AIM: To study the protective effect of edaravone on renal injury induced by chronic intermittent hypoxia and its effect on Caspase-1 mediated pyroptosis signaling pathway in rats. METHODS: Twenty four SPF male SD rats were randomly divided into normal control group, intermittent hypoxia group, intermittent hypoxia + normal saline group and intermittent hypoxia + edaravone group, with 6 rats in each group. The four groups of rats were placed in the closed feeding chamber for modeling. The oxygen concentration in the NC group was maintained at about 21%; the IH group, IH + NS group and IH + EDA group were given regular input of pure oxygen, pure nitrogen and compressed air to form anoxic-reoxygenation cycle (60 s hypoxic period + 60 s reoxygenation period). During the hypoxic period, the oxygen concentration in the chamber was reduced to 6%-7%, and the rats in the IH + EDA group were intraperitoneally injected with edaravone at a dose of 5 mg/kg per day before modeling, while the rats in the IH + NS group were intraperitoneally injected with normal saline at the same dose per day. After 8 weeks of modeling, blood and kidney tissue samples were collected to measure the levels of Crea and Urea in each group. The pathological changes and fibrosis degree of kidney were observed under light microscope after HE and Masson staining. The content of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) were determined by chemical method. The expression levels of NLRP3, Caspase-1 and IL-1β in renal tissues were determined by immunohistochemical staining. The expression levels of caspase-1 and IL-1β in renal tissues were determined by Western blot. GSDMD and IL-18 mRNA were detected by RT-PCR. RESULTS: After intermittent hypoxia exposure, serum Crea and Urea were increased significantly (P < 0.01), renal tubules were damaged by pathology, collagen fiber deposition occurred in balloon space of renal units, MDA content was increased and SOD activity was decreased (P < 0.01). Caspase-1, NLRP3, IL-1β protein expression increased (P < 0.01 or P < 0.05), GSDMD mRNA and IL-18 mRNA amplification increased (P < 0.01); After Edaravone intervention, the above indexes showed a reverse trend compared with that after intermittent hypoxia exposure, and the pathological damage of kidney was reduced (P < 0.01 or P < 0.05). CONCLUSION: Chronic intermittent hypoxia may mediate kidney injury through oxidative stress activation of caspase-1 involved in the cell pyroptosis signaling pathway, while edaravone may inhibit the activation of pyroptosis signaling pathway by scavenging oxygen free radicals and down-regulating the level of oxidative stress in the body, thus playing a protective role in kidney.

Objective:To investigate the clinicopathologic characteristics, gene mutation profile and prognostic influencing factors of diffuse large B-cell lymphoma (DLBCL) complicated with follicular lymphoma (FL) (DLBCL/FL).Methods:The clinicopathological data of 50 DLBCL/FL patients admitted to Rui Jin Hospital Affiliated of Shanghai Jiao Tong University School of Medicine from February 2018 to November 2021 were retrospectively analyzed. Targeted sequencing was performed to assess the mutation profile of 55 lymphoma-related genes. The clinicopathological characteristics were summarized to evaluate the short-term therapeutic efficacy of all patients. Kaplan-Meier method was used to analyze the overall survival (OS) and progression-free survival (PFS) of patients. Cox regression risk models were used to assess the factors affecting the OS and PFS.Results:Among 50 DLBCL/FL patients, 23 cases (46%) were male, 22 cases (44%) had an international prognosis index (IPI) score ≥ 2 points, 16 cases (32%) were double-expression lymphoma (DEL) and 4 cases (8%) were double-hit lymphoma (DHL). The complete response (CR) and overall response rates were 68% (34/50) and 78% (39/50), respectively after the first-line therapy. The median follow-up time was 23.3 months (5.1-50.9 months). The 2-year OS rate was 82.1% and 2-year PFS rate was 67.1%; and the median OS and PFS were not reached. Targeted sequencing results showed that the mutation frequencies of KMT2D, MYD88, TP53, BTG2, DTX1, EZH2, CD70, CREBBP, DUSP2, HIST1H1C, HIST1H1E and PRDM1 genes in this cohort were more than 15%. Multivariate Cox regression analysis showed that male ( HR = 4.264, 95% CI 1.144-15.896, P = 0.031) and IPI score ≥ 2 points ( HR = 6.800, 95% CI 1.771-37.741, P = 0.007) were independent risk factors of PFS in newly diagnosed DLBCL/FL patients, and TP53 mutation ( HR = 4.992, 95% CI 1.027-24.258, P = 0.046) was an risk influencing factor of OS. Conclusions:The proportion of male and female DLBCL/FL patients is similar, with a small proportion of DHL. Mutations of KMT2D, MYD88 and TP53 genes are commonly found in DLBCL/FL patients. Generally, DLBCL/FL patients can have a high overall response and good prognosis. Male and IPI score ≥ 2 points are the independent risk factors of PFS, and TP53 mutation is an independent risk factor of OS in DLBCL/FL patients.

Objective:To analyze the outcome of 15 cases with refractory systemic lupus erythematosus (SLE) treated with Belimumab, and evaluate the safety and efficacy of the therapy.Methods:A retrospective and real-world clinical research method was adopted.Fifteen children with confirmed refractory SLE and complete follow-up data were selected from the Department of Rheumatology, Beijing Children′s Hospital from April 1, 2020 to March 31, 2022.By comparing the changes of clinical symptoms, auxiliary examination results, SLE disease activity index (SLEDAI-2000) and Physician′s Global Assessment (PGA) scores as well as adverse events in different treatment periods (before treatment, 4 weeks, 8 weeks, 12 weeks, 6 months and 12 months after treatment), the safety and effectiveness of Belimumab treatment were all recorded.The counting data was expressed in percentage, the measurement data meeting the normal distribution was expressed in Mean±SD, and the two samples of measurement data were compared by t-test, P<0.05 means significant differences. Results:The ratio of male to female was 3∶2, and the onset age was (7.93±4.99) years; The basic treatment time was 4 months to 5 years and 1 month.There were 8 cases with lupus nephritis (LN), 2 cases suffering from hypocomplementemia for more than 1 year, 2 cases with central nervous system involvements, 2 cases complicated with antiphospholipid syndrome and 1 case with early-onset SLE.Of 8 LN cases, 1 case was complicated with neuropsychiatric lupus (NPLE) and distal femoral head infarction of both knees, and 3 cases were complicated with lumbar compression fractures and hip infarction.All patients were treated with regular traditional therapy to induce remission.During the maintenance period, the disease activity maintained at light to moderate levels, and it was difficult to reduce glucocorticoid.At baseline, SLEDAI-2000 score was 4-13, and PGA score was 1-2.50.Basic treatment includes glucocorticoids combined with immunosuppressants (Cyclosporine, Mycophenolate Mofetil, Leflunomide tablets) and antimalarial drugs, and Cyclophosphamide and/or Tripterygium Wilfordii were used at the same time according to the damage of target organs.The drug safety after intravenous injection of Belizumab showed that one patient in this group had respiratory tract infection symptoms 4 weeks after treatment; Another patient had a slight increase of alanine aminotransferase 8 weeks after treatment, and recovered to normal symptomatic treatment.No drug-related adverse reactions were found in the other 13 patients.After 4 weeks of treatment, the score of SLEDAI-2000 and PGA compared with the baseline level, and the difference was statistically significant (SLEDAI-2000 P=0.002; PGA P=0.006). There was no clinical recurrence.One patient with familial chilblain like lupus erythematosus showed significant improvement in rash 2 weeks after treatment, and low fever accompanied by increased rash 8 weeks after treatment; After 16 weeks of treatment, the body temperature was normal and the rash basically subsided. Conclusions:Belimumab is clinically effective in the treatment of refractory childhood SLE, with no serious adverse events reported.However, its long-term efficacy and safety need to be further studied by multi-center and long-term research with a large sample size.

  Objective  To study the demographic and clinical characteristics, correlation of genotype and phenotype and treatment of Blau syndrome to facilitate early diagnosis and timely treatment of Blau syndrome.  Methods  Seventy-two patients with Blau syndrome from 11 centers from May 2006 to April 2022 were retrospectively analyzed, and their general information, clinical data, laboratory examination and treatment medication were collected.  Results  The distribution of patients with Blau syndrome was uniform in geographical north and south of China, and there was no obvious gender bias. The mean age of onset was (14.30±12.81) months, and the age of diagnosis was (55.18±36.22) months. 35% of patients with Blau syndrome happened before 1 year old, and all patients developed before 5 years old. 87.50% (63/72) had granulomatous arthritis, 65.28% (47/72) had rash, 36.11% (26/72) had ocular involvement, 27.78% (20/72) had fever, and 15.28% (11/72) had pulmonary involvement. Arthritic manifestations of Blau syndrome were most at risk, followed by rash, ocular involvement, and fever.The first 25 months of the disease, the risk of developing a rash was the greatest. The risk of developing arthritis was the greatest between 25 months and 84 months. The main mutations were p.R334Q and p.R334W, and patients with p.R334Q mutation had relatively high incidence of fever (35.71%[5/14] vs. 14.29%[1/7], P=0.43) and ocular involvement (42.86%[6/14]vs. 28.57%[2/7], P=0.51). There was a relatively high incidence of rash (85.71%[6/7] vs. 64.29%[9/14], P=0.59) in patients with the p.R334W mutation. Forty-five patients(62.50%)were treated with a combina-tion of glucocorticoid and methotrexate. Twenty-two patients were treated with tumor necrosis factor antagonist in addition to glucocorticoid and methotrexate.  Conclusions  The risk of different clinical manifestations of Blau syndrome from high to low was arthritis, followed by rash, ocular involvement and fever. The main treatment was glucocorticoid combined with methotrexate, to which biological agents could be added.

Objective:To examine the association of abdominal obesity assessed by waist circumference (WC) with carotid intima-media thickness (cIMT) in children.Methods:The study participants were from the "Huantai Childhood Cardiovascular Health Cohort Study" conducted in Huantai County, Zibo City, Shandong Province. A convenient cluster sampling method was used to select a primary school in Huantai County to conduct the baseline survey from November 2017 to January 2018. A total of 1 515 children aged 6-11 years old were included. The first follow-up survey was conducted from November to December 2019, and a total of 981 children aged 8-13 years old were finally included after exclusion of those with high cIMT at baseline. Questionnaire survey, physical examination and ultrasonic examination were used to collect general demographic characteristics, WC and cIMT information. According to the status of WC at baseline, the participants were divided into normal WC group and abdominal obesity group. Covariance analysis was used to compare the cIMT levels of children between normal WC group and abdominal obesity group. Multivariable logistic regression models were used to evaluate the association between baseline abdominal obesity and high cIMT during the follow-up.Results:The age of 981 children was (8.5±1.5) years at the baseline. The follow-up age was (10.5±1.5) years, and 520 boys accounted for 53.0%. The cIMT of children in the abdominal obesity group was 0.54 mm, which was higher than that in the normal WC group (0.51 mm) ( P<0.001). Similarly, the prevalence of high cIMT in children with abdominal obesity (23.9%) was higher than that of normal WC group (3.9%) ( P<0.001). After adjusting for potential covariates at the baseline and during the follow-up period, compared with the normal WC group, abdominal obesity was significantly associated with high cIMT ( OR=5.78, 95% CI:3.43-9.74). Conclusion:The abdominal obesity in children could increase the risk of high cIMT.

Objective:To examine the association of abdominal obesity assessed by waist circumference (WC) with carotid intima-media thickness (cIMT) in children.Methods:The study participants were from the "Huantai Childhood Cardiovascular Health Cohort Study" conducted in Huantai County, Zibo City, Shandong Province. A convenient cluster sampling method was used to select a primary school in Huantai County to conduct the baseline survey from November 2017 to January 2018. A total of 1 515 children aged 6-11 years old were included. The first follow-up survey was conducted from November to December 2019, and a total of 981 children aged 8-13 years old were finally included after exclusion of those with high cIMT at baseline. Questionnaire survey, physical examination and ultrasonic examination were used to collect general demographic characteristics, WC and cIMT information. According to the status of WC at baseline, the participants were divided into normal WC group and abdominal obesity group. Covariance analysis was used to compare the cIMT levels of children between normal WC group and abdominal obesity group. Multivariable logistic regression models were used to evaluate the association between baseline abdominal obesity and high cIMT during the follow-up.Results:The age of 981 children was (8.5±1.5) years at the baseline. The follow-up age was (10.5±1.5) years, and 520 boys accounted for 53.0%. The cIMT of children in the abdominal obesity group was 0.54 mm, which was higher than that in the normal WC group (0.51 mm) ( P<0.001). Similarly, the prevalence of high cIMT in children with abdominal obesity (23.9%) was higher than that of normal WC group (3.9%) ( P<0.001). After adjusting for potential covariates at the baseline and during the follow-up period, compared with the normal WC group, abdominal obesity was significantly associated with high cIMT ( OR=5.78, 95% CI:3.43-9.74). Conclusion:The abdominal obesity in children could increase the risk of high cIMT.

Objective To observe the effect of the method of warming kidney and dredging collaterals on the clinical effect and the content of urine C5b-9 in patients with idiopathic membranous nephropathy with spleen kidney yang deficiency and blood stasis. Methods A total of 60 idiopathic membranous nephropathy patients with spleen kidney yang deficiency and blood stasis type were randomly divided into the conventional western medicine treatment group (control group), Jingui-Shenqi pill and Taohong-Siwu decoction plus conventional western medicine treatment group (treatment group), 30 cases in each group. The Scr was detected by deproteinized alkaline picric acid method, and BUN was detected by rate method, and serum albumin (ALb) was detected by bromocresol green dye binding method, and 24 hours urinary protein was measured by pyrogallol red colorimetry, and the double antibody sandwich ELISA method was used for detection of urinary C5b-9. Results The Jingui-Shenqi pill combined with Taohong-Siwu decoction plus conventional western medicine treatment has obvious curative effect on patients. The total effective rate was 83.3 in the treatment group (25/30), and the control group was 60％ (18/30). After treatment, the Alb (33.5 ± 7.95 g/L vs. 28.8 ± 6.10 g/L, t=2.569) in the treatment groupwas significantly higher than that in the conventional treatment group (P<0.01). While the 24 h urine protein (2.40 ± 0.92 g/24 h vs.3.60 ± 2.3 g/24 h, t=2.653), the contents of C5b-9 in urine(42.5 ± 17.50 ng/mg vs.71 ± 25.2 ng/mg, t=5.088) in the treatment group were significantly lower than those in the conventional treatment group (P<0.01). Conclusions The method of warming kidney and dredging collaterals can improve the clinical symptoms, improve serum albumin level, reduce the 24 hour urine protein and urinary C5b-9 content of idiopathic membranous nephropathy of spleen and kidney yang deficiency and blood stasis type.

Objective To analyze the efficacy and safety of tetrandrine in the adjuvant treatment of relapsed/refractory acute leukemia (except M3).Methods A total of 58 patients with relapsed/refractory acute leukemia (except M3) admitted to six tertiary hospitals in Jiangsu Province from January 2015 to December 2017 were included in this study.The tetrandrine-adjuvant standard chemotherapy regimen and standard chemotherapy regimen were given to treatment and control groups respectively.There were 17 and 41 patients in treatment and control groups.The treatment group was given tetrandrine for 5 days before the use of standard chemotherapy.The dose of tetrandrine was 4 mg ·kg-1 ·d-1,and patients had continuous oral administration of 5 days.After that,the patients in the treatment group started chemotherapy immediately.On the other side,the control group received standard chemotherapy without any other multidrug reversal medicine.Then the clinical efficacy and safety outcomes in both groups were analyzed.Results In the treatment group,5,3,and 9 cases achieved complete remission (CR),partial remission (PR),and nonremission (NR) respectively,and the total effective (CR+PR) rate was 47.06 ％ (8/17);in the control group,14,10,and 17 cases achieved CR,PR,and NR,and the total effective rate was 58.54 ％ (24/41).There was no significant difference in the total effective rate between the two groups (x2 =0.64,P =0.424).There was no significant difference in the efficacy between the two groups of patients with different genders (P ＞ 0.05).When the disease duration was 6-11 months,the difference of efficacy between the two groups was statistically significant (P =0.041).There was no significant difference in the proportion of myeloid leukemia cells,white blood cell count,platelet count,red blood cell count,and hemoglobin between the two groups before and after treatment (all P ＞ 0.05).There was no significant difference in clinical safety indicators (urine,faecal routine,liver and kidney function,and electrocardiogram) between the two groups (all P ＞ 0.05).Conclusions Tetrandrine is more effective in patients with relapsed/refractory acute leukemia (except M3) with shorter duration of disease.Compared with chemotherapy alone,the clinical efficacy of adding tetrandrine in chemotherapy cannot be considered superior to the former.

Objective To explore the molecular mechanism of Yishen Huoxue prescription in delaying the development of renal fibrosis by regulating the microRNA-126/vascular endothelial growth factor-Notch (miR-126/VEGF-Notch) signaling pathway. Methods Ninety male Sprague-Dawley (SD) rats were randomly divided into sham operation group (sham group), unilateral ureteral obstruction (UUO) model group, losartan group (50 mg·kg-1·d-1) and high, medium and low doses Yishen Huoxue prescription group (25.2, 12.6, 6.3 mL/kg). Each treatment group began to administer drugs by gavage on the day when UUO modeling was finished until the end of the experiment. Left renal tissues of rats were harvested after 7, 14 and 21 days postoperatively. The pathological changes of renal tissue were observed after hematoxylin and eosin (HE) and Masson staining under the microscope, and the renal fibrosis score was calculated. The mRNA expressions of renal tissues miR-126, VEGFA, vascular endothelial growth factor receptor-2 (VEGFR-2), Notch1 were detected by reverse transcription-polymerase chain reaction (RT-PCR). Results① Pathology results: the kidney tissue of sham group was normal. In UUO model group, renal tubules expanded and inflammatory cells in renal interstitium increased; renal tubulointerstitial fibrosis could be seen 7 days after operation, and the degree of fibrosis was gradually increased with time. The renal fibrosis score at each time point after operation in UUO model group was significantly higher than that in sham group. Compared with UUO model group, each treatment group were improved the degree of renal swelling and atrophy of renal parenchyma; the score of renal fibrosis were significantly decreased in the middle and high doses Yishen Huoxue prescription group and losartan group at the 7th day after operation (1.00±1.00, 0.91±0.58, 1.01±0.58 vs. 2.00±0.00,all P < 0.01); but there was no significant difference between low dose Yishen Huoxue prescription group and UUO model group. ② RT-PCR results: Compared with sham group, the mRNA expressions of miR-126, VEGFA, VEGFR-2 and Notch1 in renal tissues were significantly increased at each time point after operation in UUO model group. Compared with the UUO model group, the mRNA expressions of miR-126, VEGFA, VEGFR-2 and Notch1 in renal tissue of 7 days postoperatively in the middle and high doses Yishen Huoxue prescription group and the losartan group were significantly increased [miR-126(2-ΔΔCt):0.465±0.067, 0.639±0.092, 0.404±0.069 vs. 0.132±0.021; VEGFA(2-ΔΔCt): 0.024±0.005, 0.027±0.007, 0.023±0.006 vs. 0.014±0.006; VEGFR-2(2-ΔΔCt):0.021±0.007, 0.023±0.008, 0.019±0.007 vs. 0.012±0.004; Notch1(2-ΔΔCt):0.017±0.004, 0.020±0.005, 0.018±0.005 vs. 0.007±0.004; all P < 0.05]; compared with the losartan group, the mRNA expressions of each index in the middle and high doses Yishen Huoxue prescription group were increased at all the time points, but there was no significant difference between them (all P > 0.05). There was no significant difference in mRNA expression of each index between low dose Yishen Huoxue prescription group and UUO model group. Conclusions The medium and high doses of Yishen Huoxue prescription can effectively antagonize renal fibrosis. Yishen Huoxue prescription may use up-regulation the signaling pathways of miR-126/VEGF-Notch to mediate renal microvascular newly born, eventually to improve renal microvascular damage and delay the development of renal fibrosis progression.

Trisomy 8 in myelodysplastic syndrome (MDS) plays an important role in concurrent intestinal Beh?et's disease (BD) pathogenesis.Here,we reported a case of intestinal BD combined with MDS involving trisomy 8.A 48-year-old woman who has had a 20-year history of recurrent oral ulcer,perineal ulcer and iris,was diagnosed as MDS with trisomy 8 four years ago.She developed high fever and acute abdominal pain.Multiple ulcerative perforations in ileum and colon were found by endoscopy,meeting the criteria for intestinal BD.The patient was successfully treated with immunomodulatory drugs.