrospective Studies ; SARS-CoV-2 ; Ferritins ; Interleukin-6

Objective: To investigate the efficacy of laparoscopic hyperthermic intraperitoneal perfusion chemotherapy combined with intraperitoneal and systemic chemotherapy (HIPEC-IP-IV) in the treatment of peritoneal metastases from gastric cancer (GCPM). Methods: This was a descriptive case series study. Indications for HIPEC-IP-IV treatment include: (1) pathologically confirmed gastric or esophagogastric junction adenocarcinoma; (2) age 20-85 years; (3) peritoneal metastases as the sole form of Stage IV disease, confirmed by computed tomography, laparoscopic exploration, ascites or peritoneal lavage fluid cytology; and (4) Eastern Cooperative Oncology Group performance status 0-1. Contraindications include: (1) routine blood tests, liver and renal function, and electrocardiogram showing no contraindications to chemotherapy; (2) no serious cardiopulmonary dysfunction; and (3) no intestinal obstruction or peritoneal adhesions. According to the above criteria, data of patients with GCPM who had undergone laparoscopic exploration and HIPEC from June 2015 to March 2021 in the Peking University Cancer Hospital Gastrointestinal Center were analyzed, after excluding those who had received antitumor medical or surgical treatment. Two weeks after laparoscopic exploration and HIPEC, the patients received intraperitoneal and systemic chemotherapy. They were evaluated every two to four cycles. Surgery was considered if the treatment was effective, as shown by achieving stable disease or a partial or complete response and negative cytology. The primary outcomes were surgical conversion rate, R0 resection rate, and overall survival. Results: Sixty-nine previously untreated patients with GCPM had undergone HIPEC-IP-IV, including 43 men and 26 women; with a median age of 59 (24-83) years. The median PCI was 10 (1-39). Thirteen patients (18.8%) underwent surgery after HIPEC-IP-IV, R0 being achieved in nine of them (13.0%). The median overall survival (OS) was 16.1 months. The median OS of patients with massive or moderate ascites and little or no ascites were 6.6 and 17.9 months, respectively (P<0.001). The median OS of patients who had undergone R0 surgery, non-R0 surgery, and no surgery were 32.8, 8.0, and 14.9 months, respectively (P=0.007). Conclusions: HIPEC-IP-IV is a feasible treatment protocol for GCPM. Patients with massive or moderate ascites have a poor prognosis. Candidates for surgery should be selected carefully from those in whom treatment has been effective and R0 should be aimed for.
Male ; Humans ; Female ; Middle Aged ; Aged ; Aged, 80 and over ; Young Adult ; Adult ; Stomach Neoplasms/surgery* ; Peritoneal Neoplasms/secondary* ; Hyperthermic Intraperitoneal Chemotherapy ; Percutaneous Coronary Intervention ; Hyperthermia, Induced/methods* ; Combined Modality Therapy ; Laparoscopy/methods* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Perfusion ; Cytoreduction Surgical Procedures ; Survival Rate

Objective: To compare the prognostic influence and postoperative pathology of different comprehensive treatment models for adenocarcinoma of esophagogastric junction. Methods: Between January 2012 and December 2017, a total of 219 patients with adenocarcinoma of esophagogastric junction underwent surgery in Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute and were enrolled in this study. The clinicopathological data of these patients were collected. The patients were categorized into 3 groups according to different treatment models: surgery-first group, neoadjuvant chemotherapy (NAC) group and neoadjuvant chemoradiotherapy (nCRT) group. A trimatch propensity score analysis was applied to control potential confounders among the three groups by using R language software. A total of 7 covariates including gender, age, comorbidity, body mass index, clinical T stage, clinical N stage and Siewert type were included, and the caliper value was taken as 0.2. After matching, a total of 87 patients were included for analysis with 27 patients for each group. There were 82 males and 5 females, with a median age of 63 years (range: 38 to 76 years). The effect of preoperative treatment on postoperative tumor pathology among the three different comprehensive treatment models was explored by χ² test, ANOVA or Wilcoxon rank sum test. Mann-Whitney U test or χ² test were used to undergo pairwise comparisons. Kaplan-Meier method and Log-rank test were used to analyze the overall survival and progression-free survival. Results: The proportion of vascular embolism in the surgery-first group was 72.4% (21/29), which was significantly higher than NAC group (37.9% (11/29), χ²=6.971, P=0.008) and nCRT group (6.9% (2/29), χ²=26.696, P<0.01). The proportions of pathological T3-4 stage in nCRT group and NAC group were 55.2% (16/29) and 62.1% (18/29), respectively, which were significantly lower than the surgery-first group (93.1% (27/29), χ²=10.881, P=0.001; χ²=8.031, P=0.005). Compared with the NAC group (55.2% (16/29), χ²=6.740, P=0.009) and nCRT group (31.0% (9/29), χ²=18.196, P<0.01), the proportion of lymph node positivity 86.2% (25/29) were significantly higher in the surgery-first group. The 5-year overall survival rates were 62.1%, 68.6% and 41.4% for the surgery-first group, NAC group and nCRT group, respectively (χ²=4.976, P=0.083). The 5-year progression-free survival rates were 61.7%, 65.1% and 41.1% for the surgery-first group, NAC group and nCRT group, respectively. The differences in overall survival (χ²=4.976, P=0.083) and progression-free survival (χ²=4.332, P=0.115) among the three groups were nonsignificant. Conclusions: Postoperative pathology is significantly different among the three groups. Neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy could decrease the proportions of vascular embolism, pathological T3-4 stage and lymph node positivity to achieve local tumor control. The prognosis of overall survival and progression-free survival are not significantly different among the three groups.
Adenocarcinoma/pathology* ; Adult ; Aged ; Cohort Studies ; Esophagogastric Junction/pathology* ; Female ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; Propensity Score

Objective: To assess the effect of gene mutations on the efficacy of ruxolitinib for treating myelofibrosis (MF) . Methods: We retrospectively analyzed the clinical data of 56 patients with MF treated with ruxolitinib from July 2017 to December 2020 and applied second-generation sequencing (NGS) technology to detect 127 hematologic tumor-related gene mutations. Additionally, we analyzed the relationship between mutated genes and the efficacy of ruxolitinib. Results: ①Among the 56 patients, there were 36 cases of primary bone marrow fibrosis (PMF) , 9 cases of bone marrow fibrosis (ppv-mf) after polycythemia vera, and 11 cases of bone marrow fibrosis (PET-MF) after primary thrombocytosis (ET) . ②Fifty-six patients with MF taking ruxolitinib underwent NGS, among whom, 50 (89.29%) carried driver mutations, 22 (39.29%) carried ≥3 mutations, and 29 (51.79%) carried high-risk mutations (HMR) . ③ For patients with MF carrying ≥ 3 mutations, ruxolitinib still had a better effect of improving somatic symptoms and shrinking the spleen (P=0.001, P<0.001) , but TTF and PFS were significantly shorter in patients carrying ≥ 3 mutations (P=0.007, P=0.042) . ④For patients carrying ≥ 2 HMR mutations, ruxolitinib was less effective in shrinking the spleen than in those who did not carry HMR (t= 10.471, P=0.034) , and the TTF and PFS were significantly shorter in patients carrying ≥2 HMR mutations (P<0.001, P=0.001) . ⑤Ruxolitinib had poorer effects on spleen reduction, symptom improvement, and stabilization of myelofibrosis in patients carrying additional mutations in ASXL1, EZH2, and SRSF2. Moreover, patients carrying ASXL1 and EZH2 mutations had significantly shorter TTF [ASXL1: 360 (55-1270) d vs 440 (55-1268) d, z=-3.115, P=0.002; EZH2: 327 (55-975) d vs 404 (50-1270) d, z=-3.219, P=0.001], and significantly shorter PFS compared to non-carriers [ASXL1: 457 (50-1331) d vs 574 (55-1437) d, z=-3.219, P=0.001) ; 428 (55-1331) d vs 505 (55-1437) d, z=-2.576, P=0.008]. Conclusion: The type and number of mutations carried by patients with myelofibrosis and HMR impact the efficacy of ruxolitinib.
Humans ; Mutation ; Nitriles ; Primary Myelofibrosis/genetics* ; Pyrazoles ; Pyrimidines ; Retrospective Studies ; Technology ; Transcription Factors/genetics*

OBJECTIVE: To construct a HEK293 cell line stably overexpressing TrxR1 as a cell model for functional study of TrxR1 and screening of TrxR1-targeting drugs. METHODS: TrxR1 gene was amplified by PCR and ligated with the lentivirus expression vector pLVX-Puro, which was transformed into Escherichia coli and identified by Sanger dideoxy sequencing. HEK293 cells were infected with the recombinant lentivirus vector (pLVX-Puro-TXNRD1) and screened with Puromycin for cell clones with stable TrxR1 overexpression (HEK293-TrxR1-OE cells). HEK293-TrxR1-OE cells, along with HEK293 cells infected with pLVX-Puro vector (HEK293-NC) and normal HEK293 cells, were tested for mRNA and protein expression levels of TrxR1 using RT-qPCR and Western blotting. TrxR1 enzyme activity in the cells was evaluated with insulin endpoint assay and TRFS-green probe imaging. The sensitivity of the cells to auranofin, a specific TrxR1 inhibitor, was determined with CCK8 assay. RESULTS: TrxR1 gene was successfully inserted into the lentiviral vector pLVX-Puro as confirmed by DNA sequencing. The enzyme activity and mRNA and protein expression levels of TrxR1 were significantly higher in HEK293-TrxR1-OE cells than in HEK293 and HEK293-NC cells (P < 0.005). The inhibitory effects of auranofin on proliferation and cellular TrxR1 enzyme activity were significantly attenuated in HEK293-TrxR1-OE cells as compared with HEK293 and HEK293-NC cells (P < 0.005). CONCLUSION We successfully obtained a HEK293 cell line with stable TrxR1 overexpression, which shows resistance to auranofin and can be used for screening TrxR1 targeting drugs.
Auranofin ; Cell Line, Tumor ; Genetic Vectors ; HEK293 Cells ; Humans ; Lentivirus/genetics* ; RNA, Messenger ; Transfection

Objective - To establish a new non exposed intratracheal instillation method for establishing a rat silicosis model. Methods ， The specific pathogen free SD rats were randomly divided into control group and experimental group with ten rats in ， each group. Rats in the control group were given 1.0 mL of 0.9% sodium chloride solution and rats in the experimental group - were given 1.0 mL of silica suspension with a mass concentration of 50 g/L adopting to the one time intratracheal instillation ， - ， method and then followed by ventilator assisted ventilation immediately. When the tidal volume stabilized at 2.0 mL the ventilator was removed and the tracheal intubation was pulled out. Five rats in each group were sacrificed after two and four ， - Results weeks after modeling and hematoxylin eosin staining and Masson staining of lung tissue were performed. There was ， ， no death in the two groups of rats during the experiment. After two and four weeks the control group had normal lung structure ， ， ， normal alveolar cavity size no inflammatory cell infiltration thin alveolar wall only a small amount of collagen distribution ， around the lung interstitium and bronchus. At the second week of modeling the alveolar wall of the rats in the experimental ， ， ， group was slightly thickened interstitial lymphocytes and macrophages were infiltrated slight hyperplasia was found and a ， small amount of fibroblasts were visible. At the 4th week of modeling the alveolar wall of the rats in the experimental group was ， ， ， ， significantly thickened fibrous nodules were formed and fibroblasts fibrocytes collagen fibers were significantly increased. Conclusion - The combination of ventilator and non exposed intratracheal instillation method can be used to successfully ， ， . establish a rat silicosis model which is simple safe and effective

BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER NCT02063100 on ClinicalTrials.gov.

OBJECTIVE: To explore the influencing factors of low back pain and the relationship of the influence of bad working posture, weight load and frequency of load and the dose-response relationship among the occupational workers of key industries in China. METHODS: A total of 57 501 employees from 15 key industries in China were selected as research subjects using stratified cluster sampling method. The occurrence of low back pain in the past one year, as well as occupational factors such as job type, labor organization and work posture were investigated by using the Chinese version Musculoskeletal Disorders Questionnaire. RESULTS: The prevalence of low back pain in the occupational population of key industries in China was 16.4%(9 448/57 501). Multivariate Logistic regression analysis showed that the risk of low back pain in females was higher than that in males(P<0.01). Married, obese, occasional and frequent smokers, and a history of lower back disease were associated with increased risk of low back pain(all P<0.05). The risk of low back pain was associated with older age, higher education level, and lower frequency of physical exercise(all P<0.01). The risk of low back pain was higher with longer working time, greater back curvature, and the high frequency of long standing and sitting position work, uncomfortable working posture, repeated operation per minute, and lifting>5 kg weight(all P<0.01). CONCLUSION: The influencing factors of low back pain in the occupational population of key industries in China include bad working posture, high frequency load, weight load and other individual factors. There is a dose-response relationship with low back posture load and frequency of load.