ObjectiveTo observe the clinical efficacy of acupuncture combined with bloodletting and cupping in the treatment of chronic spontaneous urticaria（CSU） and to explore its potential mechanisms of action. MethodsSeventy CSU patients were randomly divided into loratadine group and acupuncture + bloodletting group， with 35 patients in each group. The loratadine group received oral loratadine tablets， 10 mg once daily in the evening. The acupuncture + bloodletting group received acupuncture at Zhongwan （CV 12）， Guanyuan （CV 4）， Tianshu （ST 25）， Zusanli （ST 36）， Sanyinjiao （SP 6）， Xuehai （SP 10）， Quchi （LI 11）， Hegu （LI 4）， Taichong （LR 3）， Baihui （GV 20）， and Shenting （GV 24）， once daily，along with bloodletting and cupping at Dazhui （GV 14） and Geshu （BL 17）， every other day. Both groups were treated for 4 weeks. The 7-day urticaria activity score（UAS7） was assessed before and after the treatment， and levels of serum immunoglobulin E （IgE）， interleukin-4 （IL-4）， interleukin-5 （IL-5）， eosinophil cationic protein （ECP）， plasma tissue factor （TF）， activated factor Ⅶ （FⅦa）， prothrombin fragment 1+2 （F1+2）， D-dimer （D-D） and complement component 5a （C5a） were detected. ResultsA total of 65 patients were included in the final analysis， 32 in the loratadine group and 33 in the acupuncture + bloodletting group. Before treatment， there was no significant difference in UAS7 score， serum IgE， IL-4， IL-5， ECP levels， or plasma TF， FⅦa， F1+2， D-D， C5a levels between groups （P＞ 0.05）. After treatment， both groups showed significant reductions in UAS7 score， serum IgE， IL-4， IL-5， and plasma TF， FⅦa， F1+2， D-D， and C5a levels compared to those before treatment （P＜0.01）. However， after treatment， there was no significant difference in UAS7 score and serum ECP， IgE， IL-4， IL-5 levels between groups （P＞0.05）. The acupuncture + bloodletting group showed lower plasma TF， FⅦa， F1+2， D-D and C5a levels compared to the loratadine group （P＜0.05 or P＜0.01）. ConclusionAcupuncture combined with bloodletting and cupping can effectively improve the skin symptoms of CSU patients and reduce the levels of inflammatory factors. The potential mechanism of action may involve the regulation of the coagulation-complement-mast cell activation axis， thereby inhibiting mast cell degranulation.

To investigate the correlation between vitamin D nutritional status and insulin resistance in pubertal adolescents.

To investigate body composition and associated factors in adolescents undergoing long-term regular sports training.

Purpose To investigate the cell components in different tumor lineages of multiple synchronous pituitary neuro-endocrine tumors(PitNETs)/neuroendocrine tumors(MSPs)and to carry out accurate histological typing,which provides an important basis for determining the follow-up plan and adjuvant therapy after surgery.Methods The clinical data of 855 pa-tients with PitNETs were collected and reclassified according to the new WHO standard.The clinicopathological features of 13 patients diagnosed as MSPs were analyzed retrospectively.The immunohistochemical EnVision two-step method was used to de-tect the expression of PIT-1,SF-1,T-PIT,GH,PRL,TSH,LH,FSH,ACTH,etc.,and related literatures were reviewed.Methods A total of 855 cases of pituitary neuroendocrine tumor from the second hospital of the Chinese Hebei Medical U-niversity were collected and reclassified according to the new WHO standard,and review the literature.Results(1)The age of patients were 39-68 years with median age of 55 years.7 cases were female and 6 were male;(2)Imaging findings:There was 1.2～3.8 cm(mean 2.5 cm)in maximum tumor di-ameter.13 patients were large adenomas,neither MSPs nor sin-gle lineage PitNETs could not assessed on imaging;(3)Clinical manifestations:3 cases had hyperprolactinemia which all contai-ning PitNETs components of PRL,one case was immature PIT-1 polyhormone cell tumor,one was dense granular prolactinoma,and one case was eosinophilic stem tumor.One patient had Cushing's disease and contained a Crook cell tumor component;two had elevated ACTH,and one had an adrenocorticotropic ad-enomatous component.In the two patients with no evidence of hormone excess,all contained gonadotropin cell tumor compo-nents;(4)Combination form:11 cases of the combination of the two cell lineages(5 cases of combination of SF-1 lineage and PIT-1 lineage;4 cases of combination of T-PIT lineage and PIT-1 lineage;1 case of null cell tumor and PIT-1 lineage;1 case of plurihormonal PitNETs and SF-1 lineage);Two cases of three cell combinations(null cell tumor,PIT-1 lineage,and T-PIT lineage);Among them,13 cases were PIT-1 lineage tumors,46.2％(6/13)were gonadotropin cell tumor,38.5％(5/13)were prolactinoma;(5)The presence of high-risk lineage tumors in the 10 patient combinations:3 immature PIT-1-lineage tumor,1 Crooke cell PitNETs,1 acidophil stem cells tumor,3 zero-cell PitNETs,and 4 silent-type sparse granular adrenocorti-cotropic hormone PitNETs;Two of them were combinations of two high-risk subtypes.Conclusion MSPs in our center are large adenomas,although their incidence is only 1.5％of Pit-NETs,2/3 cases have high-risk lineage tumor components,and the use of pituitary cell lineage transcription factors and adeno-hypophyseal hormones plays an important role in distinguishing and clarifying the different components of MSPs.

Objective:To investigate the clinicopathological characteristics of acidophil stem cell pituitary neuroendocrine tumors (PitNET)/adenoma.Methods:Five cases of acidophil stem cell PitNET/adenoma were diagnosed between May 2022 and July 2023 at the Second Hospital of Hebei Medical University, Shijiazhuang, China. The clinicopathological features of the tumor were analyzed by using histology, immunohistochemistry, and electron microscopy. The relevant literature was reviewed.Results:There were 1 male and 4 females, aged from 23 to 69 years. Patient 3 was 55 years old at the time of diagnosis and first surgery, and relapsed 5 years later. The patients′ median age was 32 years. Patients 1 and 5 showed elevated blood prolactin, with various degrees of hormonal symptoms except Patient 3, who showed only tumor compression symptoms. Imaging studies showed that all cases involved the sellar floor. The tumors of Patients 1, 2 and 5 were closely related to the cavernous sinus segment of the internal carotid artery. The tumors exhibited a diffuse growth pattern with chromophobic to slightly acidophilic cytoplasm. A few of tumor cells showed chromophobic cytoplasm. The nucleoli were conspicuous. Intranuclear inclusion bodies and variably-sized clear vacuoles were observed occasionally. Under electron microscope, marked mitochondrial abnormalities were observed, including increased mitochondria number, expanded hypertrophy, and absence of mitochondrial ridge fracture. Some mitochondrial matrices were dense, while some were vacuolated.Conclusions:Acidophil stem cell PitNET/adenoma is a rare type of pituitary adenomas/PitNETs. It often has a more clinically aggressive manner with immature cells, diffuse expression of PIT1, prolactin, and varying degrees of growth hormone expression. Because of the obvious diversity of their clinical hormone status and hormone immune expression, the diagnosis of this type tumor is still a challenge.

Objectives:To explore the effects of interatrial shunt on cardiac function and clinical prognosis of patients with heart failure with reduced ejection fraction(HFrEF). Methods:This study was a prospective single-arm study.From December 2021 to December 2022,15 consecutive patients with HFrEF from Beijing Anzhen Hospital were enrolled in this study.Interatrial shunt was performed with a D-Shant atrial shunt device.Right heart catheterization was performed before and immediately after device implantation,pulmonary capillary wedge pressure(PCWP),mean right atrial pressure(RAP),interatrial gradient pressure,mean pulmonary artery pressure,total pulmonary resistance(TPR),pulmonary vascular resistance(PVR),cardiac index(CI),and pulmonary/systemic blood flow ratio(Qp/Qs)were measured.Patients were followed-up for 12 months after procedure,changes in cardiac structure and function were evaluated by echocardiography.NYHA classification,6-minute walking distance(6MWD),and Kansas City cardiomyopathy questionnaire(KCCQ)were observed.All-cause mortality and rehospitalization for heart failure served as clinical endpoints. Results:Interatrial shunt procedure was successful in all patients.Compared with preoperative value,PCWP,interatrial gradient pressure,mean pulmonary artery pressure,and TPR were significantly decreased,while Qp/Qs was significantly increased immediately after procedure(all P<0.01).There were no significant changes in RAP,PVR,and CI post procedure(all P>0.05).There were no significant differences in shunt size,shunt velocity,and shunt pressure difference between postoperative immediately and at 12-months follow-up(all P>0.05).At 12 months,left ventricular ejection fraction was significantly higher than baseline level(P<0.05),and there were no significant changes in right atrial diameter and right ventricular fractional area change(both P>0.05).Compared with preoperative status,NYHA classification was improved,KCCQ score was increased,and the number of patients with 6MWD>450 m was increased at 12 months(all P<0.05).N-terminal pro-B-type natriuretic peptide value was significantly decreased at 12 months(P<0.05).No patient died during the 12-months follow-up period,and there were no device-related adverse events.Two patients experienced hospital readmission for heart failure. Conclusions:Implantation of interatrial shunt device could effectively improve hemodynamic parameters in patients with HFrEF and is related to significantly improved cardiac function at 12-months follow-up.

bstract: Objective To elucidate the distribution characteristics of mosquito species and the population genetic diversity of important mosquito species in the Wuyi Mountain Nature Reserve, with the aim of providing a scientific basis for the prevention and control of mosquito-borne diseases in the region. Methods Within Wuyi Mountain Nature Reserve 2022- 2023, 16 sampling sites were selected, where larvae were collected using the pipette method and adult mosquitoes were collected using the mosquito trap lamp method. Mosquito species identification was accomplished by integrating morphological characteristics and molecular identification techniques based on CO Ⅰ and CO Ⅱ gene sequences. Software tools such as ClustalX, DnaSP v5.0, and Network v4.6.1.0 were utilized to analyze the genetic differentiation (Fst), gene flow (Nm) among populations of Aedes japonicus, Aedes albopictus and Armigeres subalbatus. Results The mosquito specimens collected from the Wuyi Mountain Nature Reserve were identified as 30 species belonging to 8 genera within the Culicidae family. Among them, there were 10 species of Aedes, 13 species of Culex, 1 species each of Armigeres, Orthopodomyia, Uranotaenia, Tripyeroides, and Anopheles, and 2 species of Toxorhynchites. Analysis of the genetic structure of important mosquito populations showed that the haplotype diversity index (Hd) of Ae. japonicus was 0.994 7, with a generally moderate degree of differentiation between populations and a higher degree of genetic differentiation between populations 6 and 12; Aedeslbopictus had a haplotype diversity index of 0.634 0, with significant genetic differentiation between populations 1 and 2 compared to other groups; Armigeres subalbatus had a haplotype diversity index of 0.703 3, with substantial genetic differentiation and limited gene flow between population 2 and populations 3, 4, 6, and 7. Conclusions The mosquito species are rich in Wuyi Mountain Nature Reserve. A comprehensive survey of the composition and distribution of mosquito populations was carried out, and the characteristics of the population genetic structure of the important species of Ae. japonicus, Ae. Albopictus, and Ar. subalbatus populations were analyzed, providing valuable scientific data reference for local mosquito-borne ecological research and disease prevention and control.

Treating patients with esophageal squamous cell carcinoma (ESCC) is challenging due to the high chemoresistance. Growth differentiation factor 15 (GDF15) is crucial in the development of various types of tumors and negatively related to the prognosis of ESCC patients according to our previous research. In this study, the link between GDF15 and chemotherapy resistance in ESCC was further explored. The relationship between GDF15 and the chemotherapy response was investigated through in vitro and in vivo studies. ESCC patients with high levels of GDF15 expression showed an inferior chemotherapeutic response. GDF15 improved the tolerance of ESCC cell lines to low-dose cisplatin by regulating AKT phosphorylation via TGFBR2. Through an in vivo study, we further validated that the anti-GDF15 antibody improved the tumor inhibition effect of cisplatin. Metabolomics showed that GDF15 could alter cellular metabolism and enhance the expression of UGT1A. AKT and TGFBR2 inhibition resulted in the reversal of the GDF15-induced expression of UGT1A, indicating that TGFBR2-AKT pathway-dependent metabolic pathways were involved in the resistance of ESCC cells to cisplatin. The present investigation suggests that a high level of GDF15 expression leads to ESCC chemoresistance and that GDF15 can be targeted during chemotherapy, resulting in beneficial therapeutic outcomes.
Humans ; Esophageal Squamous Cell Carcinoma/drug therapy* ; Cisplatin/metabolism* ; Esophageal Neoplasms/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Carcinoma, Squamous Cell/genetics* ; Growth Differentiation Factor 15/therapeutic use* ; Receptor, Transforming Growth Factor-beta Type II/therapeutic use* ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic

BACKGROUND: Rheumatoid arthritis (RA), a chronic systemic autoimmune disease, is characterized by synovitis and progressive damage to the bone and cartilage of the joints, leading to disability and reduced quality of life. This study was a randomized clinical trial comparing the outcomes between withdrawal and dose reduction of tofacitinib in patients with RA who achieved sustained disease control. METHODS: The study was designed as a multicenter, open-label, randomized controlled trial. Eligible patients who were taking tofacitinib (5 mg twice daily) and had achieved sustained RA remission or low disease activity (disease activity score in 28 joints [DAS28] ≤3.2) for at least 3 months were enrolled at six centers in Shanghai, China. Patients were randomly assigned (1:1:1) to one of three treatment groups: continuation of tofacitinib (5 mg twice daily); reduction in tofacitinib dose (5 mg daily); and withdrawal of tofacitinib. Efficacy and safety were assessed up to 6 months. RESULTS: Overall, 122 eligible patients were enrolled, with 41 in the continuation group, 42 in the dose-reduction group, and 39 in the withdrawal group. After 6 months, the percentage of patients with a DAS28-erythrocyte sedimentation rate (ESR) of <3.2 was significantly lower in the withdrawal group than that in the reduction and continuation groups (20.5%, 64.3%, and 95.1%, respectively; P  < 0.0001 for both comparisons). The average flare-free time was 5.8 months for the continuation group, 4.7 months for the dose reduction group, and 2.4 months for the withdrawal group. CONCLUSION: Withdrawal of tofacitinib in patients with RA with stable disease control resulted in a rapid and significant loss of efficacy, while standard or reduced doses of tofacitinib maintained a favorable state. TRIAL REGISTRATION Chictr.org, ChiCTR2000039799.
Humans ; Quality of Life ; China ; Arthritis, Rheumatoid/drug therapy* ; Piperidines/therapeutic use* ; Treatment Outcome ; Antirheumatic Agents/therapeutic use* ; Pyrroles/therapeutic use*

Objective:To construct a real-time artificial intelligence (AI)-assisted endoscepic diagnosis system based on YOLO v3 algorithm, and to evaluate its ability of detecting focal gastric lesions in gastroscopy.Methods:A total of 5 488 white light gastroscopic images (2 733 images with gastric focal lesions and 2 755 images without gastric focal lesions) from June to November 2019 and videos of 92 cases (288 168 clear stomach frames) from May to June 2020 at the Digestive Endoscopy Center of Renmin Hospital of Wuhan University were retrospectively collected for AI System test. A total of 3 997 prospective consecutive patients undergoing gastroscopy at the Digestive Endoscopy Center of Renmin Hospital of Wuhan University from July 6, 2020 to November 27, 2020 and May 6, 2021 to August 2, 2021 were enrolled to assess the clinical applicability of AI System. When AI System recognized an abnormal lesion, it marked the lesion with a blue box as a warning. The ability to identify focal gastric lesions and the frequency and causes of false positives and false negatives of AI System were statistically analyzed.Results:In the image test set, the accuracy, the sensitivity, the specificity, the positive predictive value and the negative predictive value of AI System were 92.3% (5 064/5 488), 95.0% (2 597/2 733), 89.5% (2 467/ 2 755), 90.0% (2 597/2 885) and 94.8% (2 467/2 603), respectively. In the video test set, the accuracy, the sensitivity, the specificity, the positive predictive value and the negative predictive value of AI System were 95.4% (274 792/288 168), 95.2% (109 727/115 287), 95.5% (165 065/172 881), 93.4% (109 727/117 543) and 96.7% (165 065/170 625), respectively. In clinical application, the detection rate of local gastric lesions by AI System was 93.0% (6 830/7 344). A total of 514 focal gastric lesions were missed by AI System. The main reasons were punctate erosions (48.8%, 251/514), diminutive xanthomas (22.8%, 117/514) and diminutive polyps (21.4%, 110/514). The mean number of false positives per gastroscopy was 2 (1, 4), most of which were due to normal mucosa folds (50.2%, 5 635/11 225), bubbles and mucus (35.0%, 3 928/11 225), and liquid deposited in the fundus (9.1%, 1 021/11 225).Conclusion:The application of AI System can increase the detection rate of focal gastric lesions.