BACKGROUND: Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT), and there is no standard therapy. Avatrombopag (AVA) is a second-generation thrombopoietin (TPO) receptor agonist (TPO-RA) that has shown efficacy in immune thrombocytopenia (ITP). However, few reports have focused on its efficacy in patients diagnosed with thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: We conducted a retrospective study at the First Affiliated Hospital of the University of Science and Technology of China to evaluate the efficacy of AVA as a first-line TPO-RA in 65 patients after UCBT; these patients were compared with 118 historical controls. Response rates, platelet counts, megakaryocyte counts in bone marrow, bleeding events, adverse events and survival rates were evaluated in this study. Platelet reconstitution differences were compared between different medication groups. Multivariable analysis was used to explore the independent beneficial factors for platelet implantation. RESULTS: Fifty-two patients were given AVA within 30 days post-UCBT, and the treatment was continued for more than 7 days to promote platelet engraftment (AVA group); the other 13 patients were given AVA for secondary failure of platelet recovery (SFPR group). The median time to platelet engraftment was shorter in the AVA group than in the historical control group (32.5 days vs . 38.0 days, Z  = 2.095, P  = 0.036). Among the 52 patients in the AVA group, 46 achieved an overall response (OR) (88.5%), and the cumulative incidence of OR was 91.9%. Patients treated with AVA only had a greater 60-day cumulative incidence of platelet engraftment than patients treated with recombinant human thrombopoietin (rhTPO) only or rhTPO combined with AVA (95.2% vs . 84.5% vs . 80.6%, P  <0.001). Patients suffering from SFPR had a slightly better cumulative incidence of OR (100%, P  = 0.104). Patients who initiated AVA treatment within 14 days post-UCBT had a better 60-day cumulative incidence of platelet engraftment than did those who received AVA after 14 days post-UCBT (96.6% vs . 73.9%, P  = 0.003). CONCLUSION Compared with those in the historical control group, our results indicate that AVA could effectively promote platelet engraftment and recovery after UCBT, especially when used in the early period (≤14 days post-UCBT).
Humans ; Female ; Male ; Thrombocytopenia/etiology* ; Adult ; Retrospective Studies ; Cord Blood Stem Cell Transplantation/adverse effects* ; Middle Aged ; Adolescent ; Young Adult ; Thiazoles/adverse effects* ; Platelet Count ; Receptors, Thrombopoietin/agonists* ; Child ; Thiophenes

Evading host immunity killing is a critical step for virus survival. Inhibiting viral immune escape is crucial for the treatment of viral diseases. Serine/threonine kinase 39 (STK39) was reported to play an essential role in ion homeostasis. However, its potential role and mechanism in viral infection remain unknown. In this study, we found that viral infection promoted STK39 expression. Consequently, overexpressed STK39 inhibited the phosphorylation of interferon regulatory factor 3 (IRF3) and the production of type I interferon, which led to viral replication and immune escape. Genetic ablation or pharmacological inhibition of STK39 significantly protected mice from viral infection. Mechanistically, mass spectrometry and immunoprecipitation assays identified that STK39 interacted with PPP2R1A (a scaffold subunit of protein phosphatase 2A (PP2A)) in a kinase activity-dependent manner. This interaction inhibited DDB1 and CUL4 associated factor 1 (DCAF1)-mediated PPP2R1A degradation, maintained the stabilization and phosphatase activity of PP2A, which, in turn, suppressed the phosphorylation of IRF3, decreased the production of type I interferon, and then strengthened viral replication. Thus, our study provides a novel theoretical basis for viral immune escape, and STK39 may be a potential therapeutic target for viral infectious diseases.

Objective This study was to develop a"Spleen Deficiency Certificate Scale for County Residents"and test its reliability.It was then developed as an objective tool for Chinese medicine evidence and symptoms for the prevention and control of chronic diseases among county residents.Methods The scale was compiled based on the team's previous foundation.The reliability of the scale was evaluated using internal consistency reliability and split-half reliability,while its validity was evaluated using structural validity,content validity,calibration validity,and discriminant validity.Results The study included 213 adults from Lanxi,of whom 155 were tested for intestinal flora.Seven scale entries were identified:Fatigue,fear of cold,bland mouth,loss of appetite,diarrhea,weak bowel movements,and tooth-marked tongue.In the reliability test,Cronbach's alpha coefficient was 0.828 and McDonald's ω coefficient was 0.825.The"stomach pain"and"bloating"entries did not meet the inclusion requirements and were recommended to be deleted.The Spearman-Brown coefficient was 0.839.The exploratory factor analysis of the two common factors explained 61.6%of the cumulative variance.The calibration validity indicated that the ratio of salivary amylase activity before and after acid stimulation was 0.826±0.253 in the group with spleen deficiency.Significant differences(P<0.05)in the genera Dialister,Shigella,Leuconostoc,Photobacterium,Trabulsiella,and Parvimonas between the spleen deficiency group and the non-spleen deficiency group.Conclusion The Spleen Deficiency Scale for County Residents demonstrates good reliability and validity.

Objective To evaluate the effect of photo-activated disinfection(PAD)as a kind of adjuvant treatment on moderate to severe chronic periodontitis.Methods 21 patients with the chronic periodontitis(totally 218 selected sites)were randomly enrolled and divided into group A(minocycline hydrochloride),group B(PAD),group C(PAD + minocycline hydrochloride),and group D(no adjunctive therapy)for the adjunctive treatment after receiving the scaling and root planing(SRP).Periodontal indexs as probing depth(PD),bleeding on probing(BOP)and clinical attachment loss(CAL)were examined at the baseline,6 and 12 weeks after the treatment.Meanwhile,periodontal pathogens as Porphyromonas gingivalis(Pg)and Tannerella forsythia(Tf)from subgingival plaque of group A,B and C were detected by Real-time PCR.Results Compared with the baseline,the periodontal inflammations of all groups were improved signiffcantly at 6 and 12 weeks after the treatment(P<0.001),and group A,group B and group C were better than group D(P<0.001),group C was better than group A(P<0.001);Furthermore,the concentration of Pg and Tf was decreased significantly(P<0.001),and there was no difference among the three groups with adjunctive therapy.Conclussion As the adjunctive treatment of SRP,PAD could achieve the same and even better effect than minocycline hydrochloride ointment.

ObjectiveTo observe the effect of Qinggan Jianpi Huoxue prescription（QGJPHXP） on the polarization of M1/M2 macrophages in rats with hepatic fibrosis induced by carbon tetrachloride（CCl₄）. MethodA rat hepatic fibrosis model was established by intraperitoneal injection of 40% CCl₄-olive oil suspension twice a week at the dosage of 2.0 mL·kg^-1 for 8 weeks. After the model was successfully established， these rats were randomly divided into the model group， QGJPHXP group（32.084 g·kg^-1） and Biejiajian pills（BJJP） group（0.925 5 g·kg^-1）， with 12 rats in each group. The blank group was injected intraperitoneally with the same amount of olive oil. The rats in the administration groups were given the corresponding solution according to the dose， and the blank and model groups were given the same dose of purified water， once a day. After 4 weeks of continuous administration， the liver tissues of rats were taken and stained with hematoxylin-eosin（HE） and Masson to observe the pathological changes. The serums were collected to detect the alanine aminotransferase（ALT） and aspartate aminotransferase（AST） levels. Interleukin（IL）-6， IL-12， IL-10， IL-1β， transforming growth factor-β₁（TGF-β₁） and tumor necrosis factor-α（TNF-α） levels in liver tissues were measured by enzyme-linked immunosorbent assay（ELISA）. The expression levels of CD86 and CD206 were detected by immunohistochemistry（IHC）. Western blot and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） were used to detect the protein and mRNA expression levels of inducible nitric oxide synthase（iNOS）， arginase-1（Arg-1）， phosphorylated p38 mitogen-activated protein kinase（p-p38 MAPK）， nuclear transcription factor-κB p65（NF-κB p65） in liver tissues of rats. ResultCompared with the blank group， the hepatic cell plate was irregularly arranged, and local inflammatory cell infiltration and fibrous hyperplasia were observed， while the serum levels of ALT and AST were significantly increased in the model group（P<0.01）， and IL-1β， IL-6， IL-12， TGF-β₁， TNF-α， CD86， CD206， iNOS， p-p38 MAPK，p38 MAPK and NF-κB p65 levels in liver tissues were obviously increased（P<0.05， P<0.01）， while the levels of IL-10 and Arg-1 were obviously decreased（P<0.05， P<0.01）. Compared with the model group， QGJPHXP group reduced the degree of liver cell fibrosis，and serum levels of ALT and AST（P<0.01）， and IL-1β， IL-6， IL-12， TGF-β₁， TNF-α， CD86， iNOS， p-p38 MAPK， p38 MAPK， and NF-κB p65 levels in liver tissues were obviously decreased（P<0.05， P<0.01）， the levels of IL-10， CD206 and Arg-1 were obviously increased in the QGJPHXP group（P<0.05， P<0.01）. ConclusionQGJPHXP has ability to inhibit the activation of pro-inflammatory M1 macrophages， induce the secretion of anti-inflammatory cytokines by M2 macrophages， reduce the release of pro-fibrogenic cytokines， and promote the macrophage polarization of M1 to M2 in liver for tissue repair， thereby serving as an anti-inflammatory and anti-hepatic fibrosis drug.

Objective:The aim of this retrospective study is to evaluate the safety and efficacy of tislelizumab in patients with recurrent/metastatic head and neck squamous cell carcinoma. Methods:Six patients with recurrent/metastatic head and neck squamous cell carcinoma who received tislelizumab monotherapy in our hospital from 2018 to 2020 were retrospectively analyzed. The information of sex, age, TNM stage, efficacy, and adverse reactions were collected. All patients were recruited from the RATIONALE 102 study. The primary end point was the objective response rate, and other end points included progression-free survival and overall survival. We performed tumor immune-related gene sequencing and transcriptome sequencing analysis on the tumor tissues of the patient, and used bioinformatics methods to enrich immune cells and analyze signaling pathways. All analyses were performed using R 4.1. 0 software, SPSS Statistics 24.0 software and GraphPad Prism 8. Results:As of May 31, 2020, the median follow-up time was 26.35 months. The objective response rate with tislelizumab was 50.0%, the median progression-free survival was 6.44 months, and the estimated median survival was 20.07 months. The incidence of grade 3 or higher adverse reactions was 66.7%, including hyponatremia, hypokalemia, hypercalcemia, etc. The expression of macrophage, Treg and neutrophil-related genes are higher in immune-sensitive patients, and the signaling pathways of the intestinal immune network for IgA production, graft versus host disease and autoimmune thyroid disease are significantly activated. Conclusion:Tislelizumab was found to be controllable and tolerable in patients with recurrent/metastatic head and neck squamous cell carcinoma. The response to tislelizumab is related to immune cell infiltration and activation of immune-related signaling pathways.
Humans ; Squamous Cell Carcinoma of Head and Neck/etiology* ; Retrospective Studies ; Carcinoma, Squamous Cell/pathology* ; Neoplasm Recurrence, Local/pathology* ; Head and Neck Neoplasms ; Antineoplastic Combined Chemotherapy Protocols

BACKGROUND: How to locate pulmonary ground-glass nodules in thoracoscopic surgery is an important clinical topic in minimally invasive thoracic surgery. There is no unified localization method at present. This study intends to investigate the accuracy and security of body surface theodolitic puncture localization method in video-assisted thoracoscopic surgery for pulmonary ground-glass nodules. METHODS: The clinical data of 41 patients from August 2018 to December 2019 were analyzed retrospectively, including 28 males and 13 females. After anesthesia, the patient was located by body surface theodolitic puncture, and then partial lobectomy was performed under video-assisted thoracoscopy. The distance from the nodule to the marked suture and the distance from the nodule to the incisal margin were measured, and the accuracy of localization, the rate of complication and the success rate of surgical resection were calculated. RESULTS: A total of 51 nodules in 41 patients were located by body surface theodolitic puncture localization method. The accuracy rate was 96.1%, and the average location time was 8.3 min. Puncture bleeding occurred in 5 cases (12.2%), all of which were successfully stopped by video-assisted thoracoscopy, and there were no other complications. All patients underwent thoracoscopic partial lobectomy, including 33 cases of anatomical segmentectomy and 8 cases of wedge lobectomy. All the patients in operation process smoothly. The distance between nodule and incisal margin was measured, and all specimens were more than 2 cm, reaching a safe distance. The success rate of surgical resection was 100.0%. CONCLUSIONS In video-assisted thoracoscopic surgery for ground glass nodules of lung, the body surface theodolitic puncture localization method can be accurate, safe and simple.

Objective: To explore the establishment of the incisor extraction wound models in aesthetic area of the rats and the application effect of modified minimally invasive tooth extraction surgery, and to provide the basis for establishment of the incisor extraction wound models in aesthetic area and improvement of the healing of alveolar bone and soft tissue. Methods: Twenty-four SD rats were randomly divided into control group and experiment group («=12). The crowns of right lower incisors of the rats were removed along with the top of gingival tissue on the 9th, 6th and 3rd days before the incisors extraction, and then the incisor were extracted on the 10th day of experimental modeling. In experiment group, the incisors of rats were extracted by the modified minimally invasive incisor extraction, while in control group the conventional extraction was used to extract the incisor of the rats. The survival rates and body weights of the rats in two groups were observed before and after the incisor extraction. The complete degrees of incisor extraction of the rats in two groups were detected, and the rates of complete incisor extraction were calculated; the healing condition of soft tissue around the incisor extraction of the rats in two groups 1 week after incisor extraction and the recovery condition of mandibular alveolar bone of the rats 4 weeks after incisor extraction were compared. Results: The survival rate of the rats in experiment group was higher than that in control group ( P<0. 05). The body weights of the rats in experiment group at different time points after extraction were higher than those in control group ( P<0. 05). Compared with control group, the rate of complete incisor extration of the rats in experiment group was increased ( P<0. 01). The soft tissue around the incisor extraction wound of the rats in experiment group was completely healed within one week after incisor extraction, and new bone was found at the top of alveolar ridge four weeks after incisor extraction; meanwhile, the soft tissue around the incisor extraction wound of the rats in control group was still red and swollen one week after incisor extraction, and the trabecular structure of bone at the top of alveolar ridge was disordered found weeks after incisor extracion. and the new bone structure was poor. Conclusion: The modified minimally invasive tooth extraction surgery can significantly improve the complete extraction effect of incisors in the rats, and the soft tissue around the incisor extraction wound and the alveolar bone are healed well after minimally invasive tooth extractioa.

Objective:To evaluate the clinical characteristics and prognosis of gallbladder cancer (GBC) patients in China.Methods:This retrospective multicenter cohort study enrolled 3 528 consecutive GBC patients diagnosed between January 2010 to December 2017 in 15 hospitals from 10 provinces. There were 1 345 (38.12%) males and 2 183 (61.88%) females.The age of diagnosis was (63.7±10.8) years old (range: 26 to 99 years old) .There were 213 patients (6.04%) in stage 0 to Ⅰ, whereas 1 059 (30.02%) in stage Ⅱ to Ⅲ, 1 874 (53.12%) in stage Ⅳ, and 382 (10.83%) unavailable. Surgery was performed on 2 255 patients (63.92%) . Three hundred and thirty-six patients received chemotherapy or radiotherapy (9.52%; of which 172 were palliative); 1 101 (31.21%) received only supportive treatment.The patient source, treatment and surgery, pathology, concomitant gallstone, and prognosis were analyzed.Results:Among the 3 528 GBC patients, 959 (27.18%) were from East China, 603 (17.09%) from East-North China, 1 533 (43.45%) from Central China, and 433(12.27%) from West China. Among the 1 578 resectable tumor, 665 (42.14%) underwent radical surgery, 913 (57.86%) underwent surgery that failed to follow the guidelines.Eight hundred and ninety-one (56.46%) patients were diagnosed before surgery, 254 (16.10%) during surgery, and 381 (24.14%) after surgery (time point of diagnosis couldn′t be determined in 52 patients) .Among the 1 578 patients with resectable tumor, 759 (48.10%) had concomitant gallstone.Among the 665 patients underwent radical surgery, 69 (10.4%) showed positive resection margin, 510 (76.7%) showed negative resection margin, and 86 (12.9%) unreported margin status.The 5-year overall survival rate (5yOS) for the 3 528-patient cohort was 23.0%.The 5yOS for patients with resectable tumor was 39.6%, for patients with stage ⅣB tumor without surgery was 5.4%, and for patients with stage ⅣB tumor underwent palliative surgery was 4.7%.Conclusions:More than half GBC patients in China are diagnosed in stage Ⅳ.Curative intent surgery is valuable in improving prognosis of resectable GBC.The treatment of GBC needs further standardization.Effective comprehensive treatment for GBC is in urgent need.

Objective:To evaluate the clinical characteristics and prognosis of gallbladder cancer (GBC) patients in China.Methods:This retrospective multicenter cohort study enrolled 3 528 consecutive GBC patients diagnosed between January 2010 to December 2017 in 15 hospitals from 10 provinces. There were 1 345 (38.12%) males and 2 183 (61.88%) females.The age of diagnosis was (63.7±10.8) years old (range: 26 to 99 years old) .There were 213 patients (6.04%) in stage 0 to Ⅰ, whereas 1 059 (30.02%) in stage Ⅱ to Ⅲ, 1 874 (53.12%) in stage Ⅳ, and 382 (10.83%) unavailable. Surgery was performed on 2 255 patients (63.92%) . Three hundred and thirty-six patients received chemotherapy or radiotherapy (9.52%; of which 172 were palliative); 1 101 (31.21%) received only supportive treatment.The patient source, treatment and surgery, pathology, concomitant gallstone, and prognosis were analyzed.Results:Among the 3 528 GBC patients, 959 (27.18%) were from East China, 603 (17.09%) from East-North China, 1 533 (43.45%) from Central China, and 433(12.27%) from West China. Among the 1 578 resectable tumor, 665 (42.14%) underwent radical surgery, 913 (57.86%) underwent surgery that failed to follow the guidelines.Eight hundred and ninety-one (56.46%) patients were diagnosed before surgery, 254 (16.10%) during surgery, and 381 (24.14%) after surgery (time point of diagnosis couldn′t be determined in 52 patients) .Among the 1 578 patients with resectable tumor, 759 (48.10%) had concomitant gallstone.Among the 665 patients underwent radical surgery, 69 (10.4%) showed positive resection margin, 510 (76.7%) showed negative resection margin, and 86 (12.9%) unreported margin status.The 5-year overall survival rate (5yOS) for the 3 528-patient cohort was 23.0%.The 5yOS for patients with resectable tumor was 39.6%, for patients with stage ⅣB tumor without surgery was 5.4%, and for patients with stage ⅣB tumor underwent palliative surgery was 4.7%.Conclusions:More than half GBC patients in China are diagnosed in stage Ⅳ.Curative intent surgery is valuable in improving prognosis of resectable GBC.The treatment of GBC needs further standardization.Effective comprehensive treatment for GBC is in urgent need.