The Isolation and Structure Elucidation of Spirotetronate Lobophorins A, B, and H8 from Streptomyces sp. CB09030 and Their Biosynthetic Gene Cluster.

Lobophorins (LOBs) are a growing family of spirotetronate natural products with significant cytotoxicity, anti-inflammatory, and antibacterial activities. Herein, we report the transwell-based discovery of Streptomyces sp. CB09030 from a panel of 16 in-house Streptomyces strains, which has significant anti-mycobacterial activity and produces LOB A (1), LOB B (2), and LOB H8 (3). Genome sequencing and bioinformatic analyses revealed the potential biosynthetic gene cluster (BGC) for 1-3, which is highly homologous with the reported BGCs for LOBs. However, the glycosyltransferase LobG1 in S. sp. CB09030 has certain point mutations compared to the reported LobG1. Finally, LOB analogue 4 (O-ß-D-kijanosyl-(1→17)-kijanolide) was obtained through an acid-catalyzed hydrolysis of 2. Compounds 1-4 showed different antibacterial activities against Mycobacterium smegmatis and Bacillus subtilis, which revealed the varying roles of different sugars in their antibacterial activities.

[Improved unilateral puncture PVP based on 3D printing technology for the treatment of osteoporotic vertebral compression fracture].

OBJECTIVE: To investigate the clinical effect of unilateral percutaneous vertebroplasty (PVP) combined with 3D printing technology for the treatment of thoracolumbar osteoporotic compression fracture. METHODS: A total of 77 patients with thoracolumbar osteoporotic compression fractures from October 2020 to April 2022 were included in the study, all of which were vertebral body compression fractures caused by trauma. According to different treatment methods, they were divided into experimental group and control group. Thirty-two patients used 3D printing technology to improve unilateral transpedicle puncture vertebroplasty in the experimental group, there were 5 males and 27 females, aged from 63 to 91 years old with an average of (77.59±8.75) years old. Forty-five patients were treated with traditional bilateral pedicle puncture vertebroplasty, including 7 males and 38 females, aged from 60 to 88 years old with an average of(74.89±7.37) years old. Operation time, intraoperative C-arm X-ray times, anesthetic dosage, bone cement injection amount, bone cement diffusion good and good rate, complications, vertebral height, kyphotic angle (Cobb angle), visual analogue scale(VAS), Oswestry disability index (ODI) and other indicators were recorded before and after surgery, and statistically analyzed. RESULTS: All patients were followed up for 6 to 23 months, with preoperative imaging studies, confirmed for thoracolumbar osteoporosis compression fractures, two groups of patients with postoperative complications, no special two groups of patients' age, gender, body mass index (BMI), time were injured, the injured vertebral distribution had no statistical difference(P>0.05), comparable data. Two groups of patients with bone cement injection, bone cement dispersion rate, preoperative and postoperative vertebral body height, protruding after spine angle(Cobb angle), VAS, ODI had no statistical difference(P>0.05). The operative time, intraoperative fluoroscopy times and anesthetic dosage were statistically different between the two groups(P<0.05). Compared with the traditional bilateral puncture group, the modified unilateral puncture group combined with 3D printing technology had shorter operation time, fewer intraoperative fluoroscopy times and less anesthetic dosage. The height of anterior vertebral edge, kyphosis angle (Cobb angle), VAS score and ODI of the affected vertebrae were statistically different between two groups at each time point after surgery(P<0.05). CONCLUSION: In the treatment of thoracolumbar osteoporotic compression fractures, 3D printing technology is used to improve unilateral puncture PVP, which is convenient and simple, less trauma, short operation time, fewer fluoroscopy times, satisfactory distribution of bone cement, vertebral height recovery and kyphotic Angle correction, and good functional improvement.

Negligible particle-specific antibacterial activity of silver nanoparticles.

For nearly a decade, researchers have debated the mechanisms by which AgNPs exert toxicity to bacteria and other organisms. The most elusive question has been whether the AgNPs exert direct "particle-specific" effects beyond the known antimicrobial activity of released silver ions (Ag(+)). Here, we infer that Ag(+) is the definitive molecular toxicant. We rule out direct particle-specific biological effects by showing the lack of toxicity of AgNPs when synthesized and tested under strictly anaerobic conditions that preclude Ag(0) oxidation and Ag(+) release. Furthermore, we demonstrate that the toxicity of various AgNPs (PEG- or PVP- coated, of three different sizes each) accurately follows the dose-response pattern of E. coli exposed to Ag(+) (added as AgNO(3)). Surprisingly, E. coli survival was stimulated by relatively low (sublethal) concentration of all tested AgNPs and AgNO(3) (at 3-8 µg/L Ag(+), or 12-31% of the minimum lethal concentration (MLC)), suggesting a hormetic response that would be counterproductive to antimicrobial applications. Overall, this work suggests that AgNP morphological properties known to affect antimicrobial activity are indirect effectors that primarily influence Ag(+) release. Accordingly, antibacterial activity could be controlled (and environmental impacts could be mitigated) by modulating Ag(+) release, possibly through manipulation of oxygen availability, particle size, shape, and/or type of coating.

Comparison of lateral transperitoneal versus retroperitoneal laparoscopic adrenalectomy for pheochromocytoma: a single-centre retrospective study.

Laparoscopic adrenalectomy (LA) has became the standardized treatment for pheochromocytoma. The aim of this study was to evaluate outcomes of lateral transperitoneal and retroperitoneal LA for pheochromocytoma. Between January 2011 and December 2021, 142 patients with pheochromocytoma underwent LA via lateral transperitoneal (123 patients) or retroperitoneal (19 patients) approaches. Data of these patients were assessed to investigate the differences in perioperative outcomes and intraoperative haemodynamic parameters between the two procedures. Clinical parameters at presentation were comparable between the two groups, except for tumour size, which was larger in the transperitoneal group (50 [10-115] mm vs 35 [7-110] mm, P = 0.012). There were no significant differences between the two groups in terms of operation time, estimated blood loss, intraoperative transfusion rate, incidence of complications, conversion to open surgery, postoperative analgesic requirement, time to first oral intake, or mean hospital stay. Intraoperative haemodynamic parameters of the two groups were similar. After adjusting for tumour size using propensity score matching, both perioperative outcomes and haemodynamic parameters were still comparable. Lateral transperitoneal and retroperitoneal laparoscopic adrenalectomies provide similar perioperative and haemodynamic outcomes for surgical resection of pheochromocytoma.

[Comparison of flavonoids content in huangqi gnizhi wuwu tang of different dosages by uniform design method].

OBJECTIVE: To determine the content of flavonoids in huangqi guizhi wuwu tang (HQGZWWT) of different dosages by uniform design method and analyze their difference for clinical application. METHODS: The uniform design set five factors and 11 levels to explore the content of flavonoids. The results were analyzed by computer with the method of multiple regression analysis. RESULTS: The contribution of each medicinal material to the content of total flavonoids was Radix Astragali (51.8%), Rhizoma Zingiberis (0.967%), Rhizoma Zingiberis (0.689%), Ramulus Cinnamomi (0.381%) and Raidix Paenoiae alba (0.185%), respectively. CONCLUSION: The extraction rate of flavonoids is not directly relative to the total amount of medicines, instead, there is an optimum dosage matching for it.

Serum S100 calcium binding protein A4 improves the diagnostic accuracy of transient elastography for assessing liver fibrosis in hepatitis B.

AIM: The diagnostic performance of Fibroscan might be improved when combined with other serum fibrosis related markers. Previous study has demonstrated that S100A4 expression is associated with liver fibrosis in humans with hepatitis. This study aimed to clarify diagnostic accuracy of serum S100A4 levels for significant liver fibrosis in patients with chronic hepatitis B (CHB), and develop a combined algorithm of liver stiffness measurement (LSM) and S100A4 to predict significant liver fibrosis in CHB. METHODS: One hundred and seventy-five CHB patients who had performed liver biopsy were consecutively included. We evaluated serum S100A4 levels, LSM values and other clinically-approved fibrosis scores. RESULTS: Serum S100A4 level was higher in CHB patients with significant fibrosis, compared to those without [199.58 (33.31-1971.96) vs. 107.15 (2.10-1038.94), P<0.001]. Using receiver-operating characteristic (ROC) analyses, the area under the curves (AUC), sensitivity, specificity and accuracy of S100A4 were found to be 0.749, 62.7%, 75.9% and 0.70 for significant fibrosis (≥Stage 2), respectively. Although not superior to LSM, these results were better than the fibrosis index based on the 4 factor (FIB-4) and the aspartate aminotransferase-to-platelet ratio index (APRI) for significant fibrosis detection. An algorithm consisting of S100A4 and LSM was derived. The AUC, sensitivity, specificity and accuracy of model based on serum S100A4 level and LSM were 0.866, 86.6%, 77.8% and 0.79 for significant fibrosis detection, superior to those based on LSM alone (0.834, 76.1%, 80.7% and 0.76, P=0.041). CONCLUSION: Serum S100A4 level was identified as a fibrosis marker of liver fibrosis in patients with CHB. Combining serum S100A4 with LSM improved the accuracy of transient elastography for hepatitis B significant fibrosis detection.

Identification of p90 Ribosomal S6 Kinase 2 as a Novel Host Protein in HBx Augmenting HBV Replication by iTRAQ-Based Quantitative Comparative Proteomics.

PURPOSE: The aim of this study was to screen for novel host proteins that play a role in HBx augmenting Hepatitis B virus (HBV) replication. EXPERIMENTAL DESIGN: Three HepG2 cell lines stably harboring different functional domains of HBx (HBx, HBx-Cm6, and HBx-Cm16) were cultured. ITRAQ technology integrated with LC-MS/MS analysis was applied to identify the proteome differences among these three cell lines. RESULTS: In brief, a total of 70 different proteins were identified among HepG2-HBx, HepG2-HBx-Cm6, and HepG2-HBx-Cm16 by double repetition. Several differentially expressed proteins, including p90 ribosomal S6 kinase 2 (RSK2), were further validated. RSK2 was expressed at higher levels in HepG2-HBx and HepG2-HBx-Cm6 compared with HepG2-HBx-Cm16. Furthermore, levels of HBV replication intermediates were decreased after silencing RSK2 in HepG2.2.15. An HBx-minus HBV mutant genome led to decreased levels of HBV replication intermediates and these decreases were restored to levels similar to wild-type HBV by transient ectopic expression of HBx. After silencing RSK2 expression, the levels of HBV replication intermediates synthesized from the HBx-minus HBV mutant genome were not restored to levels that were observed with wild-type HBV by transient HBx expression. CONCLUSION AND CLINICAL RELEVANCE: Based on iTRAQ quantitative comparative proteomics, RSK2 was identified as a novel host protein that plays a role in HBx augmenting HBV replication.

[Multi-slice helical CT perfusion imaging in evaluating intracranial neoplasms and tumor-like lesions].

OBJECTIVE: To investigate the clinical value of CT perfusion in diagnosing and assessing intracranial neoplasms and tumor-like lesions. METHODS: 16-slice helical CT perfusion imaging was performed in 56 patients who were clinically suspected to have intracranial neoplasm or tumor-like lesion. With a GE-Light Speed 16-slice helical CT scanner, routine plain-CT scanning was performed to localize the central slice of the lesion. Perfusion imaging was then carried out using cine scan technique to maintain a slice thickness of 5-10 mm, a total dose of 50-70 ml of contrast-medium at an injection flow rate of 3-5 ml/s, a delay time of 7 s and a total scan time of 50 s. The images were processed using perfusion software in an ADW 4.0 workstation, meanwhile, time-density curves (TDC) of different kinds of lesions were also produced and analyzed. RESULTS: The pathological types in this series included: 29 gliomas (12 low-grade and 17 high-grade), 2 ependemomas, 2 hemangioblastomas, 1 medulloblastoma, 2 metastatic tumors, 1 lymphoma, 5 meningiomas, 2 schwannomas, 1 germinoma, 1 teratoma in the pineal region, 6 cavernous hemangiomas, 2 inflammatory granulomas, 1 tuberculoma, and 1 hyperplasia of the choroid plexus. TDC of high-grade glioma, low-grade glioma and meningioma was different from each other. The cerebral blood flow (CBF), cerebral blood volume (CBV), particularly, the permeability surface (PS) value of glioma was found to increase significantly with the escalation of tumor differentiation grade. In PS map, margin of the tumor could be clearly showed, which was very useful when hemorrhaging within the tumor occurred. CBF in meningioma was lower than that in high-grade glioma, but there was no statistical difference in CBV, MTT and PS between these two types of tumor. The features of intracranial cavernous hemangioma such as significant prolongation of MTT, different TDCs, and zero perfused areas were diverse on CTP image, which was helpful in differentiating it from the other lesions. The germinoma and teratoma had rather low CBF and CBV value, but a remarkably high PS value, furthermore, they showed a rapid escalated TDC with a slowly and continuously elevated platform. The perfusion features of schwannoma was concordant with its pathological findings. However, no visible specific feature of inflammatory lesion was found on CTP image in this series. CONCLUSION: Multi-slice helical CT perfusion imaging may be helpful in revealing histopathological features and hemodynamic changes as well as differential diagnosis of intracranial neoplasms and tumor-like lesions. When combined with other image and clinical information, CTP can play an important role in pre-operative diagnosis and treatment planning for intracranial neoplasms and tumor-like lesions.

[The rate of hepatitis B virus resistance to adefovir dipivoxil (ADV) and the evolution of hepatitis B virus in lamivudine-resistant chronic hepatitis B patients with ADV monotherapy].

OBJECTIVE: To study the resistant rate of hepatitis B virus (HBV) to ADV and the dynamic evolution of HBV in lamivudine (Lam)-resistant chronic hepatitis B (CHB) patients. METHODS: Twenty-three Lam-resistant CHB patients were assigned to a 10mg/d ADV monotherapy for 68-116 weeks. The baseline and different time point blood samples after ADV monotherapy were analyzed for ADV-resistant mutations using direct sequencing of PCR products; the evolution of HBV mutations was examined by clonal analysis of serial samples from one patient infected with ADV-associated resistant HBV strains. RESULTS: The cumulative incidence of genotypic ADV resistance at weeks 48 and 96 was 4.3% and 10.5% respectively respectively. The evolution analysis of HBV mutant strains in an ADV-resistant CHB patient showed that the proportion of YMDD mutants gradually decreased with rtA181S mutants increasing over time after ADV monotherapy, and that rtA181S+N236T mutants became the predominant strains during prolonged ADV monotherapy. The addition of Lam to the ongoing ADV treatment had poorer antiviral response in the patient with rtA181S or rtA181S+N236T mutant infection; one clone with multi-drug resistant mutations was selected during Lam and ADV combination therapy. CONCLUSION: Increased risk of adefovir resistance and selection of multi-drug resistant mutations are associated with long-term ADV monotherapy in patients with Lam-resistant chronic hepatitis B.

[A clinical research on oxymatrine for the treatment of chronic hepatitis B].

OBJECTIVE: To investigate the clinical effect of oxymatrine on chronic viral hepatitis B and to look for new methods for treating hepatitis B. METHODS: Multi-center, controlled study was used. In this study, 196 patients were allocated to oxymatrine, oxymatrine with Ara-AMP, IFN-a1b, and glucose groups to observe ALT, AST and viral marker changes. RESULTS: At the end of treatment, the rate of normal ALT, the negative rate of HBV DNA and HBeAg, and the positive rate of HBeAb were similar in oxymatrine, oxymatrine with Ara-AMP, and IFN-a1b groups. It was higher than that of glucose group. After 12 months follow up, the total effective rate is 40.8%, 60.8% and 43.1% in oxymatrine, oxymatrine with Ara-AMP, and IFN-a1b groups, respectively. CONCLUSIONS: Oxymatrine, oxymatrine with Ara-AMP, and IFN-a1b are effective to treat hepatitis B with a good negative rate of HBV DNA and HBeAg and positive rate of HBeAb.

[Clinical characteristics of 638 patients infected with hepatitis C virus by post blood transfusion, in Shanghai].

OBJECTIVE: To investigate the clinical-epidemiologic characteristics of patients with hepatitis C virus (HCV) infection by post blood transfusion. METHODS: Polymerase chain reaction (PCR) and enzyme linked immunosorbent assay (ELISA) were used to detect HCV RNA and anti-HCV, respectively. Analysis was performed on patients' age distribution, cause of primary diseases, years of exposure, ingredient and amount of transfusion, incubation period, disorder on liver function and changes on abdominal ultrasound image, etc. RESULTS: HCV RNA levels were higher than 3.0 log(10) copy/ml in 90.8% infected patients with a median as 6.10 log(10) copy/ml. 19.2% of the patients showed viral load 3.0 to 4.0 log(10) copy/ml, and 66.1% of them showed 5.0 to 6.0 log(10) copy/ml. Only 14.7% of the infected persons had HCV RNA levels higher than 7.0 log(10) copy/ml. Eighty-one point five percent (44/54) of the infected persons were confirmed as HCV RNA positive by HCV RNA qualitative analysis with HCV genotype as primarily type 1. 99.8% (636/637) of the patients were detected as anti-HCV positive by serological test. The sensitivity of serological test was higher than both quantitative and qualitative HCV RNA assays (P = 0.000, P = 0.000, respectively). HCV infection post blood transfusion was more seen in common people at 40 to 60 years old. Most cases (85.7%) had their first exposure during 1990 to 1994. More than 10% of the cases had primary diseases as obstetrics, orthopedics or gastrointestinal tract hemorrhage. 79.9% of the patients received whole blood product transfusion. The mean interval between transfusion and clinical diagnosis was 8.5 ± 5.5 years. 90.1% of the infected patients had liver function damage, while most of them showed elevated alanine aminotransferase (ALT) no more than 5 upper limits of normal (ULN), whereas Serum total bilirubin (TBIL), ALT and aspartate aminotransferase (AST) ≥ 5 × ULN level were showing more clinical manifestations (P = 0.000, P = 0.001, P = 0.009, respectively). Abdominal ultrasound among 8.9% of the infected persons showed changes in cirrhosis, and most of them were older than 50 years of age. CONCLUSION: Most of the post transfusion HCV infected cases happened in adulthood, and were mainly exposed during 1990 to 1994. Infected patients usually had their liver function damaged with elevated ALT no more than 5 × ULN and with medium HCV RNA levels. HCV genotype was mainly for type 1. Patients who were of older age showed higher incidence of cirrhosis. If a patients' infection period was longer than 5 years, he/she would show higher incidence of cirrhosis.

Discrepancy between the dynamic computed tomography and T2 magnetic resonance perfusion imaging in brain tumors: a report of 2 cases.

In this report, we separately performed dynamic computed tomographic perfusion and dynamic susceptibility contrast-T2 magnetic resonance perfusion imaging on 2 cases of brain tumors (one was a glioblastoma, and the other was a central neurocytoma). Between the 2 methods, we saw the discrepancy in values of cerebral blood volume and cerebral blood flow, differences in location of the maximal cerebral blood volume, and regions with abnormal increased cerebral blood flow besides the solid part of the tumors. Both differences and similarities of the 2 techniques with their advantages and pitfalls were analyzed in detail. The developing trends in the near future were also discussed.