OBJECTIVE: To retrospectively analyze the clinical phenotypes and genetic variants in two Chinese pedigrees affected with Hereditary hypofibrinemia (IFD) and explore their molecular pathogenesis. METHODS: Two probands and their pedigree members were admitted to the First Affiliated Hospital of Wenzhou Medical University on March 30, 2021 and May 27, 2021, respectively. Clinical phenotypes of the probands were collected, and blood clotting indexes of the probands and their pedigree members were determined. Variants of the FGA, FGB and FGG genes were analyzed by Sanger sequencing, and candidate variants were verified by sequence comparison. Bioinformatic software was used to analyze the conservation of the amino acids and pathogenicity of the proteins. Alteration in protein structure and intermolecular force before and after the variant was analyzed by simulating the protein model. RESULTS: Proband 1, a 18-year-old male, had significantly low plasma fibrinogen activity (Fg:C) and plasma fibrinogen antigen (Fg:Ag), respectively at 0.80 g/L and 1.00 g/L. Proband 2, a 43-year-old male, had slightly low Fg:C and Fg:Ag at 1.35 g/L and 1.30 g/L, respectively. The Fg:C and Fg:Ag of proband 1's father, proband 2's father and son were also below the normal level. Genetic testing showed that proband 1 had harbored a heterozygous missense variant of c.688T>G (p.Phe230Val) in exon 7 of the FGG gene, which was inherited from his father. Proband 2, his father and son all had harbored a heterozygous variant of c.2516A>C (p.Asn839Thr) in exon 6 of the FGA gene. Homology analysis showed that the Phe230 and Asn839 residues were highly conserved among homologous species. Bioinformatic analysis predicted that both p.Phe230Val and p.Asn839Thr were pathogenic variants. CONCLUSION Analysis of protein simulation model showed that the p.Asn839Thr variant has changed the hydrogen bo`nd between the amino acids, thus affecting the stability of the protein structure. The heterozygous missense variants of p.Phe230Val and p.Asn839Thr probably underlay the IFD in the two pedigrees.
Humans ; Male ; Amino Acids ; East Asian People ; Exons ; Pedigree ; Retrospective Studies ; Afibrinogenemia/genetics* ; Mutation, Missense ; Fibrinogen/genetics*

Objective:To discuss the classification and treatment of ureteroileal anastomotic stricture (UAS) after radical cystectomy.Methods:The clinical data of 34 patients with UAS after radical cystectomy in the Department of Urology of Tongji Hospital from January 2017 to January 2022 were reviewed and analyzed. There were 25 males and 9 females. The average age was (66.3±7.7)years, including 2 cases of bilateral hydronephrosis and 32 cases of unilateral hydronephrosis. The average time of UAS was detected (14.7±6.5)months after radical cystectomy. There were 32 patients of unilateral hydronephrosis and 2 patients of bilateral hydronephrosis. Two patients had undergone nephrostomy in an external hospital. Three patients had elevated leukocytes in blood routine. Among them, two patients had fever. First, nephrostomy on the hydronephrosis side and anti-infection treatment were performed. After routine blood tests showed that the white blood cells were normal and antibiotics were stopped for 24 hours without fever, the operation was performed. 34 patients had preoperative hydronephrosis of (2.7±0.6) cm. Of the 34 cases in this group, 5 cases were injected with methylene blue through a preoperative nephrostomy tube, and 29 were injected with methylene blue through the renal pelvis using an 18G puncture needle under ultrasound guidance. Using a ureteroscope to observe in the ileal bladder, methylene blue was seen in 4 cases. Methylene blue was used to guide the search for the stenosis and a super smooth guide wire was inserted. Among them, 3 cases were dilated with a 5 mm ureteral dilation balloon catheter, 1 case was dilated with a F14 ureteral access sheath, and then a F6 single J stent was inserted. Methylene blue was not seen in the ileal conduit in 30 cases, of which 16 cases were treated with a flexible ureteroscope through the nephrostomy to locate the stenosis, incised with a 30 W holmium laser. 9 cases were treated with 5 mm ureteral dilation balloon catheter, and 7 cases were treated with a F14 ureteral access sheath, and then an F6 single J stent was inserted. 14 cases were unable to find the stenosis by antegrade method. According to the operation time and patient's condition, it was decided to perform immediate or second stage dual endoscope surgery. Through the nephrostomy, a flexible ureteroscope was used to enter the stenosis along the super slide guide wire. A rigid ureteroscope was used to observe the stenosis through the ileal conduit, and the stenosis was found. The stenosis was found in 10 cases and incised with a 30 W holmium laser. 8 cases were treated with 5 mm ureteral dilation balloon catheter, and 2 cases were treated with a F14 ureteral access sheath, and then an F6 single J stent was inserted. 4 cases were still unable to accurately locate the stenosis using the dual endoscope surgery(one case was bilateral stenosis, and one side was relieved), and continued indwelling nephrostomy. The definition of successful removal of stricture in this study is that an F6 single J stent can be inserted into the ureter.Results:UAS were classified into four types based on the severity of the intraoperative findings: Type Ⅰ, the narrow ureteral lumen is more than 50% narrower than the normal ureteral lumen, but methylene blue can pass through in strands; Type Ⅱ, needle like stricture of the ureteral lumen, allowing only methylene blue filaments to pass through; Type Ⅲ, membranous atresia of the ureter, with a narrow segment of 1 to 3 mm in length, and methylene blue cannot pass through; Type Ⅳ, long segment stenosis. Of the 34 cases in this group, 4 cases were type Ⅰ, and the stenosis was dredged by retrograde method; 16 cases were type Ⅱ, and the stenotic segments were dredged by antegrade method; 10 cases were type Ⅲ, and the stenosis was dredged by the dual endoscope surgery; Four cases were of type Ⅳ (one case was of bilateral UAS, one side was of type Ⅲ, and the other side was of type Ⅳ, which was classified as type Ⅳ). The stenotic segment could not be solved through the above methods. Among the 34 patients, 30 patients were successfully relieved of anastomotic obstruction, and 1 patient with bilateral obstruction was unilaterally relieved of anastomotic obstruction. In the other 3 cases, because the stenosis segment was too long, 2 cases were changed to nephrostomy, and 1 case was changed to open surgery, with a success rate of 88.2%. UAS was classified into 4 types based on the severity of UAS seen during surgery. No serious complications occurred during and after the operation. During the follow-up of 6-24 months, the imaging evaluation of 4 patients showed that hydronephrosis was aggravated, with an average increase in creatinine of (32.5±10.9)μmol/L, requiring replacement of a single J tube. The imaging evaluation of the remaining 26 patients showed that the postoperative hydronephrosis was 0.9 ± 0.6 cm less than the preoperative hydronephrosis 2.6 ± 0.6 cm, with a statistically significant difference ( P<0.01). The quality of life score at 3 months after surgery was (1.9±0.6), which was significantly improved compared to the preoperative indwelling nephrostomy period (5.2±0.7), with a statistically significant difference ( P<0.01) Conclusions:The treatment of UAS after radical cystectomy with retrograde, antegrade, and dual endoscope surgery has a high success rate, which can help some patients avoid the inconvenience of indwelling external drainage tubes and the risk of open surgery. Choosing an appropriate surgical method can achieve the goal of treating UAS with minimal trauma.

Pulmonary hypertension (PH) is a life-threatening disease characterized by pulmonary vascular remodeling, in which hyperproliferation of pulmonary artery smooth muscle cells (PASMCs) plays an important role. The cysteine 674 (C674) in the sarcoplasmic/endoplasmic reticulum Ca²⁺ ATPase 2 (SERCA2) is the critical redox regulatory cysteine to regulate SERCA2 activity. Heterozygous SERCA2 C674S knock-in mice (SKI), where one copy of C674 was substituted by serine to represent partial C674 oxidative inactivation, developed significant pulmonary vascular remodeling resembling human PH, and their right ventricular systolic pressure modestly increased with age. In PASMCs, substitution of C674 activated inositol requiring enzyme 1 alpha (IRE1α) and spliced X-box binding protein 1 (XBP1s) pathway, accelerated cell cycle and cell proliferation, which reversed by IRE1α/XBP1s pathway inhibitor 4μ8C. In addition, suppressing the IRE1α/XBP1s pathway prevented pulmonary vascular remodeling caused by substitution of C674. Similar to SERCA2a, SERCA2b is also important to restrict the proliferation of PASMCs. Our study articulates the causal effect of C674 oxidative inactivation on the development of pulmonary vascular remodeling and PH, emphasizing the importance of C674 in restricting PASMC proliferation to maintain pulmonary vascular homeostasis. Moreover, the IRE1α/XBP1s pathway and SERCA2 might be potential targets for PH therapy.

The clinical application of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of hepatocellular carcinoma (HCC) patients. With the widespread applica-tion of ICIs in HCC, the management of immune-related adverse events (irAE) gained more and more attention. However, the complicated disease characteristics and various combination therapies in HCC throw out challenges to irAE management. Therefore, the editorial board of the 'Chinese expert consensus on the management of immune-related adverse events of hepatocellular carcinoma treated with immune checkpoint inhibitors (2021 edition)' organizes multidisciplinary experts to discuss and formulate this consensus. The consensus focuses on issues related to HCC irAE manage-ment, and puts forward suggestions, in order to improve standardized and safety clinical medication, so as to maximize the benefits of immunotherapy for patients.

Prostate cancer is a common malignant tumor in elderly men in western countries. In the past decade, the incidence and mortality of prostate cancer in China have shown a rapid upward trend. With the changes of social economy, life style and the progress of diagnosis and treatment, the epidemiological characteristics of prostate cancer are constantly changing. Therefore, understanding the epidemiological characteristics of prostate cancer is helpful to provide scientific basis for prevention and treatment of this malignant tumor. This article reviews the research progress on the morbidity, mortality, epidemiological distribution, survival and risk factors of prostate cancer in China.

Objective To investigate the predictive value of D-dimer for early neurological deteriora- tion (END) in patients with acute ischemic stroke. Methods Patients with acute ischemic stroke admitted to the Department of Neurology, the Second People ' s Hospital of Shenzhen between January 2015 and December 2017 were enrolled retrospectively. END was defined as an increase ≥2 in the National Institutes of Health Stroke Scale (NIHSS) score or an increase ≥1 in the motor function score within 7 days after admission compared with the baseline score. Demographics, baseline clinical data, and primary treatment options during hospitalization were compared between the END group and the non-END groups. Multivariate logistic regression analysis was used to determine the independent risk factors for END. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of D-dimer for END. Results A total of 625 patients were enrolled in the study, including 40 in the END group (including 3 deaths) and 585 in the non-END group. The mean hospital stay, international normalized ratio, D-dimer, uric acid, NIHSS score and modified Rankin Scale (mRS) score at admission, and the proportion of patients with complete anterior circulation infarction, large atherosclerotic stroke, and pulmonary infection were significantly higher than those in the non-END group (all P < 0. 05). There was no significant difference in the proportion of patients receiving thrombolysis, antiplatelet,anticoagulation, and statins between the two groups. ROC curve analysis showed that the area under the curve of D-dimer predicting END was 0. 810 (95％ confidence interval [CI] 0. 736-0. 884; P < 0. 001); the optimal cut-off value was 2. 35 mg/L, and the sensitivity and specificity were 54. 74％ and 96. 13％ respectively. Multivariate logistic regression analysis showed that large atherosclerotic stroke (odds ratio [OR] 1. 115, 95％ CI 1. 005-1. 390; P = 0. 003 ), D-dimer ≥2. 35 mg/L (OR 1. 055,95％ CI 1. 012-1. 150; P = 0. 001 ), NIHSS score at admission (OR 1. 191, 95％ CI 1. 006-1. 410; P <0. 001), mRS score > 1 at admission (OR 1. 755, 95％ CI 1. 139-3. 656; P = 0. 037 ), and pulmonary infection (OR 2. 598, 95％ CI 1. 132-3. 081; P = 0. 012) were the independent risk factors for END in patients with acute ischemic stroke. Conclusion D-dimer ≥2. 35 mg/L at admission has higher predictive value for END in patients with acute ischemic stroke.

Objective Exploration of the application value of the third-generation dual source CT low tube voltage (70 kVp) scanning combined with advanced modeling iterative reconstruction (ADMIRE) technique in children with adenoid examination. Methods CT scans were performed in patients with clinically suspected adenoid hypertrophy. They were divided into two groups according to the time of treatment. Group A (40 cases) : low tube voltage (70 kVp) scan, reference tube current 163 mAs, reconstruction with ADMIER, Intensity 3; Group B (40 cases) : conventional 100 kVp, reference tube current 163 mAs, conventional (filtered back-projection, FBP) reconstruction;rest of the scanning parameters remained unchanged. The subjective scores and objective quality indicators of the images (CT value, image noise, signal noise ratio (SNR) , contrast noise ratio (CNR)) and radiation dose of the two groups were compared. Results The difference of radiation dose between group A and group B was statistically significant (P < 0.05). The radiation dose of group A was lower than that of group B by 77.58％.Compared with group B, the image noise of group A increased by 0.002％; the SNR decreased by 0.01％; CNR increased by 0.03％; there was no significant difference in objective quality evaluation index and subjective score between two groups in the image quality (P> 0.05). Conclusion The third-generation dual-source CT low-tube voltage (70 kVp) combined with ADMIRE reconstruction technique for children with adenoid scan can effectively reduce the radiation dose while ensuring image quality.

Objective To compare the therapeutic efficacies of fire-needle acupuncture and Halometasone cream in treating sub-acute and chronic eczema. Method Totally 114 patients were divided into a treatment group and a control group. The treatment group was intervened by using fire-needle acupuncture, and the control group was by Halometasone cream. Itchy score and Eczema Area and Severity Index (EASI) were used for comparison before and after intervention. Result There were significant differences in comparing the markedly-effective rate and total effective rate between the fire-needle acupuncture group and the Halometasone control group according to the itchy score (P＜0.01). There were no significant differences in comparing the markedly-effective rate and total effective rate between the two groups according to EASI (P>0.05). Conclusion Fire-needle acupuncture is superior to Halometasone cream for acute and chronic eczema in relieving itch, action time and effect-sustaining duration.

Objective The prevention effect of CAUTI by long-acting antibacterial material JUC was evaluated by meta analysis.Methods China digital hospital library full-text database,Chinese biomedical literature CD database,China hosptial knowledge database (CHKD) in China national knowledge internet (CNKI),VIP information Chinese science and technology periodical database were retrieved to fully collect the literature from 1995 to 2012 regarding JUC's prevention effect of CAUTI.The inclusion and exclusion standard of literature was made,and the effect index was made from the literature.Two researchers collected the literatures independently,and the included literatures were meta-analyzed by Review Manager 4.2 software,and the risk difference of infection rate and 95％ CI were calculated in both the treatment group and control group.Those literatures which could not be meta-analyzed were performed descriptive analysis to evaluate the efficacy of JUC objectively.Results 20 related articles were retrieved,including 1 multicenter randomized control study,18 monocentric randomized control studies,and 1 uncontrolled study.3172 cases were included with 1526 cases in control group (usual care) and 1646 cases in treatment group (usual care with JUC).The difference between the two groups is significant (RD =-0.15,95％ CI:-0.18 ～-0.13,P ＜ 0.05).Conclusions Long-acting antibacterial material JUC can diminish the incidence of CAUTI significantly.

ObjectiveTo study the correlation between the etiology and clinical features of erythroderma.MethodsThe clinical data on 182 patients with erythroderma were retrospectively collected and analyzed.ResultsThe male-to-female ratio was 2.8 ∶ 1 and the average age at onset was 58.6 ± 14.6 years.Of the 182 cases,135 (74.2％) were due to pre-existing dermatoses,14 (7.7％) to drug reaction,8 (4.4％) to malignancies,while 25(13.7％) had no obvious precipitating factors.The most frequent triggering factor was systemic consumption of drugs(52 patients,28.6％ ),and glucocorticosteroid was the most prevalent causative drug.Seventy-six patients were followed up,recurrence was observed in 14 patients but not in 58 patients,and 5 patients died,2 patients with idiopathic erythroderma were finally diagnosed with mycosis fungoides (MF)after multiple skin biopsies.ConclusionsPre-existing dermatoses are the most frequent cause of erythroderma.Idiopathic erythroderma is liable to relapse,possibly associated with malignancies,and should be closely followed up.