The Predictive Efficacy of Tumor Mutation Burden (TMB) on Nonsmall Cell Lung Cancer Treated by Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.

BACKGROUND: Nonsmall cell lung cancer (NSCLC) is the most common type of lung cancer, and the majority of NSCLC patients are diagnosed at the advanced stage. Chemotherapy is still the main treatment at present, and the overall prognosis is poor. In recent years, immunotherapy has developed rapidly. Immune checkpoint inhibitors (ICIs) as the representative have been extensively applied for treating various types of cancers. Tumor mutation burden (TMB) as a potential biomarker is used to screen appropriate patients for treatment of ICIs. To verify the predictive efficacy of TMB, a systematic review and meta-analysis were conducted to explore the association between TMB and ICIs. METHOD: PubMed, EMBASE, Cochrane Library, and son on were systematically searched from inception to April 2020. Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were estimated. RESULTS: A total of 11 studies consisting of 1525 nonsmall cell lung cancer (NSCLC) patients were included. Comparison of high and low TMB: pooled HRs for OS, 0.57 (95% CI 0.32 to 0.99; P = 0.046); PFS, 0.48 (95% CI 0.33 to 0.69; P < 0.001); ORR, 3.15 (95% CI 2.29 to 4.33; P < 0.001). Subgroup analysis values: pooled HRs for OS, 0.75 (95% CI 0.29 to 1.92, P = 0.548) for blood TMB (bTMB), 0.44 (95% CI 0.26 to 0.75, P = 0.003) for tissue TMB (tTMB); for PFS, 0.54 (95% CI 0.29 to 0.98, P = 0.044) and 0.43 (95% CI 0.26 to 0.71, P = 0.001), respectively. CONCLUSIONS: These findings imply that NSCLC patients with high TMB possess significant clinical benefits from ICIs compared to those with low TMB. As opposed to bTMB, tTMB was thought more appropriate for stratifying NSCLC patients for ICI treatment.

Changes in electrical conduction of ventricular myocardium during hypothermic ischemia-reperfusion in rats with arrhythmia / 中华麻醉学杂志

Objective:To evaluate the changes in the electrical conduction of ventricular myocardium during hypothermic ischemia-reperfusion (I/R) in rats with arrhythmia.Methods:Healthy clean-grade adult male Sprague-Dawley rats, aged 2-3 months, weighing 200-300 g, were studied.The hearts were removed and retrogradely perfused with oxygenated K-H solution in a Langendorff apparatus. Sixteen isolated hearts were divided into 2 groups ( n=8 each) using a random number table method: normal control group (group C) and hypothermic I/R group (group I/R). In group C, the heart was perfused with K-H solution at 37 ℃ for 120 min.In group I/R, the heart was perfused with K-H solution at 37 ℃ for 30 min, and then perfusion was stopped, cardiac arrest was induced through injecting Thomas solution (4 ℃), the area around the heart was protected with low temperature (4 ℃) Thomas solution, and hearts were perfused with 4 ℃ Thomas solution at 30 min after cardiac arrest and with 37 ℃ K-H solution for 30 min staring from 60 min after cardiac arrest.The rats in group I/R were further divided into high-risk subgroup (I/R-H subgroup) and low-risk subgroup (I/R-L subgroup). The time of spontaneous recovery of heart beat and development of arrhythmia were recorded.At the end of reperfusion, the atrioventricular conduction 2∶1 block point (2∶1B) and ventricular electrical conduction velocity (CV) were measured and recorded by program-controlled electrical stimulation. Results:Compared with group C, CV and 2∶1B were significantly decreased in IR-L and IR-H subgroups ( P<0.05). Compared with IR-L subgroup, the time for restoration of spontaneous heart beat was significantly prolonged, the incidence of ventricular fibrillation and arrhythmia score were increased, and CV and 2∶1B were decreased in IR-H subgroup ( P<0.05). Conclusion:The electrical CV of ventricular myocardium is decreased during hypothermic I/R, which may be the mechanism of reperfusion-induced ventricular arrhythmia in rats with arrhythmia.

Role of hippocampal nNOS-PSD95 coupling in short-term memory retrieval disorder induced by sevoflurane in mice / 中华麻醉学杂志

Objective To evaluate the role of hippocampal neuronal nitric oxide synthase(nNOS)-postsynaptic dense protein 95(PSD95)coupling in short-term memory retrieval disorder induced by sevoflu-rane in mice.Methods Sixteen clean-grade healthy Kunming mice of both sexes,aged 2-3 months,weighing 30-35 g,were divided into 2 groups(n＝8 each)according to the random number table method:sevoflurane group(S group)and nNOS-PSD95 uncoupling agent ZL006 group(Z group).After successful establishment of dark avoidance memory,3.3％sevoflurane and 40％O2 were inhaled for 2 h in both groups,and normal saline 1.5 ml was intraperitoneally injected in group S and ZL006 1 mg/kg in group Z at 30 min before anesthesia.The step-through latency and error times were recorded before anesthesia and at 12 h after the end of anesthesia.The mice were then sacrificed,and hippocampal tissues were taken for de-termination of the expression of nNOS and PSD95(by Western blot)and co-expression of nNOS and PSD95(by immunoprecipitation).Results Compared with that before anesthesia,the step-through latency was significantly shortened,and the error times were increased at 12 h after anesthesia in group S(P＜0.05),and no significant change was found in the above indicators in group Z(P>0.05).Compared with group S,the step-through latency was significantly prolonged,error times were decreased,the co-expression of nNOS and PSD95 was down-regulated(P＜0.05),and no significant change was found in the expression of nNOS and PSD95 in group Z(P>0.05).Conclusion The mechanism by which sevoflurane induces short-term memory retrieval disorder may be related to promoting the coupling of nNOS to PSD95 in the hippocam-pus of mice.

Therapeutic effect of nenoxacin on patients with adult community acquired pneumonia / 中国中西医结合急救杂志

Objective To evaluate the efficacy and safety of nemonoxacin as a combination drug in the treatment of patients with adult community acquired pneumonia (CAP) in the Department of Respiratory. Methods The data of patients with CAP treated with nemonoxacin as an agent in a combined therapy and admitted to Department of Respiratory of Shengjing Hospital of China Medical University from July to October 2018 were retrospectively analyzed. The patients' symptoms, curative effects and adverse reactions were recorded. Results Totally 48 patients with CAP were treated with combined nemonoxacin, including 6 patients with severe pneumonia. All the patients were treated with intravenous drip of β-lactams combined with oral nemonoxacin 500 mg, once a day. After 3 days of treatment, the improvement rate of symptoms was 47.92% (23/48), and 89.58% (43/48) of the patients were cured or improved after (9.83±3.49) days of treatment, no adverse reactions occurred during the period of oral administration;91.67% (44/48) of the patients were satisfied with the effect of medication. Compared with 178 CAP patients who were hospitalized in Department of Respiratory in the same period in 2017, the patients' length of stay in hospital in the present study was shorter (days: 12.52±4.45 vs. 14.53±6.73, P < 0.05). Conclusion As a combination drug, nemonoxacin is a safe and effective treatment for CAP patients admitted to Department of Respiratory, it can better control symptoms, shorten hospitalization time, induce less adverse reactions and its patients' tolerance is good.

Role of hippocampal nNOS-PSD95 coupling in short-term memory retrieval disorder induced by sevoflurane in mice / 中华麻醉学杂志

Objective@#To evaluate the role of hippocampal neuronal nitric oxide synthase (nNOS)-postsynaptic dense protein 95 (PSD95) coupling in short-term memory retrieval disorder induced by sevoflurane in mice.@*Methods@#Sixteen clean-grade healthy Kunming mice of both sexes, aged 2-3 months, weighing 30-35 g, were divided into 2 groups (n=8 each) according to the random number table method: sevoflurane group (S group) and nNOS-PSD95 uncoupling agent ZL006 group (Z group). After successful establishment of dark avoidance memory, 3.3% sevoflurane and 40% O2 were inhaled for 2 h in both groups, and normal saline 1.5 ml was intraperitoneally injected in group S and ZL006 1 mg/kg in group Z at 30 min before anesthesia.The step-through latency and error times were recorded before anesthesia and at 12 h after the end of anesthesia.The mice were then sacrificed, and hippocampal tissues were taken for determination of the expression of nNOS and PSD95 (by Western blot) and co-expression of nNOS and PSD95 (by immunoprecipitation).@*Results@#Compared with that before anesthesia, the step-through latency was significantly shortened, and the error times were increased at 12 h after anesthesia in group S (P<0.05), and no significant change was found in the above indicators in group Z (P>0.05). Compared with group S, the step-through latency was significantly prolonged, error times were decreased, the co-expression of nNOS and PSD95 was down-regulated (P<0.05), and no significant change was found in the expression of nNOS and PSD95 in group Z (P>0.05).@*Conclusion@#The mechanism by which sevoflurane induces short-term memory retrieval disorder may be related to promoting the coupling of nNOS to PSD95 in the hippocampus of mice.

Antibacterial mechanism of silver nanoparticles：a dose-dependent promotion of cell apoptosis / 中国组织工程研究

BACKGROUND:Silver nanoparticles (AgNPs) show strong antibacterial effect and are not easy to have drug resistance. But the antibacterial mechanisms of AgNPs have not been wel developed. OBJECTIVE:To explain the antibacterial mechanisms of AgNPs. METHODS:We investigated the influence of Ti, TiO2 and TiO2 containing AgNPs onEscherichia coliand Staphylococcus aureus by bacterial inhibition ring test. Escherichia coli was cultured in LB liquid medium with 0, 5, 10 mg/L AgNPs. We measured the absorbance value of bacterial culture. DNA gel electrophoresis was used to study the effect of AgNPs onEscherichia coliDNA. Then we researched the character of apoptosis on Escherichia coli by Annexin V and PI staining, using flow cytometry. RESULTS AND CONCLUSION:The inhibiting effect of Ti and TiO2 onEscherichia coliandStaphylococcus aureus was not obvious. But the inhibition rings of TiO2 containing AgNPs to bacteria appeared. The absorbance value of Escherichia coliculture was reduced whenEscherichia coliwas co-cultured with AgNPs. And this decrease tendency was in direct proportion with AgNPs concentration. AgNPs reduced the amount of DNA of Escherichia coli and this tendency was directly proportional with AgNPs concentration. TheEscherichia coli apoptosis rate induced by AgNPs was increased and this tendency was positively correlated to the AgNPs concentration. These results indicate that AgNPs can induce bacterial apoptosis to influence the growth of bacteria.

Efficacy of CO2 laser in the treatment of precancerous laryngeal lesions under phonomicrosurgery and its relative factors / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the efficacy of CO2 laser treatment for patients with precancerous laryngeal lesions under phonomicrosurgery and to explore the points for attention in operation.@*METHOD@#They were all treated with phonomicrosurgery techniques as mucosal epitheliumablation or mucosal stripping by using CO2 laser. Eight patients with laryngeal papilloma were excised by CO2 laser.@*RESULT@#All patients were treated with CO2 laser surgery successfully. During follow-up of 6 to 39 months, all patients survived. Local recurrence or canceration were detected in 3 cases, of which 2 cases with laryngeal papilloma underwent CO2 laser treatment in one year post-operatively, while the other case with severe dysplasia underwent laryngeal vertical partial laryngectomy and post-operative radiotherapy one and half year postoperatively due to canceration. No local recurrence occurred until the last follow up. No severe complications such as dyspnea and hemorrhage occured.@*CONCLUSION@#CO2 laser surgery is an effective and minimally invasive treatment for precancerous laryngeal lesions. Through selecting the appropriate patient and paying attention to the operation during surgery, the adhesion of vocal cord can be reduced or even be avoided after CO2 laser surgery.

The outcomes of endoscopic septorhinoplasty with three-line-tension-relaxing technique combined with nasal bone fracture correction for traumatic nasal septum deviation / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the feasibility and the efficacy of endoscopic three lines tension relaxing septorhinoplasty combined with nasal bone fracture correction for traumatic nasal septum deviation.@*METHOD@#Clinical data of 45 cases with traumatic nasal septum deviation treated were retrospectively analysed. These patients were performed with three lines tension relaxing septorhinoplasty and nasal bone fracture correction under endoscopy 5 to 14 days after injury.@*RESULT@#All patients were followed up for more than six months. They all achieved significant efficacy and no complications occurred.@*CONCLUSION@#Endoscopic three lines tension relaxing septorhinoplasty combined with nasal bone fracture correction can achieve satisfactory curative effect and can effectively prevent the occurrence of complications.

Analysis of clinical manifestations of rhinal and pharyngeal and laryngeal amyloidosis by 12 cases / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To discuss the clinical characteristic of rhinal and pharyngeal and laryngeal amyloidosis.@*METHOD@#Twelve cases of amyloidosis was confirmed,one case of multiple myeloma accompanied pharynx nasalis, laryngeal and facial amyloidosis was diagnosed and treated by chemotherapy in department of hematology; one case of plasmacytoma accompanied amyloidosis in right inferior turbinate concha was expected by nasal endoscope under local anesthesia and was treated by chemotherapy in department of hematology; five cases of polyps of vocal cord accompanied laryngeal amyloidosis were expected under self-retaining laryngoscope; three cases of local amyloidosis in bilateral vocal cords, subglottis and trachea were expected under self-retaining laryngoscope by polypotome and/ or CO2 laser; one case of pharyngeal amyloidosis in right tonsil was treated by tonsillectomy and the other case of local amyloidosis in lingual surface of epiglottis was expected by direct laryngoscope under general anaesthesia.@*RESULT@#One case of multiple myeloma accompanied pharynx nasalis, laryngeal and facial amyloidosis died after 18 months because of cachexia accompanied pneumonia and multiple organ failure; one case of plasmacytoma accompanied amyloidosis in right inferior turbinate concha was relapse-free followed up for 2 years; five cases of polyps of vocal cord accompanied laryngeal amyloidosis were relapse-free followed up from 1 to 3 years one case of local amyloidosis in bilateral vocal cords, subglottis and trachea was relapse-free followed up for 3 years,another case of local amyloidosis in bilateral vocal cords, subglottis and trachea recurred in 4 months after operation and the other case recurred in 6 months after operation, these two recurrence cases of local amyloidosis in bilateral vocal cords, subglottis and trachea were treated again by operation and were relapse-free followed up for 6 months; two cases of pharyngeal amyloidosis (1 case of right tonsil amyloidosis and 1 case of local amyloidosis in lingual surface of epiglottis) were relapse-free followed up for 2 years.@*CONCLUSION@#The etiology of rhinal and pharyngeal and laryngeal amyloidosis is related to multiple factor. The clinical manifestations of rhinal and pharyngeal and laryngeal amyloidosis is complicated and non-specificity. To distinguish the clinical manifestations of primary amyloidosis (locality and general), secondary amyloidosis (locality and general), amyloidosis associated multiple myeloma and heredofamilial amyloidosis is important in diagnosis and treatment to reduce diagnostic errors.

High-level expression and antimicrobial activity of recombinant N-terminal porcine lactoferrin / 生物工程学报

Lactoferrin in milk is a multifunctional protein. In addition, lactoferrin has antiviral, antifungal and antiparasitic activity. In this study, the N-terminus from porcine lactoferrin (PLF-N) was designed to express the antimicrobial action of recombinant porcine lactoferrin. We cloned a 1077 bp fragment of the PLF gene from mammary gland tissue of the lactating sow at the third day. Comparing nucleotide sequence with four strains of PLF gene published on GenBank, the homology was more than 99%. With the reference template of the cloned fragment of PLF-N and optimizing codon bias, we synthesized the gene of N-terminus encoding porcine lactoferrin (PLF-NS). The high expression gene of PLF-NS was cloned into the fusion expression vector pET30b and expressed in E. coli BL21 (DE3). After induced with Isopropyl beta-D-1-Thiogalactopyranoside (IPTG), the target fusion protein was successfully expressed and identified in inclusion bodies by SDS-PAGE and Western blotting. The protein had a molecular weight of 42 kDa and accounted for 32% of the total cellular protein. After purification and renaturation, the purity of the expressed protein was 98%. The expressed PLF-NS protein showed obviously antibacterial activity. This method provides an excellent way for high expression of antimicrobial proteins when optimizing codon bias.

Clinical analysis of the positive cases of HIV antibody in otorhinolaryngology patients / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To understand the clinical condition of the positive blood serum HIV antibody cases in otorhinolaryngology patients and explore its clinical characteristic.@*METHOD@#The positive cases in otorhinolaryngology patients were detected by the primary screening test for HIV from 2005 to 2010 , then were confirmed by the confirmation laboratory WB of CDC in Chengdu City. To analyse the results of the positive cases of HIV and collate the clinical manifestation.@*RESULT@#Totally 10 serum samples were positive by the primary screening test for HIV, among them 9 were confirmed by the confirmation laboratory, and the coincidence rate was 90.00%.@*CONCLUSION@#The positive cases by the primary screening test for HIV in otorhinolaryngology patients are increasing recently, but there are some false-positive cases. The clinical manifestation of HIV/AIDS patients are multiform because of the different stage of AIDS. To attach importance to diagnoses of HIV/AIDS in otorhinolaryngology is valuable in preventing nosocomial infection and avoiding medical staff infection due to occupational exposure and also reducing the occurrence of medical dispute.