SAM protects against alveolar septal cell apoptosis in autoimmune emphysema rats.

BACKGROUND: Hypomethylation of the perforin gene promoter in CD4 + T cells, inflammation and oxidative stress, might be involved in alveolar septal cell apoptosis associated with emphysema in rats. This study aimed to investigate the effects of S-adenosylmethionine (SAM) on this kind of apoptosis in rats with autoimmune emphysema. METHODS: Twenty-four rats were randomly divided into three groups: a normal control group, a model group, and a SAM group. Pathological changes in lung tissues were observed, and the mean linear intercept (MLI) and mean alveolar number (MAN) were measured. The levels of anti-endothelial cell antibodies (AECA) in serum, alveolar septal cell apoptosis, perforin gene promotor methylation in CD4 + T cells in the spleen, and the levels of cytokines, malondialdehyde (MDA), and glutathione (GSH) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in bronchoalveolar lavage fluid (BALF) were investigated. RESULTS: The MLI, apoptosis index (AI) of alveolar septal cells, levels of AECA in serum, and levels of tumour necrosis factor-α (TNF-α), matrix metalloproteinase-9 (MMP-9) and MDA in BALF were increased, while the MAN, methylation levels, and the activities of GSH, SOD and GSH-Px in BALF were decreased in the model group compared with those in the normal control group and the SAM group (all P < 0.05). The levels of interleukin-8 (IL-8) in BALF were greater in the model group than in the normal control group (P < 0.05). CONCLUSIONS: SAM protects against alveolar septal cell apoptosis, airway inflammation and oxidative stress in rats with autoimmune emphysema possibly by partly reversing the hypomethylation of the perforin gene promoter in CD4 + T cells.

Transfer of Invitro CD4 + T Cells with Hypomethylation of Perforin Promoter into Rats' Abdomens Causes Autoimmune Emphysema.

Our previous study suggested that hypomethylation of perforin promoter of CD4 + T cells might be involved in the pathogenesis of autoimmune emphysema of rats. Whether transfer of this kind of cells hypomethylated in vitro into naive immunocompetent rats also results in emphysema is unknown yet. To test the hypothesis above, thirty Sprague Dawley (SD) rats were randomly divided into three groups: a model group (n = 10), a normal control group (n = 10) and a sham operation group (n = 10). In the model group, spleen-derived CD4 + T cells of normal rats were treated with 5-azacytidine (5-Aza), complete Freund's adjuvant and Phosphate Buffered Saline (PBS), then transferred into naive immunocompetent rats. The normal control group was injected with CD4 + T lymphocytes from spleens of normal rats and the same amount of adjuvant and PBS as above. In sham operation group, normal rats were injected intraperitoneally with complete Freund's adjuvant and PBS. Histopathological evaluations (mean linear Intercept (MLI) and mean alveolar numbers (MAN)), anti-endothelial cell antibodies (AECA) in serum and bronchoalveolar lavage fluid (BALF), lung vascular endothelial growth factor (VEGF)), the apoptotic index (AI) of alveolar septal cells and the methylation levels of perforin promoter of CD4 + T cells were investigated. The levels of the methylation above and MAN were lower in the model group than in the control and the sham operation group, while the AECA in serum and BALF, VEGF, MLI and the AI were greater (all p < 0.05). The methylation levels of perforin promoter were positively correlated with the MAN (r = 0.747, p < 0.05) and negatively correlated with AI, AECA, MLI, and VEGF (r was -0.789, -0.746, -0.743, -0.660, respectively, all p < 0.05). This study suggests that transfer of invitro CD4 + T cells with hypomethylation of perforin promoter into rats causes autoimmune emphysema, possibly by increasing expression of VEGF and promoting alveolar septal cell apoptosis.

[Pollution Characteristics of Water-soluble Ions in PM2.5 During the Lantern Festival of 2021 in Zibo City].

Based on the online ion data, we have analyzed the cause of a PM2.5 pollution episode, which happened during the Lantern Festival in Zibo in 2021. The pollution characteristics of water-soluble ion components were analyzed, the formation mechanism of secondary inorganic ions (SNA) was discussed, and the changes in the liquid water content (LWC) and pH value of particulate matter before and after pollution were comparatively analyzed. The results showed that the pollution period before the Lantern Festival (T1) and the pollution period at night (T2) ρ(WSIIs) during the Lantern Festival were 46.83 µg·m-3 and 71.18 µg·m-3, respectively, which were 2.3 times and 3.6 times that of the cleaning period, respectively. Among them, the growth multiple of SNA during the T1 period was greater[ρ(NO3-) was 2.9 times, ρ(SO42-) was 2.8 times, and ρ(NH4+) was 2.4 times] than the growth multiple of PM2.5 (2.1 times), which showed that the increase in SNA concentration during the T1 period was the main reason for the increase in PM2.5 concentration. Furthermore, the Cl-, K+, and Mg2+ concentrations, which were 4.0, 14.8, and 16.5 times that of the cleaning period, respectively, increased significantly during the T2 period, indicating that the fireworks and firecrackers caused the rapid increase in the PM2.5 concentration during the T2 period. The LWC during the pollution period was 49.37 µg·m-3, which was 2.9 times that of the cleaning period. LWC was mainly affected by RH and NH4+ during the T1 period and was also affected by Mg2+ during the T2 period. The average pH during the pollution period in Zibo was 4.79±1.54, which was 0.14 lower than that during the cleaning period. The pH during the T1 period was affected by the combined effects of SO42- and NH4+, which made it decrease 0.53 compared to that during the cleaning period. The pH value during the T2 period may be affected by the K+, Cl-, and Mg2+ emitted from the fireworks and firecrackers, causing the pH to increase 0.65 compared to that during the cleaning period. The formation mechanism showed that SO42- was mainly generated by heterogeneous hydrolysis during the pollution episode, whereas NO3- was mainly generated by homogeneous reactions. On the whole, during the pollution episode, the increase in PM2.5 concentration before the Lantern Festival was mainly caused by the increase in SNA concentration, and the increase the night of the Lantern Festival was mainly caused by setting off fireworks and firecrackers.

A Low-Producing Haplotype of Interleukin-6 Disrupting CTCF Binding Is Protective against Severe COVID-19.

Interleukin6 (IL-6) is a key driver of hyperinflammation in COVID-19, and its level strongly correlates with disease progression. To investigate whether variability in COVID-19 severity partially results from differential IL-6 expression, functional single-nucleotide polymorphisms (SNPs) of IL-6 were determined in Chinese COVID-19 patients with mild or severe illness. An Asian-common IL-6 haplotype defined by promoter SNP rs1800796 and intronic SNPs rs1524107 and rs2066992 correlated with COVID-19 severity. Homozygote carriers of C-T-T variant haplotype were at lower risk of developing severe symptoms (odds ratio, 0.256; 95% confidence interval, 0.088 to 0.739; P = 0.007). This protective haplotype was associated with lower levels of IL-6 and its antisense long noncoding RNA IL-6-AS1 by cis-expression quantitative trait loci analysis. The differences in expression resulted from the disturbance of stimulus-dependent bidirectional transcription of the IL-6/IL-6-AS1 locus by the polymorphisms. The protective rs2066992-T allele disrupted a conserved CTCF-binding locus at the enhancer elements of IL-6-AS1, which transcribed antisense to IL-6 and induces IL-6 expression in inflammatory responses. As a result, carriers of the protective allele had significantly reduced IL-6-AS1 expression and attenuated IL-6 induction in response to acute inflammatory stimuli and viral infection. Intriguingly, this low-producing variant that is endemic to present-day Asia was found in early humans who had inhabited mainland Asia since ∼40,000 years ago but not in other ancient humans, such as Neanderthals and Denisovans. The present study suggests that an individual's IL-6 genotype underlies COVID-19 outcome and may be used to guide IL-6 blockade therapy in Asian patients. IMPORTANCE Overproduction of cytokine interleukin-6 (IL-6) is a hallmark of severe COVID-19 and is believed to play a critical role in exacerbating the excessive inflammatory response. Polymorphisms in IL-6 account for the variability of IL-6 expression and disparities in infectious diseases, but its contribution to the clinical presentation of COVID-19 has not been reported. Here, we investigated IL-6 polymorphisms in severe and mild cases of COVID-19 in a Chinese population. The variant haplotype C-T-T, represented by rs1800796, rs1524107, and rs2066992 at the IL-6 locus, was reduced in patients with severe illness; in contrast, carriers of the wild-type haplotype G-C-G had higher risk of severe illness. Mechanistically, the protective variant haplotype lost CTCF binding at the IL-6 intron and responded poorly to inflammatory stimuli, which may protect the carriers from hyperinflammation in response to acute SARS-CoV-2 infection. These results point out the possibility that IL-6 genotypes underlie the differential viral virulence during the outbreak of COVID-19. The risk loci we identified may serve as a genetic marker to screen high-risk COVID-19 patients.

lncRNA NEAT1 aggravates sepsis-induced lung injury by regulating the miR-27a/PTEN axis.

Sepsis is an acute inflammatory reaction and a cause of acute respiratory distress syndrome (ARDS). In the present study, we explored the roles and underlying mechanism of the lncRNA Nuclear enriched abundant transcript 1 (NEAT1) in ARDS. The expression levels of genes, proteins and pro-inflammatory cytokines in patients with ARDS, LPS-stimulated cells and septic mouse models were quantified using qPCR, western blotting and ELISA assays, respectively. The molecular targeting relationship was validated by conducting a dual-luciferase reporter assay. Cell proliferation was assessed using the Cell Counting Kit-8 (CCK-8) assay. The cell cycle phase was determined by flow cytometry assay. The expression levels of NEAT1 and pro-inflammatory cytokines were higher in patients with ARDS and septic models than in controls. Knockdown of NEAT1 significantly increased cell proliferation and cycle progression and prolonged mouse survival in vitro and in vivo. Mechanistically, miR-27a was identified as a downstream target of NEAT1 and directly inhibited PTEN expression. Further rescue experiments revealed that inhibition of miR-27a impeded the promoting effects of NEAT1 silence on cell proliferation and cycle progression, whereas inhibition of PTEN markedly weakened the inhibitory effects of NEAT1 overexpression on cell proliferation and cycle progression. Altogether, our study revealed that NEAT1 plays a promoting role in the progression of ARDS via the NEAT1/miR-27a/PTEN regulatory network, providing new insight into the pathologic mechanism behind ARDS.

Clinical option of pemetrexed-based versus paclitaxel-based first-line chemotherapeutic regimens in combination with bevacizumab for advanced non-squamous non-small-cell lung cancer and optimal maintenance therapy: evidence from a meta-analysis of randomized control trials.

BACKGROUND: In the era of immunotherapy, it is still unclear which is the best first-line therapy for patients with oncogenic driver negative advanced non-squamous non-small cell lung cancer (NS-NSCLC) who cannot tolerate immunotherapy, or subsequent therapy for patients with oncogenic driver positive NS-NSCLC whose disease progressed on prior targeted therapy. To assess the optimal choice of first-line and maintenance treatment regimens, we performed a meta-analysis of prospective randomized controlled clinical trials (RCTs) of patients with NS-NSCLC on bevacizumab combined with chemotherapy. METHODS: All eligible RCTs comparing pemetrexed-platinum with or without bevacizumab (PP ± B) and paclitaxel-carboplatin with bevacizumab (PC + B) as a first-line therapy, or comparing bevacizumab plus pemetrexed (Pem + B) and bevacizumab alone (B) as a maintenance treatment for advanced NS-NSCLC, were included after systematically searching web databases and meeting abstracts. The main research endpoints were comparisons of overall survival (OS) and progression-free survival (PFS). The other endpoints were objective response rate (ORR), 1-year PFS rate (PFSR1y) and major grade 3/4 treatment-related adverse events. RESULTS: Data of 3139 patients from six RCTs were incorporated into analyses. Three RCTs were included in an analysis that compared PP ± B and PC + B as a first-line therapy for advanced NS-NSCLC. Patients treated with first-line PP ± B showed similar OS and ORR, but significantly improved PFS (hazard ratio [HR], 0.88) and PFSR1y (risk ratio [RR], 0.83), as compared to patients treated with PC + B (all P < 0.05). PP ± B resulted in higher rates of grade 3/4 anemia and thrombocytopenia, but lower rates of neutropenia, febrile neutropenia, and sensory neuropathy than PC + B (all P < 0.001). The other three RCTs were included in an analysis that compared Pem + B and B as a maintenance treatment. Compared with B, Pem + B maintenance treatment resulted in significant improvements in OS (HR, 0.88), PFS (HR, 0.64), and PFSR1y (RR, 0.70), but higher rates of anemia, thrombocytopenia, and neutropenia (all P < 0.001). CONCLUSION: Although the first-line PP + B regimen had longer PFS and PFSR1y than the PC + B regimen, no OS difference was observed. Addition of pemetrexed to bevacizumab as maintenance therapy significantly improved OS compared with bevacizumab maintenance alone, but led to more toxicity.

Unexplained elevation of erythrocyte sedimentation rate in a patient recovering from COVID-19: A case report.

BACKGROUND: A disease caused by a novel coronavirus virus, named coronavirus disease 2019 (COVID-19), broke out in Wuhan, China in December 2019, and spread around the word. As of March 4, 2020, 93090 confirmed cases and 2984 deaths have been reported in more than 80 countries and territories. It has triggered global public health security. However, the features and prognosis of COVID-19 are incompletely understood. CASE SUMMARY: We here report that the erythrocyte sedimentation rate (ESR) increased in a confirmed COVID patient. The high level of ESR sustained for a long time even after the patient recovered from COVID-19, while all results related to tumor, tuberculosis, rheumatic diseases, anemia, etc. cannot explain the abnormal elevation of ESR presented in this case. CONCLUSION: Although the increased ESR cannot be explained by all existing evidence, it possibly links the abnormal pathologic change in some COVID-19 patients and negative prognosis, and provides the clue to dissect the mechanism of illness progressing in COVID-19 and its prognosis.

Indolent T cell lymphoproliferative disorder of the gastrointestinal tract: an uncommon case with lymph node involvement and the classic Hodgkin's lymphoma.

Here we describe an unusual case of an indolent CD8+ T-cell lymphoproliferative disorder in the gastrointestinal tract (ITCLD-GT) accompanied by neck lymph node infiltration and new onset of classic Hodgkin's lymphoma after two years follow-up. Previously, this 42-year-old Asian man suffered from diarrhea and abdominal pain for two years. Intestinal biopsies showed a group of small to intermediate-sized lymphocytes which were monomorphic as well as arranged in a nodular pattern with no clear boundary and were diagnosed as ITCLD-GT. He did not receive chemotherapy or have any disease progression in the gastrointestinal tract (GIT) during the follow-up until a development of neck lymphadenopathy, which led to an eventual mixed cellularity type of Hodgkin's lymphoma, one type of classic HL diagnosis. Interestingly, besides the Hodgkin's cells, the same pathological T-cells in the GIT were present in the Hodgkin's lymphoma lesions. These two pathological T cells in GIT and neck lymph node had the identical histopathological and molecular abnormalities that confirmed the abenteric distant infiltration of ITCLD-GT to the neck lymph node in this patient. This is the first case of ITCLD-GT that has a definite distant lymph node invasion. ITCLD-GT usually has a relatively good prognosis but patients with ITCLD-GT may have abenteric distant infiltration. Thus, long-term follow-up and further study of the underlying mechanisms of this process are necessary.

Toxoplasma gondii infection in patients with lung diseases in Shandong province, eastern China.

Toxoplasma gondii, an intracellular protozoan parasite, can induce various clinical symptoms. T. gondii has been considered to play an important role in the pathogenesis of lung diseases. This survey was conducted to explore the correlation between T. gondii infection and lung diseases through a case-control study carried out in Shandong province, eastern China. In the present survey, T. gondii IgG antibodies were found in 76/398 (19.10%) of patients with lung diseases, which was significantly higher (P < 0.001) than the level found in the control subjects (35/398; 8.79%) through serological diagnosis. Patients with lung cancer have the highest T. gondii seroprevalence (26.19%), followed by Pulmonary cyst (25.00%), Tuberculosis (17.07%), Pneumonia (16.33%) and chronic obstructive pulmonary disease (COPD) (16.05%). Moreover, a semi-nest PCR targeted T. gondii B1 gene was employed to detect the T. gondii DNA in the blood samples. T. gondii DNA was detected in 5.53% blood samples of patients with lung diseases and 2.51% control subjects, respectively. The present study firstly shows that T. gondii has a high probability to infect the patients with lung diseases. Thus, the potential presence of T. gondii in patients with lung diseases should be appreciated during in the course of treatment and safeguard procedures should be implemented to protect vulnerable patients with lung diseases.

Immunotherapeutic effects of allogeneic mesenchymal stem cells on systemic lupus erythematosus.

Mesenchymal stem cells have been applied to treat graft versus host disease as they have immunosuppressive ability and can overcome the major histocompatibility complex-histocompatibility barrier. The potential of allogeneic mesenchymal stem cells in treating systemic lupus erythematosus (SLE) was investigated in this study. MRL/lpr mice which can develop acquired SLE-like phenotypes were selected as an animal model. Mesenchymal stem cells obtained from green fluorescent protein-transgenic ICR mice were infused into MRL/lpr mice at either the early or late stage of disease. The dosage was 1 × 106/mice per infusion. Mice were stratified into six groups including negative controls and those receiving one, two, three, four or five doses at 2-weekly intervals. The phenotypes were monitored regularly. After treatment, the spleen CD3+CD4-CD8- T and CD19+ B cells of two-dose mesenchymal stem cell-treated mice were significantly lower than those of the phosphate-buffered saline control. In terms of reducing the severity of SLE such as hair loss, skin ulcers, proteinuria and anti-dsDNA level, mesenchymal stem cells given at the early stage responded better and mice receiving two doses of mesenchymal stem cells performed better than those receiving either a lower dose (one dose) or higher doses (three, four or five doses). In conclusion, early treatment and an optimal dose of mesenchymal stem cells can effectively suppress the murine SLE model.

Impact of pulmonary interstitial lesions on efficacy and prognosis of EGFR-TKI-treated advanced non-small cell lung cancers.

BACKGROUND: This study aimed to assess the impact of pre-existing pulmonary interstitial lesions (PIL) on the efficacy and prognosis of patients with epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitor (TKI). METHODS: Patients with advanced NSCLC harboring EGFR exon 19 deletion (E19 del) or exon 21 (E21) L858R were enrolled in this study. All patients underwent high resolution computed tomography (HRCT) chest scans prior to EGFR-TKI treatment. Pre-existing PIL was graded according to HRCT imaging (PIL 0, 1, 2, and 3). Cox proportional-hazards regression models were used to identify the prognostic factors for progression-free survival (PFS). RESULTS: A total of 134 eligible patients were enrolled. The overall objective response rate (ORR) and median PFS were 73.1% and 10.0 months (95% CI: 7.51-12.49), respectively. There were 62 (46.3%), 25 (18.7%), 28 (20.9%), and 19 (14.1%) cases of PIL grade 0, 1, 2, and 3, respectively, with median PFS and ORR of 12.9 months and 80.6%, 11.0 months and 72.0%, 10.0 months and 71.4%, and 7.0 months and 52.6%, respectively. Multivariate analysis showed that squamous cell carcinoma (vs. adenocarcinoma, HR =4.33), E21 L858R (vs. E19 del, HR =1.57), and PIL grade 3 (vs. grade 0-2, HR =1.60-2.48) were poor prognostic factors for PFS (P<0.05 for all). CONCLUSIONS: Pre-existing PIL grade is an independent prognostic factor for predicting resistance to EGFR-TKIs in patients with EGFR-mutant advanced NSCLC. Higher PIL grade suggests higher risk of early progression.

[Characterization of PM10 and PM2.5 Source Profiles for Emissions from Nonmetal Mineral Products Manufacturing Processes].

In view of the insufficient source profiles for emissions from nonmetal mineral products manufacturing processes in China, a dilution sampling system was used to collect PM10 and PM2.5 samples from glassmaking, ceramics, and firebrick manufacturing sources between February and June of 2017. The characteristics of 50 chemical components in the samples were studied to identify source profiles. The results showed that the dominant composition of particulate matter in glassmaking plant profiles was Na, with percentages ranging from 9.2% to 18.5%. Ceramics profiles were enriched in Al, Si, Ca, and Fe, with percentages ranging from 1.7% to 8.7%. Refractory brick and shale manufacturing process profiles were characterized by high abundances of SO42- (36.9%-48.1%) and NH4+ (7.7%-17.0%). Chemical components in the source profiles varied with the different fuel types and desulfurization, denitrification, and dedusting methods. The coefficients of divergence (CD) between PM2.5 and PM10 from the same process were similar except for the results from the shale manufacturing process (CD values>0.3), thus indicating that the elements profiles of PM2.5 might be similar to those in PM10. Profiles of the same particle size from different processes were significantly different from one another, with CD values ranging from 0.42 to 0.76. The CD values for float glass and medicinal glass, and the CD values for the two ceramic enterprises were relatively small. The distributions of weighted differences (R/U ratios) were used to compare the differences of components between the source profiles, and results showed that the identified components for glass manufacturing, ceramic manufacturing, fireproof bricks, and page rock bricks were Na and As, Al and Ti, NO3- and NH4+, and SO42- and NH4+, respectively.

Effects of Dynamin-related Protein 1 Regulated Mitochondrial Dynamic Changes on Invasion and Metastasis of Lung Cancer Cells.

Objective: Mitochondrial imbalance of division and fusion will lead to uncontrolled cell growth. This study investigated the effects of mitochondrial dynamics regulated by dynamin-related protein 1 (Drp1) on the invasion and metastasis of lung cancer cells at the cellular level. Methods: Lentivirus-mediated RNAi and gene overexpression vectors containing shDrp1 and Lv-Drp1 were transfected into lung adenocarcinoma cell lines 95D and A549, respectively. An MTT assay was used to assess cell viability and a cell clone assay was used to evaluate the tumorigenic ability of lentivirus-infected cells. Cell invasion and wound healing assays were used to assess cell invasiveness and the migration rate after lentivirus infection. Annexin V-APC staining was used to determine the cell apoptosis rate. Results: In 95D cells, when the Drp1 gene is overexpressed (OE) the proliferation rate and apoptosis rate were significantly higher than those in the control group (NCOE) (P < 0. 05). There was no significant difference in clone number, invasion rate, and migration rate between the two groups (P > 0. 05). The proliferation rate and clone number in the shDrp1 infected 95D cell group (KD) were significantly lower than those in the control group (NCKD) (P < 0. 05). There was no difference in apoptosis rate, invasion rate, and migration rate between h (P > 0.05). In A549 cells, unlike in 95D cells, the invasion rate of the KD group was 25% lower than that of the NCKD group (P < 0.05). After 8 hours, the cell migration rates of the two groups were basically the same, but after 24 hours, the migration rate of the KD group was 10% lower than that of the NCKD group (P < 0.05). Compared with the NCOE group, the migration rate of the OE group increased significantly (P < 0.05). Conclusion: Mitochondrial Drp1 is associated with the proliferation, invasion, and metastasis of lung adenocarcinoma cells. Inhibition of Drp1 expression may contribute to anti-tumor therapy for lung cancer.

Rational application of the first-line chemotherapy and immune checkpoint inhibitors in advanced nonsmall cell lung cancer: A meta-analysis.

OBJECTIVE: To compare the relative efficacy of immune checkpoint inhibitors (ICIs) or chemotherapy (CT) alone, or their combination modality in the first-line treatment of advanced nonsmall cell lung cancer (NSCLC). METHODS: This meta-analysis was performed on the eligible randomized controlled trials (RCTs) after searching web databases and meeting abstracts. The main research endpoints were the comparisons of median overall survival (mOS), the OS rate of 6 months (OSR6m), 1 year (OSR1y) and 2 years (OSR2y), median progression-free survival (mPFS), the PFS rate of 6 months (PFSR6m) and 1-year (PFSR1y), objective response rates (ORR), and treatment-related adverse events (TRAEs). RESULTS: Eleven RCTs comprising 6278 cases were included. In the subgroup of programmed death-ligand 1 (PD-L1) ≥50%, compared with chemotherapy, the ICIs showed similar OSR6m (P > 0.05), but significantly improved efficacy in mOS, OSR1y, OSR2y, and ORR (all P < 0.05), also had less grade ≥ 3 TRAEs. Compared with pembrolizumab alone, pembrolizumab plus CT in the subgroup of PD-L1 ≥ 50% had similar mOS, OSR6m, OSR1y, and PFSR1y (all P > 0.05), but significantly improved mPFS, PFSR6m, and ORR (all P < 0.05 for interaction). Compared with the CT group, ICIs plus CT group with PD-L1 ≥ 50% or <1% showed significant benefit in OS, PFS, and ORR (all P < 0.05). However, in the ICIs plus CT group with 1% ≤ PD-L1 ≤ 49%, only PFS and ORR showed significant benefit compared with CT group (all P < 0.05), but not for results of OS. CONCLUSIONS: The findings support the rationale for using pembrolizumab alone in the first-line treatment of PD-L1 ≥ 50% advanced NSCLC due to the similar OS and lower grade ≥ 3 TRAEs. However, the combination of ICIs and chemotherapy is strongly recommended in patients with PD-L1 ≤ 49% for significant survival benefit.

Mitochondrial separation protein inhibitor inhibits cell apoptosis in rat lungs during intermittent hypoxia.

Obstructive sleep apnoea (OSA) is a very common sleep and breathing disorder that occurs in worldwide. It is important to develop a more effective treatment for OSA to overcome lung cell apoptosis during intermittent hypoxia (IH). A mitochondrial separation protein inhibitor (Mdivi-1) has been demonstrated to be a powerful tool for inhibiting apoptosis. In the present study, the protective effect and possible mechanism of apoptosis in lung cells during IH was investigated using in vivo and in vitro experiments. Following IH exposure for 4 weeks, the lung tissues of Sprague Dawley rats exhibited interstitial lesions, while Mdivi-1 reduced these pulmonary interstitial lesions. B-cell lymphoma (Bcl)-2 mRNA and protein expression levels were decreased however caspase-3, caspase-9 and dynamin-related protein 1 (Drp-1) mRNA and protein expression levels were increased. Following Mdivi-1 intervention, Bcl-2 mRNA and protein expression levels were increased while caspase-3, caspase-9 and Drp-1 mRNA and protein expression levels were decreased (P<0.05). After exposure to IH for 12 h, the apoptosis rate of WTRL1 cells in rats increased gradually with the IH time (P<0.05). Bcl-2 mRNA and protein expression levels were decreased, whereas caspase-3, caspase-9, cytochrome C (Cyt-C) and Drp-1 mRNA levels were increased, and caspase-3, caspase-9 and Drp-1 protein expression levels were increased. After Mdivi-1 intervention, Bcl-2 mRNA and protein expression levels were increased but caspase-3, caspase-9, Cyt-C and Drp-1 mRNA levels were decreased along with caspase-9, Cyt-C and Drp-1 protein expression levels which were decreased (P<0.05). The results of the present study suggest that Mdivi-1 may be a potential agent for treating OSA because it inhibits the mitochondrial pathway and reduces apoptosis.

Toxoplasma gondii Infection in Diabetes Mellitus Patients in China: Seroprevalence, Risk Factors, and Case-Control Studies.

The association between Toxoplasma gondii (T. gondii) infection and diabetes mellitus remains controversial. With the improvement of living standards, the prevalence rate of diabetes is steadily increasing in China. Thus, it is necessary to explore the possible association between toxoplasmosis and diabetes mellitus in China. Hence, case-control studies were conducted to explore the T. gondii seroprevalence and identify the risk factors and possible transmission routes of T. gondii infection in different types of diabetes, including type 1 diabetes (T1DM), type 2 diabetes (T2DM), and gestational diabetes (GDM) patients in China. Four hundred serum samples for each type of diabetes mellitus, matched with 400 control subjects for each group, were collected and examined for anti-T. gondii IgG and IgM antibodies using commercially available enzyme immunoassay kits. The total T. gondii seroprevalence in T1DM, T2DM, and GDM patients was 16.50%, 23.50%, and 21.25%, respectively. Each type of diabetes mellitus patients had a significantly higher T. gondii seroprevalence than the control subjects. Multivariate regression identified three variables as risk factors for T. gondii infection in diabetes patients, including keeping cats at home and consumption of raw oysters for T1DM patients and consumption of raw/undercooked meat and raw oysters for T2DM patients, which may help to guide future research and control policies in diabetes mellitus patients.

Diagnosis and treatment of community-acquired pneumonia in adults: 2016 clinical practice guidelines by the Chinese Thoracic Society, Chinese Medical Association.

Community-acquired pneumonia (CAP) in adults is an infectious disease with high morbidity in China and the rest of the world. With the changing pattern in the etiological profile of CAP and advances in medical techniques in diagnosis and treatment over time, Chinese Thoracic Society of Chinese Medical Association updated its CAP guideline in 2016 to address the standard management of CAP in Chinese adults. Extensive and comprehensive literature search was made to collect the data and evidence for experts to review and evaluate the level of evidence. Corresponding recommendations are provided appropriately based on the level of evidence. This updated guideline covers comprehensive topics on CAP, including aetiology, antimicrobial resistance profile, diagnosis, empirical and targeted treatments, adjunctive and supportive therapies, as well as prophylaxis. The recommendations may help clinicians manage CAP patients more effectively and efficiently. CAP in pediatric patients and immunocompromised adults is beyond the scope of this guideline. This guideline is only applicable for the immunocompetent CAP patients aged 18 years and older. The recommendations on selection of antimicrobial agents and the dosing regimens are not mandatory. The clinicians are recommended to prescribe and adjust antimicrobial therapies primarily based on their local etiological profile and results of susceptibility testing, with reference to this guideline.

First Report of Toxoplasma gondii Infection in Tuberculosis Patients in China.

In recent years, coinfection of tuberculosis (TB) and parasitosis in humans is an emerging problem in coendemic areas, which has been increasingly highlighted in developing countries. However, there is limited information about the prevalence of Toxoplasma gondii infection in TB patients. Therefore, through a case-control study, 924 TB patients hospitalized for diacrisis or treatment in northeastern and eastern China, and 924 control subjects from the general population of the same region matched with gender, age, and residence were examined for the presence of IgG and IgM antibodies to T. gondii and associated sociodemographic and behavioral characteristics in a population of TB patients. Seroprevalence of IgG antibodies to T. gondii in TB patients (122/924, 13.2%) was significantly higher than control subjects (90/924, 9.7%) (p = 0.019), and 26 (2.8%) TB patients and 19 (2.1%) controls were positive for anti-T. gondii IgM antibodies (p = 0.291), respectively. Multivariate analysis showed that T. gondii infection was associated with keeping cats at home, presence of stray cats, and consumption of raw/undercooked meat. The present study first revealed the seroprevalence of T. gondii infection in TB patients in China. Moreover, parasitological surveys should be regularly carried out among TB patients, aiming to prevent the possibility of severe toxoplasmosis.

Hepatitis E virus seroprevalence among farmers, veterinarians and control subjects in Jilin province, Shandong province and Inner Mongolia Autonomous Region, China.

China is commonly considered to be a HEV-endemic region but limited epidemiological data for HEV among farmers and veterinarians are available. Thus, a case-control study was carried out to detect the seroprevalence and assess potential risk factors associated with the acquisition of HEV infection by farmers and veterinarians in China from July 2013 to May 2015. Three hundred veterinarians and 600 farmers recruited from Jilin province, Shandong province, and Inner Mongolia Autonomous Region and 600 control subjects matched by gender, age, and residence were detected for the presence of anti-HEV IgG and IgM antibodies using enzyme immunoassays. The seroprevalences of HEV infection in farmers, veterinarians, and control subjects were 34.8%, 26.7%, and 20.2%, respectively. Farmers (P < 0.001) and veterinarians (P = 0.027) have significantly higher seroprevalence than control subjects. The highest seroprevalence of HEV infection was detected in swine farmers (49.1%) and the lowest seroprevalence was found in cattle farmers (26.5%). In veterinarians, farm animal veterinarians have a higher seroprevalence than pet veterinarians, but the difference was not significant (P > 0.05). Residence area, contact with swine and exposure with soil were significantly associated with HEV infection in the study farmers; contact with swine and source of drinking water were significantly associated with HEV infection in the study veterinarians. These results implied the high prevalence of HEV and the considerable potential for the dissemination of HEV infection in farmers and veterinarians in China. J. Med. Virol. 89:872-877, 2017. © 2016 Wiley Periodicals, Inc.