Urticarial vasculitis is a skin disease with urticaria-like lesions and a histopathological pattern of leukocytoclastic vasculitis. It is considered a "hidden rash" in traditional Chinese medicine. Xuanfu is the portal that regulates qi, blood, fluid, and the ascending, descending, exiting, and entering of nutrition qi and defensive qi. Collaterals are the pathways for the circulation of qi and blood. The two accompany each other, connecting zang-fu organs, reaching the surfaces of the skin, hair, and external body, circulating qi and fluid, and moistening and protecting the skin. Based on the theory of Xuanfu-collateral, this study aimed to clarify the etiology, pathogenesis, and treatment method of urticarial vasculitis. External assault by wind and Xuanfu blockage are believed to be the initiating factors of this disease. The malnutrition of Xuanfu and collaterals and accumulated dampness-heat are important links in the occurrence and development of urticarial vasculitis. It spreads from Xuanfu to the collaterals, and blockage of the collaterals is the immanent trend of this disease. Clinically, by closely adhering to the core pathogenesis of blockage of Xuanfu-collateral, treatment method such as using wind medicinals to open Xuanfu with pungent and dispersing properties, using the method of supplement deficiency and removing the blockage, and using medicinals to promote blood circulation and remove blood stasis to unblock the blocked collaterals. The herbs are flexibly added or subtracted to unblock Xuanfu and collaterals, harmonize qi and blood, thus all symptoms can be relieved. We hope that this study will provide new ideas for the treatment of urticarial vasculitis with traditional Chinese medicine.

Objective:To compare clinical characteristics of patients with atopic prurigo nodularis (APN) versus non-APN (NAPN), and to analyze differences in the therapeutic response to dupilumab.Methods:A retrospective study was conducted. Clinical data were collected from patients with atopic dermatitis and those with prurigo nodularis, who visited the Department of Dermatology, Southwest Hospital, Army Medical University from January 2017 to December 2022. These patients were divided into the APN group and NAPN group according to the inclusion and exclusion criteria (types of skin lesions and the presence or absence of history of atopic diseases). Clinical characteristics, laboratory examination results, and comorbidities were compared between the 2 groups, so were the eczema area and severity index (EASI) scores, investigator′s global assessment (IGA) scores and itch numeric rating scale (NRS) scores at 0, 4, 12 weeks after the treatment with dupilumab.Results:A total of 233 patients with NAPN and 177 with APN were enrolled, and their ages were 57 (48, 68) and 43 (20, 57) years, respectively. Before the treatment, the serum IgE levels and eosinophil counts were significantly higher in the APN patients than in the NAPN patients ( Z = -4.40, -3.92, respectively, both P < 0.001) ; compared with the NAPN patients, the APN patients more frequently presented with skin lesions on the trunk (71.64% [117/177] vs. 54.08% [126/233], P < 0.05), limbs (71.75% [127/177] vs. 61.37% [143/233], P < 0.05) and the whole body (28.36% [53/177] vs. 20.17% [47/233], P < 0.05) ; the incidence rates of xeroderma, erythema, papules and crusting were significantly higher in the APN patients than in the NAPN patients (all P < 0.05), and the APN patients more frequently presented with symmetrically distributed lesions; however, there were no significant differences in the incidence rates of secondary lesions such as scratches (38.98% [67/177] vs. 33.91% [79/233]) and ulcers (18.64% [33/177] vs. 18.03% [42/233]) between the two groups (both P > 0.05). The proportions of patients with chronic kidney diseases, cardiovascular diseases, liver diseases and diabetes were significantly higher in the NAPN group than in the APN group (all P < 0.05). There were 13 patients with APN and 5 with NAPN who received a 12-week dupilumab treatment and had complete follow-up results. No significant differences were observed in the EASI, IGA or NRS scores before the treatment between the 2 groups (all P < 0.05) ; after the 12-week treatment, the improvement of EASI score was significantly higher in the APN group than in the NAPN group ( P < 0.05), while there were no significant differences in the improvement of NRS and IGA scores between the 2 groups (both P > 0.05) . Conclusion:The clinical manifestations, laboratory examination results, and comorbidities differed between the NAPN and APN patients, however, they both showed good therapeutic response to dupilumab.

AIM:This study investigates the effect of fibroblast growth factor 21(FGF21)long-acting ana-logue PF-05231023 on promoting the"browning"of white adipose tissue(WAT)by inhibiting mitophagy in WAT and the molecular mechanisms involved.METHODS:Using a high-fat diet(HFD)to replicate an obesity model in mice,18 C57BL/6J mice were divided into three groups:normal control(NC)group,HFD group,and PF-05231023 intervention(PF+HFD)group,each consisting of 6 mice.After 12 weeks of feeding,the mice were anaesthetized,their eyeballs were removed to collect blood samples,and serum was separated to measure levels of total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C)、alanine aminotransferase(ALT),and aspartate aminotransferase(AST)in mouse serum.The inguinal WAT(iWAT),epididymal WAT(eWAT)and liver were collected.Part of the tis-sues were used for Western blot experiments to measure the protein levels of"browning"related markers uncoupling pro-tein-1(Ucp-1)and peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α),as well as mitophagy-related markers PTEN-induced kinase 1(Pink1),parkin,beclin-1 and microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ).Another part of the tissues was fixed in paraformaldehyde for subsequent HE and immunohistochemical staining.3T3-L1 cells were induced to mature adipocytes using the classic"cocktail"method.The CCK-8 assay was used to assess the impact of different concentrations of PF-05231023 intervention on cell viability.After 48 h of PF-05231023 intervention,the 3T3-L1 cell clumps were collected for Western blot experiments to measure the expression levels of"browning"related markers Ucp-1 and PGC-1α,as well as mitochondrial autophagy-related markers Pink1,parkin,beclin-1,and LC3-Ⅱ proteins.Oil red O staining was performed to detect cell accumulation,and immunofluorescence staining was used to mea-sure Ucp-1 protein content.Subsequently,3T3-L1 cells were divided into the normal group,PF-05231023 intervention group,Pink1 agonist MTK458 intervention group,and MTK458+PF-05231023 intervention group.Cell clumps were col-lected for Western blot experiments to measure the markers as mentioned above.RESULTS:The key findings of our study indicate that the PF-05231023 intervention did not affect energy intake in mice but significantly reduced the weight,liver weight,and fat weight of mice induced by a high-fat diet(P<0.05).The intervention also decreased lipid accumula-tion(TC,TG、LDL-C)and liver damage(ALT,AST)and alleviated hepatocyte vacuolization and adipocyte size(P<0.05).Compared with the HFD group,the PF-05231023 intervention increased the levels of Ucp-1 and PGC-1α protein expression in iWAT and eWAT(P<0.01).Immunohistochemical staining showed higher Ucp-1 protein content in the PF-05231023 intervention group than in the HFD group.The PF-05231023 intervention dose-dependently increased Ucp-1 and PGC-1α protein expression levels in mature 3T3-L1 cells(P<0.01),reduced cellular lipid accumulation,and immu-nofluorescence staining showed increased Ucp-1 protein content in mature 3T3-L1 cells after PF-05231023 intervention.The PF-05231023 intervention inhibited mitochondrial autophagy-related indicators Pink1,parkin,beclin-1,and LC3-Ⅱ protein expression levels in iWAT,eWAT,and induced mature 3T3-L1 cells(P<0.05).The MTK intervention increased Pink1,parkin,beclin-1,and LC3-Ⅱ protein expression levels,increased Ucp-1 protein expression level,compared with the MTK intervention group,after MTK and PF-05231023 co-intervention,partially decreased Pink1,parkin,beclin-1,and LC3-Ⅱ protein expression levels,and partially restored Ucp-1 protein expression level(P<0.01).CONCLUSION:(1)Intervention with PF-05231023 can improve obesity and related metabolic disorders induced by a high-fat diet in mice;(2)PF-05231023 intervention can inhibit white adipose tissue(WAT)and induce mature 3T3-L1 cell mitochondria autophagy,promoting"browning"by inhibiting mitochondrial autophagy;(3)Its mechanism may be related to the inhibi-tion of the Pink1-parkin signalling pathway.

BACKGROUND: Immune checkpoint inhibitors (ICIs) therapy lacks viable biomarkers for response and prognosis prediction. This study aimed to investigate the correlation of peripheral blood laboratory test results combined with lymphocyte subset ratios to the response and prognosis of immunotherapy in advanced lung cancer. METHODS: Advanced lung cancer patients admitted to West China Hospital, Sichuan University from May 2021 to July 2023 were prospectively enrolled in this study. Clinical data and peripheral blood were collected before and after treatment and lymphocyte subset ratios were analyzed by flow cytometry. Logistic regression was used to identify factors correlated to ICIs treatment efficacy. Cox modeling was applied to explore the prognostic factors. RESULTS: Logistic regression showed that the baseline level of transcription factor T cell factor 1 (TCF1)+CD8+ T cell ratio and peripheral white blood cell (WBC) count, lymphocyte percentage, cytokeratin 19 fragment (CYFRA21-1) after 1 cycle of ICIs treatment were the potential predictors for ICIs response (P<0.05). Cox regression analysis showed that the baseline level of TCF1+CD8+ T cell ratio (P=0.020) and peripheral WBC count after 1 cycle of ICIs treatment (P<0.001) were prognostic factors. CONCLUSIONS Patients with high baseline TCF1+CD8+ T cell ratio combined with low WBC counts and low CYFRA21-1 level after 1 cycle of ICIs treatment are more likely to benefit from ICIs therapy.
Humans ; Lung Neoplasms/drug therapy* ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; T Cell Transcription Factor 1/genetics* ; Prognosis ; CD8-Positive T-Lymphocytes ; Immunotherapy

Objective: Accumulating evidence has shown that aberrant alternative splicing events are closely associated with the onset and development of cancer. However, whether genetic variants-associated alternative splicing is linked to risk of endometrial cancer remains largely uncertain. Methods: We identified single nucleotide polymorphisms (SNPs) locates in the splicing number trait locus (sQTL) of endometrial cancer using the CancerSplicing QTL database. In parallel with bioinformatics analysis, we conducted a case-control study comprising 2,000 cases and 2,013 controls to assess the association between identified SNP which possesses mRNA splicing function and endometrial cancer susceptibility. Furthermore, we used the Kaplan-Meier Plotter, The Human Protein Atlas, SPNR, and Spliceman2 databases for sQTL and differential gene expression analyses to identify the genetic variant which most potentially influence the risk of endometrial cancer through alternative splicing to reveal the potential mechanism by which candidate SNPs regulate the risk of endometrial cancer. Results: The results indicated that SNP rs7128029 AConclusion These findings suggest that SNP rs7128029-mediated alternative splicing events in PSMD13 are associated with endometrial cancer risk and may be a potential early screening biomarker for endometrial cancer-susceptible populations.

Objective:To analyze the etiological distribution and phylogenetic characteristics of hand, foot and mouth disease (HFMD) in Qujing city of Yunnan Province in 2020.Methods:Stool samples were collected from HFMD cases in Qujing city in 2020 and virus RNA was extracted directly from treated stool suspensions. Virus VP4 gene sequences were firstly amplified using MD91/OL68-1 primer pairs and sequenced, then the virus serotypes were determined by BLAST search on the GenBank. Virus entire VP1 gene sequences were amplified and sequenced. Virus serotypes were identified online using Enterovirus Genotyping Tool Version 0.1. Sequences of reference virus genotypes/sub-genotypes were downloaded according to references. Phylogenetic trees were constructed by MEGA5.2 software and the genetic characteristics were analyzed.Results:A total of 47 strains of enteroviruses (EVs) were detected with a detection rate of 10.22% (47/460). The detected viruses were coxsackievirus A4 (CVA4, 0.65%, 3/460), CVA6 (7.83%, 36/460), CVA10 (0.87%, 4/460) and CVA16 (0.87%, 4/460). All were enterovirus species A (EVA), while other group viruses were not detected. The predominant virus was CVA6, accounting for 7.83% (36/460). EVA71 was not detected. CVA4 strains of C2 and C4 subgenotypes were co-circulating strains in Qujing city. CVA6 subgenotype D3a and CVA16 subgenotype B1a were also circulated in Qujing city. All CVA10 strains were in a separate lineage.Conclusions:Similar to the previous situation in China, the detection rates of EVA71 and CVA16 were very low, even zero. This study showed that CVA6 was the predominant virus, indicating a HFMD outbreak caused by CVA6 in Qujing city in 2020. The phylogenetic analysis showed CVA10 isolates belonged to a separate lineage, which might be unique to Qujing city. Laboratory and molecular epidemiological surveillance of non-EVA71 and non-CVA16 viruses, especially CVA6 and CVA10 should be strengthened in the future.

Objective:To investigate the risk factors of cervical lymph node metastasis (LNM) and survival analysis in patients with medullary thyroid carcinoma (MTC) .Methods:93 patients with MTC admitted to the Department of General Surgery and Department of Otorhinolaryngology, First Medical Center of PLA General Hospital from Sep. 2008 to Aug. 2020 were analyzed retrospectively, including 45 males and 48 females, with an average age of 47 years old. SPSS 26.0 statistical software was used for data processing of the initial surgical year and procedures, tumor pathological stages, preoperative calcitonin (Ctn) level, preoperative carcinoembryonic antigen (CEA) level, LNM status, recurrence free survival (RFS) , etc. The risk factors of LNM and prognosis of MTC patients were analyzed by COX univariate and multivariate regression. Kaplan Meier method was used to estimate the survival rates of independent risk factors affecting prognosis and draw their survival curves.Results:The median follow-up time of 93 patients was 53 months, ranging from 2 to 192 months. The 1-year, 3-year, 5-year and 10-year survival rates were 97.8%, 96.6%, 94.6% and 88.9% respectively. Multivariate COX regression analysis showed that Initial surgical procedures ( P=0.018) and preoperative Ctn level ( P=0.012) were independent risk factors of central cervical LNM. Preoperative Ctn level ( P=0.028) and Capsule invasion ( P=0.024) were the independent risk factors of lateral cervical LNM. Preoperative Ctn level≥180.30 pg/ml and ≥234.15pg/ml indicated central and lateral cervical LNM respectively (all P<0.001) . Distant metastasis was an independent risk factor of RFS ( P=0.037) of MTC. Conclusions:Standardized surgical procedures are recommended for initial treatment of MTC, which can reduce the possibility of residual occult metastasis and the risk of reoperation. Distant metastasis affects prognosis of MTC.

Objective:To study the diagnostic value of the artificial intelligence (AI) diagnostic system, ACR TI-RADS classification and AI+ ACR TI-RADS combined diagnostic performance in benign and malignant thyroid nodules and its guiding significance for surgical treatment.Methods:From Nov. 1, 2021, to Feb. 26, 2022, 349 patients with 605 thyroid nodules who received surgical treatment in Department of Thyroid (Hernia) Surgery, Department of General Surgery, the First Medical Center of the PLA General Hospital, were selected. There were 95 males and 254 females, male: female=1:2.67, aged 16-78 years, and the nodule diameter was 0.2-5.6 cm. SPSS 26.0 and R studio software were used for data processing. AI diagnostic system, ACR TI-RADS grading and AI+ ACR TI-RADS combined diagnostic efficacy were statistically analyzed, respectively. ROC curve analysis was performed in parallel.Results:The AUC value of AI+ ACR TI-RADS combined diagnosis was 0.900, greater than 0.857 of AI diagnostic system and 0.788 of ACR TI-RADS, and the difference was statistically significant ( Z= 7.631, both P<0.001) . The sensitivity of the combined diagnosis was 95.32%, the specificity was 84.61%, the accuracy was 92.56%, the positive predictive value was 94.69%, the negative predictive value was 86.27%, the missed diagnosis rate was 4.68%, and the misdiagnosis rate was 15.38%, which were better than the other two diagnostic methods. With an excellent coincidence rate with postoperative pathological results ( Kappa=0.804, P<0.001) . The accuracy of combined diagnosis in identifying the maximum diameter of different tumors was 89.58% for d≤0.5 cm, 96.09% for 0.54.0 cm, better than the other two diagnostic methods. Conclusions:The combined application of AI+ACR TI-RADS has a certain primary screening value in evaluating thyroid nodule properties. The combined diagnosis of the two can more effectively determine the benign and malignant thyroid nodules.

Objective:To investigate the epidemiological and clinicopathological characteristics of thyroid cancer.Methods:Data of 13 673 thyroid cancer patients admitted to the First Medical Center of PLA General Hospital from Jan. 2014 to Dec. 2019 were retrospectively analyzed. According to the admission criteria, 9 662 patients were screened out, including 2 768 males and 6 894 females, with an average age of 43.98±11.28 years. According to the year of diagnosis and treatment, the incidence of thyroid cancer, the changing trend of age of new cases, the average length of hospitalization, the pathological classification of the tumor, the size of the primary tumor, multifocal tumor, and the rate of lymph node metastasis were statistically analyzed. The surgical methods were summarized and discussed.Results:① Characteristics of population economics: the ratio of males to females were 1.00:2.49, the number of cases increased year by year, and the rate of increase of female was higher than that of male. The average age of onset of the patients was (43.98±11.28) years old, and the incidence rate of the young population increased by 6.0%, showing a younger trend. The mean length of hospital stay was (7.21±2.85) d, and the length of hospital stay decreased. ② Clinicopathological features: There were 9 513 cases of papillary thyroid carcinoma (PTC) (98.46%) , 45 cases of follicular thyroid carcinoma (FTC) (0.47%) , 58 cases of medullary carcinoma (MTC) (0.60%) and 18 cases of poorly differentiated thyroid carcinoma (PDTC) (0.19%) . There were 2 cases (0.02%) of undifferentiated thyroid carcinoma (ATC) and 26 cases (0.26%) of a particular type. The tumor size was (1.10±0.85) cm, among which the microcarcinoma (D ≤1 cm) accounted for 64.5% and showed an increasing trend year by year, with the fastest growth rate. There were 3 809 cases of multifocal carcinoma (39.4%) , and the proportion of multifocal carcinoma increased year by year in recent 3 years. The central region and lateral region lymph node metastasis rates were 33.0% and 13.0%, respectively. Correlation analysis showed that the differences were statistically significant except for pathological types ( P<0.05) . ③ Surgical methods: in the first 3 years, 2 224 patients (84.2%) underwent normative primary resection, which increased to 94.9% in the last 3 years. In the first 3 years, 2 033 patients (77.0%) underwent central lymph node dissection, which increased to 91.8% in the last 3 years. In the first 3 years, 188 cases (50.5%) underwent normative lateral cervical dissection, which increased to 71.6% in the last 3 years. Conclusions:The incidence of thyroid cancer is increasing year by year, showing a younger trend; Papillary carcinoma accounts for 98.5% of thyroid cancer. The proportion of microcarcinoma and multifocal carcinoma is increasing. The rate of lymph node metastasis in the central region and lateral region is increasing; surgery is gradually standardized, and it is necessary to standardize the diagnosis and treatment of thyroid cancer and postoperative follow-up.

Objective: To compare laparoscopic cholecystectomy (LC) with or without percutaneous transhepatic gallbladder drainage (PTGD) for acute severe cholecystitis. Methods: According to the predefined inclusion and exclusion criteria, 23 articles were selected for this meta-analysis. All patients were treated with LC with or without PTGD. A meta-analysis was used to analyze the clinical efficacy. Results: Compared with LC, all the surgical indicators of LC with PTGD were significantly better than LC alone (all P≤0.05), including the operation time: 95%CI(-27.24, -9.27); intraoperative blood loss: 95%CI(-50.25, -40.19); postoperative hospital stay: 95%CI(-3.63, -0.64); rates of conversion to open abdomen: OR=0.48, 95%CI(0.32, 0.74); rates of incision infection: OR=0.49, 95%CI(0.25, 0.99); drainage tube indwelling time: 95%CI(-2.07, -1.19); gastrointestinal function recovery time: 95%CI(-1.73, -0.77); rates of bile leakage: OR=0.23, 95%CI(0.12, 0.44); and rates of complications: OR=0.36, 95%CI(0.27, 0.48). Conclusion Compared with LC alone, PTGD+ LC is the preferred treatment for acute severe cholecystitis.