BACKGROUND: There are few multi-city studies on the association between temperature and mortality in basin climates. This study was based on the Sichuan Basin in southwest China to assess the association of basin temperature with non-accidental mortality in the population and with the temperature-related mortality burden. METHODS: Daily mortality data, meteorological and air pollution data were collected for four cities in the Sichuan Basin of southwest China. We used a two-stage time-series analysis to quantify the association between temperature and non-accidental mortality in each city, and a multivariate meta-analysis was performed to obtain the overall cumulative risk. The attributable fractions (AFs) were calculated to access the mortality burden attributable to non-optimal temperature. Additionally, we performed a stratified analyses by gender, age group, education level, and marital status. RESULTS: A total of 751,930 non-accidental deaths were collected in our study. Overall, 10.16% of non-accidental deaths could be attributed to non-optimal temperatures. A majority of temperature-related non-accidental deaths were caused by low temperature, accounting for 9.10% (95% eCI: 5.50%, 12.19%), and heat effects accounted for only 1.06% (95% eCI: 0.76%, 1.33%). The mortality burden attributable to non-optimal temperatures was higher among those under 65 years old, females, those with a low education level, and those with an alternative marriage status. CONCLUSIONS Our study suggested that a significant association between non-optimal temperature and non-accidental mortality. Those under 65 years old, females, and those with a low educational level or alternative marriage status had the highest attributable burden.
Female ; Humans ; China/epidemiology* ; Cities ; Cold Temperature ; Hot Temperature ; Mortality ; Temperature ; Time Factors ; Middle Aged ; Male

Neuronomodulation refers to the modulation of neural conduction and synaptic transmission (i.e., the conduction process involved in synaptic transmission) of excitable neurons via changes in the membrane potential in response to chemical substances, from spillover neurotransmitters to paracrine or endocrine hormones circulating in the blood. Neuronomodulation can be direct or indirect, depending on the transduction pathways from the ligand binding site to the ion pore, either on the same molecule, i.e. the ion channel, or through an intermediate step on different molecules. The major players in direct neuronomodulation are ligand-gated or voltage-gated ion channels. The key process of direct neuronomodulation is the binding and chemoactivation of ligand-gated or voltage-gated ion channels, either orthosterically or allosterically, by various ligands. Indirect neuronomodulation involves metabotropic receptor-mediated slow potentials, where steroid hormones, cytokines, and chemokines can implement these actions. Elucidating neuronomodulation is of great significance for understanding the physiological mechanisms of brain function, and the occurrence and treatment of diseases.
Ligands ; Neurons/metabolism* ; Synaptic Transmission/physiology* ; Ion Channels/metabolism* ; Hormones/metabolism*

Objective     To explore the timing and safety of limited-period lung cancer surgery in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods     Clinical data of of patients infected with COVID-19 undergoing lung cancer surgery (an observation group) in the Department of Thoracic Surgery of Guangdong Provincial People's Hospital, the Department of Thoracic Surgery of General Hospital of Southern Theater Command of PLA, and the Department of Cardiothoracic Surgery of the First Affiliated Hospital of Guangdong Pharmaceutical University from December 2022 to January 2023 were retrospectively analyzed and compared with patients who underwent surgery during the same period but were not infected with COVID-19 (a control group), to explore the impact of COVID-19 infection on lung cancer surgery. Results     We finally included 110 patients with 73 patients in the observation group (28 males and 45 females at age of 52.62±12.80 years) and 37 patients in the control group (22 males and 15 females at age of 56.84±11.14 years). The average operation time of the observation group was longer than that of the control group, and the incidence of anhelation was higher than that of the control group (P<0.05). There were no statistcal differences in blood loss, length of hospital stay, moderate or above fever rate, degree of cough and chest pain, or blood routine between the two groups. Conclusion    It is safe and feasible to perform lung cancer surgery early after recovery for COVID-19 patients with lung cancer.

Humans ; COVID-19 ; Quarantine ; Renal Dialysis ; SARS-CoV-2 ; Hospitals

Immunosuppressive cells in the pancreatic cancer microenvironment play an important role in tumor development. Various immunosuppressive cytokines are secreted by these cells. Immunosuppressive cells may also influence the chemotherapeutic effect as well as promote drug resistance. Gemcitabine, albumin-bound paclitaxel, and other first-line chemotherapy agents not only suppress the proliferation of pancreatic cancer cells directly but also indirectly reinforce the anti-tumor effect of immune cells. However, chemo-therapeutic drugs may also induce immunosuppression, drug resistance, and tumor progression. In this review, we summarize the im-munosuppressive features of the pancreatic cancer microenvironment and its reciprocal relationship with chemotherapy, aiming to op-timize the current chemotherapy strategies from the perspective of the tumor immune microenvironment.

Objective:To study the relation between promyelocytic leukemia protein (PML) and gastric and colorectal cancers , and explore the relation between PML and epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) .Methods:The expression situations of PML ,EGFR ,and VEGF in gastric and colorectal cancer were detected by immunohistochemistry ,and their relations with tumor invasions ,lymph node metastases ,TNM stages and patients’ survival were analyzed .Results:PML was positively expressed in normal tissue adjacent to gastrointestinal cancer .The rate of PML deficiency was 33 .8% (54/160) in gastric cancer tissue ,while it was 38 .1% (64/168) in colorectal cancer tissue .PML deficiency in gastric cancer tissue was positively correlated with gastric wall invasion (P<0 .001) ,lymph node metastases (P=0 .018) and TNM stage (P<0 .001) ,and the survival period of patients with positive PML was longer than that of patients with negative PML (52 months vs 39 months , P<0 .001) .Age ,PML deficiency and TNM stage were the independent risk factors of gastric cancer prognosis .PML deficiency in colorectal cancer tissue was positively correlated with TNM stage (P=0 .012) ,and the survival period of patients with positive PML was longer than that of patients with negative PML (53 months vs 44 months , P= 0 .001) .The positive expression of EGFR was positively correlated with colorectal wall invasion (P<0 .001) ,lymph node metastases (P<0 .001) and TNM stage (P<0 .001) .PML deficiency ,TNM stage and EGFR expression were the independent risk factors of colorectal cancer prognosis .PML expression was negatively correlated with EGFR and VEGF expression (P<0 .05) .Conclusions:PML deficiency may promote the progression of gastric and colorectal cancer by up‐regulating the expression of EGFR and VEGF .PML deficiency is correlated with prognosis of gastric and colorectal cancer patients .

OBJECTIVETo investigate the expression and significance of CCL5 in patients with esophageal carcinoma.

METHODSUsing reverse transcriptase polymerase chain reaction (RT-PCR), the expressions of CCL5/CD8/granzyme B/perforin in tumor and corresponding adjacent tissues from esophageal carcinoma patients were examined. Flow cytometry (FACS) was used to detect the percentages of CD8(+) T cells and CCR5(+)CD8(+) T cells in TIL and PBMC from the patients. Transwell assay was performed to study the effect of CCL5 on the migration of T cells in vitro. T test and Spearman correlation analysis were performed.

RESULTSThe mRNA expressions of CCL5 and perforin were 0.348 2 ± 0.300 1 and 0.181 9 ± 0.118 6, respectively, in the tumor samples, while their expressions in adjacent samples were 0.279 6 ± 0.138 0 and 0.118 0 ± 0.109 8, respectively, with no statistically significant differences between them (P > 0.05 for both). The mRNA expressions of CD8 and granzyme B were significantly higher in the tumor tissues than in adjacent tissues (0.464 9 ± 0.300 8 vs. 0.279 0 ± 0.173 4, 0.648 7 ± 0.516 0 vs. 0.469 7 ± 0.259 1; P < 0.05 for both). The relative expression of CCL5 was positively correlated with that of CD8, perforin and granzyme B (r(CD8) = 0.272, P = 0.034; r(perforin) = 0.305, P = 0.026; r(granzymeB) = 0.108, P = 0.012) in the tumor sites. FACS data revealed that the proportions of CD8(+) T cells in TIL and PBMC were (45.86 ± 16.09)% and (34.05 ± 15.07)%, respectively, showing a significant difference (P = 0.022). Similarly, CCR5(+)CD8(+) T cells fraction in TIL (48.12 ± 26.75)% was much higher than that in PBMC (19.53 ± 13.67) % (P < 0.001). Transwell assay showed that CCL5 protein enhanced the migration of T cells, supporting that CCL5 is crucial for CD8(+) T cells recruitment in vivo. Intriguingly, CCL5 expression was down-regulated in advanced patients (stage IIb-IV). The accumulation of CD8(+) T cells and CCR5(+)CD8(+) T cells was strongly reduced in advanced patients, suggesting that CCL5 expression may be involved in the local control of the disease and its reduction may be involved in disease progression.

CONCLUSIONSThe current data indicate the involvement of CCL5 in the regulation of CD8(+) T cell entry into tumor lesions in esophageal carcinoma patients. This process may affect the disease status and potentially as a prognostic factor for cancer patients. Enhancing local CCL5 expression in tumor lesions may represent a novel strategy in esophageal cancer therapy.

CD8-Positive T-Lymphocytes ; Chemokine CCL5 ; metabolism ; Disease Progression ; Esophageal Neoplasms ; metabolism ; Flow Cytometry ; Humans ; Leukocytes, Mononuclear ; Lymphocytes, Tumor-Infiltrating

Objective To investigate the role of steroids on the intracellular signal transduction mechanism of nongenomic effects for L 929 cells to uptake glycine. Methods The labeled glycine in L 929 cells was measured by scintillation technique. After L 929 cells were incubated with labeled glycine and steroid and/or other chemical reagents, the effects of steroids and their mechanism were determined. Results Corticosterone, aldosterone, estradiol, dexamethone and hydrocortisone inhibited glycine uptake by L 929 cells to various extents. There was no substantial difference between the effects of bovine serum album conjugated corticosterone and corticosterone 21 sulfate on glycine uptake. The inhibitor of G protein, GDP ? S, could partially block the effects of corticosterone and aldosterone. The inhibitor of phospholipase C, neomycine, did not inhibit the effect of corticosterone. The inhibitor of protein kinase C, Chelerythrine, partially blocked the effect of corticosterone. The activator of protein kinase C (phorbol 12 myristate, 13, acetate) seemed to imitate the effect of corticosterone. The activator of cAMP, Forskolin, and the inhibitor of protein kinase A, H 89 , blocked the effect of corticosterone. Conclusion The rapid inhibitory effects of steroids on glycine uptake in L 929 cells are nongenomic, and their signal transduction is through the pathway of G protein protein kinase C.

Objective: To investigate the effect of glucocorticoid on high K + induced catecholamine secretion in PC12 cells. Methods: High performance liquid chromatography with electrochemical detection were used to measure catecholamine secreted by PC12 cells. Results:(1) After PC12 cells were pretreated with various concentration of corticosterone at 37℃ for 5 min and then stimulated with various concentration of high K + for different time periods, the inhibitory effect of corticosterone on catecholamine secretion was found in a dose dependent manner. (2) When the duration of high K + treatment was prolonged, the inhibitory effect of corticosterone on catecholamine secretion tended to be attenuated. Conclusion: Glucocorticoid can rapidly inhibit the catecholamine secretion induced by high K + in PC12 cells. [

AIM To investigate the nongenomic effects of steroids on glycine uptake in L 929 cells. METHODS L 929 cells were incubated with labeled glycine, steroids, and/or other reagents. With liquid scintillation technique, the labeled glycine in L 929 was measured. RESULTS Steroids could rapidly inhibit the glycine uptake. Action intensity of steroids was different. Effects of CORT and ALD were dose-dependent. There was no difference in effects between corticosterone 21-sulfate and B-BSA. Inhibitor for cytoplasm receptor of glucocorticoids could partially block the effect of CORT. Extracelullar Ca 2+ could influence the effect of CORT. CONCLUSION Effects of steroids on glycine uptake in L 929 cells are nongenomic. Steroids may take effect through membrane receptors. The receptors of CORT in membrane are similar to those of glucocorticoids in cytoplasm.