Long-segment lichen sclerosus (LS) urethral stricture is a challenge for urologists. Limited data are available for surgeons to make a surgical decision between Kulkarni and Asopa urethroplasty. In this retrospective study, we investigated the outcomes of these two procedures in patients with LS urethral stricture. Between January 2015 and December 2020, 77 patients with LS urethral stricture underwent Kulkarni and Asopa procedures for urethroplasty in the Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine (Shanghai, China). Of the 77 patients, 42 (54.5%) underwent the Asopa procedure and 35 (45.5%) underwent the Kulkarni procedure. The overall complication rate was 34.2% in the Kulkarni group and 19.0% in the Asopa group, and no difference was observed ( P = 0.105). Among the complications, no statistical difference was observed in the incidence of urethral stricture recurrence ( P = 0.724) or glans dehiscence ( P = 0.246) except for postoperative meatus stenosis ( P = 0.020). However, the recurrence-free survival rate between the two procedures was significantly different ( P = 0.016). Cox survival analysis showed that antiplatelet/anticoagulant therapy use ( P = 0.020), diabetes ( P = 0.003), current/former smoking ( P = 0.019), coronary heart disease ( P < 0.001), and stricture length ( P = 0.028) may lead to a higher hazard ratio of complications. Even so, these two techniques can still provide acceptable results with their own advantages in the surgical treatment of LS urethral strictures. The surgical alternative should be considered comprehensively according to the patient characteristics and surgeon preferences. Moreover, our results showed that antiplatelet/anticoagulant therapy use, diabetes, coronary heart disease, current/former smoking, and stricture length may be contributing factors of complications. Therefore, patients with LS are advised to undergo early interventions for better therapeutic effects.
Male ; Humans ; Urethral Stricture/etiology* ; Retrospective Studies ; Constriction, Pathologic/surgery* ; Lichen Sclerosus et Atrophicus/surgery* ; Treatment Outcome ; Urologic Surgical Procedures, Male/methods* ; China ; Urethra/surgery* ; Postoperative Complications/etiology* ; Mouth Mucosa ; Diabetes Mellitus/etiology* ; Anticoagulants ; Coronary Disease

OBJECTIVE: To investigate a family with congenital dysfibrinogenemia, and analyze the risk of hemorrhage and thrombosis and blood transfusion strategies. METHODS: Prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT) of the proband and her family members were detected by automatic coagulometer, fibrinogen (Fg) activity and antigen were detected by Clauss method and PT algorithm respectively. Meanwhile, thromboelastometry was analyzed for proband and her family members. Then, peripheral blood samples of the proband and her family members were collected, and all exons of FGA, FGB and FGG and their flanks were amplified by PCR and sequenced to search for gene mutations. RESULTS: The proband had normal APTT and PT, slightly prolonged TT, reduced level of Fg activity (Clauss method). The Fg of the proband's aunt, son and daughter all decreased to varying degrees. The results of thromboelastogram indicated that Fg function of the proband and her family members (except her son) was basically normal. Gene analysis showed that there were 6233 G/A (p.AαArg35His) heterozygous mutations in exon 2 of FGA gene in the proband, her children and aunt. In addition, 2 polymorphic loci were found in the family, they were FGA gene g.9308A/G (p.AαThr331Ala) and FGB gene g.12628G/A (p.BβArg478Iys) polymorphism, respectively. The proband was injected with 10 units of cryoprecipitate 2 hours before delivery to prevent bleeding, and no obvious bleeding occurred during and after delivery. CONCLUSION Heterozygous mutation of 6233G/A (p.AαArg35His) of FGA gene is the biogenetic basis of the disease in this family with congenital dysfibrinogenemia.
Humans ; Child ; Female ; Fibrinogen/genetics* ; Pedigree ; Afibrinogenemia/genetics* ; Mutation ; Blood Transfusion

Humans ; Child ; Neurofibromatosis 1/drug therapy* ; Benzimidazoles/therapeutic use*

Krüppel-like transcription factor 2 (KLF2) plays a key regulatory role in endothelial inflammation, thrombosis, angiogenesis and macrophage inflammation and polarization, and up-regulation of KLF2 expression has the potential to prevent and treatment atherosclerosis. In this study, trichostatin C (TSC) was obtained from the secondary metabolites of rice fermentation of Streptomyces sp. CPCC 203909 as a KLF2 up-regulator by using a high throughput screening model based on a KLF2 promoter luciferase reporter assay. TSC significantly inhibited the adhesion of tumor necrosis factor-α (TNFα) induced monocytes (THP-1) to human umbilical vein endothelial cells (HUVECs). Western blot results showed that TSC decreased TNFα induced the protein expression increase of vascular cell adhesion molecule-1 (VCAM-1), and thereby inhibited endothelial inflammation. The results of histone deacetylase (HDAC) overexpression and molecular docking experiments showed that TSC upregulated the expression of KLF2 by inhibiting subtypes of HDAC 4/5/7. In conclusion, this study suggests that TSC up-regulates the expression of KLF2 through inhibiting HDAC 4/5/7 and thus inhibits TNFα induced endothelial inflammation, and it has the potential to prevent and treat atherosclerosis.

AIM: To investigate the effects of primary acquired nasolacrimal duct obstruction(PANDO)on the tear film and ocular surface using LipiView ocular surface interferometer and Keratograph 5M anterior segment analyzer.METHODS: A self-controlled clinical trials. A total of 40 patients diagnosed with unilateral PANDO for at least 6mo who were admitted to our department from September 2021 to March 2022 were enrolled in the study, and the healthy eyes of the patients were assessed as control group. The LipiView ocular surface interferometer and Keratograph 5M anterior segment analyzer were used to measure the changes in related parameters of the tear film and ocular surface in both eyes.RESULTS: The non-invasive tear meniscus height(NITMH), stimulated NITMH, loss rate of upper meibomian gland, nasal and temporal ciliary redness index, temporal conjunctival redness index of the affected eyes were higher than healthy eyes(P<0.05), but there were no statistical differences in the non-invasive break-up time(NIBUT), loss rate of lower meibomian gland, nasal conjunctival redness index, dry eye grading, blink responses, partial blink rate and lipid layer thickness(LLT)between the both eyes(P>0.05).CONCLUSION: PANDO may lead to the aggravation of ocular surface inflammation and the loss of upper meibomian gland, and damage the ocular surface of patients. Attention should be paid to the early treatment of PANDO.

OBJECTIVE: To investigate the effect of celastrol on the proliferation and apoptosis of human multiple myeloma (MM) cell lines, reveal the relationship between IRAK4/ERK/p38 signaling pathway and celastrol regulating the proliferation and apoptosis of H929 and ARP-1 cells, and explore whether celastrol combined with bortezomib has synergistic effect. METHODS: CCK-8 method was used to detect the viability of MM cell lines H929 and ARP-1 treated by different concentrations of celastrol, bortezomib, and their combination, and the synergistic effect was determined by Kim's formula. The apoptosis rate of H929 cells and necrosis rate of ARP-1 were detected by Annexin V/PI method. The expression of key proteins and apoptosis proteins in IRAK4/ERK/p38 signaling pathway were detected by Western blot. RESULTS: Celastrol could significantly inhibit the proliferation of H929 and ARP-1 cells (r=0.9018, r=0.9244) and induce apoptosis in a time-dependent manner. Compared with the control group, celastrol could significantly up-regulate the expression of PARP and cleaved caspase-3 while down-regulate the expression of p-IRAK4, p-ERK, and p-p38 in H929 and ARP-1 cells. Celastrol and bortezomib alone inhibited the proliferation of H929 and ARP-1 cells. Compared with celastrol and bortezomib alone, their combination had lower cell survival rate and higher apoptosis rate (P<0.05). CONCLUSION Celastrol can inhibit the proliferation and promote the apoptosis of H929 and ARP-1 cells, which may be related to inhibiting the phosphorylation of IRAK4 and blocking the activation of IRAK4/ERK/p38 signaling pathway. Celastrol combined with bortezomib has synergistic effect, which can more effectively inhibit the proliferation and induce apoptosis of H929 and ARP-1 cells.
Apoptosis ; Bortezomib/pharmacology* ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Interleukin-1 Receptor-Associated Kinases ; Multiple Myeloma ; Pentacyclic Triterpenes ; Signal Transduction

OBJECTIVE: Through analysis of ABO blood group gene typing technology, to assist in the identification of difficult clinical serological specimens. METHODS: A total of 10 forwardreverse typing ambiguous samples were collected from January 2021 to August 2021 in our hospital.ABO genotypes were analysed by gene sequencing. RESULTS: The genotypes of 10 ABO ambiguous blood group samples were A102/BW11, A102/BW12, O02/O02, A102/B303, A102/B101, BW11/O02, B101/O04, BW11/O01, BW11/O01, A101/O02, respectively. The genotype results of 6 cases was consistent with the serological phenotype, and the serological phenotype of 4 cases were different from the geno sequencing. CONCLUSION ABO blood groups genotyping technology combined with serological typing can be used for accurate typing of ambiguous blood group, and better ensure the safety of blood transfusion.
ABO Blood-Group System/genetics* ; Alleles ; Blood Grouping and Crossmatching ; Exons ; Genotype ; Phenotype

Objective:To evaluate the clinical effect of anterior clinoid process grinding in the treatment of ophthalmic / superior clinoid process aneurysms and sellar tumors.Methods:The clinical data of 16 patients who underwent anterior clinoid process grinding in Sanbo Brain Hospital, Capital Medical University from January 2015 to July 2021 were analyzed retrospectively. There were 1 patient with recurrent craniopharyngioma, 1 patient with recurrent pituitary adenoma, 13 patients with aneurysms, and 1 patient with suprasellar granulosa cell tumor combined with ophthalmic aneurysm of right internal carotid artery. The Modified Rankin Scale (mRS) score was used to evaluate the situation at discharge and in the medium-and-long term.Results:Sixteen patients underwent anterior clinoidprocess grinding. At discharge and the latest follow-up, the mRS scores of the patients were 0-2. A total of 15 aneurysms were treated, and there were no symptoms of visual loss or visual field defect after operation. No cerebrospinal fluid leakage occurred in all patients.Conclusions:The grinding of anterior clinoid process can effectively and fully stretch the optic nerve and internal carotid artery, and can observe the tumor neck at the lower end of pituitary stalk and the ocular segment/superior clinoid process of internal carotid artery under direct vision. It is one of the important auxiliary methods for the treatment of sellar lesions.

OBJECTIVE: To observe the changes of serum metabolites in patients with multiple myeloma (MM) by metabonomics, and explore the potential biomarkers for diagnosis, prognosis, and progression of MM. METHODS: Serum samples were collected from 26 patients with MM and 50 healthy controls. The data detected by liquid chromatography-mass spectrometry (LC-MS) was input into SIMCA-14.0 software for multivariate statistical analysis. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to analyze the changes of metabolites. RESULTS: The metabolic change of uric acid and trans-vaccenic acid in serum samples of MM patients was 9.39 times and 2.77 times of these in healthy people, respectively, which were significantly higher than those of healthy people, and the difference was statistically significant(P<0.01). CONCLUSION Uric acid and trans-vaccenic acid are expected to be important metabolic indicators for the diagnosis, prognosis, and efficacy evaluation of MM, thus providing some clues for the pathogenesis of MM.
Biomarkers ; Chromatography, Liquid ; Discriminant Analysis ; Humans ; Mass Spectrometry ; Metabolomics ; Multiple Myeloma

Osteoprotegerin (OPG), secreted by osteoblasts, is a marker of bone turnover. OPG can inhibit osteoclastic differentiation by binding receptor activator of nuclear factor-κB ligand (RANKL). In this study, we found that rutaecarpine (RUT) had the up-regulating OPG activity, and it could significantly increase OPG protein levels in both mouse embryonic osteogenic precursor MC3T3-E1 and human osteosarcoma U-2OS cells. Osteoblastogenic differentiation calcified nodules staining results showed that RUT significantly promoted the osteogenic differentiation of MC3T3-E1 cells. Osteoclastic differentiation tartrate resistant acid phosphatase (TRAP) staining results showed that RUT obviously inhibited the osteoclast differentiation of mouse macrophages RAW264.7 induced by RANKL. In vivo studies showed that low-dose RUT group (5 mg·kg^-1·day^-1) and high-dose RUT group (45 mg·kg^-1·day^-1) treatments for 3 months significantly increased bone density in ovariectomized (OVX) rats; calcein double labeling experiment and toluidine blue staining results indicated that low-dose RUT group promoted bone formation and decreased bone loss in vivo; immunohistochemistry results showed that low-dose RUT group increased the expression of OPG in rat femur. All animal procedures were performed in accordance with the regulations of the Institutional Animal Care and Use Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences. In summary, this study demonstrated that RUT could up-regulate OPG expression and had promoting osteoblastic differentiation and inhibiting osteoclastic differentiation effects in vitro and in vivo.