Objective:To investigate the correlation between complement C3 and urine protein level and proteinuria remission status in patients with primary membranous nephropathy (PMN), and better guide individualized clinical treatment.Methods:It was a single-center retrospective study. The clinical data of PMN patients who underwent renal biopsy in the First Affiliated Hospital of Nanjing Medical University from January 2017 to June 2022 were collected. Patients with 24 h urinary protein ≥ 3.5 g were followed up after receiving standard treatment, and the last outpatient or inpatient review was used as the end point of follow-up. 24 h urine protein was collected to evaluate the remission status of proteinuria. Kaplan-Meier method was used to analyze the correlation between serum and renal complements and proteinuria remission. Cox regression analysis method was used to analyze the correlation between serum C3 level and renal tissue C3 deposition and proteinuria remission.Results:This study included 507 PMN patients with 312 (61.54%) males, aged 54 (43, 64) years old. Compared with 24 h urinary protein < 3.5 g group, proportion of males ( χ2=22.479, P<0.001), age ( Z=-2.521, P=0.012), systolic blood pressure ( Z=-4.148, P<0.001), diastolic blood pressure ( Z=-4.084, P<0.001), serum anti-phospholipase A2 receptor (PLA2R) antibody titer ( Z=-7.019, P<0.001), total cholesterol ( Z=-8.796, P<0.001), triglyceride ( Z=-6.158, P<0.001), low density lipoprotein cholesterol ( Z=-8.716, P<0.001), serum creatinine ( Z=-7.368, P<0.001), serum C3 ( Z=-3.663, P<0.001), serum C4 ( Z=-6.560, P<0.001), proportion of glucocorticoid use ( χ2=116.417, P<0.001) and proportion of immunosuppressant use ( χ2=53.839, P<0.001) were all higher, while serum albumin ( Z=12.518, P<0.001), estimated glomerular filtration rate ( Z=6.345, P<0.001) and serum IgG ( Z=7.321, P<0.001) were all lower in 24 h urinary protein ≥3.5 g group. There were 268 patients included in the follow-up cohort with baseline 24 h urinary protein of 7.15 (5.14, 10.24) g, serum anti-PLA2R antibody titer of 61.44 (14.35, 193.24) RU/ml, serum C3 of 1.005 (0.864, 1.150) g/L, and serum C4 of 0.260 (0.214, 0.317) g/L. Kaplan-Meier survival curve showed that the incomplete remission rate of proteinuria in serum C3 > 1.005 g/L group was lower than that in serum C3 ≤ 1.005 g/L group (log-rank χ2=4.757, P=0.029). There was no significant difference in the incomplete remission rate of proteinuria between serum C4 ≤ 0.260 g/L group and serum C4 > 0.260 g/L group (log-rank χ2=3.543, P=0.060). Renal C1q (log-rank χ2=0.167, P=0.683) and C4 (log-rank χ2=1.927, P=0.165) deposition had no significant effects on proteinuria remission in PMN patients. The incomplete remission rate of proteinuria in patients with renal C3 deposition was higher than that in patients without renal C3 deposition (log-rank χ2=7.018, P=0.008). Univariate Cox regression analysis showed that serum C3 level and C3 deposition in renal tissues were influencing factors of incomplete remission of proteinuria (both P<0.05), while adjusting for gender, age, mean arterial pressure, serum anti-PLA2R antibody, serum albumin and 24 h urinary protein, serum C3 ≤ 1.005 g/L ( HR=1.374, 95% CI 1.021-1.849, P=0.036), C3 deposition in renal tissues ( HR=1.949, 95% CI 1.098-3.460, P=0.023), and serum C3 ≤ 1.005 g/L combined with C3 deposition in renal tissues ( HR=1.472, 95% CI 1.093-1.983, P=0.011) were independent influencing factors of incomplete remission of proteinuria. Conclusions:The serum C3 level and C3 deposition in renal tissues are closely related to urinary protein level and proteinuria remission status in PMN patients. The patients with higher urinary protein have higher serum C3. For patients with massive proteinuria, serum C3 ≤ 1.005 g/L, C3 deposition in renal tissues, serum C3 ≤ 1.005 g/L combined with C3 deposition in renal tissues are independent risk factors of incomplete remission of proteinuria.

Objective:To investigate the clinical features, diagnosis and treatment of oblique vaginal septum syndrome (OVSS).Methods:The clinical data of 80 patients with OVSS admitted to The Second Hospital of Hebei Medical University from July 2005 to July 2023 were retrospectively analyzed. According to the classification system of OVSS proposed by Female Genital Anomalies Study Group, Chinese Obstetricians and Gynecologists Association in 2021, the patients were divided into four groups. The clinical manifestations, accompanied urinary system abnormalities, diagnosis and treatment methods and treatment outcomes were observed.Results:According to the above classification system, among the 80 patients with OVSS, 35 patients (44%, 35/80) were categorized as type Ⅰ, 33 patients (41%, 33/80) were categorized as type Ⅱ, 2 patients (3%, 2/80) were categorized as type Ⅲ and 10 patients (13%, 10/80) were categorized as type Ⅳ. The main onset symptom of patients was periodic abdominal pain (70%, 56/80), vaginal bleeding (20%, 16/80), dysuria or fecal impaction (15%, 12/80), vaginal mucopurulent discharge (10%, 8/80). The morbidity of combined urinary system abnormalities was 88% (70/80), and the most common urinary system abnormality was ipsilateral renal agenesis (81%, 65/80). Bilateral kidneys were normal in 13% (10/80) patients, and 6% (5/80) were combined with other urinary system abnormalities. A total of 74 patients underwent vaginal oblique septectomy or septum excision. Five of the 10 patients with type Ⅳ underwent hysterectomy on the cervical atresia side, 4 patients received hysteroscopy combined with cervicoplasty+oblique septotomy or septum excision, and one patient selected delayed menstruation. Two patients underwent laparoscopic resection of the dysplasia kidney and ectopic ureter which opening to the vagina. Eleven patients with endometriosis cyst, hydrosalpinx or empyema underwent laparoscopic surgery.Conclusions:The main symptom of type Ⅰ and Ⅳ patients is abdominal pain, while the main symptom of type Ⅱ and Ⅲ patients is bleeding. Magnetic resonance imaging (MRI) has advantages in the evaluation of complex OVSS, and MRI is recommended before operation to exclude other axial reproductive tract dysplasia and complex urinary system dysplasia. If there is leakage of urine, vaginal discharge or complex deformity, it is necessary to multidisciplinary discussion and formulate a reasonable surgical plan. The first treatment is related to the prognosis of patients especially children, and should be highly valued.

Although significant progress has been made in the development of novel targeted drugs for the treatment of acute myeloid leukemia(AML)in recent years,chemotherapy still remains the mainstay of treatment and the overall survival is poor in most patients.Here,we demonstrated the antileukemia activity of a novel small molecular compound NL101,which is formed through the modification on bendamustine with a suberanilohydroxamic acid(SAHA)radical.NL101 suppresses the proliferation of myeloid malignancy cells and primary AML cells.It induces DNA damage and caspase 3-mediated apoptosis.A genome-wide clustered regularly interspaced short palindromic repeats(CRISPR)library screen revealed that phosphatase and tensin homologous(PTEN)gene is critical for the regulation of cell survival upon NL101 treatment.The knockout or inhibition of PTEN significantly reduced NL101-induced apoptosis in AML and myelodysplastic syndrome(MDS)cells,accompanied by the activation of protein kinase B(AKT)signaling pathway.The inhibition of mammalian target of rapamycin(mTOR)by rapamycin enhanced the sensitivity of AML cells to NL101-induced cell death.These findings uncover PTEN protein expression as a major determinant of chemosensitivity to NL101 and provide a novel strategy to treat AML with the combination of NL101 and rapamycin.

Objective:To investigate the role of protein phosphatase 4 catalytic subunit (PP4C) in regulating hepatitis B virus X protein (HBx) levels and its effects on the biological functions of HBx, thus to provide a potential therapeutic targets for hepatitis B virus (HBV)-related hepatocellular carcinoma.Methods:In vivo and in vitro interactions between HBx and PP4C were analyzed by co-immunoprecipitation (Co-IP) and GST pull-down assay. Recombinant plasmids of PP4C and HBx were co-transfected with Lipofectamine 3000 reagents into hepatoma cells to detect the protein levels of HBx by Western blot. The half-life of HBx in the transfected cells treated with cycloheximide (CHX) were detected. The phosphorylation assay was used to evaluate the effects of PP4C on HBx phosphorylation. CCK8 assay, wound healing assay and Matrigel invasion chamber assay were used to analyze the effects of PP4C on the biological functions of HBx. Results:PP4C interacted with HBx in vivo and in vitro. PP4C overexpression significantly increased the protein level and stability of HBx and the phosphorylation assay confirmed that PP4C overexpression decreased the serine phosphorylation of HBx in hepatoma cells. PP4C overexpression enhanced the migration and invasion of hepatoma cells, but had no significant effects on the proliferation. Conclusions:The interactions between HBx and PP4C promoted the stability of HBx and ultimately enhanced the migration and invasion of hepatoma cells, and the mechanisms might be related to the decrease of HBx serine phosphorylation by PP4C. This study provided a theoretical basis for further investigation of the pathogenic mechanisms of HBx, and targeting PP4C and HBx interaction might provide insights for developing novel treatment for HBV-related hepatocellular carcinoma.

Phytochemical investigation on the methanolic extract of Mastic by using various chromatographic techniques led to the isolation of 9 compounds. Based on the analysis of spectroscopic data(NMR and MS) and/or comparisons with the data reported in the literature, their structures were elucidated as 3β,8α,13-trihydroxypolypoda-14-methoxy-14-methyl-17,21-diene(1), 4-hydroxymyrtenal(2),3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1, 2-diol(3), 2-oxo-Δ~3-4,5,5-trimethylcyclopentynyl acidic acid(4),(1S,2R,3R,5R)-6,6-dimethyl-4-methylidenebicyclo[3.1.1]-heptane-2,3-diol(5),(4R)-1-methyl-4-(1-hydroxyisopropyl)cyclohexene-6-one(6), 6,6-dimethyl-4-hydroxy[3.1.1]hept-2-ene-2-carboxylic acid(7), 6,6-dimethyl[3.1.1]hept-2-ene-2-carboxylic acid(8), 6,6-dimethyl-4-oxobicyclo[3.1.1]hept-2-ene-2-carboxylic acid(9). Compound 1 is a new compound and 2-9 were isolated from this species for the first time. In vitro cytotoxicity assay results indicated that compounds 1, 6 and 7 showed significant inhibitory effects against human lung cancer cell line A549 with IC_(50) values of 20.4, 25.1 and 22.5 μmoL·L~(-1).
Humans ; Magnetic Resonance Spectroscopy ; Phytochemicals ; Pistacia

Retrospective analysis of 18 cases of occupational acute 1, 2-dichloroethane (1, 2-DCE) poisoning. The results showed that all patients have the main manifestations such as dizziness, headache, unresponsiveness and other symptoms of nervous system damage; Brain CT showed varying degrees of diffuse white matter lesions. Brain MRI showed extensive involvement of white matter in both cerebral hemispheres. Affected white matter area presented low intensity on T1WI, hyperintensity on T2WI and T2-Flair; Lumbar puncture examination of cerebrospinal fluid (CSF) pressure (262.5±48.39) mm H₂O; After treatment, the required time for CSF pressure to restore was (161.56±75.27) days (50-280) days. Summary, Occupational acute 1, 2-DCE poisoning caused by toxic encephalopathy can be manifested as persistent abnormalities in CSF pressure, and the CSF pressure drops slowly during treatment; Early head CT and lumbar puncture examination will be helpful for early detection of intracranial pressure in toxic encephalopathy caused by acute 1, 2-DCE poisoning. Dynamic monitoring of CSF provides guidance for acute 1, 2-DCE poisoning with a long time of treatment and various types of dehydrating agents.

Objective: To investigate the efficacy and safety of Posaconazole (Posa) in prophylaxis and salvage treatment of invasive fungal infections (IFI) during neutropenia in pediatric patients with leukemia. Methods: A total of 18 pediatric patients (55 case-time) with leukemia in neutropenia stage receiving Posa treatment from December 2015 to August 2017 in Zhujiang Hospital of Southern Medical University, were analyzed retrospectively.Taking one induction chematherapy or one consolidation chemotherapy stage receiving Posa treatment was defined as 1 case-time. Results: Out of 18 participants, 13 cases were patients with acute myeloid leukemia (AML) and 5 cases were patients with acute lymphocytic leukemia (ALL), including 36 males and 19 females.Median age of the participants was 7 years, ranged from 10 months to 14 years.Out of 55 case times, 45 of them were of primary prevention and the neutropenia periods ranged from 4 to 46 days, with the median of 15 days, and 93.33% of them were prevented from fungal infection.However, 3 of the 45 cases had sudden fungal infections and the Voriconazole was an effective treatment, and no one died.Six cases in this study experienced secondary prevention, and no patient experienced reinfection.The neutropenia terms of the 6 cases ranged from 10 to 17 days, with the median of 14 days.Four patients who suffered from Voriconazole and/or Carbophenol therapy failure received Posa as a rescue therapy and the response rate was 100%.None of patients had Posa intolerance due to severe adverse reaction and no Posa treatment-related grade Ⅱ toxic effects occurred. Conclusions Posa is an effective and safe therapy for pediatric patients with leukemia and IFI, and available for long-time usage.Serious adverse reaction is rare.

Objective To investigate the expression levels of IFN-γ, IL-4, IL-6 in the plasma of HBV chronic patients.To acknowledge the correlation between the immune function of T-cell with chronic hepatitis B virus.Methods The expression levels of IFN-γ, IL-4, IL-6 in the plasma were determined by ELISA in 42 cases of chronic hepatitis B (CHB group), 30 cases of cirrhosis (LC group), 30 cases of primary liver cancer (HCC group) and 30 cases of health control (NC group).Combine with the load of HBV DNA, HBeAg and ALT, the expression levels of IFN-γ, IL-4, IL-6 were re-analysed.Results The expression levels of IFN-γ, IL-4 and IL-6 in the researched groups were statistically significantly different.The expression levels of IFN-γ, IL-4, IL-6 in CHB, LC and HCC groups were higher than NC group with significance.The expression level of IL-4 in the CHB group was higher than LC and HCC groups with significance.The expression level of IL-6 in the HCC group was higher than CHB and LC groups with significance.Compared with the control group, the ratio of IFN-γ/IL-4 in CHB, LC and HCC groups were decreased with significance.There was significantly positive correlation between the expression level of IL-4 with the load of HBV DNA (r=0.757, P＜0.001).The expression level of IFN-γhad negative correlation between the load of HBV DNA (r=-0.786, P＜0.001) with the level of ALT (r=-0.713, P＜0.001) with significance.There was no significant correlation between HBeAg with the cytokines in the serum of patients with chronic HBV.Conclusion The results showed the immune function of T-cell play important role in chronic HBV patients.That would provide a good basis on CHB treatment.The expression levels of IL-6 were higher in HCC group with significance, which provided the direction for the deep study of liver cancer.

Bone morphogenetic protein-2 (BMP-2) and basic fibroblast growth factor (bFGF) are two important signaling molecules for natural bone repair that are widely applied in the field of bone tissue engineering. BMP-2 accelerates the maturation and mineralization of osteoblasts, and bFGF exhibits significant effects on the promotion of cell division and angiogenesis. The osteogenesis mechanism of BMP-2 differs from that of bFGF, leading to a potentially complementary role between the two proteins. The use of a suitable dose of bFGF in combination with BMP-2 in bone tissue engineering synergistically promotes the formation of new bone and exhibits a better repair effect than either single growth factor. However, the suitable dose range of BMP-2 and bFGF in combination should be further clarified. The mechanism of the synergism and antagonism between BMP-2 and bFGF must be further delineated, and a drug delivery system that better simulates the growth factor release pattern during natural bone repair remains to be designed.

Ablation Techniques ; adverse effects ; methods ; Humans ; Lung Neoplasms ; diagnostic imaging ; radiotherapy ; surgery ; Postoperative Complications ; prevention & control ; therapy ; Radio Waves ; therapeutic use ; Radiotherapy, Image-Guided ; adverse effects ; methods ; Treatment Outcome