Background::Although the treatment of peripheral T-cell lymphoma (PTCL) has undergone advancements during the past several years, the response rate and long-term effects with respect to patients with PTCL remain unsatisfactory—particularly for relapsed or refractory (R/R) patients. This phase II trial was designed to explore the efficacy and safety of an all-oral regimen of chidamide plus prednisone, cyclophosphamide, and thalidomide (CPCT) for R/R PTCL patients who could not tolerate the standard chemotherapy for a variety of reasons.Methods::We conducted a multicenter phase II clinical trial in which we combined chidamide (30 mg twice weekly) with prednisone (20 mg daily after breakfast), cyclophosphamide (50 mg daily after lunch), and thalidomide (100 mg daily at bedtime) (the CPCT regimen) for a total of fewer than 12 cycles as an induction-combined treatment period, and then applied chidamide as single-drug maintenance. Forty-five patients were ultimately enrolled from August 2016 to April 2021 with respect to Chinese patients at nine centers. Our primary objective was to assess the overall response rate (ORR) after the treatment with CPCT.Results::Of the 45 enrolled patients, the optimal ORR and complete response (CR)/CR unconfirmed (CRu) were 71.1% (32/45) and 28.9% (13/45), respectively, and after a median follow-up period of 56 months, the median progression-free survival (PFS) and overall survival (OS) were 8.5 months and 17.2 months, respectively. The five-year PFS and OS rates were 21.2% (95% confidence interval [CI], 7.9-34.5%) and 43.8% (95% CI, 28.3-59.3%), respectively. The most common adverse event was neutropenia (20/45, 44.4%), but we observed no treatment-related death.Conclusion::The all-oral CPCT regimen was an effective and safe regimen for R/R PTCL patients who could not tolerate standard chemotherapy for various reasons.Trial Registration::ClinicalTrials.gov, NCT02879526.

Objective:To investigate the vaccination status, characteristics and prognosis of patients suffering from a combination of COVID-19 and chronic lymphocytic anemia (CLL) in China.Methods:Clinical data of 328 patients with chronic lymphocytic leukemia (CLL) who were first diagnosed with COVID-19 and treated in the Department of Hematology of Jiangsu Provincial People’s Hospital between November 2022 and February 2023 were retrospectively analyzed. Univariate and multivariate analysis of data of patients with severe/critical COVID-19 were conducted by applying the binary logistic regression model.Results:The median age of the CLL patients was 60 (24-87) years. 23.5% (77/328) of these patients suffered from severe/critical COVID-19 infection. Univariate analysis of the data demonstrated that a combination of factors including age >67 years ( OR=2.15, 95% CI 1.24- 3.73, P=0.006), diabetes ( OR=2.09, 95% CI 1.05-4.20, P=0.037), chronic hepatitis B ( OR=2.91, 95% CI 1.30-6.51, P=0.010), CLL progressive ( OR=3.79, 95% CI 1.57-9.15, P=0.003) and CD20 antibody-based treatments within three months prior to the COVID-19 infection ( OR=2.79, 95% CI 1.35-5.77, P=0.006) were the risk factors for severe/critical COVID-19. According to the multivariate analysis, CLL progressive ( OR=2.98, 95% CI 1.10-8.10, P=0.033) was an independent risk factor for severe/critical COVID-19 and administration of the BTK (Bruton tyrosine kinase) inhibitor monotherapy might exert a protective effect and influence a positive outcome of the COVID-19 infection ( OR=0.38, 95% CI 0.16-0.90, P=0.028). Among the 242 patients who were followed up until October 2023, 9.1% (22/242) had multiple subsequent COVID-19 infections (≥3), and 2.1% (5/242) had persistent COVID-19 infections (patients with persistent positive test for the SARS-CoV-2 antigen testing until missing follow-up for any reason). The peak value of the anti-SARS-CoV-2-IgG titres was observed between three and four months post symptom onset (median: 3.511 S/CO vs 1.047 S/CO, P<0.05). The levels of immunoglobulin A gradually decreased following infection with COVID-19, and its trough levels were attained between two to four weeks post infection (median: 0.30 g/L vs 0.74 g/L, P<0.05). According to this study the mortality of patients suffering from a combination of COVID-19 infection and CLL was 2.7% (9/328), and the main reason for their death was respiratory failure and heart failure. Conclusions:A low rate of COVID-19 vaccination and a high rate of severe/critical COVID-19 infection was observed in the CLL patients. CLL progressive was associated with severe/critical COVID-19. Anti-CD20-based treatments received within the past three months might be a risk factor for exacerbation of COVID-19 infection, whereas a monotherapy with BTK inhibitors exert a protective effect and improve outcome of COVID-19 infection.

Perianal Paget's disease (PPD) is a rare malignant cutaneous tumor. This paper reported a case of PPD complicated by lung adenocarcinoma and anal canal cancer. The patient, a 76-year-old female, had been experiencing recurrent lower abdominal pain and perianal pruritus for the past 5 years. Upon physical examination, a cauliflower-like neoplasm in size of 5 cm×6 cm was observed on the right perianal skin, with local skin ulceration and a small amount of fluid discharge. The left perianal skin was also involved. In thoracoknee position, a hard mass was palpable in the rectal submucosa at 5-6 points 2 cm from the anal verge. Chest CT revealed multiple lesions in both lungs, indication of metastatic tumors. Further evaluation with fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) indicated multiple hypermetabolic nodules in the lungs, hypermetabolic lymph nodes throughout the body, early FDG uptake in a small patch of skin on the left hip, and increased FDG uptake in the anorectal region. Histopathological examination confirmed the diagnosis of lung adenocarcinoma. This resulted in the patient being diagnosed with PPD, lung adenocarcinoma, anal canal cancer, and systemic multiple lymph node metastasis. The combination of PPD with gastrointestinal tumors and other metachronous malignant tumors is highly prevalent. Colonoscopy, FDG-PET/CT, histopathology, and immunohistochemistry play crucial roles in early identification of local lymph node and distant involvement, facilitating the evaluation of potential malignant tumors and differential diagnosis. Treating methods for PPD are currently diverse, including postoperative combined or single chemotherapy, radiotherapy, targeted therapy, and photodynamic therapy. As trerapeutical options continue to develop, the extent and efficacy of surgery need to be reassessed.
Female ; Humans ; Aged ; Paget Disease, Extramammary/pathology* ; Fluorodeoxyglucose F18 ; Positron Emission Tomography Computed Tomography ; Adenocarcinoma of Lung/complications* ; Lung Neoplasms/complications*

Objective To investigate the effect and mechanism of human umbilical cord mesenchymal stem cell exosomes(Exo)on pulmonary inflammation in chronic obstructive pulmonary disease(COPD)rats.Methods A total of 18 male SD rats were randomly divided into the control group,the COPD group and the COPD + Exo group with 6 rats in each group.COPD rat model was estalished by giving cigarette smoke and lipopolysaccharide(LPS)inhalation in the COPD group and the COPD + Exo group.Rats in the COPD + Exo group were injected with 100 μL of human umbilical mesenchymal stem cell exosome diluent(containing 2×107 exosomes)via tail vein.The control group and the COPD group were given equal amounts of phosphate buffered solution.One week after intervention,rats were killed and the peripheral blood,alveolar lavage fluid(BALF)and lung tissue samples were collected.The histopathological changes in lung tissue of each group were observed using Hematoxylin and Eosin(HE)staining.The number of inflammatory cells in peripheral blood was counted by fully automated hematology analyzer.The serum levels of IL-1β,IL-6 and TNF-α were detected by enzyme-linked immunosorbent assay(ELISA).The expression levels of IL-1β,IL-6 and TNF-α mRNA in lung tissue were detected by qRT-PCR.Western blot assay was used to detect the protein expression levels of TLR4,p-NF-κB p65 and IκBα in lung tissue.Results In the control group,the structure of pulmonary alveolus was intact and regular,while in the COPD group,the structure of alveolus was disordered,some alveolus expanded irregularly,fused into bullae and even ruptured.The alveolar septa were widened and filled with a large number of inflammatory cells.Compared with the COPD group,the COPD+ Exo group had more intact alveolar structure and less infiltration of inflammatory cells in the alveolar septum.The inflammatory cells in peripheral blood decreased.The expression levels of IL-1β,IL-6 and TNF-α in serum and lung tissue were decreased(P<0.05).The expression of TLR4 and IκBα protein in lung tissue were increased,while the expression of p-NF-κb p65 protein decreased(P<0.05).Conclusion Human umbilical cord mesenchymal stem cell exosomes can alleviate pulmonary inflammation in COPD rats by modulating TLR4/NF-κB signaling pathway,thereby playing a lung-protective effect.

OBJECTIVE To explore the intestinal absorption characteristics of saikosaponins. METHODS Based on everted intestinal sac model， using accumulative absorption amount （Q） and absorption rate constant （Ka） as indexes， UHPLC-MS/MS technique as a method， the absorption of saikosaponin A， B2， C， D and F from total saponins of Bupleurum chinense （8 g/mL， by crude drug） in the duodenum， jejunum and ileum was detected. RESULTS The correlation coefficients （r） of the regression equations for the absorption of saikosaponins A， B2， C and F in the duodenum， jejunum and ileum were all higher than 0.95， while the r of saikosaponin D in the above intestinal segments was lower than 0.95； compared with the absorption of the same composition in the duodenum， the Q and Ka of saikosaponin A and C circulating in jejunum and ileum for 120 min， as well as the Q and Ka of saikosaponin F circulating in the ileum for 120 min were significantly decreased （P＜0.05）. CONCLUSIONS Saikosaponin A and the other 4 saikosaponins are all absorbed in the duodenum， jejunum and ileum； among them， saikosaponin A， B2， C and F are linearly absorbed， which conforms to the zero-order absorption characteristics， but saikosaponin D shows non- linear absorption.

Enterotoxigenic Escherichia coli（ETEC）infection can induce watery diarrhea，leading to dehydration，electrolyte disturbance，and even death in severe cases. Recombinant B subunit/inactivated whole-cell cholera（rBS/WC）vaccine is effective in preventing ETEC infectious diarrhea. On the basis of the latest evidence on etiology and epidemiology of ETEC，as well as the effectiveness，safety，and health economics of rBS/WC vaccine，National Clinical Research Center for Child Health（The Children’s Hospital，Zhejiang University School of Medicine）and Zhejiang Provincial Center for Disease Control and Prevention invited experts to develop expert consensus on rBS/WC vaccine in prevention of ETEC infectious diarrhea. It aims to provide the clinicians and vaccination professionals with guidelines on using rBS/WC vaccine to reduce the incidence of ETEC infectious diarrhea.

The clinical data for a patient with primary lung adenocarcinoma complicated with pulmonary hamartoma, who admitted to Zunyi Medical University Hospital in September 2020, was retrospectively analyzed. The 62-years-old male visited outpatient service because of dysphagia in March 2015, and the pulmonary nodules were found. In September 2020, the computed tomography indicated the enlarged nodule in the lower lobe of left lung with lobulation, and there was ground glass nodule in the upper lobe of left lung. After thoracoscopic wedge surgery, the primary pulmonary adenocarcinoma in the upper lobe of left lung and pulmonary hamartoma in the lower lobe of left lung were confirmed by pathology. Whole exon sequencing revealed that kinesin family member 20B (KIF20B) gene was not expressed in lung adenocarcinoma, but was expressed in pulmonary hamartoma. The clinical manifestations of lung adenocarcinoma complicated with pulmonary hamartoma was not typical, which could locate in the same side and different sides of the lung. The imaging manifestations of the 2 kinds of tumors were diverse and can not be completely distinguished. The pathological examination after surgery is the gold standard, and the possibility of malignant transformation of pulmonary hamartoma should be warned.
Adenocarcinoma of Lung/complications* ; Hamartoma/surgery* ; Humans ; Kinesins ; Lung/pathology* ; Lung Neoplasms/surgery* ; Male ; Middle Aged ; Retrospective Studies

Humans ; Computed Tomography Angiography ; Deep Learning ; Coronary Angiography ; Coronary Artery Disease ; Tomography, X-Ray Computed ; Coronary Stenosis/diagnosis* ; Retrospective Studies ; Fractional Flow Reserve, Myocardial ; Predictive Value of Tests

OBJECTIVE：To establish a method for online detection of antioxidant active components in Glycyrrhiza uroalensis decoction pieces ，and to identify it. METHODS ：The free radical scavenging rate of 1，1-diphenyl-2-trinitrobenzene hydrazine （DPPH）was determined to evaluate the antioxidant activity of G. uralensis decoction pieces. HPLC-UV-DPPH method was used to screen the anti oxidant active components of G. uralensis decoction pieces. HPLC-TOF/MS was used to obtain mass spectrum data and Qualitive Analyst B 06.00 Build 6.0.633.0 software was used to analyze data. Through contrast analysis of UV absorption spectrum，online chromatogram ，mass spectrum information of G. uralensis and the retention time of each compound ，accurate molecular weight ，antioxidant active components were identified by referring to relevant literature. Validation test was also conducted. RESULTS ：DPPH free radical scavenging rate in 8 batches of G. uralensis decoction pieces ranged 55.71％-60.17％. Seven antioxidative active compounds ，including avolomotor ，8-isopentenyl naringin ，yellow lupulin weitone ，isoflavone B ，3′， 4′-dimethoxy3-hydroxy-6-methyl flavone ，glycyrrhizin E and glycyrrhizin H ，could be screened from G. uralensis decoction pieces. After validation ，the peak area of inverted peak generated by online reaction was positively correlated with DPPH free radical scavenging rate. CONCLUSIONS ：Established method is simple and accurate ，and can be used to quickly screen and identify the main antioxidant components of G. uralensis decoction pieces ；the peak area of inverted peak can be used to evaluate the antioxidant active components of G. uralensis decoction pieces.

BK polyomavirus-associated nephropathy (BKPyVAN) is a common cause of allograft failure. However, differentiation between BKPyVAN and type I T cell-mediated rejection (TCMR) is challenging when simian virus 40 (SV40) staining is negative, because of the similarities in histopathology. This study investigated whether donor-derived cell-free DNA (ddcfDNA) can be used to differentiate BKPyVAN. Target region capture sequencing was applied to detect the ddcfDNAs of 12 recipients with stable graft function, 22 with type I TCMR, 21 with proven BKPyVAN, and 5 with possible PyVAN. We found that urinary ddcfDNA levels were upregulated in recipients with graft injury, whereas plasma ddcfDNA levels were comparable for all groups. The median urinary concentrations and fractions of ddcfDNA in proven BKPyVAN recipients were significantly higher than those in type I TCMR recipients (10.4 vs. 6.1 ng/mL,