Objective:To further improve the understanding of paroxysmal nocturnal hemoglobinuria (PNH), we retrospectively analyzed and summarized the clinical characteristics, treatment status, and survival status of patients with PNH in Zhejiang Province.Methods:This study included 289 patients with PNH who visited 20 hospitals in Zhejiang Province. Their clinical characteristics, comorbidity, laboratory test results, and medications were analyzed and summarized.Results:Among the 289 patients with PNH, 148 males and 141 females, with a median onset age of 45 (16-87) years and a peak onset age of 20-49 years (57.8% ). The median lactic dehydrogenase (LDH) level was 1 142 (604-1 925) U/L. Classified by type, 70.9% (166/234) were classical, 24.4% (57/234) were PNH/bone marrow failure (BMF), and 4.7% (11/234) were subclinical. The main clinical manifestations included fatigue or weakness (80.8%, 235/289), dizziness (73.4%, 212/289), darkened urine color (66.2%, 179/272), and jaundice (46.2%, 126/270). Common comorbidities were hemoglobinuria (58.7% ), renal dysfunction (17.6% ), and thrombosis (15.0% ). Moreover, 82.3% of the patients received glucocorticoid therapy, 70.9% required blood transfusion, 30.7% used immunosuppressive agents, 13.8% received anticoagulant therapy, and 6.3% received allogeneic hematopoietic stem cell transplantation. The 10-year overall survival (OS) rate was 84.4% (95% CI 78.0% -91.3% ) . Conclusion:Patients with PNH are more common in young and middle-aged people, with a similar incidence rate between men and women. Common clinical manifestations include fatigue, hemoglobinuria, jaundice, renal dysfunction, and recurrent thrombosis. The 10-year OS of this group is similar to reports from other centers in China.

Objective:To observe the clinical characteristics and treatment prognosis of patients with ocular toxocariasis (OT).Methods:A retrospective clinical trial. From March 2018 to September 2021, 40 eyes of 40 OT patients diagnosed by ophthalmic examination in the First Affiliated Hospital of Zhengzhou University were included in the study. All patients underwent best corrected visual acuity (BCVA) and scanning laser ophthalmoscope (SLO) examination. Color Doppler ultrasound flow imaging (CDFI), fluorescein fundus angiography (FFA) and optical coherence tomography (OCT) were performed in 25, 26 and 26 eyes, respectively. Among the 40 patients, there were 23 males (57.5%, 23/40) and 17 females (42.5%, 17/40). All patients were monocular. Thirty patients (75.0%, 30/40) were younger than 18 years old, with the mean age of (9.60±0.60) years. Ten patients (25.0%, 10/40) were great than or equal to 18 years old, with the mean age of (34.60±4.52) years. Thirty-three patients (82.5%, 33/40) lived in rural areas for a long time. There were 27 patients (67.5%, 27/40) with a history of contact with dogs and cats. In 40 eyes, peripheral granuloma (peripheral type), posterior pole granuloma (posterior pole type), vitreous opacity similar to endophthalmitis (turbid type) and hybrid type were 18(45.0%, 18/40), 11(27.5%, 11/40), 6(15.0%, 6/40) ang 5(12.5%,5/40), respectively. All patients were treated with drugs and/or surgery after definite diagnosis. There were 28 eyes of peripheral type, posterior pole type and hybrid type, 17 eyes were treated with surgery and 11 eyes with drug treatment, respectively. Five eyes with turbid type were only treated with drugs. In 40 patients, 33 patients participated in follow-up. The follow-up time after treatment was (18.78±9.44) months. The improvement of BCVA was observed. The number of eyes with different BCVA before and after treatment was compared by χ2 test or Fisher's test. Results:At the first visit, the BCVA ranged from light perception to 0.6, including 20 eyes with BCVA <0.1, 13 eyes with BCVA 0.1-0.3, and 7 eyes with BCVA >0.3. The posterior vitreous anterior limiting membrane was thickened in 24 eyes (60.0%, 24/40). There were 27 eyes (67.5%, 27/40) with lamellar vitreous opacity and 22 eyes (55.0%, 22/40) with peripheral/posterior pole granulomas. Among 25 eyes examined by CDFI, 14 eyes (56.0%, 14/25) showed characteristic stratified or diffuse opacity in vitreous body. Of the 26 eyes examined by FFA, 15 eyes (57.7%, 15/26) had "fern-like" leakage of retinal capillaries, and the lesion had a patchy non-perfused area. In 26 eyes examined by OCT, epiretinal membrane, cystoid macular edema and vitreoretinal traction were 8 (30.8%, 8/26), 5 (19.2%, 5/26) and 2 (7.7%, 2/26) eyes, respectively. At the last follow-up, compared with before treatment, the BCVA of 5 eyes with turbid type increased, and the difference was statistically significant ( P<0.05). In 28 eyes with peripheral type, posterior pole type and hybrid type, 17 eyes with surgical treatment improved BCVA, and the difference was statistically significant ( χ2=6.258, P<0.05). In 11 eyes only treated with drugs, BCVA remained unchanged, and the difference was not statistically significant ( χ2=0.594, P>0.05). Conclusions:OT patients are mostly children; retinal granulomas, gray-white hyperplastic membrane behind lens or vitreous stratified opacity are specific characteristics. OT is mainly treated by glucocorticoid drugs and vitrectomy.

Objective:To compare the safety and efficacy of the " step-up approach" versus the " step-jump approach" in treatment of infected pancreatic necrosis (IPN).Method:The clinical data of IPN patients who underwent step-up strategy or step-jump strategy treatment at the Department of Pancreatic and Biliary Surgery of the First Affiliated Hospital of Harbin Medical University from December 2018 to November 2022 were analyzed retrospectively. Propensity score matching (PSM) was done based on the nearest neighbor matching method (1: 1 ratio). After matching the baseline data (the caliper value was 0.01), a total of 62 patients with IPN were included, including 41 males and 21 females, aged (41.1±13.1) years old. Patients who were treated with the step-up strategy were included in the step-up group, while patients who were treated with the step-jump strategy were included in the step-jump group. There were 31 patients in each group after PSM, and the treatment effect of the two groups were compared.Results:Of the 62 patients with IPN, 43 received surgical intervention, and 19 were managed successfully using symptomatic anti-inflammatory treatment or percutaneous catheter drainage. The total hospitalization cost of patients in the step-jump group was significantly higher than that in the step-up group [122 000 (73 000, 179 000) yuan vs. 88 000 (46 000, 144 000) yuan, P=0.034]. The overall cure rate of IPN patients in the step-jump group was 93.5%(29/31). The 2 patients who died had type Ⅲ IPN. In the IPN patients in the step-up group were all cured, and the overall cure rate was 100%(31/31), with no death. There were no statistical differences between the two groups in the rates of death, postoperative complications, residual infection, debridement ≥2 times, and positive bacterial culture in blood or drainage fluid (all P>0.05). A total of 19.4% (12/62) patients had postoperative complications, including 4 patients with abdominal bleeding, 3 patients with new organ dysfunction, 2 patients with gastrointestinal bleeding, 2 patients with gastrointestinal fistula, and 1 patient with venous thrombosis in both lower limbs. Conclusion:Both the step-up treatment strategy and the step-jump treatment strategy were safe and effective for treatment of IPN patients.

Abstract OBJECTIVE To investigate the effect and mechanism of flavonoids from Sophora flavescens Ait. on testicular tissue damage in male mice induced by local heat stress in the scrotum. METHODS TCMSP database was used to screen the targets of flavonoids in Sophora flavescens Ait., and the bioinformatics analysis was performed on the target. The mouse model of scrotal heat stress was used and the flavonoids of Sophora flavescens Ait. was used for intervention. The sperm density and sperm aberration rate of mice in each group were measured, and the morphological changes of testicular tissue were observed. Tumor necrosis factor-α (TNF-α) and interleukin 17(IL-17) mRNA and protein levels in testicalar were detected of by q-PCR and Western blotting. Na+-K+-ATPase, Mg2+-ATPase, Ca2+-ATPase, lactate dehydrogenase(LDH), sorbitol dehydrogenase(SDH) activity, malondialdehyde (MDA), NO, TNF-α level and the content of testosterone in serum were detected in tissue homogenate. RESULTS Heat stress could lead to the decrease of sperm density and increase of aberrant sperm, the obvious thinning of testicular spermatogenic epithelium, the decrease of cell level and quantity, the significant decrease of ATPase, LDH, SDH activities, and the increase of MDA, NO content, TNF-α and IL-17 expression in testicular tissue. After the intervention with 250, 500 mg·kg-1·d-1 flavonoids of Sophora flavescens Ait., the quality of sperm and the damage of testicular tissue morphology were improved. The level of TNF-α and IL-17 in serum and testicular tissue were decreased, and the activity of ATPase, SDH and the level of testosterone were increased. CONCLUSION The mechanism of flavonoids of Sophora flavescens Ait. is through inhibiting the inflammatory factor TNF-α and IL-17 levels, improve the anti-lipid peroxidation ability and inhibite the role of NO, enhance the activity of energy enzymes in spermatogenesis, improve the level of serum testosterone, and improve the reproductive disorders caused by heat stress.

The fall armyworm (FAW), Spodoptera frugiperda, is a destructive pest native to America and has recently become an invasive insect pest in China. Because of its rapid spread and great risks in China, understanding of FAW genetic background and pesticide resistance is urgent and essential to develop effective management strategies. Here, we assembled a chromosome-level genome of a male FAW (SFynMstLFR) and compared re-sequencing results of the populations from America, Africa, and China. Strain identification of 163 individuals collected from America, Africa and China showed that both C and R strains were found in the American populations, while only C strain was found in the Chinese and African populations. Moreover, population genomics analysis showed that populations from Africa and China have close relationship with significantly genetic differentiation from American populations. Taken together, FAWs invaded into China were most likely originated from Africa. Comparative genomics analysis displayed that the cytochrome p450 gene family is extremely expanded to 425 members in FAW, of which 283 genes are specific to FAW. Treatments of Chinese populations with twenty-three pesticides showed the variant patterns of transcriptome profiles, and several detoxification genes such as AOX, UGT and GST specially responded to the pesticides. These findings will be useful in developing effective strategies for management of FAW in China and other invaded areas.
Animals ; China ; Genomics ; Humans ; Male ; Pesticides ; Spodoptera/genetics* ; Transcriptome

Different fragments of SARS-CoV-2 nucleocapsid (N) protein were expressed and purified, and a fluorescence immunochromatography method for detection of SARS-CoV-2 total antibody was established. The effect of different protein fragments on the performance of the method was evaluated. The N protein sequence was analyzed by bioinformatics technology, expressed in prokaryotic cell and purified by metal ion affinity chromatography column. Different N protein fragments were prepared for comparison. EDC reaction was used to label fluorescence microsphere on the synthesized antigen to construct sandwich fluorescence chromatography antibody detection assay, and the performance was systemically evaluated. Among the 4 prepared N protein fragments, the full-length N protein (N419) was selected as the optimized coating antigen, N412 with 0.5 mol/L NaCl was used as the optimal combination; deleting 91-120 amino acids from the N-terminal of N412 reduced non-specific signal by 87.5%. the linear range of detection was 0.312-80 U/L, the limit of detection was 0.165 U/L, and the accuracy was more than 95%. A fluorescence immunochromatographic detection method for analysis of SARS-CoV-2 total antibody was established by pairing N protein fragments. The detection result achieved 98% concordance with the commercially available Guangzhou Wanfu test strip, which is expected to be used as a supplementary approach for detection of SARS-CoV-2. The assay could also provide experimental reference for improving the performance of COVID-19 antibody detection reagents.
Antibodies, Viral ; COVID-19 ; Chromatography, Affinity ; Fluorescent Antibody Technique ; Humans ; Microspheres ; SARS-CoV-2 ; Sensitivity and Specificity

Objective:To explore the clinical application and long-term safety of hydroxychloroquine sulfate (HCQ) in the treatment of rheumatic diseases.Methods:A multi-center cross-sectional study was conducted between August 2017 and August 2018 in a random sample of eleven medical institutions of rheumatology and immunology in China. Patients who took HCQ for more than 3 months were enrolled into this study. The cumulative dose and long-term side effects of HCQ were recorded. The changes of laboratory indexes before and after treatment with HCQ were analyzed. Categorical variables were presented with counts and proportions, and evaluated by Chi-square test. Continuous parametric data were presented as Mean±standard deviation, and evaluated by Student's t test or Mann-Whitney U test. P-values less than 0.05 were considered statistically significant. Results:A total of 886 patients with rheumatic diseases were enrolled into this study, including 505 cases with systemic lupus erythematosus (57.0%), 210 cases with rheumatoid arthritis (23.7%), 80 cases with Sj?gren's syndrome (9.0%), 57 cases with undifferentiated connective tissue disease (6.4%), 12 cases of systemic vasculitis (1.4%), 10 cases of mixed connective tissue disease (1.1%), 7 cases of myositis (0.8%) and 5 cases with systemic sclerosis (0.6%). The most common long-term side effects of HCQ was skin or mucous lesions (12.4%) and vision problems (8.0%). Other adverse reactions included problems of digestive system (3.0%), nervous system (2.1%), musculoskeletal system (1.1%) and cardiovascular system (0.9%). 140 cases (15.8%) had stopped taking HCQ during the treatment. More than half of them decided to stop taking medicine by themselves. Fifty-four patients (6.1%) stopped using HCQ due to side effects while 24 of them took it again, and another 12 patients (1.4%) stopped the drug due to remission of illness. Patients were divided into three groups according to the cumulative dose of HCQ: less than 500 g, 500-1 000 g and more than 1 000 g respectively. There was significant difference in the incidence of long-term side effects among the three groups ( χ2=6.382, P=0.041). The last group (more than 1 000 g) suffered the highest incidence of long-term adverse reactions (37.1%). No severe adverse drug reactions were observed in this study. Conclusion:Hydroxychloroquine is widely used in the treatment of rheumatic diseases. The incidence of long-term side effects is 20.4%, is 6.1% lead to drug withdrawal, which are especially related to the cumulative doses. It should be adjusted properly according to the clinical application.

Objective To analyze the prognostic impact of Ikaros family zinc finger 1(IKZF1)mutation on adult Philadelphia chromosome (Ph1) positive acute lymphoblastic leukemia (ALL) patients.Methods IKZF1 mutation was detected in 63 adult Phi positive ALL patients at diagnosis using capillary electrophoresis.Recruited patients were treated in our center and other three hospitals in Ningbo from January 2014 to January 2017.Clinical data were collected and retrospectively analyzed.Results Thirty-nine (61.9％) patients were positive IKZF1 mutation in this cohort.The white blood cell (WBC) count in IKZF1 mutation group was significantly higher than that of mutation negative group [(64.6±11.3)× 109/L vs.(33.7±5.6)×109/L,P＜0.05].Patients with WBC count over 30×109/L accounted for 56.4％ in IKZF1 mutation group.Complete remission (CR) rate in the IKZF1 mutation group was also lower than that of negative group after induction chemotherapy (64.1％ vs.75.0％,P＞0.05).IKZF1 was a negative prognostic factor but not independent factor for survival by univariate and multivariate analyses.Patients were divided into chemotherapy and allogeneic transplantation groups.The 3-year overall survival (OS) rate and 3-year leukemia-free survival (LFS) rate in IKZF1 mutation group were significantly lower than those of negative group in both transplantation group (42.3％ vs.59.3％;31.2％ vs.50.0％;respectively,both P＜0.05) and chemotherapy group (24.8％ vs.40.0％;19.0％ vs.34.3％;respectively,both P＜0.05).Conclusion IKZF1 mutation is a poor prognostic factor for adult Ph1 positive ALL patients.

Objective To evaluate the prognostic value of preoperative neutrophil-to lymphocyte ratio (NLR) in invasive breast carcinomas of no special type.Methods we retrospectively analyzed the clinical and pathological data of all breast cancer patients at Shanghai Huangpu District Cental Hospital from Jan.2012 to Dec.2012.The optimal cutoff value was obtained by ROC.The difference among variables was calculated by chi-square test.DFS and OS were estimated using Kaplan-Meier method.Cox analysis was performed to analyze clinical parameters for their prognostic relevance.Results A total of 493 were eligible.The optimal cutoff value of NLR was 2.057.The sensitivity was 0.767 and specifity was 0.327 at the optimal cutoff point.Univariate analysis showed that patients with NLR higher than 2.057 had significantly lower DFS (P=-0.001) than patients with NLR equal or lower than 2.057,while the overall survival rate was not statistically different (P=0.131).The Cox proportional multivariate hazard model revealed that higher NLR was independently related with poor DFS with hazard ratio 5.649(95％ confidence interval 3.128-10.201,P=0.002).Conclusions Preoperative NLR is an independent predictor of DFS in breast cancer patients.Further validation and a feasibility study are required before it can be considered for clinical use.

Objective To investigate the clinical efficacy of free flap transplantation in repairing the Gustilo type ⅢB and ⅢC fractures of tibia and fibula combined with soft tissue defects.Methods A retrospective case series study was conducted on the clinical data of 46 patients who had Gustilo type ⅢB and ⅢC fractures of tibia and fibula with soft tissue defects admitted from June 2013 to January 2017.There were 34 males and 12 females,aged 1-67 years (mean,39 years).The wound defect areas ranged from 6 cm × 20 cm to 7 cm × 38 cm.According to the Gustilo fracture classification,there were 31 cases of type ⅢB and 15 cases of type ⅢC.According to the AO fracture typing,there were five cases of type A,23 type B,and 18 type C.All patients were repaired with free flap transplantation,among which 40 patients were treated with anterolateral thigh flap and six with latissimus dorsi flap.The areas of anterolateral thigh flap ranged from 6 cm × 13 cm to 14 cm ×32 cm,and those of the latissimus dorsi flap from 6 cm × 22 cm to 7 cm × 40 cm.Efficacy was evaluated by flap survival rate,complications,fracture healing time,lower limb function scoring system (LEFS),and skin flap function.Results All limbs were salvaged successfully.One case of total flap necrosis and eight cases of postoperative crisis occurred.After active exploration and treatment,three cases were seen distal local necrosis,and the total survival rate was 91％.Infection at the donor site was found in two cases.The complication incidence rate was 4％.All patients were followed up for 7-42 months,with an average of 19 months.The fracture healing time averaged 43.5 weeks,and the LEFS score averaged 54 points.According to the seven indexes of flap function,the results were excellent in 1 1 cases,good in 29 cases,fair in four cases,and poor in two cases,with an excellent and good rate of 87％.Conclusion Free flap transplantation can achieve satisfactory efficacy in treating Gustilo type ⅢB and ⅢC of tibia and fibula combined with soft tissue defects,with high limb salvage rate and good function recovery.