[Research progress of Wallis dynamic stabilization system for lumbar degenerative diseases].

Wallis dynamic stabilization system is a surgical approach in the non-fusion technique of lumbar spine, consisting of interspinous blockers and dacron artificial ligaments that provide stability to the spine while maintaining a degree of motion in the affected segment. Recent studies have demonstrated the significant benefits of Wallis dynamic stabilization system in treating lumbar degenerative diseases. It not only improves clinical symptoms, but also effectively delays complications such as adjacent segmental degeneration. This paper aims to review the literature related to the Wallis dynamic stabilization system and degenerative diseases of the lumbar spine to describe the long-term prognostic effect of this system in the treatment of such diseases. This review provides a theoretical basis and reference for selecting surgical methods to treat degenerative diseases of the lumbar spine.

Induction immune-checkpoint inhibitors for resectable oncogene-mutant NSCLC: A multicenter pooled analysis.

Despite limited efficacy of immunotherapy for advanced non-small-cell lung cancer (NSCLC) with driver mutations, whether neoadjuvant immunotherapy could be clinically valuable in those patients warrants further investigation. We utilized 40 oncogene-mutant NSCLC treated with induction immunotherapy from a large consecutive multicenter cohort. Overall response rate was 62.5% while 2 patients had disease progression. Of 39 patients that received surgery, R0 resection rate was 97.4%. The major pathological response (MPR) rate was 37.5% and the pathological complete response (pCR) rate was 12.5%. Pre-treatment PD-L1 expression was not a predictive biomarker in these patients. Median disease-free survival for all oncogenic mutation and EGFR mutation was 28.5 months. Indirect comparison through integrating CTONG1103 cohort showed neoadjuvant immunotherapy plus chemotherapy yielded the most superior efficacy among erlotinib and chemotherapy for resectable EGFR-mutant NSCLC. No MPR patients were identified with neoadjuvant immunotherapy plus chemotherapy for uncommon EGFR insertion or point mutations. Our results indicated the potential clinical feasibility of neoadjuvant immunotherapy for resectable localized oncogene-mutant NSCLC especially for EGFR-mutant NSCLC.

Preparation of Magnesium Hydroxide Flame Retardant from Hydromagnesite and Enhance the Flame Retardant Performance of EVA.

In this study, hydromagnesite, a rare natural hydrated alkaline magnesium carbonate, was used to synthesize magnesium hydroxide (MH) as a flame retardant for ethylene-vinyl acetate (EVA) to enhance its fire resistance and smoke suppression. Various concentrations of sodium hydroxide (NaOH) were used to alter the morphology and the flame-retardant efficiency of synthesized MH. EVA/MH composites were prepared through melt blending, and the influence of NaOH on the flame retardancy and mechanical properties was investigated by means of the limiting oxygen index (LOI), cone calorimeter test (CCT) and tensile test. The flame retardancy results demonstrated that composites exhibited remarkably improved flame retardant properties after introducing MH, reflected by an increase in the LOI value from 20% for neat EVA to roughly 38%. Additionally, the peak of heat release rate (pHRR), the total heat release (THR) and the peak of the smoke production rate for EVA3 were decreased by 37.6%, 20.7% and 44.4% compared with neat EVA, respectively. In the meantime, increasing char residues were also observed. The incorporation of different MH concentrations had a limited effect on the mechanical properties of the EVA/MH composites.

Real-World Scenario of Patients With Lung Cancer Amid the Coronavirus Disease 2019 Pandemic in the People's Republic of China.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) outbreak throughout the world has affected millions of people in many ways, putting a huge burden on the health care system. The ongoing outbreak of this respiratory disease has posed critical challenges to public health, research, and medical communities around the world. This study aimed at evaluating the impact of COVID-19 pandemic on patients with lung cancer in the People's Republic of China. METHODS: We collected data on 397 inpatients from a single center during 4 weeks of the pandemic (2020 group) and that of 2504 inpatients during the same period (4 wk) in the past 5 years (2015-2019 group). A questionnaire was used to investigate the medical demands of 803 patients with lung cancer at 65 hospitals in 20 provinces in the People's Republic of China during the pandemic. We evaluated the incidence data of COVID-19 in Guangdong to analyze the tendency of the pandemic and compared it with inpatient data. RESULTS: The number of hospitalizations and lung cancer-related operations had steadily increased from 2015 to 2019 but reduced by an average of 26.72% (133.8) and 57.18% (45.4) in 2020. The hospital capacity decreased by 28.00% (35 inpatient beds) during the pandemic period of infection with severe acute respiratory syndrome coronavirus 2. The pandemic caused a greater impact on medical work related to lung cancer after the Chinese New Year holiday. Patients were most concerned about long waiting times for outpatient services, inpatient beds, physical examinations, or operations (406; 50.56%); the possibility of infection with the novel coronavirus (359; 44.71%); and the difficulties in getting to a hospital owing to transportation outages (279; 34.74%). Patients in stage I and II revealed having less fear about disease progression (14 [18.18%] and four [14.81%], respectively), had lower proportions of delayed medical arrangement (15 [19.48%] and six [22.22%], respectively), and complained less about complex treatment procedures (12 [15.58%] and five [18.52%], respectively). Patients in the high-infected area (345, 56.74%) complained more frequently about longer booking periods than those in the low-infected area (61, 31.28%). CONCLUSIONS: The treatment of patients with lung cancer has been affected by the pandemic to some extent. We provide suggestions on both clinical diagnosis and treatment strategies for lung cancer to optimize the process, given the urgency of the current circumstances. The demand for medical support among patients with lung cancer or other life-threatening diseases should be given sufficient attention, especially during the current COVID-19 outbreak.

Integrated Exploitation of the Structural Diversity Space of Chemotherapy Drugs to Selectively Inhibit HER2 T798M Mutant in Lung Cancer.

An acquired T798M gatekeeper mutation in human epidermal growth factor receptor 2 (HER2) kinase can cause drug resistance to anti-HER2 chemotherapy drugs in lung cancer. Previously, the reversible pan-kinase inhibitor staurosporine has been found to selectively inhibit the HER2 T798M mutant over wild-type kinase, suggesting that the staurosporine scaffold is potentially to develop mutant-selective inhibitors. Here, we systematically evaluated the chemical space of staurosporine scaffold-based compounds in response to HER2 T798M mutation at structural, energetic and molecular levels by using an integrated analysis strategy. With this strategy, we were able to identify several novel wild-type sparing inhibitors with high or moderate selectivity, which are comparable to or even better than that of the parent compound staurosporine. Molecular modeling and structural analysis revealed that noncovalent contacts can form between the side chain of mutated residue Met798 and selective inhibitor ligands, which may improve the favorable interaction energy between the kinase and inhibitor and reduce the unfavorable desolvation penalty upon the kinase-inhibitor binding.

Promoter methylation of tumor suppressor genes in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a prevalent and fatal cancer in China and other Asian countries. Epigenetic silencing of key tumor suppressor genes (TSGs) is critical to ESCC initiation and progression. Recently, many novel TSGs silenced by promoter methylation have been identified in ESCC, and these genes further serve as potential tumor markers for high-risk group stratification, early detection, and prognosis prediction. This review summarizes recent discoveries on aberrant promoter methylation of TSGs in ESCC, providing better understanding of the role of disrupted epigenetic regulation in tumorigenesis and insight into diagnostic and prognostic biomarkers for this malignancy.

E-cadherin promotes proliferation of human ovarian cancer cells in vitro via activating MEK/ERK pathway.

AIM: E-cadherin is unusually highly expressed in most ovarian cancers. This study was designed to investigate the roles of E-cadherin in the carcinogenesis and progression of ovarian cancers. METHODS: Human ovarian adenocarcinoma cell line SKOV-3 was examined. E-cadherin gene CDH1 in SKOV-3 cells was knocked down via RNA interference (RNAi), and the resultant variation of biological behavior was observed using CCK-8 and colony formation experiment. E-cadherin-mediated Ca(2+)-dependent cell-cell adhesion was used to study the mechanisms underlying the effects of E-cadherin on the proliferation and survival of SKOV-3 cells. The expression levels of E-cadherin, extracellular signal-related kinase (ERK), phosphorylated ERK (P-ERK) were measured using Western blot assays. RESULTS: Transfection with CDH1-siRNA for 24-96 h significantly suppressed the growth and proliferation of SKOV-3 cells. E-cadherin-mediated calcium-dependent cell-cell adhesion of SKOV-3 cells resulted in a rapid increase of P-ERK, but did not modify the expression of ERK protein. The phosphorylation of ERK in the cells was blocked by pretreatment with the MEK1 specific inhibitor PD98059 (50 µmol/L), but not by the PI3K inhibitor wortmannin (1 µmol/L) or PKA inhibitor H89 (10 µmol/L). CONCLUSION: E-cadherin may function as a tumor proliferation enhancer via activating the MEK/ERK pathway in development of ovarian epithelial cancers.

TRIB3 functional Q84R polymorphism is a risk factor for metabolic syndrome and carotid atherosclerosis.

OBJECTIVE: To determine the association of TRIB3 Q84R polymorphism with metabolic syndrome (MetS) and carotid atherosclerosis. RESEARCH DESIGN AND METHODS: A case-control study enrolled 513 Chinese subjects in three groups: control, MetS, and obese. The functional TRIB3 Q84R polymorphism was genotyped among subjects undergoing carotid ultrasonography. The clinical and biochemical characteristics were determined. RESULTS: For individuals with the TRIB3 R84 allele, the odds ratio for developing MetS was 2.349 (P = 0.018), abdominal obesity 2.351 (P = 0.012), hypertriglyceridemia 2.314 (P = 0.00003), and insulin resistance 1.697 (P = 0.023). Likewise, the odds ratio for individuals with the TRIB3 R84 allele to develop thickened intima-media thickness was 2.208 (P = 0.040). CONCLUSIONS: Individuals with the functional TRIB3 Q84R polymorphism are at risk for MetS. The TRIB3 R84 allele especially predisposes to carotid atherosclerosis in part through the effects of abdominal obesity, hypertriglyceridemia, and insulin resistance.

[Effects of taurine and zinc on activity of NOS and expression of nNOS in cerebral cortex of acute hypoxic mice].

OBJECTIVE: To explore the effect of taurine and zinc on vigor of nitric oxide synthase (NOS) and the expression level of neuronal nitric oxide synthase (nNOS) in the cerebral cortex of acute hypoxic mice and the their neuroprotective effects. METHODS: Model of acute hypoxic mice was duplicated, NADPH-d histochemistry and nNOS immunohistochemistry were used to investigate the changes of NOS in different groups. RESULTS: Compared with the NS group, the anoxia endurance of the zinc sulfate group was increased 33.06%, while that of the taurine and zinc sulfate group was increased 26.83% than that of the zinc sulfate group (P < 0.05). Compared with the NS group, the number of NADPH-d positive neurons and nNOS positive neurons in cerebral cortex of zinc sulfate group were significantly decreased, while those of the taurine and zinc sulfate group were significantly decreased than the zinc sulfate group (P < 0.05). CONCLUSION: Both taurine and zinc could prolong the anoxia endurance, perhaps they might play an important role in decreasing the level of nitric oxide synthase to protect the brain against hypoxic damage.

[Protection of lithium on hippocampal cholecystokinin and nitric oxide synthase neuron in lead exposed rats].

OBJECTIVE: To investigate the effect of lithium on hippocampal cholecystokinin (CCK) and neuronal nitric oxide synthase (nNOS) positive neurons and its relationship to the learning and memory ability of lead exposed rats. METHODS: Wistar rats were randomly divided into the control group, the lead group, four lead + LiCl (3, 30, 300, 3,000 mg/kg) groups. Four lead + LiCl groups were fed with food containing 3, 30, 300, 3,000 mg/kg LiCl respectively. The lead + LiCl groups and the lead group were administered with distilled water containing 0.2% PbAc. The body weight was measured and the difference of body development was observed. Y-maze test was used for studying the effects of lead on the learning and the memory ability in rats. ABC immunohistochemistry was used for investigating the changes of CCK positive neurons in hippocampus of lead-exposed rats. RESULTS: Compared with the control group and the lead + LiCl groups, the learning and memory ability of lead exposed rats was significantly higher (P < 0.05). The number of CCK positive neurons in hippocampus lead exposed rats fed with lithium (3, 30, 300 mg/kg) was significantly higher than that in the lead exposed rats (P < 0.05). CONCLUSION: The lead may damage the learning-memory ability of the rats. It might be related to the changes of CCK positive neurons in hippocampus in lead exposed rats. The lithium of the low dose might play an important role in preventing lead-induced damages.

[Effects of zinc on activity of NOS and expression of nNOS in hippocampus of acute hypoxic mice].

AIM: To explore the effect of zinc on vigor of nitric oxide synthase (NOS) and the expression level of neuronal nitric oxide synthase (nNOS) in the hippocampus of acute hypoxic mice and the protective effects of zinc. METHODS: Model of acute hypoxic mice was duplicated, NADPH-d histochemistry and nNOS immunohistochemistry were used to investigate the changes of NOS in different groups. RESULTS: Compared with the NS group, the hypoxia endurance of the zinc group was significantly increased; the number of NOS positive neurons and nNOS positive neurons in hippocampus and CA1 were significantly decreased. CONCLUSION: Zinc might play an important role in decreasing the level of NOS in hippocampus to protect the brain against hypoxic damage.

[Inducible nitric oxide synthase gene expression in the testis of rats instilled with depleted uranium particles].

OBJECTIVE: To explore genital toxicity of depleted uranium (DU) by studying the changes of inducible nitric oxide synthase (iNOS) in the testis of rats instilled with DU particles. METHODS: Wistar rats were exposed to DU by means of different dosages of DU particles intratracheal instillation. The samples of the testis were collected 3 months later, and iNOS mRNA was determined by reverse-transcription PCR (RT-PCR). Semiquantitative analysis of the RT-PCR products was made with a transilluminator. RESULTS: iNOS mRNA was not observed in the control group. Compared with the control, there were significant increases of OD in the PCR products of all the DU groups (P < 0. 05 ); OD rose gradually from the DU 1 mg group to the DU 3 mg group, peaked in the latter, and subsided significantly in the DU 5 mg group (P < 0.05). CONCLUSION: Intratracheal instilled DU particles play a key role in iNOS mRNA expression of the rat testis. The iNOS mRNA expression will weaken when the DU dosage reaches a certain level, which may attribute to the complex of DU's chemical toxicity and radiation effects.

[Effects of lithium on rat hippocampus cholecystokinin protein expression and learning and memory].

OBJECTIVE: To investigate the effects of lithium on brain development, leaning and memory, we observed the effects of lithium chloride on rat body weight, learning ability and memory capacity. METHODS: Wistar rats were randomly divided into control group and four lithium chloride (LiCl) groups. Four LiCl groups were feed with food containing 3, 30, 300, 3000 mg/kg LiCl respectively. Control group was feed with normal food. By means of measuring the body weight, using Y-maze test and ABC immunohistochemistry, we observed the difference of the body weight gains and Y-maze training times of different groups, and the changes of CCK positive neurons in hippocampus. RESULTS: Compared with control group, 3, 30 mg/kg LiCl groups could increase the body weight and improve the ability of learning and memory of rats(P < 0.01), however, these of the rats of 300, 3000 mg/kg group were lower (P < 0.05). The numbers of CCK positive neurons in hippocampus of 3, 30, 300 mg/kg groups were significantly increased compared with control group (P < 0.05), that of 3000mg/kg group was lower than control group (P < 0.05). CONCLUSION: Low dose of lithium can improve the growth, the learning ability and the memory capacity obviously, but high dose of lithium could result in harmful effects.

[Effects of lithium on primary cultured cerebrocortical neurons of rat].

OBJECTIVE: To explore the neuroprotection and the impact on brain development of lithium, the effects of lithium salt on the growth and survival of primary cultured cerebrocortical neurons were studied. METHODS: The technique of primary cultured cerebrocortical neurons of newborn rats with serum-free medium was established, and the growth and survival of neurons treated with different doses of lithium chloride (0.625, 1.250, 2.500, 5.000, 10.000 mmol/L) were observed. The length of neuronal synapse, cell viability by MTT reduction assay were also measured. RESULTS: The neurons were brighter, germinated rapidly, the neuronal synapse lengthened markedly, and the neurons viability was also better after treated with lithium chloride. Among the five doses, 5.000 mmol/L had the best effect [(53.80 +/- 5.84) micro m, P < 0.01]. CONCLUSION: Lithium chloride can promote the growth and survival of neurons.

[Effect of taurine on NOS activity in hippocampus of rat exposed lead].

OBJECTIVE: To study the effect of taurine on lead-induced damage to the ability of learning and memory. METHODS: Using NADPH-d histochemistry method to study the change of rat NOS positive neurons in hippocampus. Rats in experimental groups were fed with different doses of lead in drinking water (0.011, 0.110 g/L), and different doses of taurine (5, 10 g/kg). RESULTS: Taurine (10 g/kg) could increase the number of NOS positive neurons in CA1 and dentate gyrus subregion in hippocampus of rats exposed to lead. The number of NADPH-d positive neurons in CA1 and dentate gyrus subregion for low lead (0.011 g/L) and high taurine (10 g/kg) group (51.80 +/- 4.68, 47.40 +/- 4.20, respectively) were higher than those in the low lead (0.011 g/L) group (41.20 +/- 5.32, 39.87 +/- 3.81, respectively, P < 0.05). CONCLUSION: Taurine may antagonize lead-induced damage to the ability of learning and memory.

[Protection of zinc on hippocampal cholecystokinin of lead-exposed rat].

OBJECTIVE: To investigate the relationship between the effects of zinc on hippocampal cholecystokinin (CCK) positive neurons and learning and memory ability of lead-exposed rats. METHODS: Thirty-six Wistar rats were divided into control group, lead-exposed group (drunk 6.15 mmol/L of lead solution) and lead-zinc group (drunk 6.15 mmol/L of lead + 3.10 mmol/L of ZnSO(4) solution) randomly. Y-maze test was used to study learning and memory ability in rats; Atomic absorption method was used to determine serum and hippocampal lead content; ABC immunohistochemistry and quantitative graphic analysis were used to investigate the changes of CCK positive neurons in different hippocampal subfields in lead-exposed rats. RESULTS: The learning and memory ability in lead-exposed rats were significantly lower (P < 0.05) while the serum and hippocampal lead content in lead-exposed rat were significantly higher (P < 0.05) than those in control and lead-zinc group. The number and optical density of CCK positive neurons in CA(1) and CA(3) areas of lead-exposed rats were significantly lower (P < 0.05) than those in control and lead-zinc group. No differences in these indexes between the control and lead-zinc group were found (P > 0.05). CONCLUSION: Lead may damage the learning and memory ability and affect the number of CCK positive neurons in lead-exposed rats. Zinc might play an important role in preventing lead-induced damages.

Nitrile biotransformations for highly efficient and enantioselective syntheses of electrophilic oxiranecarboxamides.

Catalyzed by a nitrile hydratase/amidase-containing microbial Rhodococcus sp. AJ270 whole-cell catalyst, a number of racemic trans-2,3-epoxy-3-arylpropanenitriles 1 underwent rapid and efficient hydrolysis under very mild conditions to afford 2R,3S-2-arylglycidamides 2 in excellent yield with enantiomeric excess higher than 99.5%. The overall enantioselectivity of the biotransformations originated from the combined effects of a dominantly high 2S-enantioselective amidase and low 2S-enantioselective nitrile hydratase involved in the cell. The influence of the substrates on both reaction efficiency and enantioselectivity was also discussed in terms of steric and electronic effects.