Objective: To investigate the expression and distribution of NOS2 and NOS3 in human non-small cell lung cancer (NSCLC),and to evaluate the relationship between their expression and tumor angiogenesis and lymph node metastasis. Methods: the expression of NOS2, NOS3 and IMVD in 95 patients with NSCLC were examined using immunohistochemical methods (S-P), and the relationship between them and many clinicopathological parameters was analyzed. Results: The positive expression of NOS3 was associated with histological subtype, IMVD and lymph node metastases of NSCLC(P

Objective:To investigate the LOH at regions on chromosomal arm 8p22,11p15,17p13 and its relationship with clinicopathological parameters. Methods:Thirty-four paraffin-embedded tumor and corresponding noncancerous tissues were analysed. PCR was used to amplified three microsatellite markers D8S136,D11S988 and TP53 located at these chromosomal regions. PCR products were electrophoresed on 6%polyacrylamide gel and detected using silver staining. The P53, c-erBb-2,PR,ER status were determined by immunohistochemistry. Results:Of the three markers we studied, D8S136 was detected LOH at a frequency of 12 in 34 tumors(35.29%). D11S988 and TP53 were detected LOH at a frequency of 5 in 34 tumors(14.71%). There were no obvious associations between LOH at D11S988、TP53 and clinicopathological parameters, but the tumors with LOH at D8S136 were significant larger than that without LOH(P=0.0049). Conclusion: Invasive ductal carcinoma of the breast has a frequent LOH on chromosome 8p22. The loss or inactivation of putative tumor suppressor genes on 8p22 may contribute to the excessive growth of the tumors.

Objective:To evaluate the application value of simplified augmented reality (AR) technique in the location of puncture point before drainage of supratentorial hemorrhage in the elderly.Methods:One hundred and sixty-three senile patients with supratentorial cerebral hemorrhage (amount of bleeding: 30-60 mL) treated by hematoma drainage from February 2018 to February 2020 were chosen in our study; 85 patients (observation group) were treated with AR technique assisted drainage, and 78 patients (control group) accepted drainage assisted by virtual reality (VR) technique (3D slicer software) combined with AR technique (Sina software). The differences of preoperative location time, accuracy rate of catheter placement, sufficient drainage rate of hematoma within 72 h of surgery, postoperative pulmonary infection rate, postoperative Intensive Care Unit staying time, and favorable prognosis rate were compared between the two groups.Results:The accuracy of the catheter placement (95.3% vs. 94.9%), sufficient drainage rate of hematoma within 72 h of surgery (96.5% vs. 96.2%), postoperative pulmonary infection rate (21.2% vs. 19.2%), postoperative Intensive Care Unit staying time ([75.5±16.7] h vs. [81.5±19.5] h), favorable prognosis rate (75.3% vs. 70.5%) between the observation group and control group showed no significant differences ( P>0.05), but the preoperative location time in the observation group was significantly shorter than that in the control group ([12.2±6.5] min vs. [37.5±11.3] min, P<0.05). Conclusion:On the basis of no significant difference in the accuracy and therapeutic effect of catheter placement, drainage assisted by simplified AR technique is more convenient and faster than that by VR combined with AR technique.

PURPOSE: The purpose of this study is to evaluate the effect of different wave length of low power laser on early fracture healing. METHODS AND MATERIALS: Nine week old female English Hartley guinea pigs were used for this experiment. Sixty guinea pigs were divided into three groups, and then right femur was fractured and fixed with an intramedullary nail. The frequency of 632 nm and 830 nm semi-conductor laser machines were used. Finally, 46 guinea pigs were survived (including 14 cases in control group, 16 cases in 632 nm group and 16 cases in 830 nm group). Guinea pigs were sacrificed at 3 and 6 weeks separately. The gross, radiologic and histologic findings were assessed by the Modified Zorlu Scoring System. The statistical evaluation was done by repetitive measured ANOVA test. RESULTS: In the gross findings and radiologic findings, both of 632 nm and 830 nm radiation groups showed a greater amount of callus formation at postoperative 3 weeks with statistical significance (P<0.01) compared to the control group. Quantity of callus formation in 830 nm group was larger than that in 632 nm group although there was no significant difference (P>0.05). The result of histological findings showed that an increase of osteoblastic proliferation in two radiation groups was greater than that in the control group at 3 and 6 weeks (P<0.01). Enhancement of osteoblastic proliferation was greater in 830 nm group compared to in 632 nm group at 3 weeks (P<0.05). The comparison between the experimental groups for wave length of 632 nm and 830 nm at 6 weeks showed significant difference (P<0.05). CONCLUSION: In this study, it became known that applying 632 nm and 830 nm wavelength laser to the fracture site accelerate bony union, and 830 nm wavelength laser showed earlier bony union than 630 nm wavelength laser.
Animals ; Bony Callus ; Female ; Femur ; Fracture Healing* ; Guinea Pigs ; Humans ; Osteoblasts

Objective:To investigate the value of CT angiography (CTA) point sign in the treatment of patients with moderate amount basal ganglia hemorrhage at ultra-early stage by trephination and drainage or craniotomy, and its influence in the prognoses.Methods:One hundred and twenty-six patients with moderate amount basal ganglia hemorrhage (30-60 mL) admitted to our hospital from March 2017 to March 2019 were chosen in our study; these patients were evaluated and conformed to have the same tolerance of craniotomy or drainage; and their families agreed to the ultra-early surgical treatments; their clinical data were retrospectively collected. They all accepted CTA before operation. Among them, 68 were into the craniotomy group, including 38 into CTA spot sign negative sub-group and 30 into positive sub-group; 58 were into the trephination and drainage group, including 39 into CTA spot sign negative sub-group and 19 into positive sub-group. The differences of favorable prognosis rate and postoperative re-hemorrhage rate were compared between the craniotomy group and trephination and drainage group, as well as each two sub-groups.Results:The favorable prognosis rate and postoperative re-hemorrhage rate of patients in the craniotomy group (61.8% and 2.9%) were significantly lower as compared with those in the trephination and drainage group (82.8% and 15.5%, P<0.05). In the craniotomy group, the favorable prognosis rate and postoperative re-hemorrhage rate in the CTA spot sign positive sub-group (60.0% and 4.8%) were higher than those in the negative sub-group (63.2% and 2.1%), without significant differences ( P>0.05); in the trephination and drainage group, the favorable prognosis rate and postoperative re-hemorrhage rate in the CTA spot sign positive sub-group (63.2% and 36.8%) were significantly different as compared with those in the negative sub-group (92.3% and 5.1%, P<0.05). Conclusion:Among patients with moderate amount basal ganglia hemorrhage, prognoses can be effectively improved in the following treatments: if the patients have negative CTA spot sign, are evaluated to have low risk of postoperative re-hemorrhage after craniotomy or drainage, and are considered that the prognosis by drainage is better than that by craniotomy, trephination and drainage should be selected; if the patients have positive CTA spot sign, and are evaluated to have lower risk of postoperative re-hemorrhage by craniotomy than that by drainage, craniotomy should be selected.

OBJECTIVETo analysis the genotypes of wild type hepatitis A virus circulated in Xinjiang Hetian of China in 2006.

METHODSThe Vp1-2A region of HAV genome was amplified and sequenced from serum samples collected in Xinjiang Hetian of China in 2006, and subjected to phylogenetic analysis by Neighbor Joining (NJ) method.

RESULTSThe nucleotide sequence differences in the VP1-2A region among Xinjiang Hetian HAV strains ranged from 0%-3.9%, all belonged to sub-genotype 1A. Genetically similar strains were identified among Xinjiang Hetian 2006 and Xinjiang Yili 2005 of China isolates. Only 0-2 amino acid differences were found among the Xinjiang Hetian HAV isolates in the VP1-2A region.

CONCLUSIONThere were different HAV strains existing in the investigated areas, these strains may have different transmission pathways for the spread of the disease. The results indicate the usefulness of molecular epidemiological methods in studying changes in the circulating HAV strains and in tracing transmission routes, and also for effectively control measures to prevent the spread of the disease.

China ; epidemiology ; Genotype ; Hepatitis A ; epidemiology ; immunology ; virology ; Hepatitis A Antibodies ; blood ; Hepatitis A Virus, Human ; classification ; genetics ; immunology ; isolation & purification ; Humans ; Molecular Sequence Data ; Phylogeny ; RNA, Viral ; blood ; genetics ; Viral Structural Proteins ; genetics

In order to improve the positional adaptability of our previously reported naphthyl diaryltriazines (NP-DATAs), synthesis of a series of novel biphenyl-substituted diaryltriazines (BP-DATAs) with a flexible side chain attached at the C-6 position is presented. These compounds exhibited excellent potency against wild-type (WT) HIV-1 with EC values ranging from 2.6 to 39 nmol/L and most of them showed low nanomolar anti-viral potency against a panel of HIV-1 mutant strains. Compounds and had the best activity against WT, single and double HIV-1 mutants and reverse transcriptase (RT) enzyme comparable to two reference drugs (EFV and ETR) and our lead compound NP-DATA (). Molecular modeling disclosed that the side chain at the C-6 position of DATAs occupied the entrance channel of the HIV-1 reverse transcriptase non-nucleoside binding pocket (NNIBP) attributing to the improved activity. The preliminary structure-activity relationship and PK profiles were also discussed.

Our recent studies for nonnucleoside reverse transcriptase inhibitors identified a highly potent compound JK-4b against WT HIV-1 (EC₅₀ = 1.0 nmol/L), but the poor metabolic stability in human liver microsomes (t _1/2 = 14.6 min) and insufficient selectivity (SI = 2059) with high cytotoxicity (CC₅₀ = 2.08 μmol/L) remained major issues associated with JK-4b. The present efforts were devoted to the introduction of fluorine into the biphenyl ring of JK-4b, leading to the discovery of a novel series of fluorine-substituted NH₂-biphenyl-diarylpyrimidines with noticeable inhibitory activity toward WT HIV-1 strain (EC₅₀ = 1.8-349 nmol/L). The best compound 5t in this collection (EC₅₀ = 1.8 nmol/L, CC₅₀ = 117 μmol/L) was 32-fold in selectivity (SI = 66,443) compared to JK-4b and showed remarkable potency toward clinically multiple mutant strains, such as L100I, K103N, E138K, and Y181C. The metabolic stability of 5t was also significantly improved (t _1/2 = 74.52 min), approximately 5-fold higher than JK-4b in human liver microsomes (t _1/2 = 14.6 min). Also, 5t possessed good stability in both human and monkey plasma. No significant in vitro inhibition effect toward CYP enzyme and hERG was observed. The single-dose acute toxicity test did not induce mice death or obvious pathological damage. These findings pave the way for further development of 5t as a drug candidate.

Objective: The docking and superantigen activity sites of staphylococcal enterotoxin-like W (SElW) and T cell receptor (TCR) were predicted, and its SElW was cloned, expressed and purified. Methods: AlphaFold was used to predict the 3D structure of SElW protein monomers, and the protein models were evaluated with the help of the SAVES online server from ERRAT, Ramachandran plot, and Verify_3D. The ZDOCK server simulates the docking conformation of SElW and TCR, and the amino acid sequences of SElW and other serotype enterotoxins were aligned. The primers were designed to amplify selw, and the fragment was recombined into the pMD18-T vector and sequenced. Then recombinant plasmid pMD18-T was digested with BamHⅠand Hind Ⅲ. The target fragment was recombined into the expression plasmid pET-28a(+). After identification of the recombinant plasmid, the protein expression was induced by isopropyl-beta-D- thiogalactopyranoside. The SElW expressed in the supernatant was purified by affinity chromatography and quantified by the BCA method. Results: The predicted three-dimensional structure showed that the SElW protein was composed of two domains, the amino-terminal and the carboxy-terminal. The amino-terminal domain was composed of 3 α-helices and 6 β-sheets, and the carboxy-terminal domain included 2 α-helices and 7 antiparallel β-sheets composition. The overall quality factor score of the SElW protein model was 98.08, with 93.24% of the amino acids having a Verify_3D score ≥0.2 and no amino acids located in disallowed regions. The docking conformation with the highest score (1 521.328) was selected as the analysis object, and the 19 hydrogen bonds between the corresponding amino acid residues of SElW and TCR were analyzed by PyMOL. Combined with sequence alignment and the published data, this study predicted and found five important superantigen active sites, namely Y18, N19, W55, C88, and C98. The highly purified soluble recombinant protein SElW was obtained with cloning, expression, and protein purification. Conclusions: The study found five superantigen active sites in SElW protein that need special attention and successfully constructed and expressed the SElW protein, which laid the foundation for further exploration of the immune recognition mechanism of SElW.
Humans ; Enterotoxins/genetics* ; Superantigens/genetics* ; Catalytic Domain ; Selenoprotein W/metabolism* ; Receptors, Antigen, T-Cell