Purpose::Vibrio vulnificus ( V. Vulnificus) infection is characterized by rapid onset, aggressive progression, and challenging treatment. Bacterial resistance poses a significant challenge for clinical anti-infection treatment and is thus the subject of research. Enhancing host infection tolerance represents a novel infection prevention strategy to improve patient survival. Our team initially identified cytochrome P4501A1 (CYP1A1) as an important target owing to its negative modulation of the body's infection tolerance. This study explored the superior effects of the CYP1A1 inhibitor bergamottin compared to antibiotic combination therapy on the survival of mice infected with multidrug-resistant V. Vulnificus and the protection of their vital organs. Methods::An increasing concentration gradient method was used to induce multidrug-resistant V. Vulnificus development. We established a lethal infection model in C57BL/6J male mice and evaluated the effect of bergamottin on mouse survival. A mild infection model was established in C57BL/6J male mice, and the serum levels of creatinine, urea nitrogen, aspartate aminotransferase, and alanine aminotransferase were determined using enzyme-linked immunosorbent assay to evaluate the effect of bergamottin on liver and kidney function. The morphological changes induced in the presence of bergamottin in mouse organs were evaluated by hematoxylin and eosin staining of liver and kidney tissues. The bacterial growth curve and organ load determination were used to evaluate whether bergamottin has a direct antibacterial effect on multidrug-resistant V. Vulnificus. Quantification of inflammatory factors in serum by enzyme-linked immunosorbent assay and the expression levels of inflammatory factors in liver and kidney tissues by real-time quantitative polymerase chain reaction were performed to evaluate the effect of bergamottin on inflammatory factor levels. Western blot analysis of IκBα, phosphorylated IκBα, p65, and phosphorylated p65 protein expression in liver and kidney tissues and in human hepatocellular carcinomas-2 and human kidney-2 cell lines was used to evaluate the effect of bergamottin on the nuclear factor kappa-B signaling pathway. One-way ANOVA and Kaplan-Meier analysis were used for statistical analysis. Results::In mice infected with multidrug-resistant V. Vulnificus, bergamottin prolonged survival ( p = 0.014), reduced the serum creatinine ( p = 0.002), urea nitrogen ( p = 0.030), aspartate aminotransferase ( p = 0.029), and alanine aminotransferase ( p = 0.003) levels, and protected the cellular morphology of liver and kidney tissues. Bergamottin inhibited interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α expression in serum (IL-1β: p = 0.010, IL-6: p = 0.029, TNF-α: p = 0.025) and inhibited the protein expression of the inflammatory factors IL-1β, IL-6, TNF-α in liver (IL-1β: p = 0.010, IL-6: p = 0.011, TNF-α: p = 0.037) and kidney (IL-1β: p = 0.016, IL-6: p = 0.011, TNF-α: p = 0.008) tissues. Bergamottin did not affect the proliferation of multidrug-resistant V. Vulnificus or the bacterial load in the mouse peritoneal lavage fluid ( p = 0.225), liver ( p = 0.186), or kidney ( p = 0.637). Conclusion::Bergamottin enhances the tolerance of mice to multidrug-resistant V. Vulnificus infection. This study can serve as a reference and guide the development of novel clinical treatment strategies for V. Vulnificus.

Background: and Purpose Intravenous tenecteplase (TNK) efficacy has not been well demonstrated in acute ischemic stroke (AIS) beyond 4.5 hours after onset. This study aimed to determine the effect of intravenous TNK for AIS within 4.5 to 24 hours of onset. Methods: In this pilot trial, eligible AIS patients with diffusion-weighted imaging (DWI)-fluid attenuated inversion recovery (FLAIR) mismatch were randomly allocated to intravenous TNK (0.25 mg/kg) or standard care within 4.5–24 hours of onset. The primary endpoint was excellent functional outcome at 90 days (modified Rankin Scale [mRS] score of 0–1). The primary safety endpoint was symptomatic intracranial hemorrhage (sICH). Results: Of the randomly assigned 80 patients, the primary endpoint occurred in 52.5% (21/40) of TNK group and 50.0% (20/40) of control group, with no significant difference (unadjusted odds ratio, 1.11; 95% confidence interval 0.46–2.66; P=0.82). More early neurological improvement occurred in TNK group than in control group (11 vs. 3, P=0.03), but no significant differences were found in other secondary endpoints, such as mRS 0–2 at 90 days, shift analysis of mRS at 90 days, and change in National Institutes of Health Stroke Scale score at 24 hours and 7 days. There were no cases of sICH in this trial; however, asymptomatic intracranial hemorrhage occurred in 3 of the 40 patients (7.5%) in the TNK group. Conclusion This phase 2, randomized, multicenter study suggests that intravenous TNK within 4.5–24 hours of onset may be safe and feasible in AIS patients with a DWI-FLAIR mismatch.

OBJECTIVE: To explore the clinical effect of Kirschner wire intramedullary fixation in the treatment of both-bone forearm fractures in children of high altitude area. METHODS: From August 2020 to December 2021, 19 children were treated with Kirschner wire intramedullary fixation including 11 males and 8 females, aged from 4 to 13 years old with an average of (8.16±2.71) years old. The course of disease was 1 to 10 days, with a mean of (4.11±2.51) d. First, close reduction was performed. If the reduction was unsuccessful, limited open reduction was performed, followed by Kirschner wire intramedullary fixation of the radius and ulna. The fracture healing was evaluated by X-ray after operation, and the curative effect was evaluated by Anderson forearm function score standard. RESULTS: The wound healed well after operation, 2 cases had clinical manifestations of needle tail irritation after operation, and the symptoms disappeared after removing the internal fixation. The average follow-up time was(7.68±3.50) months (3 to 14 months). X-ray showed that all fracture healing in follow-up, Anderson forearm function score showed excellent in 16 cases, good in 2 cases and fair in 1 case at the final follow-up. CONCLUSION Children with fractures in plateau areas often have delayed medical treatment, lack of medical conditions and insufficient compliance. Based on these characteristics, Kirschner wire intramedullary fixation for the treatment of children's double forearm fractures has the advantages of small injury and rapid recovery. It is a kind of operation method that can be popularized.
Male ; Female ; Humans ; Child ; Child, Preschool ; Adolescent ; Bone Wires ; Forearm ; Altitude ; Treatment Outcome ; Fractures, Bone/surgery* ; Fracture Fixation, Internal/methods* ; Radius Fractures/surgery* ; Fracture Fixation, Intramedullary/methods*

Objective: To analyse the clinical and gene characteristics of GRIN2B gene related neurological developmental disorders in children. Methods: The data of 11 children with GRIN2B gene related neurological developmental disorders from November 2016 to February 2021 were collected from Department of Neurology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health and analyzed retrospectively. The clinical features, electroencephalogram (EEG), brain imaging and gene testing results were summarized. Results: Among 11 children 6 were boys and 5 were girls. Two of them were diagnosed with developmental and epileptic encephalopathy. The ages of seizures onset were 3 months and 9 months, respectively. Seizure types included epileptic spasm, tonic seizures, tonic spasm and focal seizures, and 1 patient also had startle attacks. EEG showed interictal multifocal epileptiform discharges. Both of them were added with more than 2 anti-seizure drugs, which were partially effective but could not control. They had moderate to severe mental and motor retardation. The phenotype of 9 cases was developmental delay or intellectual disability without epilepsy, age of visit 1 year to 6 year and 4 months of whom 5 cases had severe developmental delay, 2 cases had moderate and 2 cases had mild delay. Multi-focal epileptiform discharges were observed in 3 cases, no abnormality was found in 3 cases, and the remaining 3 cases did not undergo EEG examination. Ten cases underwent brain magnetic resonance imaging (MRI), 6 cases had nonspecific abnormalities and 4 cases were normal. Nine GRIN2B gene heterozygous variants were detected by next-generation sequencing in these 11 patients, 8 cases had missense variants and 1 case had nonsense variant, all of which were de novo and 3 of which were novel. Missense variants were found in 10 patients, among them 6 cases had severe developmental delay, 3 cases had moderate and 1 case had mild developmental delay, but the patient with nonsense variant showed mild developmental delay without epilepsy. Conclusions: The phenotypes of GRIN2B gene related neurological developmental disorders in children are diverse, ranging from mild intellectual impairment without epilepsy to severe epileptic encephalopathy. Patients with epileptic phenotype usually have an onset age of infancy, and spasm and focal seizures are the most common seizure types. And the epiletice episodes are refractory. Most of the patients with missense variants had severe developmental delay.
Child ; Developmental Disabilities/genetics* ; Electroencephalography ; Epilepsy/genetics* ; Female ; Humans ; Infant ; Male ; Retrospective Studies ; Seizures/genetics* ; Spasms, Infantile/genetics*

China/epidemiology* ; Coronary Angiography ; Coronary Artery Disease/diagnosis* ; Humans ; Registries ; Risk Assessment ; Risk Factors

BACKGROUND: Albuvirtide is a once-weekly injectable human immunodeficiency virus (HIV)-1 fusion inhibitor. We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs. METHODS: We carried out a 48-week, randomized, controlled, open-label non-inferiority trial at 12 sites in China. Adults on the World Health Organization (WHO)-recommended first-line treatment for >6 months with a plasma viral load >1000 copies/mL were enrolled and randomly assigned (1:1) to receive albuvirtide (once weekly) plus ritonavir-boosted lopinavir (ABT group) or the WHO-recommended second-line treatment (NRTI group). The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks. Non-inferiority was prespecified with a margin of 12%. RESULTS: At the time of analysis, week 24 data were available for 83 and 92 patients, and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups, respectively. At 48 weeks, 80.4% of patients in the ABT group and 66.0% of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL, meeting the criteria for non-inferiority. For the per-protocol population, the superiority of albuvirtide over NRTI was demonstrated. The frequency of grade 3 to 4 adverse events was similar in the two groups; the most common adverse events were diarrhea, upper respiratory tract infections, and grade 3 to 4 increases in triglyceride concentration. Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group. CONCLUSIONS: The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug. This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02369965; https://www.clinicaltrials.gov.Chinese Clinical Trial Registry No. ChiCTR-TRC-14004276; http://www.chictr.org.cn/enindex.aspx.
Adult ; Anti-HIV Agents/adverse effects* ; Antiretroviral Therapy, Highly Active ; China ; Drug Therapy, Combination ; HIV Infections/drug therapy* ; HIV-1 ; Humans ; Maleimides ; Peptides ; Ritonavir/therapeutic use* ; Treatment Outcome ; Viral Load

ObjectiveThe development of new endovascular imaging techniques has optimized surgical treatment strategies. In this paper, we investigated the effect of rotational atherectomy (RA) guided by intravascular ultrasound (IVUS) on long-term postoperative follow-ups.MethodsClinical data of 211 patients who underwent RA in the Department of Cardiology, Nanjing Drum Tower Hospital from November 2011 to December 2018 were retrospectively analyzed, and they were divided into IVUS Group (116 patients) and Non-IVUS Group (95 patients) according to whether they underwent the guidance of intravascular ultrasound or not. Basic information of all patients, coronary artery lesions and details of operation and other clinical data were collected. The long-term prognosis of the patients was collected and compared by telephone or outpatient follow-ups.ResultsThe head diameter, average stent diameter and total hospitalization expenses of the IVUS Group were significantly higher than those of the Non-IVUS Group, and the differences were statistically significant [(1.53±0.19) mm vs (1.46±0.14) mm, P=0.001; (3.09±0.48) mm vs (2.87±0.30) mm, P<0.001; (57,300±18,300) yuan vs (49,300±16,600) yuan, P=0.001]. The all-cause case fatality rate and cardiogenic case fatality rate of the IVUS Group were lower than those of the Non-IVUS Group (7.5% vs 16.7%, P=0.048; 1.9% vs 11.9%, P=0.005); There were no significant differences in the incidence of long-term major adverse cardiovascular events (MACE), myocardial infarction, target vessel revascularization and non-fatal stroke between the two groups (P>0.05). Multivariate COX regression analysis showed that the cardiogenic mortality was significantly reduced in the IVUS Group (HR=0.10, 95%CI: 0.02~0.63, P=0.014), but there was no statistically significant difference between the two groups in the incidence of all-cause death and long-term MACE (P>0.05).ConclusionCompared with the Non-IVUS Group, IVUS-guided RA can significantly reduce the incidence of long-term cardiogenic death and total hospitalization expenses.

OBJECTIVE: To investigate whether ginsenoside-Rb1 (Gs-Rb1) improves the CoCl-induced autophagy of cardiomyocytes via upregulation of adenosine 5'-monophosphate-activated protein kinase (AMPK) pathway. METHODS: Ventricles from 1- to 3-day-old Wistar rats were sequentially digested, separated and incubated in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum for 3 days followed by synchronization. Neonatal rat cardiomyocytes were randomly divided into 7 groups: control group (normal level oxygen), hypoxia group (500 μmol/L CoCl), Gs-Rb1 group (200 μmol/L Gs-Rb1 + 500 μmol/L CoCl), Ara A group (500 μmol/L Ara A + 500 μmol/L CoCl), Ara A+ Gs-Rb1 group (500 μmol/L Ara A + 200 μmol/L Gs-Rb1 + 500 μmol/L CoCl), AICAR group [1 mmol/L 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) + 500 μmol/L CoCl], and AICAR+Gs-Rb1 group (1 mmol/L AICAR + 200 μmol/L Gs-Rb1 + 500 μmol/L CoCl). Cells were treated for 12 h and cell viability was determined by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and cardiac troponin I (cTnI) levels were detected by enzyme-linked immunosorbent assay (ELISA). AMPK activity was assessed by 2',7'-dichlorofluorescein diacetate (DCFH-DA) ELISA assay. The protein expressions of Atg4B, Atg5, Atg6, Atg7, microtubule-associated protein 1A/1B-light chain 3 (LC3), P62, and active-cathepsin B were measured by Western blot. RESULTS: Gs-Rb1 significantly improved the cell viability of hypoxia cardiomyocytes (P<0.01). However, the viability of hypoxia-treated cardiomyocytes was significantly inhibited by Ara A (P<0.01). Gs-Rb1 increased the AMPK activity of hypoxia-treated cardiomyocytes. The AMPK activity of hypoxia-treated cadiomyocytes was inhibited by Ara A (P<0.01) and was not affected by AICAR =0.983). Gs-Rb1 up-regulated Atg4B, Atg5, Beclin-1, Atg7, LC3B II, the LC3B II/I ratio and cathepsin B activity of hypoxia cardiomyocytes (P<0.05), each of these protein levels was significantly enhanced by Ara A (all P<0.01), but was not affected by AICAR (all P>0.05). Gs-Rb1 significantly down-regulated P62 levels of hypoxic cardiomyocytes (P<0.05). The P62 levels of hypoxic cardiomyocytes were inhibited by Ara A (P<0.05) and were not affected by AICAR (P=0.871). CONCLUSION Gs-Rb1 may improve the viability of hypoxia cardiomyocytes by ameliorating cell autophagy via the upregulation of AMPK pathway.

Objective: To investigate the effect of pituitrin-water separation on hemoglobin and ovarian function in laparoscopic ovarian chocolate cyst removal. Methods: From February 2018 to February 2019, 82 patients with ovarian chocolate cyst removed by laparoscopy were selected from the Second Affiliated Hospital of Wenzhou Medical University.They were randomly divided into observation group and control group according to the digital table, with 41 cases in each group.The control group underwent traditional laparoscopic tear-and-tear ovarian cyst removal, while the observation group underwent pituitrin-water separation.The changes of perioperative indicators, the decrease of hemoglobin (Hb) before and after operation, the positive rate of normal ovarian tissue on cyst wall and the number of normal follicles attached to cyst wall, the changes of serum hormone levels before and after operation were compared between the two groups. Results: The amount of bleeding during operation in the observation group [(58.97±8.74)mL] was less than that in the control group [(118.93±24.21)mL], and the operation time in the observation group[(57.46±8.27)min] was shorter than that in the control group [(87.38±10.19)min] , the differences were ststistically significant between the two group(t=14.916, 14.598, all P<0.05). There was no statistically significant difference in the time of anal exhaust between the two groups (P>0.05). The decrease of Hb in the observation group [(0.71±0.16)g/L] was lower than that in the control group [(1.27±0.35)g/L] (t=9.318, P<0.05). The positive rate of normal ovarian tissue on cyst wall in the observation group (21.95%) was lower than that in the control group (56.10%), the number of normal follicles attached to the cyst wall in the observation group (2.65±0.49) was less than that in the control group (4.86±1.24) , the differences were ststistically significant between the two group(χ²=10.045, t=10.613, all P<0.05). The serum level of E₂ [(398.21±17.84)pmol/L] in the observation group was higher than that in the control group [(367.83±15.21)pmol/L], while FSH [(6.72±0.28)mIU/mL] and LH [(5.23±0.38)mIU/mL] levels in the observation group were lower than those in the control group [(7.19±0.35)mIU/mL and (5.69±0.31)mIU/mL], the differences were ststistically significant between the two group (t=8.298, 6.714, 6.006, all P<0.05). Conclusion The method of pituitrin-water separation is effective in laparoscopic ovarian chocolate cyst removal, which can reduce the injury during operation, has little effect on hemoglobin and improve the ovarian reserve function of patients.

BACKGROUND: Heterotopic ossification (HO) is a known complication of hip arthroscopy. We investigated incidence of HO after hip arthroscopy and determined whether revision for HO improved outcome. METHODS: A retrospective study was conducted on 242 patients (140 men and 102 women, mean age: 36.2 ± 9.5 years) who underwent hip arthroscopy for femoroacetabular impingement (FAI) between January 2016 and January 2018. The average follow-up period was 22.88 ± 11.74 months (range: 11-34 months). Thirteen (5.37%) cases of HO (six men and seven women, five left hips and eight right hips; mean age: 37.5 ± 4.7 years) were observed. Among them, four cases with HO with obvious pain symptoms and persistent non-remission underwent revision surgery to remove HO. Monthly follow-up was conducted. Visual analog scale (VAS), modified Harris Hip Score (mHHS), and non-Arthritis Hip Score (NAHS) were evaluated and compared between HO and non-HO patients. Independent sample t test, Mann-Whitney U test and the Chi-square test were used for inter-group comparisons. HO degree was evaluated using Brooker classification. Symptoms and function were evaluated before and after revision. RESULTS: A total of 242 patients were involved in this study. Thirteen cases (5.4%) had imaging evidence of HO. Nine (9/13) were classified as Brooker stage I, three (3/13) Brooker stage II, and one (1/13) Brooker stage III. HO was detected by ultrasonography as early as 3 weeks after operation. After primary surgery, the mHHS of the HO group and non-HO group increased by 13.00 (8.50, 25.50) and 24.00 (14.00, 34.50) points (Z = -1.80, P = 0.08), NAHS increased by 18.00 (9.50, 31.50) and 26.00 (13.50, 36.00) points (Z = -1.34, P = 0.18), and VAS decreased by 3.00 (2.00, 4.00) and 4.00 (3.00, 4.50) points (Z = -1.55, P = 0.12). Average follow-up time after revision was 9.00 ± 2.94 months; mHHS increased by 34.75 points (t = -55.23, P < 0.01) and NAHS by 28.75 points (t = -6.03, P < 0.01), and VAS decreased by 4 points (t = 9.80, P < 0.01). HO and non-HO patients were similar for demographic and surgical data, and clinical and functional scores. CONCLUSION HO incidence after arthroscopic treatment of FAI is similar to that found in previous studies. Most HO have no effect on clinical symptoms. Patients who undergo revision HO resection show improvement in pain and joint function.
Adult ; Arthroscopy ; adverse effects ; Female ; Femoracetabular Impingement ; surgery ; Hip Joint ; pathology ; surgery ; Humans ; Male ; Middle Aged ; Ossification, Heterotopic ; diagnosis ; etiology ; Retrospective Studies ; Treatment Outcome