Objective:To analyze the efficacy and safety of daratumumab plus dexamethasone in the treatment of renal injury patients with light chain amyloidosis, and to provide clinical reference.Methods:It was a single center retrospective observational study. The clinical data before and after daratumumab treatment of renal injury patients with light chain amyloidosis treated with daratumumab plus dexamethasone from December 2021 to August 2022 were retrospectively collected. The hematologic response, kidney response, prognosis, and adverse events were analyzed. The treatment regimen was 16 mg/kg intravenous infusion of daratumumab on day 1 + 20 mg intravenous push of dexamethasone on day 1-2, once every 2 weeks. The follow-up was up to February 28, 2023.Results:The study included 18 patients, with age of (58.4±7.7) years old, and a male to female ratio of 11∶7. Eleven patients were newly diagnosed and 7 patients were retreated. There were 7, 5, 5 and 1 patients, respectively at the stage Ⅰ, Ⅱ, Ⅲ and Ⅳ of light chain amyloidosis according to 2012 Mayo stage criteria. The median course of disease before onset was 2.5 (1.0, 8.0) months and the follow-up time was (8.7±2.8) months. The patients received (10±3) times of treatment. The overall hematologic response rates were 9/13, 11/13 and 13/13 at 1 month, 3 months, and 6 months respectively after treatment, meanwhile 8/13, 10/13 and 12/13 achieved at least very good partial response at 1 month, 3 months, and 6 months respectively (the other 5 patients did not undergo detailed evaluation due to baseline difference of serum free κ and λ light chain <20 mg/L). The median duration of hematologic response was 16 (13, 40) days. At 3 months, 6 months and the end of follow-up, 10, 13 and 13 of 18 patients respectively achieved renal response, and the median duration of response was 66 (26, 182) days. During follow-up, the median difference of serum free κ and λ light chain decreased by 93% (72%, 97%). Until the last follow-up, one patient died of organ hemorrhage. Other infusion reactions, leukopenia, neutropenia and infection all improved after symptomatic treatments.Conclusion:Daratumumab plus dexamethasone treatment is effective for light chain amyloidosis nephropathy in inducing hematologic remission and kidney remission, with good safety.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Objective:Exploring the role and mechanism of gremlin-1 in lipotoxicity-mediated pancreatic β-cell dysfunction.Methods:The model of lipid toxicity-mediated pancreatic β-cell dysfunction was constructed using palmitic acid(PA) to treat mouse pancreatic β-cells(MIN6). Initially, to clarify the effects of lipotoxicity on islet β-cells, the cellular lipid deposition and changes in the levels of insulin caused by PA were detected. The effects of PA on gremlin-1 expression and its downstream signaling pathway BMPs/Smads were further investigated using qPCR and Western Blot assay. Subsequently, recombinant mouse gremlin-1 protein and BMP signaling pathway inhibitor LDN193189 were used to intervene the cells to explore the effects of gremlin-1 and its downstream signaling pathway BMPs/Smads on pancreatic islet β-cells.Results:PA could reduce pancreatic β-cell viability and insulin secretion capacity( P<0.05). Meanwhile, PA inhibited the expression and secretion of cell gremlin-1 and upregulated BMP-4 and its downstream Smad-1 and Smad-5( P<0.05). Intervention of cells with recombinant mouse gremlin-1 protein resulted in a significant elevation of insulin secretion and a concomitant decrease in the expression of key molecules in the BMP4/Smads signaling pathway( P<0.05). And inhibition of the BMP4/Smads signaling pathway ameliorated PA-induced pancreatic β-cell dysfunction. Conclusion:Gremlin-1 is involved in the regulation of lipotoxicity-mediated pancreatic islet β-cell dysfunction, and this effect may be associated with activation of BMP4/Smads signaling pathway.

Hepatitis B virus (HBV) infection is a common cause of liver disease in China, and with the continuous progress in the research on antiviral therapy for chronic hepatitis B, the indications for antiviral therapy are constantly expanding. However, there are still controversies over the indications for antiviral therapy in patients with chronic hepatitis B (CHB), especially those with negative HBV. By analyzing the limitations of HBV DNA detection, the risk of HBV reactivation in HBV-negative CHB patients, the risk of disease progression in the DNA-negative population with compensated hepatitis B cirrhosis, antiviral response, and the economic benefits of antiviral therapy, this article proposes the necessity of antiviral therapy for HBV-negative HBsAg-positive patients with compensated hepatitis B cirrhosis.

Spinal cord injury (SCI) causes motor, sensory, and autonomic dysfunctions. The gut microbiome has an important role in SCI, while short-chain fatty acids (SCFAs) are one of the main bioactive mediators of microbiota. In the present study, we explored the effects of oral administration of exogenous SCFAs on the recovery of locomotor function and tissue repair in SCI. Allen's method was utilized to establish an SCI model in Sprague-Dawley (SD) rats. The animals received water containing a mixture of 150 mmol/L SCFAs after SCI. After 21 d of treatment, the Basso, Beattie, and Bresnahan (BBB) score increased, the regularity index improved, and the base of support (BOS) value declined. Spinal cord tissue inflammatory infiltration was alleviated, the spinal cord necrosis cavity was reduced, and the numbers of motor neurons and Nissl bodies were elevated. Enzyme-linked immunosorbent assay (ELISA), real-time quantitative polymerase chain reaction (qPCR), and immunohistochemistry assay revealed that the expression of interleukin (IL)‍-10 increased and that of IL-17 decreased in the spinal cord. SCFAs promoted gut homeostasis, induced intestinal T cells to shift toward an anti-inflammatory phenotype, and promoted regulatory T (Treg) cells to secrete IL-10, affecting Treg cells and IL-17⁺ γδ T cells in the spinal cord. Furthermore, we observed that Treg cells migrated from the gut to the spinal cord region after SCI. The above findings confirm that SCFAs can regulate Treg cells in the gut and affect the balance of Treg and IL-17⁺ γδ T cells in the spinal cord, which inhibits the inflammatory response and promotes the motor function in SCI rats. Our findings suggest that there is a relationship among gut, spinal cord, and immune cells, and the "gut-spinal cord-immune" axis may be one of the mechanisms regulating neural repair after SCI.
Animals ; Rats ; Interleukin-17 ; Rats, Sprague-Dawley ; Recovery of Function ; Spinal Cord Injuries/drug therapy* ; T-Lymphocytes, Regulatory ; Receptors, Antigen, T-Cell, gamma-delta/immunology*

Objective:To investigate the correlation between serum miR-122-5p and FOXO3 levels and osteoporosis (OP) in postmenopausal women with non-alcoholic fatty liver disease (NAFLD) .Methods:The clinical data and serum of 30 postmenopausal women with NAFLD and 48 postmenopausal women with no-NAFLD were collected. The levels of miR-122-5p and FOXO3 in serum were detected by qRT-PCR. Triglycerides, high-density lipoproteins, and low-density lipoproteins were detected by biochemical autoanalyzer. The bone mineral density of lumbar vertebrae 1-4, Wards triangular bone, femoral neck, greater trochanter and total hip was detected by bone mineral density analyzer. The correlation between the above clinical indicators and OP was analyzed.Results:The expression of miR-122-5p in postmenopausal female NAFLD patients (0.76±0.28) was lower than that in non-NAFLD patients (1±0.31) ( t=3.43, P=0.001) . The downstream target gene FOXO3 of miR-122-5p was identified by bioinformatics website analysis. The expression of FOXO3 in postmenopausal female NAFLD patients (1.31±0.30) was higher than that in non-NAFLD patients (1±0.27) ( t=4.73, P<0.001) . Student’ s t test and Logistic regression analysis showed that triglyceride, miR-122-5p and FOXO3 levels were risk factors for NAFLD (all P<0.05) . Pearson correlation coefficient showed that miR-122-5p level was significantly positively correlated with BMD of femoral neck ( r=0.488, P=0.006) , greater trochanter ( r=0.367, P=0.046) and whole hip ( r=0.404, P=0.027) . FOXO3 level was negatively correlated with bone mineral density of femoral neck ( r=-0.445, P=0.014) and whole hip ( r=-0.507, P=0.004) , while other indexes were not significantly correlated (all P>0.05) . Conclusion:Decreased serum miR-122-5p level and increased FOXO3 level in postmenopausal women with NAFLD may increase the risk of OP.

Objective:To study the clinical characteristics of patients with brucella bloodstream infection in different age groups, and provide a basis for clinicians to take targeted diagnosis and treatment measures. Methods:Demographic data and general condition (age, sex, occupation, location, onset season, source of infection, clinical stage), clinical characteristics (main clinical symptoms and complications), and laboratory test results (routine and pathogenic tests) of adult patients with brucella bloodstream infection admitted to the Affiliated Hospital of Chengde Medical College from January 2015 to January 2020 were collected. According to the age stratification standards recommended by the World Health Organization, the patients were divided into a young group (18 - 44 years old), a middle-aged group (45 - 59 years old), and an elderly group (≥60 years old), and various indicators among different age groups were compared and analyzed. Results:A total of 75 patients were included, including 15 cases (20.00%) in the young group, 37 cases (49.33%) in the middle-aged group, and 23 cases (30.67%) in the elderly group. Among them, 61 cases (81.33%) were males and 14 cases (18.67%) were females, with statistically significant differences in gender ratios among different age groups (χ 2 = 7.28, P = 0.021). The majority of patients were farmers (64 cases, 85.33%), and 92.00% (69/75) of the patients came from rural areas. The main sources of infection were infected cattle and sheep, and contaminated food (39 cases, 52.00%). The main season of onset was spring and summer (45 cases, 60.00%). The clinical staging was mainly in the acute phase (66 cases, 88.00%). In terms of clinical symptoms, the young group of patients had no symptoms of low back pain, while the incidence rates of low back pain in the middle-aged and elderly groups were 35.14% (13/37) and 30.43% (7/23), respectively. There was a statistically significant difference between the three groups (χ 2 = 6.98, P = 0.031). In terms of complications, there were no cases of concurrent spondylitis in the young group of patients. The incidence rates of spondylitis in the middle-aged and elderly groups were 32.43% (12/37) and 34.78% (8/23), respectively. There was a statistically significant difference among the three groups (χ 2 = 6.86, P = 0.032). In terms of routine laboratory examinations, there were statistically significant differences in the proportion of blood lymphocytes and albumin levels among patients of different age groups ( F = 3.41, 3.27, P = 0.038, 0.044). In terms of pathogenic examination, there was a statistically significant difference in the median alarm time for positive blood culture among patients of different age groups ( H = 9.54, P = 0.008), with the middle-aged group having the longest (66.24 h) and the elderly group having the shortest (58.80 h). Conclusions:The clinical characteristics of patients with brucella bloodstream infection vary among different age groups, middle-aged and elderly patients are prone to low back pain symptoms, accompanied by spondylitis. Clinicians should pay attention to the patient's own characteristics and provide targeted diagnosis and treatment.

Objective:To investigate the risk factors of non-alcoholic fatty liver disease (NAFLD) in patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) breast cancer (HR+/HER2-BC) and the impact of NAFLD on the survival of patients.Methods:54 HR+BC patients were enrolled in this study. The liver fat accumulation was examined by magnetic resonance imaging (MRI). The patients were divided into two groups: non-NAFLD and NAFLD. Student's t test or Fisher's test was used to analyze the clinical indicators of the two groups. Logistic univariate and multivariate tests were used to analyze the clinical risk factors related to NAFLD. Receiver operating characteristic curve (ROC curve) was used to further analyze the sensitivity of clinical risk factors to predict the diagnosis of NAFLD. The Disease-free survival (DFS) and Overall survival (OS) of the two groups were analyzed by Log-rank (Mantel-Cox) test. Results:There were 22 NAFLD patients and 32 non-NAFLD patients diagnosed by MRI. Student's t test or Fisher's test showed that BMI, waist circumference, AST, ALT, GGT, TG, LDL and HDL were statistically different between the two groups (all P<0.05). Logistic univariate and multivariate analysis showed that AST ( OR=1.05, 95% CI: 1.02-1.10, P=0.007), GGT ( OR=1.04, 95% CI: 1.01-1.09, P=0.038), TG ( OR=1.03, 95% CI: 1.01-1.06, P=0.011) and HDL ( OR=1.06, 95% CI: 1.01-1.12, P=0.037) were the risk factors associated with NAFLD. ROC curve analysis showed that the combination of AST, GGT, TG and HDL had high sensitivity in predicting NAFLD (AUC=0.869, P<0.05). There was no difference in DFS ( HR=1.830, 95% CI: 0.983-3.409, P=0.057) or OS ( HR=2.482, 95% CI: 0.761-8.093, P=0.132) between the two groups. Conclusion:AST, GGT, TG and HDL are the independent risk factors for NAFLD in HR+BC patients during treatment, but concurrent NAFLD has no significant effect on DFS or OS.

Objective:To access the clinical efficacy and safety of hydroxychloroquine (HCQ) in treatment of IgA nephropathy (IgAN).Methods:The data of IgAN patients who were diagnosed by renal biopsy in the First Affiliated Hospital, College of Medicine, Zhejiang University from May 2016 to August 2020 and had been treated with HCQ for more than 6 months without other immunosuppressants were retrospectively analyzed. The efficacy and side effects were compared between groups according to the baseline urine protein/creatinine ratio (UPCR) or whether combined with renin-angiotensin-aldosterone system inhibitor (RAASi).Results:A total of 121 patients were enrolled, including 45 males (37.19%). At baseline, the median UPCR was 0.69(0.45, 1.00) g/g; the median estimated glomerular filtration rate (eGFR) was 93.46(73.14, 115.67) ml·min -1·(1.73 m 2) -1; the median serum creatinine was 80.00(61.00, 98.00) μmol/L, and the serum albumin was (44.39±3.36) g/L. After HCQ treatment, UPCR and red blood cells were significantly decreased compared with baseline (all P<0.05). Triglyceride, total cholesterol and low-density lipoprotein cholesterol were also significantly decreased during the follow-up period. Serum creatinine, eGFR, serum albumin and serum uric acid remained stable. After 6 months of follow-up, the total remission rate was 56.88%, including 15.60% of partial remission and 41.28% of complete remission; at the end of follow-up, the median follow-up time was 280.00(214.00, 411.00) days and the total remission rate was 56.20%, including 9.92% of partial remission and 46.28% of complete remission. Group analysis showed that the remission rate was 60.53% ( n=76) and 48.48% ( n=33) at 6 months (Mann-Whitney U test, Z=-2.331, P=0.020) and 57.65% ( n=85) and 52.78% ( n=36) at the end of follow-up (Mann-Whitney U test, Z=-1.673, P=0.094) between patients with baseline UPCR<1 g/g and patients with baseline UPCR≥1 g/g; and the remission rate was 66.67% ( n=30) and 53.16% ( n=79) at 6 months (Mann-Whitney U test, Z=1.062, P=0.288) and 61.29% ( n=31) and 54.44% ( n=90) at the end of follow-up (Mann-Whitney U test, Z=0.930, P=0.352) between patients with single HCQ and patients with HCQ+RAASi. For side effects, the eGFR of 2 patients decreased by more than 30% compared with baseline, 1 patient relapsed and 1 patient developed blurred vision. Conclusions:HCQ is safe and effective for the treatment of IgAN.

Objective:To investigate the efficacy and safety of individualized rituximab rescue therapy for active lupus nephritis with acute kidney injury (AKI).Methods:The clinical data of lupus nephritis patients with AKI treated with rituximab at the Kidney Disease Center of the First Affiliated Hospital of Zhejiang University School of Medicine from April 2017 to June 2020 were collected, and the renal remission rate and adverse events after rituximab treatment were analyzed retrospectively. The Kaplan-Meier method was used to calculate the cumulative incidence of patients' remission.Results:There were 13 patients enrolled, including 8 females, and aged (35.23±15.92) years old. The urinary protein/creatinine ratio was (5.22±1.57) g/g before rituximab treatment. Four patients were on dialysis at admission, and 9 patients without dialysis had serum creatinine of (223.22±85.73) μmol/L. Eight patients were confirmed as proliferative lupus nephritis by renal biopsies, including 7 cases with crescent formation and 1 case with thrombotic microangiopathy (TMA), and the other 5 cases without renal biopsies were clinically diagnosed as TMA. The dose of rituximab was (815±516) mg (200-2 100 mg), and all the patients reached the state of peripheral blood B cells clearance (CD19 + B cell count was<5/μl). After the first treatment of rituximab, the median time to B-cell clearance was 21(15, 35) days, and 8 patients reached B-cell depletion (CD19 + B cell count was 0). The remission rate was 12/13 (two cases reached complete remission, and 10 cases reached partial remission). Three cases stopped dialysis, and 1 case (with glomerulosclerosis of 52.94%) entered maintaining dialysis. The relapse times in the maintenance remission period of 7 patients with refractory lupus nephritis declined significantly from (1.57±0.53) times in a median history of 60(20, 109) months to (0.43±0.79) times in a median history of 18(10, 23) months after the use of rituximab ( P=0.015). After using rituximab, the incidence of infection was 7/13. The median time from the use of rituximab to infection was 26(4, 44) days. Pulmonary infection (5/13) was the most common type and all infected patients recovered after anti-infection treatment. Conclusions:Rituximab can be used in the treatment of active lupus nephritis with AKI, especially in patients with crescent formation and TMA, but the infection should be paid close attention to and prevented.