Objective:This study investigated the efficacy and safety of denosumab (DENOS) versus zoledronic acid (ZOL) in the bone disease treatment of newly diagnosed multiple myeloma.Methods:The clinical data of 80 patients with myeloma bone disease (MBD) at the Fifth Medical Center of PLA General Hospital between March 1, 2021 and June 30, 2023 were retrospectively reviewed. Eighteen patients with severe renal impairment (SRI, endogenous creatinine clearance rate<30 ml/min) were treated with DENOS, and 62 non-SRI patients were divided into DENOS (30 patients) and ZOL group (32 patients) .Results:Hypocalcemia was observed in 26 (33%) patients, and 22 patients developed hypocalcemia during the first treatment course. The incidence of hypocalcemia in the non-SRI patients of DENOS group was higher than that in the ZOL group [20% (6/30) vs 13% (4/32), P=0.028]. The incidence of hypocalcemia in SRI was 89% (16/18). Multivariate logistic regression analysis revealed that endogenous creatinine clearance rate<30 ml/min was significantly associated with hypocalcemia after DENOS administration ( P<0.001). After 1 month of antiresorptive (AR) drug application, the decrease in the serum β-C-terminal cross-linked carboxy-telopeptide of collagen type I concentrations of SRI and non-SRI patients in the DENOS group were significantly higher than that in the ZOL group (68% vs 59% vs 27%, P<0.001). The increase in serum procollagen type Ⅰ N-terminal propeptide concentrations of patients with or without SRI in the DENOS group were significantly higher than that in the ZOL group (34% vs 20% vs 11%, P<0.05). The level of intact parathyroid hormone in each group increased after AR drug treatment. None of the patients developed osteonecrosis of the jaw and renal adverse events, and no statistically significant differences in the overall response rate, complete remission and stringent complete remission rates were found among the groups ( P>0.05), and the median PFS and OS time were not reached ( P>0.05) . Conclusions:In the treatment of MBD, DENOS minimizes nephrotoxicity and has strong AR effect. Hypocalcemia is a common adverse event but is usually mild or moderate and manageable.

The study was a retrospective study. The clinical data of 866 patients with IgA nephropathy (IgAN) in Beijing Anzhen Hospital, Capital Medical University from March 2010 to March 2021 were analyzed, to investigate the clinical pathology and renal prognosis of IgAN patients with intrarenal arteriolosclerosis, and to preliminarily explore whether abnormal activation of complement system is involved in the injury of arteriolosclerosis. The patients were divided into renal arteriolar lesions group and non-renal arteriolar lesions group according to the renal histopathology, and the differences of clinical pathological manifestations, prognosis between the two groups were compared. The results showed that, compared with the non-renal arteriolar lesions group ( n=236), IgAN patients in the renal arteriolar lesions group ( n=630) had higher proportions of hypertension and malignant hypertension, higher levels of urinary albumin-creatinine ratio, 24-hour urine protein quantification and serum uric acid, lower estimated glomerular filtration rate, and more severe MEST-C lesions of the Oxford classification (all P < 0.05). Cox regression analysis results showed that intrarenal arteriolosclerosis was the independent risk factor affecting the progression of IgAN to ESRD ( HR=6.437, 95% CI 2.013-20.585, P=0.002). Renal histopathology showed that the deposition of complement C3c on the wall of intrarenal arterioles in the renal arteriolar lesions group ( n=98) was stronger than that in non-renal arteriolar lesions group ( n=18, P < 0.05). IgAN patients with renal arteriolosclerosis present with serious clinical and pathological manifestations, and renal prognosis. Abnormal activation of complement system may be involved in the pathogenesis of intrarenal arteriolosclerosis.

Objective:To document any effect of combining respiratory-muscle resistance training with feedback respiratory electrical stimulation in rehabilitating the diaphragm function and lung function of stroke survivors.Methods:Sixty hemiplegic stroke survivors were randomly assigned to an observation group or a control group, each of 30. Both groups were given conventional rehabilitation, including respiratory-muscle resistance training. The observation group additionally received feedback respiratory electrical stimulation twice a day, six days a week for 3 weeks. Before and after the treatment, ultrasound was used to measure the end-inspiratory and end-expiratory thickness of the diaphragm. Diaphragm movement during quiet breathing and deep breathing was also observed, and the diaphragm thickening fraction was calculated. The incidence of diaphragm dysfunction on the affected and healthy sides of the two groups before and after the treatment was also analyzed and compared.Results:Diaphragm dysfunction on either side had decreased significantly more in the observation group than in the control group after the treatment. The observation group also showed significantly greater average improvement in the thickening functions and in diaphragm movement on both the affected and healthy sides during quiet breathing and deep breathing. All of the pulmonary function indicators improved significantly in both groups after the treatment, but those of the observation group were, on average, significantly better than the control group′s averages.Conclusions:Combining 3 weeks of respiratory muscle resistance training with electrical stimulation feedback can effectively increase the bilateral thickness of the diaphragm and diaphragm movement in deep breathing of hemiplegic stroke survivors. That reduces the incidence of diaphragm dysfunction.

Objective:To analyze the comorbidity status and influencing factors of hypertension, diabetes, and dyslipidemia among middle-aged and elderly Chinese adults and to provide support for the "co-management of three diseases".Methods:Using the relevant information collected from the National Chronic Disease and Risk Factor Surveillance in China in 2018, 134 950 permanent residents aged ≥45 years were selected as the research objects. After being weighed, the prevalence and comorbidity of hypertension, diabetes, and dyslipidemia in residents with different groups were compared; a multivariate logistic regression model was used to explore the influencing factors of comorbidity of the "three diseases".Results:The prevalence of hypertension, diabetes, and dyslipidemia among middle-aged and elderly Chinese adults were 46.0% (95% CI:45.1%-47.0%), 19.5% (95% CI:18.7%-20.2%), 43.3% (95% CI:42.3%-44.4%), respectively. The comorbidity rates of hypertension and diabetes, hypertension and dyslipidemia, and diabetes and dyslipidemia were 12.3% (95% CI:11.7%-12.8%), 22.8% (95% CI:22.1%-23.4%),11.6% (95% CI:11.1%-12.0%), respectively; the comorbidity rate of hypertension, diabetes, and dyslipidemia was 7.6% (95% CI: 7.2%-8.0%). These comorbidity rates increased with age and BMI, which was more significant in the urban areas than rural areas and more outstanding in North and Northeast China ( P<0.05). The comorbidity rate of hypertension, diabetes, and higher cholesterol was 1.9% (95% CI:1.7%-2.1%). The comorbidity rate of hypertension, diabetes, and higher low-density lipoprotein was 1.6% (95% CI:1.4%-1.7%), which was higher in women than in men ( P<0.05). Multivariate logistic regression results showed that male, age, city, overweight/obesity, excessive drinking, physical inactivity, daily sedentary behavior time ≥5 hours, and sleep duration <7 hours were risk factors for the comorbidity of the "three diseases". Conclusions:The comorbidity of hypertension, diabetes, and dyslipidemia, is common among middle-aged and elderly adults in China; comprehensive prevention and control of risk factors and "co-management of three diseases" are critical measures for health promotion in middle-aged and elderly populations.

Objective:This study aimed to evaluate the efficacy and safety of daratumumab as a maintenance treatment after autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with newly diagnosed multiple myeloma (NDMM) .Methods:The clinical data, hematological and renal response, and safety of 15 post-transplant patients with NDMM who had received daratumumab maintenance between May 1, 2022 and June 30, 2023 were retrospectively analyzed.Results:Fifteen patients (11 males and 4 females) with a median age of 58 (41-72) years were included. Thirteen patients did not receive daratumumab during induction therapy and auto-HSCT, 6 patients had renal impairment, and nine patients had high-risk cytogenetics. The median infusion of daratumumab was 12 (6-17) times, and the median duration of maintenance was 6 (1.5-12) months. The treatment efficacy was evaluated in all 15 patients, and daratumumab maintenance therapy increased the rate of stringent complete response from 40% to 60%. The renal response rate and median estimated glomerular filtration rate of six patients with RI-NDMM were also improved. During daratumumab maintenance therapy, the most common hematological grade 3 adverse event (AE) was lymphopenia [4 of 15 patients (26.67%) ], whereas the most common nonhematologic AEs were infusion-related reactions [7 of 15 patients (46.67%) ] and grade 3 pneumonia [5 of 15 patients (33.33%) ]. The five patients with pneumonia were daratumumab naive [5 of 13 patients (38.46%) ], with a median of 8 (6-10) infusions. Among them, the chest computed tomography of three patients showed interstitial infiltrates, and treatment with methylprednisolone was effective. With a median follow-up of 12 months, the 1-year overall survival rate was 93.33%, and only one patient died (which was not related to daratumumab treatment) .Conclusions:Daratumumab was safe and effective as a maintenance agent for post-auto-HSCT patients with NDMM, and AEs were controllable. The most common nonhematologic AE was grade 3 pneumonia, and a less dose-intense maintenance regimen for the first 8 weeks could reduce the incidence of pneumonia.

Objective:To observe any short-term effect of combining respiratory muscle training with feedback respiratory electrical stimulation on the pulmonary function and respiratory muscle strength of stroke survivors.Methods:Sixty stroke survivors were randomly divided into an observation group ( n=30) and a control group ( n=30). Both groups were given conventional rehabilitation 6 days a week for 3 weeks, but the observation group also received respiratory muscle training with feedback electrical stimulation. Before and after the treatment, both groups′ pulmonary functioning and respiratory muscle strength were measured, and also their trunk control, skill in the activities of daily living and fatigue level. The trunk impairment scale (TIS), modified Barthel index (MBI) and fatigue severity scale (FSS) were used. The incidence of stroke-associated pneumonia (SAP) was also compared between the two groups. Results:After the treatment, average forced vital capacity, forced expiratory volume in 1 second, maximum voluntary ventilation, peak expiratory flow, maximum inspiratory pressure, maximum expiratory pressure, as well as the average TIS and MBI scores of both groups had improved significantly, and there was a significant decrease in the average FSS scores. After the intervention, all of the average measurements of the experimental group were significantly better than the control group′s averages except their MBI scores. There was no significant difference in the incidence of SAP.Conclusions:Three weeks of respiratory muscle training combined with electrical stimulation feedback can effectively improve the pulmonary function, respiratory muscle strength and inspiratory muscle endurance of stroke survivors, resulting in better coughing ability, trunk control and reduced fatigue.

Objective:To investigate the mutation of epidermal growth factor receptor (EGFR), the expression of programmed death ligand 1 (PD-L1), cell proliferation-associated antigen (Ki-67) in elderly patients with non-small cell lung cancer (NSCLC), and their correlation with clinical feature such as gender, histological type and TNM stage.Methods:The tissue samples of 340 elderly NSCLC patients with definite histopathological diagnosis were collected from January 2020 to December 2020 in Huadong Hospital Affiliated to Fudan University, including 195 males and 145 females, age between 68.9±6.0 years. Patients were grouped according to clinical features such as gender, histological type and TNM stage. The expression of EGFR mutation, PD-L1 and Ki-67 were detected by Super-ARMS and immunohistochemistry. The correlation between tnem and clinical features was statistically analyzed, and the correlation between EGFR mutation and PD-L1/Ki-67 expression was further analyzed separately.Results:In elderly NSCLC patients′ tissues, the positive rate of EGFR mutation was 48.53% (165/340). L858R and 19del mutations were the most common types, which were 56.36% (93/165), 30.30% (50/165) respectively. The mutation rate of EGFR was higher in women, lung adenocarcinoma, well-differentiated, and low-stage patients, which were 65.52% (95/145), 53.77% (164/305), 56.75% (143/252), 52.53% (135/257) respectively. In addition, the positive rate of PD-L1 expression was higher in elderly patients with non-adenocarcinoma lung cancer and poorly differentiated adenocarcinoma, which were 37.14% (13/35), 24.53% (13/53) respectively. The negative rate of PD-L1 expression was higher in elderly patients with NSCLC in stage Ⅰ+Ⅱ, no lymph node metastasis and weakly positive Ki-67, which were 89.11% (229/257), 87.63% (248/283), 94.71% (197/208) respectively. Correlation analysis showed that EGFR mutation was negatively correlated with the expression of PD-L1 and Ki-67 (PD-L1: r=-0.22, P<0.001; Ki-67: r=-0.32, P<0.001). Conclusion:There is a negatively correlation between EGFR mutation and the expression of PD-L1 and Ki-67 in elderly NSCLC, suggesting that the combined detection of EGFR mutation and PD-L1 expression could provide the basis for precise targeted therapy for elderly NSCLC patients.

Objective:To study the correlation between circulating tumor cells (CTC) and the degree of pathological invasion, recurrence and metastasis of urothelial carcinoma, and so to explore the clinical value of CTC detection in bladder cancer.Methods:A total of 142 patients with urothelial carcinoma in Huadong Hospital Affiliated to Fudan University were enrolled as cancer group from July 2016 to January 2018. According to the degree of tumor invasion, cancer group was divided into the non-muscle-invasive group (49 cases) and the muscle-invasive group(93 cases). In addition, 52 patients with benign urinary tract lesions admitted were selected as the benign group and 56 patients with non-urinary tract diseases and non-tumor as the control group. A total of 3.2 ml of venous anticoagulant blood from each subject was collected. CTC was enriched by negative enrichment using the magnetic beads coated with monoclonal antibody Cluster 45 of differentiation (CD45) to capture and remove white blood cells, and identified by chromosome 8 probe(CEP8) fluorescence in situ hybridization (FISH) technique. CD45-/4′,6′-diamidino-2-phenylindole+/CEP8>2(CD45-/DAPI+/CEP8>2) cells were judged as CTC. SPSS22.0 statistical software was used for statistical analysis.Results:≥2 CTCs/3.2 ml in blood was set as cutoff value. CTC positive rates in bladder cancer group, benign group and control group were 70.42%(100/142), 28.85%(15/52) and 8.93%(5/56), respectively, and there was a significant difference (χ 2=70.496, P=0.000). There was a statistically difference ( U=2 863.5, P=0.011) in the mean count of CTC(2 CTCs/3.2 ml vs 4 CTCs/3.2 ml) between the two groups. The proportion of≥5 CTCs/3.2 ml in the muscle-invasive group was 40.86% (38/93), which was significantly higher than that in the non-muscle-invasive group, 18.37% (9/49) (χ 2=7.330, P=0.007). Cystoscope follow-up of 65 patients treated with transurethral resection of the bladder tumor showed that the recurrence and metastasis rate in patients with≥5 CTCs/3.2 ml was as high as 47.62% (10/21), compared with 11.36% (5/44) of patients with<5 CTCs/3.2 ml (χ 2=10.530, P=0.001). Among 59 patients undergoing radical cystectomy, no significant difference was found in tumor diameter >3 cm, positive surgical margins and positive lymph nodes among all groups according to CTC negative or positive and CTC number ( P>0.05). But the recurrence and metastasis rate of patients with ≥5 CTCs/3.2 ml (59.10%) was significantly higher than that of patients with <5 CTCs/3.2 ml (6/30)(χ 2=8.364, P=0.004). Conclusion:The number of CTC increased with the deepening of tumor invasion; Tumor recurrence and metastasis increased significantly in the patients with ≥5/3.2 ml CTCs in blood.

Objective: To explore the efficacy and prognostic factors of hematopoietic stem cell transplantation (HSCT) for the treatment of patients with anaplastic large cell lymphoma (ALCL) . Methods: The clinical records of 33 ALCL patients after HSCT were collected and analyzed retrospectively to evaluate the rates of overall survival (OS) and recurrence after autologous (auto-HSCT) and allogeneic HSCT (allo-HSCT) and the factors influencing prognosis. Results: The median-age of this cohort of 33 ALCL cases at diagnosis was 31 (12-57) years old with a male/female ratio of 23/10, 24 cases (72.7%) were ALK⁺ and 9 ones (27.3%) ALK^-. Of them, 25 patients (19 ALK⁺ and 6 ALK^-) underwent auto-HSCT and 8 cases (5 ALK⁺ and 3ALK^-) allo-HSCT with a median follow-up of 18.7 (4.0-150.0) months. Disease states before HSCT were as follows: only 6 patients achieved CR status and received auto-HSCT, 16 patients achieved PR (14 cases by auto-HSCT and 2 ones allo-HSCT) , the rest 11 cases were refractory/relapse (5 cases by auto-HSCT and 6 ones allo-HSCT) . There were 7 cases died of disease progression (5 after auto-HSCT and 2 allo-HSCT) and 5 cases treatment-related mortality (TRM) (2 after auto-HSCT and 3 allo-HSCT) , TRM of two groups were 8.0% and 37.5%, respectively. Both the median progression-free survival (PFS) and OS were 15 months after auto-HSCT, the median PFS and OS after allo-HSCT were 3.7 (1.0-90.0) and 4.6 (1.0-90.0) months, respectively. There was no statistically significant difference in terms of survival curves between the two groups (OS and PFS, P=0.247 and P=0.317) . The 2-year OS rates in auto-HSCT and allo-HSCT groups were 72% and 50%, respectively. The 5-year OS rates in auto-HSCT and allo-HSCT groups were 36% and 25%, respectively. Conclusion ALCL treated by chemotherapy produced high rates of overall and complete responses. Chemotherapy followed by auto-HSCT remained to be good choice for patients with poor prognostic factors. High-risk patients should be considered more beneficial from allo-HSCT.

Objective: To evaluate clinical outcomes of autologous (auto-HSCT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) for angioimmunoblastic T-cell lymphoma (AITL) . Methods: From June 2007 to June 2017, clinical data of AITL patients who underwent HSCT in eight hospitals were assessed retrospectively. Results: Of 19 patients, 13 male and 6 female with a median age of 50 (32-60) years old, 12 auto-HSCT and 7 allo-HSCT recipients were enrolled in this study, all donors were HLA-identical siblings. Two of allo-HSCT recipients were relapsed auto-HSCT ones. There were 5 patients (5/12) in complete response (CR) status and 7 (7/12) in partial remission (PR) status before transplantation in auto-HSCT group, and 2 (2/7) in PR status and 3 (3/7) in progression disease (PD) status before transplantation in allo-HSCT group. The median follow-up for the surviving patients was 46.5 months (range, 1-100 months) for the whole series, two patients lost in auto-HSCT group. Three patients developed acute graft-versus-host disease (aGVHD) and 5 chronic graft-versus-host disease (cGVHD) after allo-HSCT. Three patients died of primary disease and 1bleeding in auto-HSCT group. One patient died of primary disease and 2 transplantation-related mortality in allo-HSCT group. The 3-year cumulative overall survival (OS) were 56% (95%CI 32%-100%) and 57% (95%CI 30%-100%) for auto-HSCT and allo-HSCT, respectively (P=0.979) . The 3-year cumulative progression-free survival (PFS) were 34% (95%CI 14%-85%) and 57% (95%CI 30%-100%) for auto-HSCT and allo-HSCT, respectively (P=0.451) . Conclusion Both auto-HSCT and allo-HSCT were optimal choices for AITL. In clinical practice, which HSCT was better for AITL patients should be based on comprehensive factors including sensitivity to chemotherapy, risk stratification and disease status at transplantation.