Objective:To explore the clinical effect of lenalidomide combined with anti-B-cell maturation antigen chimeric antigen receptor T cell (anti-BCMA CAR-T) in the treatment of relapsed/refractory multiple myeloma (RRMM).Methods:The clinical data of a patient with RRMM who underwent lenalidomide combined with anti-BCMA CAR-T therapy in Henan Province Hospital of Traditional Chinese Medicine in January 2020 were analyzed. Clinical manifestations, diagnosis and treatment were also analyzed, and the related literature was reviewed.Results:The patient was a 51-year-old man who was diagnosed as IgD-λ multiple myeloma (MM) in October 2015. The patient achieved remission after 10 courses of chemotherapy regimens including immunomodulators and proteasome inhibitors, followed by autologous hematopoietic stem cell transplantation. MM relapsed after 14 months of transplantation. His disease continued to progress after multiple chemotherapy regimens and mouse or human-derived anti-BCMA CAR-T therapy. After a conditioning chemotherapy regimen of fludarabine and cyclophosphamide, the patient took lenalidomide on day 1 and was infused human-derived anti-BCMA CAR-T cells on the next day. Grade 3 cytokine releasing syndrome (CRS) appeared after infusion, and was resolved after symptomatic treatment. Very good partial response (VGPR) was achieved on day 14 after anti-BCMA CAR-T treatment. VGPR had been maintained for more than 3 months by press time.Conclusion:Lenalidomide combined with anti-BCMA CAR-T therapy is feasible and effective in the treatment of RRMM.

Objective To investigate the status of work fatigue of the disabled and the healthy so that we get to know their employment quality and compressive strength, and then provide the theory basis for the national policy formulation and vocational rehabilitation. Methods We randomly investigated 280 employees (220 disabled, 60 healthy people) in 3 companies from 3 provinces with Fatigue Impact Scale (FIS). Results There was no statistically significant difference between disabled and healthy people about work fatigue, and also that of 3 domains including psycho-social, cognitive and physical activity. After comparison of 40 items on FIS，the disabled had higher fatigue than that of the healthy in 4 items which belonged to psycho-social domain (P<0.05). Conclusion Disabled people are no less than healthy people in compression capability and working capability. They should believe in themselves, and their family and the employees should have more confidence about their work capability than before. Government should provide some support with them on job retention.

Objective To evaluate the efficacy and tolerability of zonisamide (ZNS) as add-on therapy in patients with refractory partial seizures.Methods In this Chinese muiticenter, double-blind, randomized, placebo-contrclled trial, ZNS was compared with placebo add-on therapy in 217 patients (intent-to treat (ITT) population) with uncontrolled partial-onset seizures.All patients entered a 3-month baseline period followed by a 4-week titration interval and a 12-week maintenance period.The starting dose of ZNS group was 100 mg/d, increased by 100 mg/d every week and reached the goal of 400 mg/d.The main outcome was measured by the median of the percentage of decreased seizure frequency.The secondary ouwomes points included the percentage of patients who had seizure attacks decreased by more than 50%,and adverse events.Results The median of the percentage of decreased seizure frequency in ZNS group was 33.33%, and the placebo group was 0.Thirty-eight patients (34.23%) experienced more than 50% reduction in the seizure frequency in ZNS group, compared with 19.81% of patients (21 cases) in the placebo group (χ2 =5.7159,P =0.0168) ; Moreover, 13 (11.71%) patients in ZNS group and 5 patients in placebo group were seizure free, 25 patients in ZNS group and 16 patients in placebo group who had seizure attacks decreased by more than 50%.The availability rate in ZNS group was higher than placebo group (34.23% vs 19.81%, U=2.4701, P=0.0135).The most common adverse events in ZNS group were drowsiness, fatigue, decreased appetite, gastrointestinal complaints, insomnia and constipation.Conclusion Zonisamide treatment was generally well tolerated and was associated with significant reductions in seizure frequency as adjunctive treatment for partial-onset seizures.

Objective:To explore the clinical features of ultrasound intervention combined with antibiotics in the treatment of Klebsiella pneumoniae liver abscess, and to provide a reference for clinical treatment.Methods:The clinical data of 100 patients with Klebsiella pneumoniae liver abscess treated in Beijing Friendship Hospital Affiliated to Capital Medical University from January 2015 to November 2020 were analyzed retrospectively. The patient's gender, age, abscess diameter, number of abscesses, abscess separation, air cavity formation and length of hospital stay were recorded. The blood white blood cell (WBC), neutrophil percentage (GR%), platelet count (PLT), C-reactive protein (CRP), procalcitonin (PCT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), prothrombin activity (PTA) before and after treatment were analyzed.Results:After treatment, the infection indexes (WBC, GR%, PLT, CRP, PCT) were significantly decreased, and the liver function indexes (ALT, AST, TBIL, PTA) were significantly improved ( P<0.05). Patients were divided into two groups according to diabetes. The results showed that the diabetic group was prone to air cavity formation (χ 2=8.632, P=0.003), and there was no significant difference between other clinical indicators among the groups ( P>0.05). Diabetes mellitus group was divided into two groups based on hemoglobin A1c (HbA1c) 9%. The results showed that the HbA1c>9% group was younger ( t=2.861, P=0.006), more male (χ 2=6.81, P=0.013), and more prone to form multiple abscesses (χ 2=10.304, P=0.001), while the other clinical indicators were not statistically significant. Conclusions:Ultrasound intervention combined with antibiotics can effectively treat liver abscess. Patients with diabetes are prone to air cavity formation, which should be paid more attention in clinic.

When chimeric antigen receptor T cells (CAR-T) failed to treat relapsed and refractory B-cell malignancies, some researchers try to improve the efficacy by enhancing the function of CAR-T. It is a new hotspot of drug development and clinical research, and significant achievements have been made in this area recently. Multi-targeted CAR-T, lenalidomide, decitabine, programmed death 1 inhibitor and ibrutinib can all enhance the function of CAR-T. This article reviews the recent progress of enhancing the function of CAR-T in relapsed and refractory B-cell malignancies.

Objective:To explore the efficacy and safety of anti-B cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) for the retreatment of relapsed and refractory multiple myeloma (RRMM).Methods:The clinical data of 10 RRMM patients who received anti-BCMA CAR-T therapy for the second time (CART2) in Henan Province Hospital of Traditional Chinese Medicine due to failure or recurrence after their first anti-BCMA CAR-T (CART1) therapy from January 2017 to June 2021 were retrospectively analyzed. The treatment, efficacy and adverse events of patients receiving CART2 therapy were summarized; and the objective response rate (ORR), median duration of response (DOR) and incidence of adverse reactions were compared between CART1 and CART2.Results:Among 10 patients, 8 were males and 2 were females, with a median age of 57 years (41-70 years). Patients' 3-month ORR after CART1 therapy was 90%, and the median DOR was 16.0 months (3.0-27.0 months). CART2 used human-derived anti-BCMA CAR-T to treat 6 cases and mouse-derived anti-BCMA CAR-T to treat 4 cases. The 3-month ORR of patients receiving CART2 therapy was 40%, and the median DOR was 8.5 months (3.0-11.0 months). Among 9 patients who received mouse-derived anti-BCMA CAR-T in CART1 therapy, 4 of them received the same product again and none of them showed curative effect. Among 6 patients retreated with human-derived anti-BCMA CAR-T, 4 patients (66.7%) of them achieved partial remission (PR) or better. During CART1 therapy, 10 patients developed grade 1-2 cytokine release syndrome (CRS), and 7 patients developed different degrees of decrease in leukocyte, neutrophil absolute count (ANC) and platelet. Among patients who achieved effective outcomes after receiving CART2 therapy, 4 patients of them developed grade 1-2 CRS, and different degrees of decrease in white blood cell, ANC and thrombocytopenia. Immune effector cell-related neurotoxicity syndrome was not observed.Conclusions:Anti-BCMA CAR-T is effective and safe to retreat RRMM. The ORR and DOR of patients receiving CART2 therapy are lower than those of patients receiving CART1 therapy. CRS and cytopenia are common adverse reactions.

Objective To assess and compare the incidence,clinical characteristics,treatment,and prognosis of acute heart failure patients from different grades hospitals in Beijing.Methods In this prospective internet prognosis registered study (Beijing AHF Registry),a total of 3 335 consecutive patients admitted to 14 emergency departments in Beijing from January 1st 2011 to September 23rd 2012 were enrolled.According to hospital grade,these patients were divided into two groups,349 patients were from secondary hospitals,and 2 956 patients were from tertiary hospitals.Results Among the 3 335 patients,the medium age was 71 (58,79) years,and male accounted for 53.16％.The most common underlying disease were coronary disease (43.27％),hypertension (17.73％),cardiomyopathy (16.07％) etc.The average treatment time in Emergency Department was 66.82 h.The emergency department mortality rate was 3.81％ (127 cases).The 30-day and 1-year cumulative all-cause mortality were 15.3％ and 32.27％,respectively.The 30-day and 1-year cumulative all-cause readmission were 15.64％ and 46.89％,respectively.Compared with patients in tertiary hospitals,patients in secondary hospitals had more onset acute heart failure patients (63.64％ vs.49.93％),shorter emergency department treatment time (12 h vs.41 h),lower discharge rate (3.43％ vs.37.45％) and emergency department mortality(1.58％ vs.4.09％).Compared with those in tertiary hospitals,1-year cumulative all-cause mortality (25.6％ vs.33.2％),cardiovascular disease mortality (20.2％ vs.26.0％),aggravated heart failure mortality (22.4％ vs.28.8％) were lower in secondary hospitals.Following propensity score matching,compared to tertiary hospitals,patients in secondary hospitals showed lower utilization rate of beta-blockers and ACEFARB (4.51％ vs.28.17％,1.41％ vs.9.58％),except the pironolactone.Conclusion Acute heart failure in emergency department is associated with a high mortality rate and readmission rate.There is still a big gap between guidelines recommend medication current treatments for acute heart failure.

OBJECTIVETo observe clinical efficacy of using free anterolateral thigh flaps with iliotibial tracts in repairing skin and soft tissue defects around the knee joints with patellar ligament defects.

METHODSTwelve patients with skin and soft tissue defects around the knee joints and patellar ligament defects were hospitalized from June 2010 to June 2014. The defects of skin and soft tissue ranged from 7 cm × 6 cm to 16 cm × 12 cm in area, and patellar ligament ranged from 5 to 12 cm in length and 2.5 to 4.0 cm in width. Free anterolateral thigh flaps with iliotibial tracts were used to repair these defects. During reconstruction of patellar ligament, both ends of iliotibial tract were successively folded to form tendon-like three-layer structure at first, and then the newly formed structure was wrapped around the broken ends of patellar ligament and fixed with suture. The flap size ranged from 9 cm × 8 cm to 18 cm × 14 cm. The iliotibial tract ranged from 7 to 14 cm in length and 8 to 12 cm in width. The donor sites were closed by grafting with autologous split-thickness skin harvested from thigh or trunk, and parked with gauze. Immediately after operation, the knee joints were fixed in extension with orthosis for 6 weeks. Weight bearing training of affected limbs being kept in extension position was started from 2 weeks after operation, and flexion and extension exercise of affected knee joints was begun from 6 weeks after operation. Before operation and 12 months after operation, the degree of pain around the knee joints and knee joint function were evaluated with the international knee documentation committee knee uation form, and the ranges of flexion and extension of knee joints were also evaluated. The integrity of reconstructed patellar ligament was assessed by color Doppler ultrasound from 6 to 12 months after operation. The occurrence of surgery-related complications was observed in all patients within 12 months after operation.

RESULTS(1) After operation, all flaps survived well, and all wounds healed well. (2) The average score of pain around the knee joint was increased from 31 points before operation to 77 points in 12 months after operation. The average score of knee joint function was increased from 14 points before operation to 65 points in 12 months after operation. Before operation, the average ranges of flexion and extension of knee joint were respectively 89° and 65°, and they were respectively increased to 130° and decreased to 15° in 12 months after operation. From 6 to 12 months after operation, color Doppler ultrasound showed that the condition of reconstructive patellar ligaments in all patients was good without the need for further surgical intervention; the superficial sensation of the flaps was recovered in different degrees. No surgery-related complication was observed in all patients within 12 months after operation.

CONCLUSIONSFree grafting of anterolateral thigh flap with iliotibial tract is an effective and reliable method for repairing skin and soft tissue defects around the knee joints combined with patellar ligament defects, and the surgical procedure can recover function and appearance of knee joint satisfactorily.

Extremities ; Fascia Lata ; Humans ; Knee ; Knee Joint ; Patellar Ligament ; surgery ; Range of Motion, Articular ; Reconstructive Surgical Procedures ; methods ; Skin ; Skin Transplantation ; Surgical Flaps ; Thigh ; Wound Healing

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a genetic cardiac muscle disease that accounts for approximately 30% sudden cardiac death in young adults. The Ser358Leu mutation of transmembrane protein 43 (TMEM43) was commonly identified in the patients of highly lethal and fully penetrant ARVD subtype, ARVD5. Here, we generated TMEM43 S358L mouse to explore the underlying mechanism. This mouse strain showed the classic pathologies of ARVD patients, including structural abnormalities and cardiac fibrofatty. TMEM43 S358L mutation led to hyper-activated nuclear factor κB (NF-κB) activation in heart tissues and primary cardiomyocyte cells. Importantly, this hyper activation of NF-κB directly drove the expression of pro-fibrotic gene, transforming growth factor beta (TGFβ1), and enhanced downstream signal, indicating that TMEM43 S358L mutation up-regulates NF-κB-TGFβ signal cascade during ARVD cardiac fibrosis. Our study partially reveals the regulatory mechanism of ARVD development.

In previous studies, we found that truncated rotavirus VP4* (aa 26-476) could be expressed in soluble form in Escherichia coli and confer high protection against rotavirus in the mouse mode. In this study, we further improved the immunogenicity of VP4* by polymerization. The purified VP4* was polymerized through incubation at 37 ℃ for 24 h, and then the homogeneity of the particles was analyzed by HPLC, TEM and AUC, while the thermal stability and antigenicity was analyzed by DSC and ELISA, respectively. Finally, the immunogenicity and protective efficacy of the polymers analyzed by a mouse maternal antibody model. The results showed that VP4* aggregated into homogeneous polymers, with high thermostability and neutralizing antibody binding activity. In addition, VP4* polymers (endotoxin <20 EU/dose) stimulated higher neutralizing antibodies and confer higher protection against rotavirus-induced diarrhoea compared with the VP4* trimers when immunized with aluminium adjuvant. In summary, the study in VP4* polymers provides a new strategy for the development of recombinant rotavirus vaccines.
Animals ; Antibodies, Viral ; Antigens, Viral ; Capsid ; Capsid Proteins ; Mice ; Polymerization ; Rotavirus ; Rotavirus Infections