【Objective】 To explore the expression of USP9X in platelets and its effect on platelet function. 【Methods】 The expression of USP9X in human and mouse was evaluated by PCR and Western blot. Platelets from young and old mice were separated and prepared, and the expression of USP9X was detected. USP9X inhibitos were used to assess the regulation of USP9X in platelet function, including aggregation, ATP release and spreading. Platelet lysates were collected in different time points to evaluate the change of phosphorylation of Akt in USP9X inhibitors treated platelets. 【Results】 Both human and mouse platelets expressed USP9X. Compared to the young mice, the old mice showed significantly enhanced expression of USP9X(P<0.05). To assess the effect of USP9X on platelet function, USP9X inhibitor was used to pre-incubate platelets for 30 min and platelet function were examined later. Results showed that USP9X inhibitor significantly decreased platelet activation including aggregation, ATP release and spreading(P<0.05). Compared to the control group, the inhibitor treated group showed a significant decrease in the spreading area after 45 minutes. The Western blot results showed a significant decrease in Akt phosphorylation levels of platelets in the USP9X inhibitor treated group. 【Conclusion】 Both human and mouse platelet express USP9X, and inhibition of USP9X decreased platelet function including aggregation, ATP release and spreading. USP9X can also influence the phosphorylation of Akt. The inhibitor of USP9X may become a potential therapeutic target for thrombosis intervention.

Objective To evaluate the rabbit modle of frozen shoulder induced by persistent strain injuries and ice com-pression.Methods Twelve clean,healthy male New Zealand rabbits with a mass of(2 500±500)g were selected and randomly divided into a blank group and a control group with 6 rabbits in each group.In the control group,the rabbits were modeled with persistent strain injuries and ice compression,the general conditions of the rabbits and the active and passive activities of the shoulder joint were observed and their body weights were recorded.MRI was performed on the affected shoulder joints at 6 d and 29 d after modelling to observe the fluid and soft tissue;HE staining was used to observe the morphology of the rabbit bi-ceps longus tendon and the synovial membrane of the joint capsule;Masson staining was used to observe the fibrous deposits of the rabbit biceps longus tendon and the synovial membrane of the joint capsule,and the fibrous deposits were analysed semi-quantitatively by Image J software.Results Six days after the end of modeling,the active movement of the shoulder joints in the control group was limited,the passive movement was not significantly limited,and they walked with a limp;29 days after the end of the modeling,the active and passive movements of the shoulder joints in the model group were severely limited.Com-pared with the blank group(2.50±0.14)kg,the body weight of the model group(2.20±0.17)kg was significantly reduced(P＜0.01).MRI showed that 6 days after modelling,the muscles around the shoulder joint were not smooth in shape,the joint cap-sule structure was narrowed and a large amount of fluid was seen in the joint cavity;29 days after modelling,the muscles around the shoulder joint were rough in shape,structure of the joint capsule was unclear and the fluid in the joint cavity was reduced compared with 6 days after modelling.Pathological staining showed that the long-headed biceps tendon fibres in the control group were disorganised,curled or even broken,and the synovial tissue of the joint capsule was heavily vascularised,with col-lagen fibre deposits and severe inflammatory cell infiltration.The fiber deposition of the long head of biceps brachii in the mod-el group[(23.58±3.41)％,(27.56±3.70)％]and synovial tissue[(41.78±5.59)％,(62.19±7.54)％]were significantly higher than those in the blank group[(1.79±1.03)％,(1.29±0.63)％]at 7 and 30 days after modeling and synovial tissue fiber de-position[(8.15±3.61)％,(11.29±7.10)％],as shown by the semi-quantitative analysis of Masson staining results by Image J software.And the longer the time,the more severe the fibrosis(P＜0.01).Conclusion The behavioral,imaging and pathological findings showed that the rabbit frozen shoulder model with persistent strain injuries and ice compression is consistent with the clinical manifestations and pathogenesis of periarthritis,making it an ideal method for periarthritis research.

OBJECTIVE: To evaluate the efficacy and safety of Cidan Capsule combined with adjuvant transarterial chemoembolization (TACE) in patients with a high risk of early recurrence after curative resection of hepatocellular carcinoma (HCC). METHODS: A multicenter, randomized controlled trial was conducted in patients with high-risk recurrence factors after curative resection of HCC from 9 medical centers between July 2014 and July 2018. Totally 249 patients were randomly assigned to TACE with or without Cidan Capsule administration groups by stratified block in a 1:1 ratio. Postoperative adjuvant TACE was given 4-5 weeks after hepatic resection in both groups. Additionally, 125 patients in the TACE plus Cidan group were administrated Cidan Capsule (0.27 g/capsule, 5 capsules every time, 4 times a day) for 6 months with a 24-month follow-up. Primary endpoints included disease-free survival (DFS) and tumor recurrence rate (TRR). Secondary endpoint was overall survival (OS). Any drug-related adverse events (AEs) were observed and recorded. RESULTS: As the data cutoff in July 9th, 2018, the median DFS was not reached in the TACE plus Cidan group and 234.0 days in the TACE group (hazard ratio, 0.420, 95% confidence interval, 0.290-0.608; P<0.01). The 1- and 2-year TRR in the TACE plus Cidan and TACE groups were 31.5%, 37.1%, and 60.8%, 63.4%, respectively (P<0.01). Median OS was not reached in both groups. The 1- and 2-year OS rates in TACE plus Cidan and TACE groups were 98.4%, 98.4%, and 89.5%, 87.9%, respectively (P<0.05). The most common grade 3-4 AEs included fatigue, abdominal pain, lumbar pain, and nausea. One serious AE was reported in 1 patient in the TACE plus Cidan group, the death was due to retroperitoneal mass hemorrhage and hemorrhagic shock, and was not related to study drug. CONCLUSIONS Cidan Capsule in combination with TACE can reduce the incidence of early recurrence in HCC patients at high-risk of recurrence after radical hepatectomy and may be an appropriate option in postoperative anti-recurrence treatment. (Registration No. NCT02253511).

Panax ginseng(PG)and Panax notoginseng(PN)are highly valuable Chinese medicines(CM).Although both CMs have similar active constituents,their clinical applications are clearly different.Over the past decade,RNA sequencing(RNA-seq)analysis has been employed to investigate the molecular mechanisms of extracts or monomers.However,owing to the limited number of samples in standard RNA-seq,few studies have systematically compared the effects of PG and PN spanning multiple conditions at the transcriptomic level.Here,we developed an approach that simultaneously profiles transcriptome changes for multiplexed samples using RNA-seq(TCM-seq),a high-throughput,low-cost workflow to molecularly evaluate CM perturbations.A species-mixing experiment was conducted to illustrate the accuracy of sample multiplexing in TCM-seq.Transcriptomes from repeated samples were used to verify the robustness of TCM-seq.We then focused on the primary active components,Panax notoginseng sa-ponins(PNS)and Panax ginseng saponins(PGS)extracted from PN and PG,respectively.We also char-acterized the transcriptome changes of 10 cell lines,treated with four different doses of PNS and PGS,using TCM-seq to compare the differences in their perturbing effects on genes,functional pathways,gene modules,and molecular networks.The results of transcriptional data analysis showed that the tran-scriptional patterns of various cell lines were significantly distinct.PGS exhibited a stronger regulatory effect on genes involved in cardiovascular disease,whereas PNS resulted in a greater coagulation effect on vascular endothelial cells.This study proposes a paradigm to comprehensively explore the differences in mechanisms of action between CMs based on transcriptome readouts.

Depression syndromes(anxiety and depression), as typical psychological disorders, often coexist with and mutually influence coronary heart disease(CHD). They constitute a psycho-cardiology disease involving both the blood vessels of the heart and the spirit of the heart. Based on the theory of "coexistence of diseases and depression syndromes", it was proposed that CHD and depression syndromes coexisted independently and were causally related. The factors of depression syndromes go through the entire course of CHD and have different causal relationships at different stages, leading to a pathogenic process of "depression causing disease" or "disease causing depression". In the chronic latent period, phlegm predominates, with depression leading to the production of phlegm. Phlegm accumulation and Qi stagnation initiate a mutual damage process of psycho-cardiology, marking the onset of the disease. In the pathological development period, blood stasis becomes predominant. Depression leads to blood stasis, which further obstructs Qi circulation, accelerating disease progression. In the acute attack period, toxicity becomes crucial. Depression transforms into toxicity, damaging Qi and blood, disturbing the balance of the mind, and inducing a sudden and severe exacerbation of the disease. Based on this, the approach of treating phlegm and depression together, treating blood stasis and depression together, and treating toxicity and depression together by stages was established. Research has found that this approach can simultaneously improve organic damage and emotional disorders, and also has a regulating effect on micro-level syndrome indicators, achieving harmonization of psycho-cardiology in the treatment.
Humans ; Medicine, Chinese Traditional ; Depression/diagnosis* ; Coronary Disease/diagnosis* ; Mucus ; Syndrome ; Anxiety

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.
Female ; Humans ; Male ; Aged ; Middle Aged ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy* ; Prognosis ; Lymphoma, B-Cell ; Immunohistochemistry ; Immunoglobulin Heavy Chains/therapeutic use*

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R² of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.
Pregnancy ; Child ; Humans ; Female ; Glycated Hemoglobin ; Cohort Studies ; Diabetes Mellitus/diagnosis* ; Sensitivity and Specificity ; ROC Curve

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Objective:To explore the current status of surgery for portal hypertension to grasp current status and future development of surgery in China.Methods:This study is jointly sponsored by China Hepatobiliary & Pancreatic Specialist Alliance & Portal Hypertension Alliance in China (CHESS).Comprehensive surveying is conducted for basic domestic situations of surgery for portal hypertension, including case load, surgical approaches, management of postoperative complications, primary effects, existing confusion and obstacles, liver transplantation(LT), laparoscopic procedures and transjugular intrahepatic portosystemic shunt(TIPS), etc.Results:A total of 8 512 cases of portal hypertension surgery are performed at 378 hospitals nationwide in 2021.Splenectomy plus devascularization predominated(53.0%)and laparoscopy accounted for 76.1%.Primary goal is preventing rebleeding(67.0%) and 72.8% of hospitals used preventive anticoagulants after conventional surgery.And 80.7% of teams believe that the formation of postoperative portal vein thrombosis is a surgical dilemma and 65.3% of hospitals practiced both laparoscopy and TIPS.The major reasons for patients with portal hypertension not receiving LT are due to a lack of qualifications for LT(69.3%)and economic factors(69.0%).Conclusions:Surgery is an integral part of management of portal hypertension in China.However, it is imperative to further standardize the grasp of surgical indications, the handling of surgical operation and the management of postoperative complications.Moreover, prospective, multi-center randomized controlled clinical studies should be performed.