Guided by the theory of latent pathogens， it is believed that the basic pathogenesis of adult-onset Still's disease is the latent pathogens in the deep yin level. The onset of the disease is fundamentally characterized by the deficiency of both qi and yin as the root， with dampness， heat， phlegm， and blood stasis as the branch， which triggered by intruding pathogens activate the latent pathogens in yin level. The treatment focuses on nourishing yin and dispersing heat as the key therapeutic method. It is proposed that clearing and resolving dampness-heat， expelling pathogens outward， dispersing the latent pathogens， reinforcing healthy qi and consolidating the root， boosting qi and nourishing yin as treatment idea. In clinic， Qinghao Biejia Decoction （青蒿鳖甲汤） could be used as the basic formula， and modified with characteristic herb pairs such as Qinghao （Artemisia annua） - Digupi （Lycium chinense） to enrich yin and clear heat， and enforce the power of clearing deficient heat； Biejia （Lawsonia inermis） - Xuchangqing （Vincetoxicum mukdenense） to enrich yin and activate blood， unblock the collaterals and dissipate masses； Duhuo （Angelica biserrata） - Mudanpi （Paeonia × suffruticosa） to dispel wind and activate blood， resolve dampness and unblock the collaterals， so as to clear and warm simultaneously， and regulate qi and blood at the same time； and Chuanshanlong （Dioscorea nipponica） - Difuzi （Bassia scoparia） to dissolve stasis and dispel phlegm， explore and dispel latent pathogens.

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

BACKGROUND:Reducing the rate of abnormal fertilization is an effective approach to improving the efficacy of in vitro fertilization and reducing patients'financial strain.However,the current research on abnormal fertilization has focused on exploring the types of prokaryotic nuclei and their generation mechanisms,as well as analyzing embryos formed by abnormal fertilization,chromosomal ploidy and utilization value.There is a lack of clinical prediction models for abnormal fertilization based on retrospective studies. OBJECTIVE:To construct a nomogram model to predict abnormal female factors in in vitro fertilization. METHODS:A total of 5 075 patients undergoing treatment for conventional in vitro fertilization at Nanxishan Hospital of Guangxi Zhuang Autonomous Region from March 2017 to March 2022 were retrospectively analyzed.The male confounders were calibrated on a 1:1 propensity score with a match tolerance of 0.02,and 1 672 cases were successfully matched.According to the Vienna Consensus,patients with≥60%normal fertilization capacity were included in the normal fertilization group(n=836)and those with<60%normal fertilization capacity were included in the abnormal fertilization group(n=836).The model and validation groups were obtained by random sampling at a ratio of 7:3.Factors related to the occurrence of abnormal fertilization following conventional in vitro fertilization in the model group were screened using univariate analysis and the best matching factors were selected using the Least Absolute Shrinkage and Selection Operator(LASSO)and included in a multifactorial forward stepwise Logistic regression to identify their independent influencing factors and plot a nomogram.Finally,the prediction model was validated for discrimination,accuracy and clinical application efficacy using receiver operating characteristic curves,calibration curves,clinical decision curves and clinical impact curves. RESULTS AND CONCLUSION:The univariate analysis indicated the factors influencing the occurrence of abnormal fertilization were age,controlled ovarian hyperstimulation protocol,number of assisted pregnancies,years of infertility,infertility factors,anti-mullerian hormone,sinus follicle count,basal luteinizing hormone,luteinizing hormone concentration on the human chorionic gonadotropin day,and estradiol level on human chorionic gonadotropin injection day(P<0.05).LASSO regression further identified the best matching factors,including age,microstimulation protocol,number of assisted pregnancies,years of infertility,anti-mullerian hormone,luteinizing hormone level on human chorionic gonadotropin injection day,and estradiol level on human chorionic gonadotropin injection day(P<0.05).Multifactorial forward stepwise Logistic regression results showed that age,microstimulation protocol,number of assisted conceptions,years of infertility,anti-mullerian hormone,and estradiol level on human chorionic gonadotropin injection day were independent influencing factors for the occurrence of abnormal fertilization following conventional in vitro fertilization.The receiver operating characteristic curves showed an area under the curve of 0.761(0.746,0.777)for the model group and 0.767(0.733,0.801)for the validation group,indicating that the model has good discrimination.The mean absolute error of the calibration curve was 0.044,and the Hosmer-Lemeshow test indicated that there was no significant difference between the predicted probability of abnormal fertilization and the actual probability of abnormal fertilization(P>0.05),indicating the prediction model has good consistency and accuracy.The clinical decision curves and clinical impact curves showed that the model and validation groups had the maximum net clinical benefit at valve probability values of 0.00-0.52 and 0.00-0.48,respectively,and there was a good clinical application efficacy in this valve probability range.To conclude,the nomogram model has good discrimination and accuracy as well as clinical application efficacy for predicting the occurrence of abnormal fertilization in women undergoing conventional in vitro fertilization based on age,microstimulation protocol,number of assisted conceptions,years of infertility,anti-mullerian hormone,and estradiol level on human chorionic gonadotropin injection day.

Fibromyalgia syndrome （FMS） is a refractory， chronic non-articular rheumatic disease characterized by widespread pain throughout the body， for which there are no satisfactory therapeutic drugs or options. There are rich Chinese medical therapies， and some non-drug therapies， such as acupuncture， Tai Chi， and Ba-Duan-Jin， have shown satisfactory efficacy and safety and definite advantages of simultaneously adjusting mind and body. FMS is taken as a disease responding specifically to traditional Chinese medicine （TCM） by the National Administration of Traditional Chinese Medicine in 2018. In order to clarify the research progress in FMS and the clinical advantages of TCM/integrated Chinese and Western medicine， the China Academy of Chinese Medicine organized a seminar for nearly 20 experts in Chinese and Western medicine， including rheumatology， psychology， acupuncture and moxibustion， and encephalopathy， with the topic of difficulties in clinical diagnosis and treatment of FMS and advantages of TCM and Western medicine. The recommendations were reached on the difficulties in early diagnosis and solutions of FMS， mitigation of common non-specific symptoms， preferential analgesic therapy， TCM pathogenesis and treatment advantages， and direction of treatment with integrated Chinese and Western medicine. FMS is currently facing the triple dilemma of low early correct diagnosis， poor patient participation， and unsatisfactory benefit from pure Western medicine treatment. To solve the above problems， this paper suggests that rheumatologists should serve as the main diagnostic force of this disease， and they should improve patient participation in treatment decision-making， implement exercise therapy， and fully utilize the holistic and multidimensional features of TCM， which is effective in alleviating pain， improving mood， and decreasing adverse events. In addition， it is suggested that FMS treatment should rely on both TCM and Western medicine and adopt multidisciplinary joint treatment， which is expected to improve the standard of diagnosis and treatment of FMS in China.

Objective:To evaluated the clinical efficacy of a reduced-intensity preconditioning regimen for single non-blood-related umbilical cord blood transplantation (sUCBT) in the treatment of severe aplastic anemia (SAA) .Methods:The clinical data of 63 patients with SAA who underwent sUCBT from January 2021 to July 2023 at the Department of Hematology of the First Affiliated Hospital of USTC were retrospectively analyzed. Fifty-two patients received total body irradiation/total bone marrow irradiation (TMI) combined with fludarabine or a cyclophosphamide- conditioning regimen (non-rATG group) , while 11 patients received rabbit anti-human thymocyte immunoglobulin (rATG) combined with TMI, fludarabine, or the cyclophosphamide-conditioning regimen (rATG group) . All patients received cyclosporine A and mycophenolate mofetil for graft-versus-host disease (GVHD) prophylaxis. Complications post-transplantation and long-term survival were compared between the two groups.Results:The baseline parameters were balanced between the two groups ( P>0.05) . In the rATG group, all patients achieved stem cell engraftment, and in the non-rATG group, five patients had primary graft failure. There was no significant difference in the cumulative incidence of neutrophil engraftment at 42 days after transplantation or platelet engraftment at 60 days between the two groups. The incidence of grade Ⅱ-Ⅳ acute GVHD in the rATG group was significantly lower than in the non-rATG group (10.0% vs. 46.2% , P=0.032) , and the differences in the cumulative incidences of grade Ⅲ/Ⅳ acute GVHD and 1-year chronic GVHD were not statistically significant ( P=0.367 and P=0.053, respectively) . There were no significant differences in the incidences of pre-engraftment syndrome, bacterial bloodstream infections, cytomegalovirus viremia, or hemorrhagic cystitis between the two groups ( P>0.05 for all) . The median follow-up time for surviving patients was 536 (61-993) days, and the 1-year transplantation related mortality (TRM) of all patients after transplantation was 13.0% (95% CI 6.7% -24.3% ) . Among the patients in the non-rATG and rATG groups, 15.5% (95% CI 8.1% -28.6% ) and 0% ( P=0.189) , respectively, had mutations. The 1-year overall survival (OS) rate of all patients after transplantation was 87.0% (95% CI 75.7% -93.3% ) . The 1-year OS rates in the rATG group and non-rATG group after transplantation were 100% and 84.5% , respectively (95% CI 71.4% -91.9% ) ( P=0.198) . Conclusion:The preliminary results of sUCBT with a low-dose irradiation-based reduced-intensity conditioning regimen with fludarabine/cyclophosphamide for the treatment of patients with SAA showed good efficacy. Early application of low-dose rATG can reduce the incidence of acute GVHD after transplantation without increasing the risk of implantation failure or infection.

Background::With an increasing number of patients with hematological malignancies being treated with umbilical cord blood transplantation (UCBT), the correlation between immune reconstitution (IR) after UCBT and graft-versus-host disease (GVHD) has been reported successively, but reports on double-negative T (DNT) cell reconstitution and its association with acute GVHD (aGVHD) after UCBT are lacking.Methods::A population-based observational study was conducted among 131 patients with hematological malignancies who underwent single-unit UCBT as their first transplant at the Department of Hematology, the First Affiliated Hospital of USTC, between August 2018 and June 2021. IR differences were compared between the patients with and without aGVHD.Results::The absolute number of DNT cells in the healthy Chinese population was 109 (70-157)/μL, accounting for 5.82 (3.98-8.19)% of lymphocytes. DNT cells showed delayed recovery and could not reach their normal levels even one year after transplantation. Importantly, the absolute number and percentage of DNT cells were significantly higher in UCBT patients without aGVHD than in those with aGVHD within one year ( F = 4.684, P = 0.039 and F = 5.583, P = 0.026, respectively). In addition, the number of DNT cells in the first month after transplantation decreased significantly with the degree of aGVHD increased, and faster DNT cell reconstitution in the first month after UCBT was an independent protective factor for aGVHD (HR = 0.46, 95% confidence interval [CI]: 0.23-0.93; P = 0.031). Conclusions::Compared to the number of DNT cells in Chinese healthy people, the reconstitution of DNT cells in adults with hematological malignancies after UCBT was slow. In addition, the faster reconstitution of DNT cells in the early stage after transplantation was associated with a lower incidence of aGVHD.

Objective To explore the value of CT enterography(CTE)in the clinical treatment efficacy evaluation of Crohn's disease(CD).Methods A total of 55 patients with CD confirmed by clinical and pathology were selected.All patients both underwent CTE and enteroscopy before and after treatment.After treatment,the patients were divided into the good curative effect group and the poor curative effect group according to Crohn's disease activity index(CDAI).The CT findings were both analyzed before and after treatment.Results There were significant differences in bowel wall thickness,bowel wall attenuation,bowel wall thickness type and"comb sign"of 55 CD patients before and after treatment(P＜0.05).After treatment,phlegmon,abscess,swollen lymph node enlargement,and intestinal fistula all decreased from 18％,7％,27％,and 2％to 2％,2％,9％,and 0％,respectively.Also,there were significant differences in bowel wall thickness,bowel wall attenuation,bowel wall thickness type and"comb sign"between the good curative effect group and the poor curative effect group(P＜0.05).Logistic regression analysis and receiver operating characteristic(ROC)curve analysis showed bowel wall thickness,bowel wall attenuation and bowel wall thickness type were the most valuable parameters for the treatment efficacy evaluation of CD patients.Conclusion CTE can fully show intestinal lesions and extrenteral complications,and is of great value in evaluating clinical treatment efficacy of patients.

Objective:To investigate the effect of inflammatory factors(IL-2,INF-γ,IL-10,TNF-α)and CD4+and CD8+T cells in vaginal lavage in high-grade cervical squamous intraepithelial lesions(HSIL)and early cervical cancer(CC).Methods:To collect clinical data of HSIL(n=120)and early CC patients(n=44)after high-risk human papilloma virus(HR-HPV)infection.And healthy middle-aged women not infected with HR-HPV were randomly selected as control.The clinical data of the subjects in three groups were compared,inflammatory factors distribution and ratio of CD4+and CD8+T cells in serum and vaginal lavage fluid were compared.Multivariate Logistic regression performed to analyze the influencing factors of HSIL progression to early CC,ROC and calibration plot were drawn to evaluate the model.Results:The difference was not statistically significant in serum IL-2,INF-γ,IL-10,TNF-α levels,CD4+T cell distribution,CD8+T cell distribution and CD4+/CD8+ratio in sub-jects of control group,HSIL group and early CC group(P>0.05).The difference was statistically significant in the vaginal lavage levels of IL-2,INF-γ,IL-10,TNF-α levels,CD4+T cell distribution,CD8+T cell distribution and CD4+/CD8+ratio(P<0.05),plus the level of HSIL patients was higher than that of control subjects(P<0.05).Logistic regression analysis showed that parity>2(OR=3.119,95%CI:4.353～6.737)and the percentage of CD4+T cells in vaginal lavage fluid(OR=0.327,95%CI:0.188-0.478)in model 2(P<0.001,AUC=0.908),CD4+/CD8+(OR=0.809,95%CI:0.356-1.868)(P<0.001,AUC=0.873)in model 3 has an independent influence on the development of HSIL to early CC;the difference is not significant(Z=1.550 4,P=0.121)in ROC curves of the two models.CD4+/CD8+ratio as only one indictor in Model 3 can be good predic-tion,and the calibration curve of this model is close to the standard curve.Conclusions:After HR-HPV infection,the systemic immune status does not participate in HSIL and HSIL progression to early CC,but the cervical local immune status is involved,in which CD4+/CD8+T cell ratio is an independent protective factor.

Objective:To investigate the correlation between lumbar bone mineral density (BMD), musculoskeletal perfusion andmuscle mass.Methods:From May 2019 to August 2020, totally 91 patients who applied for CT perfusion (CTP) examination of abdomen (the scan range included the vertebral body of L1－L3) in Shanghai Tenth People′s Hospital of Tongji University were retrospectively analyzed. The mean BMD of L1－L3 vertebral body was measured by quantitative CT (QCT) at the same time of CT plain scan. According to BMD, the subjects were divided into normal BMD group ( n=33), osteopenia group ( n=41) and osteoporosis (OP) group ( n=17). The L3 level perivertebral muscle mass index and fat fraction were calculated based on QCT examination. The lumbar vertebral and perivertebral muscle perfusion parameters were measured based on CTP images. The parameters of QCT and CTP among three groups were analyzed by Kruskal-Wallis H test or one-way ANOVA. The correlation analysis was conducted between these parameters using Pearson or Spearman analysis. Results:The differences of the perivertebral muscle mass index and fat fraction among three groups were statistically significant ( P<0.05). The differences of the lumbar vertebral perfusion parameters including blood flow (BF), blood volume (BV) and flow extraction product (FE) among three groups were statistically significant ( P<0.05), and BF, BV and FE were positively correlated with BMD ( r=0.444, 0.312 and 0.266 respectively, all P<0.05; adjusted for age and gender r=0.437, 0.340 and 0.337 respectively, all P<0.05). There was no statistically significant difference in perivertebral muscle perfusion parameters among three groups ( P>0.05). Perivertebral muscle mass index was negatively correlated with fat fraction ( r=-0.599, P<0.001; adjusted for age and gender r=-0.404, P<0.001), and there was no correlation between perivertebral muscle mass index and muscle perfusion parameters, as well as perivertebral muscle fat fraction and muscle perfusion parameters. Conclusions:With the changes of BMD, bone mass and perivertebral muscle mass at L3 level are synchronous. Decreased vertebral bone mass is accompanied with reduced perivertebral muscle mass, increased muscle fat and decreased bone perfusion. The changes of vertebral perfusion and perivertebral muscle perfusion at L3 level are asynchronous, which implies that reduced perfusion in OP patients may be confined to the bone.

Objective:To explore the feasibility and efficacy of umbilical cord blood transplantation (UCBT) in the treatment of paroxysmal nocturnal hemoglobinuria (PNH).Methods:From May 2014 to December 2019, clinical data were retrospectively reviewed for 7 PNH patients undergoing UCBT. The grades were severe ( n=6) and extremely severe ( n=1). The causes were primary PNH ( n=4) and PNH-aplastic anemia (AA) syndrome ( n=3). There were 5 males and 2 females with a median age of 29 (20-47) years, a median weight of 60(50-71) kg and a median time from diagnosis to transplantation of 62.5(7.7-171) months. All of them were accompanied by transfusion dependence. Myeloablative ( n=6) and reduced-intensity ( n=1) pretreatment was offered. The regimen of preventing GVHD was cyclosporine A plus short-term mycophenolate mofetil without ATG. The median number of input nucleated cells was 2.4(1.71-4.28)×10 7/kg and the median number of CD34+ cells 1.58(0.88-3.02)×10 5/kg. Results:Neutrophil and erythroid engraftment was obtained with a median neutrophil engraftment time of 17(15-21) days and a median erythroid engraftment time of 27. Engraftment time of 37(25-101) days for platelets >20×10 9/L and 62(27-157) days for platelets >50×10 9/L. The incidence of 100-day acute GVHD was 28.6%(95%CI 0-55.3%). The severity of GVHD was grade Ⅱ° acute ( n=2) and mild ( n=1). The median follow-up period was 13.5(3-71.4) months. Six patients survived while another with PNH-AA syndrome with iron overload died of gastrointestinal hemorrhage. The 2-year overall survival rate was 83.3%(95%CI 27.3-97.5%). Conclusions:With excellent engraftment and survival in the treatment of PNH, UCBT is indicated for patients without HLA full-match donor. PNH-AA syndrome with iron overload may be one of the important prognostic factors.