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【Objective】 To determine the risk factors of urinary sepsis secondary to minimally invasive percutaneous nephrolithotomy (mPCNL) in patients with negative preoperative urine culture (UC). 【Methods】 A total of 274 patients with negative preoperative UC treated with mPCNL during Jan.2016 and Jun. 2021 were retrospectively analyzed. The incidence of urinary sepsis was observed, and the general data of patients with or without urinary sepsis after mPCNL were compared. logistic regression model was used to analyze the risk factors of urinary sepsis after mPCNL. 【Results】 Urinary sepsis occurred in 11 cases (4.01%). Univariate analysis showed that urinary sepsis was associated with gender, body mass index, stone load, diabetes, urine WBC ≥2+, urinary nitrite, procalcitonin, and operation time. Multivariate logistic regression analysis showed that the independent risk factors of urinary sepsis after mPCNL included diabetes (OR=2.34, 95%CI=1.051-5.43, P=0.037), stone load (OR=7.51, 95%CI=3.17-7.38, P=0.045), urine WBC≥2+ (OR=4.57, 95%CI=6.75-11.38, P=0.032), urinary nitrite positive (OR=6.45, 95%CI=0.93-26.87, P=0.028) and operation time≥120 min (OR=3.53, 95%CI=1.41-8.85, P=0.042). 【Conclusion】 Diabetes, stone load, urinary WBC ≥2+, positive urinary nitrite and operation time ≥120 minutes are the risk factors of urinary sepsis after mPCNL in patients with negative urine culture.
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The continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants poses challenges to the effectiveness of neutralizing antibodies. Rational design of antibody cocktails is a realizable approach addressing viral immune evasion. However, evaluating the breadth of antibody cocktails is essential for understanding the development potential. Here, based on a replication competent vesicular stomatitis virus model that incorporates the spike of SARS-CoV-2 (VSV-SARS-CoV-2), we evaluated the breadth of a number of antibody cocktails consisting of monoclonal antibodies and bispecific antibodies by long-term passaging the virus in the presence of the cocktails. Results from over two-month passaging of the virus showed that 9E12+10D4+2G1 and 7B9-9D11+2G1 from these cocktails were highly resistant to random mutation, and there was no breakthrough after 30 rounds of passaging. As a control, antibody REGN10933 was broken through in the third passage. Next generation sequencing was performed and several critical mutations related to viral evasion were identified. These mutations caused a decrease in neutralization efficiency, but the reduced replication rate and ACE2 susceptibility of the mutant virus suggested that they might not have the potential to become epidemic strains. The 9E12+10D4+2G1 and 7B9-9D11+2G1 cocktails that picked from the VSV-SARS-CoV-2 system efficiently neutralized all current variants of concern and variants of interest including the most recent variants Delta and Omicron, as well as SARS-CoV-1. Our results highlight the feasibility of using the VSV-SARS-CoV-2 system to develop SARS-CoV-2 antibody cocktails and provide a reference for the clinical selection of therapeutic strategies to address the mutational escape of SARS-CoV-2.
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Numerous mutations in the spike protein of SARS-CoV-2 B.1.1.529 Omicron variant pose a crisis for antibody-based immunotherapies. The efficacy of emergency use authorized (EUA) antibodies that developed in early SARS-CoV-2 pandemic seems to be in flounder. We tested the Omicron neutralization efficacy of an early B cell antibody repertoire as well as several EUA antibodies in pseudovirus and authentic virus systems. More than half of the antibodies in the repertoire that showed good activity against WA1/2020 previously had completely lost neutralizing activity against Omicron, while antibody 8G3 displayed non-regressive activity. EUA antibodies Etesevimab, Casirivimab, Imdevimab and Bamlanivimab were entirely desensitized by Omicron. Only Sotrovimab targeting the non-ACE2 overlap epitope showed a dramatic decrease activity. Antibody 8G3 efficiently neutralized Omicron in pseudovirus and authentic virus systems. The in vivo results showed that Omicron virus was less virulent than the WA1/2020 strain, but still caused deterioration of health and even death in mice. Treatment with 8G3 quickly cleared virus load of mice. Antibody 8G3 also showed excellent activity against other variants of concern (VOCs), especially more efficient against authentic Delta plus virus. Collectively, our results suggest that neutralizing antibodies with breadth remains broad neutralizing activity in tackling SARS-CoV-2 infection despite the universal evasion from EUA antibodies by Omicron variant.
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Emerging SARS-CoV-2 variants are threatening the efficacy of antibody therapies. Combination treatments including ACE2-Fc have been developed to overcome the evasion of neutralizing antibodies (NAbs) in individual cases. Here we conducted a comprehensive evaluation of this strategy by combining ACE2-Fc with NAbs of diverse epitopes on the RBD. NAb+ACE2-Fc combinations efficiently neutralized HIV-based pseudovirus carrying the spike protein of the Delta or Omicron variants, achieving a balance between efficacy and breadth. In an antibody escape assay using replication-competent VSV-SARS-CoV-2-S, all the combinations had no escape after fifteen passages. By comparison, all the NAbs without combo with ACE2-Fc had escaped within six passages. Further, the VSV-S variants escaped from NAbs were neutralized by ACE2-Fc, revealing the mechanism of NAb+ACE2-Fc combinations survived after fifteen passages. We finally examined ACE2-Fc neutralization against pseudovirus variants that were resistant to the therapeutic antibodies currently in clinic. Our results suggest ACE2-Fc is a universal combination partner to combat SARS-CoV-2 variants including Delta and Omicron.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) continue to wreak havoc across the globe. Higher transmissibility and immunologic resistance of VOCs bring unprecedented challenges to epidemic extinguishment. Here we describe a monoclonal antibody, 2G1, that neutralizes all current VOCs and has surprising tolerance to mutations adjacent to or within its interaction epitope. Cryo-electron microscopy structure showed that 2G1 bound to the tip of receptor binding domain (RBD) of spike protein with small contact interface but strong hydrophobic effect, which resulted in nanomolar to sub-nanomolar affinities to spike proteins. The epitope of 2G1 on RBD partially overlaps with ACE2 interface, which gives 2G1 ability to block interaction between RBD and ACE2. The narrow binding epitope but high affinity bestow outstanding therapeutic efficacy upon 2G1 that neutralized VOCs with sub-nanomolar IC50 in vitro. In SARS-CoV-2 and Beta- and Delta-variant-challenged transgenic mice and rhesus macaque models, 2G1 protected animals from clinical illness and eliminated viral burden, without serious impact to animal safety. Mutagenesis experiments suggest that 2G1 could be potentially capable of dealing with emerging SARS-CoV-2 variants in future. This report characterized the therapeutic antibodies specific to the tip of spike against SARS-CoV-2 variants and highlights the potential clinical applications as well as for developing vaccine and cocktail therapy.
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Objective To discuss The Clinical Significance of Eosinophil (EOS) in urosepsis. Methods A total of 99 patients of urosepsis in Department of Urology,Guangdong Provincial TCM Hospital from Mar. 2013 to Jul. 2016 were selected as research objects by retrospective analysis. The patients were classified into groupEOS= 0 andgroup EOS > 0,group PCT(procalcitonin)≥ 2 ng/mL andgroup PCT 0 group,the percentage of EOS in PCT≥2 ng/mL groupwere lower than PCT<2 ng/mL group,difference were significant(P<0.05). And The Independent-Sample Testalso showed that the percentage of EOS of the Urosepsis group was definitely lower than the UTI group without Sepsis. Difference was statistically significant. Concusions The percentage of EOS could be applied to assess the severity of urosepsis, monitor the disease progression and evaluate the infection control. The cost was lower than PCT in therapeuticprocess ofurosepsis.
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Objective To investigate the efficacy and safety of Shuo Tong ureteroscopy in the treatment of upper ureteric stones.Methods The data of 832 patients,who underwent Shuo Tong ureteroscopy combined with holmium laser for the treatment of upper ureteric stones were collected between July 2014 and February 2017.The patients accepted general anesthesia under lithotomy position.After dilating the ureter,a ureteral access sheath was inserted along the guide wire.Finally,stones were broken and clean up by Shuo Tong ureteroscope.According to the stone size,823 patients were divided into ≤2.0 cm group (n=112,13.6％),2.1-3.0 cm group (n =395,48.0％),3.1-4.0 cm group (n =257,31.2％),＞ 4.0 cm group (n =59,7.2％)The stone free rate(SFR) and post-operative complications were observed.Results Among 983 operations,663 cases accepted one-stage operations and 160 cases accepted second stage operations.the operative time and postoperative hospital stay were 23-145 min(mean 74.8 ± 35.3) and 1-5 days(mean 1.9 ±0.8),respectively.The SFR in the first day and one month after operation was 75.6％ and 83.8％,respectively.The stone free rate in each group were 89.3％,82.5％,61.1％,52.5％ at first day after operation respectively(P ＜ 0.05).While,the SFR after one month were 95.5％,87.6％,72.0％,61.0％ in each group,respectively(P ＜ 0.05).Fever rate after operation was 11.1％,ureteral injury rate was 1.9％,severe hematuria rate was 0.6％,stone street formation rate was 1.2％,perirenal hematoma rate was 0.4％.All patients were improved after conventional treatment.Conclusion Shuo Tong ureteroscopy is a safe treatment with high stone free rate for upper ureteric stones.
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Objective To investigate the efficacy and safety of Shuo Tong ureteroscopy in the treatment of upper ureteric stones.Methods The data of 832 patients,who underwent Shuo Tong ureteroscopy combined with holmium laser for the treatment of upper ureteric stones were collected between July 2014 and February 2017.The patients accepted general anesthesia under lithotomy position.After dilating the ureter,a ureteral access sheath was inserted along the guide wire.Finally,stones were broken and clean up by Shuo Tong ureteroscope.According to the stone size,823 patients were divided into ≤2.0 cm group (n=112,13.6％),2.1-3.0 cm group (n =395,48.0％),3.1-4.0 cm group (n =257,31.2％),＞ 4.0 cm group (n =59,7.2％)The stone free rate(SFR) and post-operative complications were observed.Results Among 983 operations,663 cases accepted one-stage operations and 160 cases accepted second stage operations.the operative time and postoperative hospital stay were 23-145 min(mean 74.8 ± 35.3) and 1-5 days(mean 1.9 ±0.8),respectively.The SFR in the first day and one month after operation was 75.6％ and 83.8％,respectively.The stone free rate in each group were 89.3％,82.5％,61.1％,52.5％ at first day after operation respectively(P ＜ 0.05).While,the SFR after one month were 95.5％,87.6％,72.0％,61.0％ in each group,respectively(P ＜ 0.05).Fever rate after operation was 11.1％,ureteral injury rate was 1.9％,severe hematuria rate was 0.6％,stone street formation rate was 1.2％,perirenal hematoma rate was 0.4％.All patients were improved after conventional treatment.Conclusion Shuo Tong ureteroscopy is a safe treatment with high stone free rate for upper ureteric stones.
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Histone deacetylase (HDAC) overactivity in colorectal cancer (CRC) promotes cancer progression. In the current study, we showed that 4SC-202, a novel class I HDAC inhibitor (HDACi), potently inhibited survival and proliferation of primary human colon cancer cells and established CRC lines (HT-29, HCT-116, HT-15, and DLD-1). Yet, the same 4SC-202 treatment was non-cytotoxic to colon epithelial cells where HDAC-1/-2 expressions were extremely low. 4SC-202 provoked apoptosis activation in CRC cells, while caspase inhibitors (z-VAD-CHO and z-DVED-CHO) significantly alleviated 4SC-202-exerted cytotoxicity in CRC cells. Meanwhile, 4SC-202 induced dramatic G2-M arrest in CRC cells. Further studies showed that AKT activation might be an important resistance factor of 4SC-202. 4SC-202-induced cytotoxicity was dramatically potentiated with serum starvation, AKT inhibition (by perifosine or MK-2206), or AKT1-shRNA knockdown in CRC cells. On the other hand, exogenous expression of constitutively active AKT1 (CA-AKT1) decreased the sensitivity by 4SC-202 in HT-29 cells. Notably, 4SC-202, at a low concentration, enhanced oxaliplatin-induced in vitro anti-CRC activity. In vivo, we showed that oral gavage of 4SC-202 inhibited HT-29 xenograft growth in nude mice, and when combined with oxaliplatin, its activity was further strengthened. Together, these pre-clinical results indicate that 4SC-202 may be further investigated as a valuable anti-CRC agent/chemo-adjuvant.
Subject(s)
Antineoplastic Agents/pharmacology , Benzamides/pharmacology , Colorectal Neoplasms/pathology , Histone Deacetylase Inhibitors/pharmacology , Animals , Apoptosis/drug effects , Blotting, Western , Cell Line, Tumor , Cell Proliferation/drug effects , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Gene Knockdown Techniques , Humans , Mice , Mice, Inbred C57BL , Mice, Nude , Xenograft Model Antitumor AssaysABSTRACT
BACKGROUND/AIMS: This study was to investigate whether transforming growth factor-β1 (TGF-β1) plays a role in hyperalgesia in chronic pancreatitis (CP) and the underlying mechanisms. METHODS: CP was induced in male adult rats by intraductal injection of trinitrobenzene sulfonic acid (TNBS). Abdominal hyperalgesia was assessed by referred somatic behaviors to mechanical stimulation of rat abdomen. Dil dye injected into the pancreas was used to label pancreas-specific dorsal root ganglion (DRG) neurons. Whole cell patch clamp recordings and calcium imaging were performed to examine the effect of TGF-β1 on acutely isolated pancreas-specific DRG neurons. Western blot analysis was carried out to measure the expression of TGF-β1 and its receptors. RESULTS: TNBS injection significantly upregulated expression of TGF-β1 in the pancreas and DRGs, and TGF-β1 receptors in DRGs (T9-T13) in CP rats. Intrathecal injection of TGF-β receptor I antagonist SB431542 attenuated abdominal hyperalgesia in CP rats. TGF-β1 application depolarized the membrane potential and caused firing activity of DRG neurons. TGF-β1 application also reduced rheobase, hyperpolarized action potential threshold, and increased numbers of action potentials evoked by current injection of pancreas-specific DRG neurons. TGF-β1 application also increased the concentration of intracellular calcium of DRG neurons, which was inhibited by SB431542. Furthermore, intrathecal injection of TGF-β1 produced abdominal hyperalgesia in healthy rats. CONCLUSIONS: These results suggest that TGF-β1 enhances neuronal excitability and increases the concentration of intracellular calcium. TGF-β1 and its receptors are involved in abdominal hyperalgesia in CP. This and future study might identify a potentially novel target for the treatment of abdominal pain in CP.
Subject(s)
Adult , Animals , Humans , Male , Rats , Abdomen , Abdominal Pain , Action Potentials , Blotting, Western , Calcium , Diagnosis-Related Groups , Fires , Ganglia, Spinal , Hyperalgesia , Injections, Spinal , Membrane Potentials , Neurons , Pancreas , Pancreatitis, ChronicABSTRACT
PurposeThere is a certain correlation between parameters of CT perfusion imaging and pathological type and angiogenesis in lung cancer, in order to discuss the value of CT perfusion imaging parameters such as blood volume (BV), blood flow (BF), time to peak (TTP) and peak enhancement image (PEI) for prognosis, this study is designed to observe the relationship between the parameters of CT perfusion imaging and micro lymphovascular density (MLVD) in non-small cell lung cancer (NSCLC).Materials and Methods 100 patients were enrolled in the study, all of them underwent CT perfusion imaging and 60 were diagnosed NSCLC by pathology, immunohistochemical staining was performed to determine the expressions of MLVD of the 60 NSCLC, and the correlation analyses were carried out to determine the relationship between CT perfusion imaging and MLVD.Results The expression of MLVD was the most in the peripheral tissue of cancer (25.16±1.28), the next in the cancer tissue (16.38±3.58), and the least in the normal lung tissue (7.56±4.38), the difference was statistically significant (P<0.05). There was positive correlation between MLVD with BF and BV of the tumor (r=0.643 and 0.598, P<0.01).Conclusion Some parameters of CT perfusion imaging are correlated with MLVD, the invasion and metastasis in lung carcinoma can be predicted to some extent according to this correlation. Parameters of CT perfusion imaging such as BF and BV are correlated with MLVD in patients with NSCLC, thus can be used to predict the invasion and metastasis of lung cancer.
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Hematogenous metastasis is common in lung cancer, and except for small cell lung cancer and melanoma, tumors with extensive metastasis seldom involve the prostate. The treatment of lung adenocarcinoma with prostate metastasis relies mainly on systemic chemotherapy with rigorous treatment of the primary lesions and metastatic palliative radiotherapy. Comprehensive treatment integrating traditional Chinese medicine may improve the quality of life of the patients.
Subject(s)
Aged , Humans , Male , Adenocarcinoma , Pathology , Lung Neoplasms , Pathology , Neoplasm Metastasis , Prostatic NeoplasmsABSTRACT
Objective To investigate the relationship of the expression of vascular endothelial growth factor (VEGF)and the mi-crovessel density (MVD)with multi-slice spiral CT perfusion imaging.Methods 80 patients with solitary pulmonary nodules under-went perfusion scan by 16-slice spiral CT.Among them,45 diagnosed as lung cancer by pathology were enrolled in the study.After surgery,the slice of the pecimen was selected similar to the corresponding slice of CT images,and the immunohistochemical staining was performed to determine the expression of VEGF and the MVD.Spearman correlation analysis was used to determine the rela-tionship of expression of VEGF and the MVD with CT perfusion parameters.Results There was more expression of VEGF and the MVD in NSCLC.There were positive correlations between VEGF,MVD and BF (both P<0.05).The peak enhancement image (PEI)and TTP have significant correlations with MVD (P<0.05).Conclusion Some parameters of lung CT perfusion imaging are correlated with MVD and VEGF.
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Objective To investigate the expression characteristics of Glypican3 ,MMP-9 and MMP-14 in primary hepatocellular carcinoma ,and to focus on their roles on the development ,progress and metastasis of tumor .Methods 102 cases of primary hepato-cellular carcinoma were taken as the observation group and 80 cases of normal liver tissues as the control group .The expressions of Glypican3 ,MMP-9 and MMP-14 were detected by the immunohistochemistry method and their expression difference in different clinicopathological characteristics and the correlation were investigated .Results The positive rates of Glypican3 ,MMP-9 and MMP-14 expressions in the observation group were significantly higher than those in the control group .The positive rates of Glypi-can3 ,MMP-9 and MMP-14 expressions were closely correlated with the tumor volume ,differentiation degree ,lymph node metasta-sis ,vessel infiltration ,membrane invasion and PCNA expression .The correlation analysis showed that the positive relationships were found between Glypican3 and MMP-9 ,between Glypican3 and MMP-14 and between MMP-9 and MMP-14 in the observation group(r=0 .48 ,P=0 .024 1 ;r=0 .46 ,P=0 .013 2;r=0 .43 .P=0 .031 3) .The survival analysis showed that expressions of Glypi-can3 ,MMP-9 and MMP-14 were correlated with the patient′s prognosis .Conclusion The higher-expressions of Glypican3 ,MMP-9 and MMP-14 may promote the occurrence and development of primary hepatocellular carcinoma .Detecting the postoperative expres-sions of Glypican3 ,MMP-9 and MMP-14 has certqain value to judge the prognosis in primary hepatocellular carcinoma .
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Objective To improve the diagnosis and therapy of uroseptic shock by percutaneous nephrolithotomy. Methods Five cases clinical data of uroseptic shock by percutaneous nephrolithotomy were analyzed retrospectively. Results Incidence rate of uroseptic shock by percutaneous nephrolithotomy was 0.5 % (5/1120), total deaths rate was 0.2 % (2/1120), death rate of uroseptic shock was 40%(2/5). Conclusions Uroseptic shock by percutaneous nephrolithotomy is extremely dangerous complication and primary death cause. Its characteristic such as: better masking, urgent onset,quick progress and high death rate. It is benefit to decrease incidence rate and mortality by prehension characteristic,control risk factor, early diagnosis and therapy.
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Human kallikrein-1 (hK1) gene was cloned from kidney tissues cDNA, it was inserted into the plasmid pPICZalphaA, then the yeast expression vector pPICZalpha-hK1 was constructed. After transformed into Pichia pastoris host X33, high-level expression transformants were screened by escalating the concentration of Zeocin (from 500 to 700 microg/mL) of YPD plate and medium. When temperature was 30 degrees C, pH 6.0 with induction duration of 64 hours in the 30 L fermenter, the highest yield can reach about 6500 u/L (1.25 g/L). The variation of glycosylation resulted in two kinds of molecules, i.e. rhK1-H with a heavy molecular weight and rhK1-L with a light one. rhK1 was purified from the supernatant through Phenyl hydrophobic interaction, Cu(2+)-charged Chelating and Anion-exchange chromatography. 0.28 g rhK1-H and 0.62 g rhK1-L can be purified from one liter supernatant. The yield recovery was 72% with a purity of > 96%. So far our yield of rhK1 is superior than known recombinant expression method reported by other researchers.
Subject(s)
Humans , Amino Acid Sequence , Base Sequence , Chromatography, Ion Exchange , Methods , Genetic Vectors , Genetics , Kidney , Metabolism , Molecular Sequence Data , Pichia , Genetics , Metabolism , Recombinant Proteins , Genetics , Tissue Kallikreins , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To examine the prevalence and the sequence of the genes of new genotypes of hepatitis G virus (HGV) in Guangxi, China.</p><p><b>METHODS</b>Serum samples were collected from 85 intravenous drug abusers (IVDAs), 80 patients with liver diseases (PLDs) and 50 blood donors (BDs). All sera (n=215) were tested by using EIA for HBsAg, anti-HCV and anti-HIV, and by using nested PCR for HGV RNA. In 62 subjects positive for HGV, HGV RNA was sequenced, and a phylogenetic tree was constructed for analyzing genotypes of HGV.</p><p><b>RESULTS</b>HGV RNA was detected in 85 of 215 serum samples (39.53%). The positivity rates for HBsAg, anti-HCV and anti-HIV were 39.07%, 42.79% and 0, respectively. First, 11 nucleotide sequences were determined and the isolates were grouped into three clusters with HGV. 5 of 11 HGV isolates clustered in a distinct phylogenetic branch (genotype Asia) which was different from the described GBV-C and HGV sequences, suggesting the presence of a new genotype of HGV in this locality. Second, 51 nucleotide sequences were determined and analyzed for their genotypes of HGV, and showed genotype GBV-C (3.23%), genotype HGV 30-65% and new genotype (genotype Asia) 64.51%, respectively.</p><p><b>CONCLUSIONS</b>There were subgenotypes in 3 genotypes of HGV; The predominant genotypes of HGV were genotype Asia and genotype HGV among IVDAs, PLDs, and BDs patients in Guangxi, China.</p>
Subject(s)
Adult , Female , Humans , Male , Blood Donors , China , Epidemiology , GB virus C , Genetics , Genotype , Hepatitis C , Epidemiology , Liver Diseases , Virology , Polymerase Chain Reaction , RNA, Viral , Genetics , Sequence Analysis, RNA , Substance Abuse, Intravenous , VirologyABSTRACT
【Objective】 To establish a postoperative recovery scale for Chinese people and to make a preliminary assessment for the scale.【Methods】Programmatic decision-making method was used to establish the basic items and structure of the scale.And then 70 postoperative patients were sampled to assess the scale by grading their recovery.【Results】The postoperative recovery scale had a good validity in contents and structure,and a good reliability and responsiveness.【Conclusion】The postoperative recovery scale established preliminarily can be used as the initial scale for evaluating the recovery of postoperative patients treated by traditional Chinese and western medicine.
