Objective:To explore the efficacy and safety of olverembatinib in treatment of chronic myeloid leukemia (CML) progressed to acute lymphoblastic leukemia with D241E mutation.Methods:The diagnosis and treatment of a patient with D241E mutant CML progressed to acute lymphoblastic leukemia admitted to the Fourth People's Hospital of Jinan in December 2018 were retrospectively analyzed, and relevant literature was reviewed.Results:The patient was a 47-year-old female, and her blood test result was abnormal during physical examination. She was diagnosed as CML and received treatment with imatinib and dasatinib for 2 years. The disease progressed to philadelphia chromosome (Ph)-positive acute B-lymphoblastic leukemia with BCR-ABL mutation (a D241E mutation). After 3 courses of chemotherapy combined with a targeted drug (ponatinib), the patient achieved complete remission, while the minimal residual disease continued to be positive. The patient received 1 course of chemotherapy combined with olverembatinib from the 4th course of treatment. After olverembatinib monotherapy maintenance therapy for 36 months, the patient achieved molecular complete remission with minimal residual disease. The patient developed complications such as skin pigmentation and elevated lipid levels, but all complications were tolerable.Conclusions:The application of olverembatinib in D241E mutant CML progressed to acute lymphoblastic leukemia can help patients obtain sustained molecular biological remission and good safety.

OBJECTIVE: To investigate the regulatory effect of electroacupuncture (EA) at "Neiguan" (PC6) on mitochondrial autophagy in rats with myocardial ischemia-reperfusion injury (MIRI) at different phases (ischemia and reperfusion phases), and to explore the bidirectional regulatory effects of EA at "Neiguan" (PC6) and its potential mechanism. METHODS: Forty-five male SD rats were randomly divided into 6 groups according to the random number table method, namely, sham-operation group (n=9), model-A group (n=6), model-B group (n=9), EA-A1 group (n=6), EA-B1 group (n=6), and EA-B2 group (n=9). Except the rats in the sham-operation group, the MIRI model was established in the other groups with the physical ligation and tube pushing method. In the model-A group, the samples were collected directly after ligation, and in the model-B group, the samples were collected after ligation and reperfusion. In the EA-A1 group, EA was delivered while the ligation was performed, and afterwards, the samples were collected. In the EA-B1 group, while the ligation was performed, EA was operated at the same time, and after reperfusion, the samples were collected. In the EA-B2 group, during ligation and the opening of the left anterior descending branch of the coronary artery, EA was delivered, and after reperfusion, the samples were collected. EA was performed at bilateral "Neiguan" (PC6), with a disperse-dense wave, a frequency of 2 Hz/100 Hz, a current of 1 mA, and a duration of 30 min. HE staining was employed to observe the morphology of cardiomyocytes, TUNEL was adopted to detect the apoptosis of cardiomyocytes, transcriptome sequencing was to detect the differentially expressed genes in the left ventricle, JC-1 flow cytometry was to detect the mitochondrial membrane potential (MMP) of cardiomyocytes, Western blot was to detect the protein expression of phosphatase and tensin homolog-induced kinase 1 (Pink1), Parkin and p62 in the left ventricle of rats, and ELISA was to detect the levels of serum creatine kinase isoenzyme (CK-MB) and cardiac troponin I (cTn-I) in the rats. RESULTS: Compared with the sham-operation group, the cardiomyocytes of rats in the model-B group were severely damaged, with disordered arrangement, unclear boundaries, broken muscle fibers, edema and loose distribution; and the cardiomyocytes in the EA-B2 group were slightly damaged, the cell structure was partially unclear, the cells were arranged more regularly, and the intact cardiomyocytes were visible. Compared with the sham-operation group, the apoptosis of cardiomyocytes increased in the model-B group (P<0.001); and when compared with the model-B group, the apoptosis alleviated in the EA-B2 group (P<0.001). The differentially expressed genes among the EA-B2 group, the sham-operation group and the model-B group were closely related to cell autophagy and mitochondrial autophagy. Compared with the sham-operation group, MMP of cardiomyocytes was reduced (P<0.001), the protein expression of Pink1, Parkin, and p62 of the left ventricle and the levels of serum CK-MB and cTn-I were elevated in the model B group (P<0.001). In comparison with model-A group, the MMP of cardiomyocytes and the levels of serum CK-MB and cTn-I were reduced (P<0.001, P<0.05), and the protein expression of Pink1 in the left ventricle rose in the EA-A1 group (P<0.01). Compared with the model-B group, MMP of cardiomyocytes increased (P<0.001), the protein expression of Pink1, Parkin, and p62 of the left ventricle, and the levels of serum CK-MB and cTn-I decreased (P<0.001) in the EA-B1 group and the EA-B2 group. When compared with the EA-A1 group, MMP of cardiomyocytes increased (P<0.001), and the protein expression of Pink1, Parkin, and p62 of the left ventricle, and the levels of serum CK-MB and cTn-I decreased in the EA-B1 group (P<0.01). CONCLUSION EA at "Neiguan" (PC6) can ameliorate MIRI in rats, which may be achieved through the Pink1/Parkin-mediated mitochondrial autophagy pathway. EA can alleviate myocardial injury by enhancing mitochondrial autophagy at the ischemia phase, and it can reduce reperfusion injury by weakening mitochondrial autophagy at the reperfusion phase.
Animals ; Electroacupuncture ; Male ; Myocardial Reperfusion Injury/metabolism* ; Rats, Sprague-Dawley ; Rats ; Acupuncture Points ; Autophagy ; Humans ; Mitochondria/genetics*

Objective To retrospectively analyze the efficacy of subinguinal microscopic ligation in the treatment of painful varicocele in military patients,and to explore the associated factors for postoperative pain relief.Methods A total of 105 patients who underwent subinguinal microscopic ligation due to left varicocele combined with scrotal pain between June 2019 and June 2022 in the First Navy Hospital of Southern Theater Command were retrospectively analyzed.The age,degree of varicocele,visual analogue scale(VAS)score,surgical time,and complications were investigated.All patients were followed up for six months,and the efficacy,recurrence,and pain relief were assessed by physical examination and color Doppler ultrasound.Results The mean age of the patients was 24.13 years old,and surgical time was 85.02 min.The overall effective rate was 97.14%,and the complete remission rate,partial remission rate,and no response rate of postoperative pain were 77.14%,16.19%,and 6.67%,respectively.During the follow-up period,3 patients experienced recurrence(2.86%),1 patient(0.95%)had hydrocele,and 2 patients(1.9%)suffered from epididymitis.There was a significant correlation between the degree of preoperative varicocele and postoperative pain relief rate(P<0.001).Conclusion Microsurgical ligation is an effective treatment for scrotal pain caused by varicocele.There is a certain correlation between the degree of varicocele and postoperative pain relief,which can be used for predicting therapeutic effects.

Objective To explore the enrichment method of the crude alkaloid of Zanthoxylum nitidum(Roxb.)DC.(Z.nitidum),which can inhibit the proliferative activity of human erythroid leukemia cells(HEL cells)in vitro,and to provide a scientific basis for the antitumor activity of Z.nitidum.Methods Z.nitidum was extracted using different concentrations of ethanol(60%,70%,80%,90%,and 100%)to determine the optimum extraction conditions according to the highest extraction rate.Static and dynamic adsorption determined the adsorption capacity of different macroporous resins(HPD 100,XDA-5,D101,HPD 722,HPD 400)on the ethanol extracts from Z.nitidum.The effects of crude alkaloids on the proliferation activity of HEL cells in each group were studied by the MTT method.Results Z.nitidum was extracted from 60%,70%,80%,90%,and 100%ethanol,and the extract with 60%ethanol concentration had the highest yield(11.937±0.002)%.Static and dynamic adsorption experiments showed that the adsorption capacity of the above five kinds of macroporous resins was 1∶500(extract of Z.nitidum∶macroporous resin).The crude alkaloids enriched by different macroporous resins have different effects on the proliferation activity of HEL cells.The inhibition rates(%)at a concentration of 80 μg·mL-1 of Z.nitidum were(59.62±3.46)%(XDA-5),(55.81±5.16)%(HPD 100),(59.33±1.33)%(D101),(79.63±1.02)%(HPD 722),and(83.97±0.38)%(HPD 400),respectively.HPD 400 macroporous resin-enriched crude alkaloids inhibited the proliferation of HEL cells most significantly(P<0.01).Conclusion The process of enriching the crude alkaloids of Z.nitidum using macroporous resin was simple and feasible,and the crude alkaloids enriched by HPD 400 showed significant inhibitory effects on HEL cells with good anti-leukemic activity.

Objective:To explore the distribution characteristics of memory B cells and its relationship with bone erosion in patients with rheumatoid arthritis (RA), and to further understand the mechanism of B cells in the pathogenesis of RA.Methods:B cell subsets in peripheral blood of 200 RA patients and 50 healthy individuals were detected by flow cytometry. According to the surface markers CD19, CD27 and lgD, B cells were divided into CD19 +CD27 +lgD - switched memory B cells, CD19 +CD27 +lgD + non-switched memory B cells, CD19 +CD27 -lgD - double-negative memory B cells and CD19 +CD27 -lgD + naive B cells. B cells in RA patients with various disease activity score, course of disease and treatment were analyzed. Patients were divided into four groups according to the results of joint ultrasonography, including patients without bone erosion, patients with hand bone erosion, patients with knee bone erosion and patients with hand and knee bone erosion. The relationship between the distribution of B cell subsets, autoantibodies and RA bone erosion were analyzed. Differences between the groups were analyzed by independent-samples t test, Mann-Whitney U test and χ2 test. The analysis of variance, Kruskal-Wallis analysis were used for multi-group comparison, Spearman correlation analysis was also used for correlation analysis. Results:①RA patients showed significantly decreased non-switched memory B cells [(9.5±6.7)% vs (12.1±4.7)%, t=2.46, P=0.015] and increased double negative memory B cells [(3.8±2.5)% vs(2.7±1.3)%, t=-4.74, P<0.001] in comparison to healthy individuals. The percentage of non-switched memory B cells were decreased in RA patients with moderate disease activity [(8.4±4.7 )% vs (12.4±7.5)%, t=3.13, P=0.001] and high disease activity [(7.8±7.6)% vs (12.4±7.5)%, t=3.00, P=0.003] in comparison to those in RA patients who achieved remission. Meanwhile, the na?ve B cells [(70.3±15.0)% vs (63.9±14.6)%, t=-2.15, P=0.034] were increased in RA patients with moderate disease activity. No difference was found in RA patients with different disease courses. Total B cells [(4.8±2.9)% vs (7.2±4.1)%, t=-3.24, P=0.001], non-switched memory B cells (7.6±4.3)% vs (10.0±7.1)%, t=-2.63, P=0.010) in RA patients who received prednisone treatment were decreased, while double-negative memory B cells (4.9±3.0)% vs (3.6±2.3)%, t=-2.79, P=0.006] were increased compared with those in RA patients without prednisone treatment. Non-switched memory B cells was decreased in RA patients with hand and knee erosion compared with RA patients without erosion [6.8%(2.5%, 9.5%) vs 9.7%(5.5%, 17.5%), Z=-2.12, P=0.034]. Double negative memory B cells in subgroup with keen erosion [3.3%(2.7%, 5.0%) vs 2.6%(1.9%, 3.8%), Z=-2.09, P=0.036]as well as with hand and knee erosion [3.9%(2.3%, 5.6%) vs 2.6%(1.9%, 3.8%), Z=-2.41, P=0.016] were higher than those in patients without erosion. In addition, higher serum RF level was found in subgroup RA patients with hand and knee erosion compared with subgroup of RA patients without erosion [141.0 (38.0, 874.0) U/ml vs 53.5 (10.0, 106.0)U/ml, Z=-2.07, P=0.039]. Meanwhile, the positive rate of ACPA in RA patients with bone erosion of hand was significantly higher than that of RA patients without bone erosion [81%(52/64) vs 64%(38/59), χ2=4.44, P=0.043). Conclusions:The results suggest that the increase of double negative memory B cells, the decrease of non-switched memory B cells and higher level of autoantibodies may closely relate to bone erosion of RA, which may be one of the pathogenesis of disability in RA.

【Objective】 To investigate the clinical characteristics and risk factors of systemic lupus erythematosus （SLE） combined with symptomatic knee osteonecrosis （KON）. 【Methods】 We retrospectively analyzed the clinical data of 26 cases of SLE with KON treated in the Department of Rheumatology and Immunology， The First Affiliated Hospital of Xi’an Jiaotong University， from April 2013 to December 2019. 【Results】 The age of the 26 patients （2 males and 24 females） was （35.3±9.0） years old at the diagnosis of KON， and the course of SLE was （48.7±35.1） months. The time from glucocorticoids initiation to the development of KON was （37.8±42.7） months， the maximum dosage of methylprednisolone was （197.7±290.7）mg and the cumulative dosage was （6.02±6.66）g. Six of the patients had a history of large-dose glucocorticoids impulse therapy. All of them had a history of immunosuppressant treatment. SLEDAI score was （11.23±5.46） at the onset of SLE and （4.46±4.81） at the onset of KON. The most common initial symptoms were edema and arthritis. The most common systemic damages were blood system damage and lupus nephritis. The most common immunological abnormalities were positive antinuclear antibody （25/26）， positive anti-SSA/Ro52kD antibody （16/26）， and positive anti-SmD1 antibody （15/26）. There were 4 patients with positive anticardiolipin antibody （ACA）. Bone metabolism was characterized by vitamin D3 （Vit-D3） deficiency， insufficient N-terminal osteocalcin （N-OST）， and increased β-C-terminal telopeptide of type I collagen （β-CTx）. In 9 out of the 26 patients， SLE was combined with aseptic necrosis of the femoral head. Multifocal bone necrosis （at least 3 lesions） was common （12/26）. Longer disease course and glucocorticoids using time， larger cumulative dose and ACA positive were seen in patients with multifocal bone necrosis compared with those who had one lesion site. 【Conclusion】 KON most possibly occurs 3 to 4 years after the diagnosis of SLE， which is associated with high disease activity， large hormone dose， and long duration in the treatment process. Multifocal bone necrosis is easily seen in patients with severe disease， large initial hormone dose and high cumulative dose， as well as in ACA positive patients.

【Objective】 To detect autoantibodies in Chinese systemic sclerosis (SSc) patients and analyze the relationship between clinical phenotype and autoantibodies in SSc. 【Methods】 We sequentially included 93 SSc patients. Their general information and clinical data were gathered. The differences in clinical characteristics among autoantibody negative and positive groups were analyzed statistically. 【Results】 Anti-nuclear antibodies were detected in 82 (88.2%) SSc patients. The positive rate of autoantibodies was detected in 26 cases (28.0%) of anti-Scl-70 antibody, 24 cases (25.8%) of anti-SSA/Ro-52 antibody, 19 cases (20.4%) of anti-U1-snRNP antibody, and 16 cases (17.2%) in anti-CENP-B antibody, respectively. The patients with positive anti-SSA/Ro-52 antibody had a significantly higher morbidity rate of pulmonary arterial hypertension (P=0.016). Patients with anti-Scl-70 antibody showed a higher incidence rate of digital tip ulcers or gangrene (P=0.004) and cardiac damage (P=0.014). The patients with anti-U1-snRNP antibody had a higher prevalence of pulmonary arterial hypertension (P=0.047) and Raynaud’s phenomenon (P=0.019), and showed an increased trend in the occurrence of interstitial lung disease (P=0.058). Those with anti-CENP-B antibody had a lower IgG level (P=0.049) and higher ALP (P=0.010) and γ-GT (P=0.003). The incidence of autoimmune liver disease was increased in anti-CENP-B positive patients (P=0.001). 【Conclusion】 Different autoantibodies in SSc are associated with clinical phenotype, and may contribute to the diagnosis, evaluation, and prognostic judgment of the disease.

【Objective】 To evaluate musculoskeletal ultrasound (MSUS) detected subclinical synovitis of rheumatoid arthritis (RA) with different clinical remission criteria so as to explore the clinical characteristics of subclinical synovitis. 【Methods】 Forty-six consecutive patients with RA in clinical remission [disease activity score-28 (DAS28)≤2.6] underwent clinical and MSUS examinations at baseline and 1 year follow-up. Clinical remission was defined according to the DAS28 using the erythrocyte sedimentation rate (DAS28-ESR) and C-reactive protein level (DAS28-CRP), clinical disease activity index (CDAI), simplified clinical disease activity index (SDAI), and American College of Rheumatology/European League Against Rheumatism criteria Boolean (ACR/EULAR criteria). Subclinical synovitis was assessed by MSUS. Differences between the subclinical synovitis and non-subclinical synovitis groups were analyzed. 【Results】 The percentages of patients who achieved DAS28-ESR, DAS28-CRP, CDAI, SDAI, and ACR/EULAR remission at baseline and 1 year were 97.8%, 95.6%, 67.4%, 54.3%, 52.2% and 91.3%, 93.5%, 54.3%, 50.0%, and 45.6%, respectively. Subclinical synovitis was detected in 55.5%, 54.5%, 45.2%, 40.0%, 41.6% and 45.2%, 46.5%, 40.0%, 39.1%, and 38.1% of these patients, respectively. There were 45.6% and 41.3% patients who fulfilled all the criteria, yet 38.1% and 36.8% still had evidence of subclinical synovitis at baseline and 1 year. Compared with the patients without subclinical synovitis, those with subclinical synovitis had a significantly positive rate of anti-CCP antibody and a higher disease activity score at baseline (P<0.05). 【Conclusion】 MSUS detected subclinical synovitis is common. The positive anti-CCP antibody and higher disease activity score at baseline may be related to subclinical synovitis in patients with RA in clinical remission.

Objective To evaluate the current situation of quality of life and psychological status of pediatric recipients after kidney transplantation and analyze the influencing factors. Methods Ninety-six pediatric recipients undergoing kidney transplantation were enrolled in this study. Baseline data of the recipients were collected. The quality of life was assessed by Pediatric Quality of Life Inventory 3.0 (PedsQL^TM3.0). The psychological status was evaluated by Strengths and Difficulties Questionnaire (SDQ). The influencing factors of postoperative quality of life and psychological status of pediatric kidney transplant recipients were subject to univariate and multivariate analyses. Results The total score of quality of life of pediatric kidney transplant recipients was (71±14) and (12.4±5.8) for the total difficulty score. Univariate analysis showed that gender, postoperative body mass index (BMI) and postoperative complications were the influencing factors of the total score of quality of life of pediatric kidney transplant recipients (all P < 0.05). Gender, postoperative complications and follow-up time were the influencing factors of the total difficulty score of pediatric kidney transplant recipients (all P < 0.05). Multivariate analysis demonstrated that gender, postoperative BMI, postoperative complications, dialysis type before kidney transplantation were the influencing factors of postoperative quality of life of pediatric kidney transplant recipients, whereas gender, postoperative complications and follow-up time were the influencing factors of postoperative psychological status (all P < 0.05). Conclusions The quality of life and psychological status of pediatric kidney transplant recipients are good. In clinical practice, special attention should be paid to those children who are female, with low BMI after kidney transplantation, postoperative complications and short follow-up time. Preventive interventions are recommended to further improve the quality of life of the children.

Objective:To investigate the frequency of myeloid dendritic cells (mDC) and plasmacytoid dendritic cells (pDC) in peripheral blood of patients with systemic lupus erythematosus (SLE) and their relationship with renal injury.Methods:The frequency of peripheral mDC and pDC in 102 SLE patients and 10 healthy controls were detected by flow cytometry. The quantitative data were expressed by [ M( P25, P75)]. The measurement data of the two groups with non-normal distribution was analyzed by Mann Whitney U test. The correlation between the two groups was analyzed by Spearman rank correlation analysis and multiple linear regression. Results:The frequency of pDC [14.00%(7.92%, 19.65%) vs 24.55%(19.68%, 32.90%), Z=-3.163, P<0.01] and mDC [21.25%(13.28%, 32.83%) vs 34.85%(24.58%, 41.93%), Z=-2.607, P<0.01] in the peripheral blood of 102 patients with SLE were significantly lower than those of healthy controls. The frequency of pDC [9.09%(7.31%, 17.38%) vs 24.55%(19.68%, 32.90%), Z=-3.033, P=<0.01] and mDC [9.40%(7.88%, 21.60%) vs 34.85%(24.58%, 41.93%), Z=-3.231, P<0.01] in 12 patients with newly diagnosed SLE were also significantly lower than those in healthy controls. After adjustedfor confounding factors, multivariate analysis showed that SLEDAI level was the main factor influencing the frequency of pDC ( P=0.019) and mDC ( P<0.01). In addition, pDC[8.02%(2.25%, 9.97%) vs 16.70%(11.80%, 24.60%), Z=-2.490, P=0.015] and mDC[8.80%(5.99%, 12.80%) vs 20.20%(11.20%, 42.80%), Z=-2.226, P=0.029] in patients with active LN were also significantly lower than that of patients with stable LN. The mDC frequency was positively correlated with the levels of complement C3 ( r=0.455, P<0.01) and C4 ( r= 0.289, P, P<0.01). Conclusion:The frequency of mDC and pDC in SLE patients is significantly abnormal, which is closely related to disease activity. In addition, pDC and mDC may be involved in the occurrence and development of LN.