[Effect of peripheral blood inflammatory indicators on the efficacy of immunotherapy in patients with advanced non-small cell lung cancer and chronic obstructive pulmonary disease].

Objective: To investigate the impact of peripheral blood inflammatory indicators on the efficacy of immunotherapy in patients with advanced non-small cell lung cancer (NSCLC) complicated with chronic obstructive pulmonary disease (COPD). Methods: A retrospective cohort study was performed to include 178 patients with Ⅲ-Ⅳ NSCLC complicated with COPD who received at least 2 times of immunotherapy in Xinqiao Hospital of the Army Medical University from January 2019 to August 2021. Baseline peripheral blood inflammatory indicators such as interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α) were collected within 2 weeks before the first treatment, with the last one being on or before February 7, 2022. X-tile software was used to determine the optimal cut-off value of peripheral blood inflammatory indicators. The Cox multivariate regression models were used to analyze the factors affecting progression free survival (PFS) and overall survival (OS). Results: Among the 178 patients, there were 174 males (97.8%) and 4 females (2.2%); the age ranged from 42 to 86 (64.3±8.3) years old.There were 30 cases (16.9%) of immunotherapy monotherapy, 114 cases (64.0%) of immunotherapy combined with chemotherapy, 21 cases (11.8%) of immunotherapy combined with antivascular therapy, and 13 cases (7.3%) of immunotherapy combined with radiotherapy. The median follow-up period was 14.5 months (95%CI: 13.6-15.3 months). The objective response rate (ORR) and disease control rate (DCR) were 44.9% (80/178) and 90.4% (161/178) for the whole group, the median PFS was 14.6 months (95%CI: 11.6-17.6 months), and the median OS was 25.7 months (95%CI: 18.0-33.4 months). The results of Cox multivariate analysis showed that IL-6>9.9 ng/L (HR=5.885, 95%CI: 2.558-13.543, P<0.01), TNF-α>8.8 ng/L (HR=3.213, 95%CI: 1.468-7.032, P=0.003), IL-8>202 ng/L (HR=2.614, 95%CI: 1.054-6.482, P=0.038), systemic immune inflammatory index (SII)>2 003.95 (HR=2.976, 95%CI: 1.647-5.379, P<0.001) were risk factors for PFS, and advanced lung cancer inflammation index (ALI)>171.15 was protective factor for PFS (HR=0.545, 95%CI: 0.344-0.863, P=0.010). IL-6>9.9 ng/L(HR=6.124, 95%CI: 1.950-19.228, P<0.002), lactate dehydrogenase (LDH)>190.7 U/L (HR=2.776, 95%CI: 1.020-7.556, P=0.046), SII>2 003.95 (HR=4.521, 95%CI: 2.241-9.120, P<0.001) were risk factors for OS, and ALI>171.15 was a protective factor for OS (HR=0.434, 95%CI: 0.243-0.778, P=0.005). Conclusion: Baseline high levels of IL-6, TNF-α, IL-8, SII, LDH, and low levels of ALI are risk factors for poor prognosis in patients with advanced NSCLC-COPD receiving immunotherapy.

[Effect of preimplantation genetic testing for aneuploidies on pregnancy outcome in patients with unexplained recurrent spontaneous abortion].

Objective: To investigate the effect of preimplantation genetic testing for aneuploidies (PGT-A) on pregnancy outcome and perinatal outcome of single live birth in patients with unexplained recurrent spontaneous abortion (URSA). Methods: The clinical data of 351 cycles of the first transfer of a blastocyst through whole embryo freezing in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from 2019 to 2021 were retrospectively analyzed. According to whether PGT-A was performed before the transfer, the patients were divided into two groups: the PGT-A group (160 cycles) and the control group (191 cycles) were treated with in vitro fertilization/intracytoplasmic sperm microinjection (IVF/ICSI). To adjust for confounding factors, propensity score matching (PSM) was carried out in a 1∶1 ratio between the two groups of patients. After matching, 98 patients in the PGT-A group and 98 patients in the control group were compared for pregnancy outcome and perinatal outcome of singleton live births. Results: Before PSM, the female age in the PGT-A group was (33.6±4.0) years, lower than that in the control group (34.5±4.5) years (P=0.049). Male age in the PGT-A group was (33.6±4.1) years, lower than that in the control group (35.3±5.1) years (P<0.001). There were statistically significant differences between the two groups in infertility factors, female body mass index (BMI), years of infertility, number of spontaneous abortions, basal follicle stimulating hormone (FSH), endometrial thickness on the day of transfer and the percentage of high-quality blastocysts (all P values<0.05); After PSM, there was a statistically significant difference in fertilization methods and infertility factors between the two groups (P<0.05), while other differences were not statistically significant (all P values>0.05); There were statistically significant differences between the two groups in implant rate [63.3% (62 cycles) vs. 49.0% (48 cycles), P=0.044], clinical pregnancy rate [63.3% (62 cycles) vs. 49.0% (48 cycles), P=0.044], and live birth rate [42.9% (42 cycles) vs. 28.6% (28 cycles), P=0.037]. There was no statistically significant difference in perinatal outcomes between the PGT-A group and the control group in obtaining single birth live births (P>0.05). Conclusion: Compared with conventional IVF/ICSI assisted pregnancy, PGT-A assisted pregnancy significantly improves implantation rate, clinical pregnancy rate, and live birth rate in URSA patients. PGT-A improves the pregnancy outcomes in URSA patients but not perinatal outcomes in patients with singleton live births.

[Similarities and differences of myocardial metabolic characteristics between HFpEF and HFrEF mice based on LC-MS/MS metabolomics].

Objective: To reveal the similarities and differences in myocardial metabolic characteristics between heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) mice using metabolomics. Methods: The experimental mice were divided into 4 groups, including control, HFpEF, sham and HFrEF groups (10 mice in each group). High fat diet and Nω-nitroarginine methyl ester hydrochloride (L-NAME) were applied to construct a"two-hit"HFpEF mouse model. Transverse aortic constriction (TAC) surgery was used to construct the HFrEF mouse model. The differential expression of metabolites in the myocardium of HFpEF and HFrEF mice was detected by untargeted metabolomics (UHPLC-QE-MS). Variable importance in projection>1 and P<0.05 were used as criteria to screen and classify the differentially expressed metabolites between the mice models. KEGG functional enrichment and pathway impact analysis demonstrated significantly altered metabolic pathways in both HFpEF and HFrEF mice. Results: One hundred and nine differentially expressed metabolites were detected in HFpEF mice, and 270 differentially expressed metabolites were detected in HFrEF mice. Compared with the control group, the most significantly changed metabolite in HFpEF mice was glycerophospholipids, while HFrEF mice presented with the largest proportion of carboxylic acids and their derivatives. KEGG enrichment and pathway impact analysis showed that the differentially expressed metabolites in HFpEF mice were mainly enriched in pathways such as biosynthesis of unsaturated fatty acids, ether lipid metabolism, amino sugar and nucleotide sugar metabolism, glycerophospholipid metabolism, arachidonic acid metabolism and arginine and proline metabolism. The differentially expressed metabolites in HFrEF mice were mainly enriched in arginine and proline metabolism, glycine, serine and threonine metabolism, pantothenate and CoA biosynthesis, glycerophospholipid metabolism, nicotinate and nicotinamide metabolism and arachidonic acid metabolism, etc. Conclusions: HFpEF mice have a significantly different myocardial metabolite expression profile compared with HFrEF mice. In addition, biosynthesis of unsaturated fatty acids, arachidonic acid metabolism, glycerophospholipid metabolism and arginine and proline metabolism are significantly altered in both HFpEF and HFrEF mice, suggesting that these metabolic pathways may play an important role in disease progression in both types of heart failure.

[Therapeutic effect of amniotic membrane-fibrin sealant cement on severe ocular surface alkali burn in rabbits].

Objective To prepare a biologically active amniotic membrane powder and explore its preservation conditions, and to evaluate the efficacy of the amniotic membrane (AM)-fibrin sealant (FS) cement made from the amniotic powder on the rabbit severe ocular surface alkali burn model. Methods Experimental research. Fresh AM was air-dried, cooled with liquid nitrogen, ground into amniotic powder and sterilized by radiation. The expression of transformed growth factor, nerve growth factor receptor (NGFR), hepatocyte growth factor (HGF), epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) after preparation and 10, 20 and 30 days after storage at room temperature, 4 ℃ and -20 ℃ was tested and compared with that in the fresh AM. The AM-FS cement containing different concentrations of amniotic powder and no amniotic powder was diluted. Rabbit corneal epithelial cells were cultured for 72 hours. The effects of different concentrations of amniotic powder on epithelial cell growth were observed by light microscopy, and the amniotic powder concentration with the largest absorbance value at 450 nm was selected for subsequent animal experiments. Thirty-two right eyes of 32 rabbits as the severe ocular surface alkali burn model were divided using the random counting method into the AM-FS cement group, fresh AM transplantation group, FS group and antibiotic control group (8 rabbits each group) and given different interventions. After weekly observation of corneal repair, hematoxylin and eosin staining, immunohistochemical staining of monocyte chemotaxis protein 1 (MCP-1)and vascular endothelial growth factor (VEGF) were performed and detected by light microscopy at 28 days. The logFC values of the growth factor or receptor expression difference ratio were corrected by BH; the data were analyzed by t-test and analysis of variance. Results: The expression of TGF in the amniotic membrane powder compared with the fresh amniotic membrane group (logFC=-0.11), and the expression of NGFR (HGF, EGF, bFGF) was higher than that of the fresh amniotic membrane group (logFC=-2.07, 0.72, 0.46, 2.62; P<0.05); the expression of HGF, bFGF and EGF in amniotic membrane powder stored for 10 days and 20 days were no lower than fresh amniotic membrane; at 30 days, the expression of growth factors or receptors except HGF and bFGF were decreased, and HGF, bFGF and EGF were no less than 4 ℃ and -20 ℃.The maximum A value was obtained for 0.25 mg/ml of the amniotic membrane powder after 72 hours of the CEC culture 0.98±0.05. The corneal recovery was better in the AM-FS and fresh amniotic membrane transplant groups, with corneal turbidity scores of 3.75±0.46 and 3.50±0.46, respectively, on 28 days, lower than antibiotics (4.29±0.45) (t=2.480, 3.629; P=0.019, 0.001). The corneal neovascular area in the antibiotic control group was compared with the other three groups (t=4.040, 4.339, 2.820; all P<0.001); the corneal neovascular area in the AM-FS group was (9.88±0.20) and (18.96±0.18) mm2 at 7 and 28 days. The corneal neovascularization area at 7 and 28 days in the fresh AM group [(9.54±0.22) and (18.08±0.96) mm2] was smaller than the AM-FS group (t=3.085, 3.017, P=0.005, 0.005). Despite the tiny statistical difference (0.34, 0.88), there was no clinical difference. Hematoxylin and eosin staining showed corneal structures were intact in the AM-FS and fresh AM groups, the epithelial arrangement became normal, and the corneal healing was superior to the FS and antibiotic control groups. Immunohistochemistry showed that the positive expression of VEGF in the fresh AM group was weaker than that in the remaining three groups. MCP-1 was expressed to a similar extent in the AM-FS and fresh AM groups. Conclusions: The active cytokine had high expression and stable properties at room temperature. The AM-FS cement containing 0.25 mg/ml amniotic powder can promote the repair of corneal epithelium, reduce inflammatory reaction and corneal neovascularization after alkali burning in rabbit eyes.

[Prevalence and risk factors for pterygium in six rural regions of Yunnan Province].

Objective: To investigate the prevalence and risk factors of pterygium in the rural population aged 40 years and above of 12 ethnic groups in 6 regions of Yunnan Province. Methods: This was a cross-sectional study. According to the method of multistage stratified sampling, samples of the rural population aged 40 years and above were collected from 12 ethnic groups (Han, Yi, Tibetan, Lisu, Bai, Naxi, Zhuang, Miao, Dai, Jingpo, Hani, and Lahu) in six areas (Diqing, Lijiang, Wenshan, Dehong, and Pu'er) of Yunnan Province from March 2019 to November 2019. Anterior segment examination was carried out in the target population with a hand-held slit-lamp, according to which pterygium was diagnosed, while the posterior segment of the eye was assessed by direct ophthalmoscopy. A field questionnaire survey was also conducted. A two-level model was used to study the effects of the location, nationality, sex, age, occupation, outdoor activities, smoking, and alcohol consumption on the prevalence of pterygium, with the ethnic group as the high level and the individual as the low level. Results: Among 9 617 subjects, the total prevalence rate of pterygium was 22.6%, which was adjusted to 19.6% according to the age and gender data of the Statistics Bureau of Yunnan Province. There was significant difference in prevalence of pterygium among six regions after adjusting for age and sex (χ2=146.50, P<0.001). The prevalence of pterygium was the highest in Wenshan (29.4%), followed by Chuxiong (24.4%), Diqing (17.5%), Pu'er (17.5%), Dehong (15.8%), and Lijiang (15.7%) (χ2=146.50, P<0.001). The results of the single factor analysis showed that there was statistically significant difference among different groups of age, gender, nationality, location, history of smoking, drinking, eating habits, sleeping time, continuous use of eye drops, temperature, humidity, altitude, longitude, latitude, and ultraviolet ray (P<0.05). However, the results of the multivariate analysis showed that the main risk factors of pterygium were female(OR=1.357,95%CI:1.173~1.568), advanced age(OR=1.540,95%CI:1.301~1.823), location(OR=1.713,95%CI:1.000~2.667), continuous use of eye drops(OR=1.177,95%CI:1.034~1.340), and more than 40 years of alcohol drinking(OR=1.525, 95%CI: 1.108~2.099), and the protective factor was more than 40 years of smoking(OR=0.723,95%CI:0.544~0.960). Conclusions: The prevalence of pterygium varies greatly among different regions in Yunnan Province. The main factors affecting the prevalence are sex, age, region, smoking history, and drinking history.

[Present situation and countermeasures of technical support system of occupational disease prevention and control in China].

Objective: To analyze the current situation and existing problems of the technical support system for occupational disease prevention and control in china, and to put forward development measures and suggestions. Methods: In January 2021, a cluster method was used to conduct a questionnaire survey on the relevant institutions of national occupational disease prevention and control technology support. Mainly investigate the development of occupational disease prevention and control centers (institutes) , municipal and county-level disease control centers, occupational health examination, occupational disease diagnosis and occupational health intermediary services. Data are described by number and composition ratio (%) , and descriptive analysis is made on the data. Results: As of December 2020, there were 140 occupational disease prevention and control centers (institutes) nationwide, an increase of 65 compared with 2019. There were 323 municipal and 2704 county-level centers for disease control and prevention, accounting for 97.00% (323/333) and 95.01% (2704/2846) of the total number of centers for disease control and prevention. There were 4520 occupational health examination institutions, 587 occupational disease diagnosis institutions, 1093 occupational health technical service institutions and 623 radiological health technical service institutions. Conclusion: The supporting force and ability of occupational disease prevention and control technology need to be improved, and the strength of occupational disease prevention and control hospitals (institutes) is still weak; The municipal and county-level centers for disease control and prevention need to further improve their conditions and capabilities; The number of occupational health examination, occupational disease diagnosis, treatment and rehabilitation institutions was relatively insufficient.

[Eosinophilic solid and cystic renal cell carcinoma: a clinicopathological analysis of four cases].

Objective: To study the clinicopathological characteristics and prognosis of eosinophilic solid and cystic renal cell carcinoma (ESC RCC). Methods: The clinical pathologic data of 4 cases of ESC RCC diagnosed and treated from 2017 to 2019 at the Second Hospital of Longyan City, the Second Affiliated Hospital of Fujian Medical University, and the Zhangzhou Municipal Hospital were collected. The expression of different antibodies was detected by immunohistochemistry, and the diagnosis and differentiate diagnosis were investigated. Results: The 4 ESC RCC cases included 2 males and 2 females, the average age of these patients was 40 years, ranged from 31 to 51 years. The tumors were composed of solid area mixed with giant vesicles and microcapsules of varying sizes. The cyst cavity was lined by neoplastic cells with voluminous eosinophilic cytoplasm and hobnail arrangement. The solid area appeared as diffuse flaky, dense acinar or nested arrangement, the local area was island-shaped and tubular, mixed with a small amount of histiocytes and lymphocytes. Neoplastic cells contained voluminous eosinophilic cytoplasm with obvious fine or coarse particles, eosinophilic globules in part of the cytoplasm, and intracytoplasmic vacuoles in some areas. Immunohistochemical results showed that tumor cells were CK20 expressed (3/3, 2 cases were sparsely positive and 1 case was patched strongly positive), Vimentin (4/4) and CD10 (4/4) sparsely positive, while Actin, HMB45, Melan-A, CD117 and CK7 were negative in all cases. Ki-67 proliferation index was about 1%. Two cases were followed up and the progression free survival were 18 and 24 months, respectively. Conclusions: ESC RCC has unique histomorphological manifestations, CK20(+ ) and CK7(-) are helpful for its diagnosis, and it has common molecular karyotype changes, supporting it as a unique tumor entity. The overall prognosis of the patient is good.

[Evaluation of the fresh air purification system in the classroom under heavy pollution weather].

Evaluate the effect of the fresh air purification system on the improvement of indoor PM2.5 levels in a primary school classroom in Jinan City, Shandong Province. Our purpose is to explore the optimal operating time of the fresh air system and the main factors that affect the fresh air purification system to improve indoor air quality. From December 9, 2019 to December 10, 2019, two classrooms of the same area on the third floor of a primary school building in Jinan City, Shandong Province were selected as monitoring points. During the operation of the fresh air purification system, the PM2.5 concentration in the classroom is reduced by an average of 48.1%-61.5% compared to the outdoor PM2.5 concentration. After running for about 2 hours, the indoor PM2.5 concentration decreased to a relatively stable concentration level. The operating time of the fresh air purification system, student activities between classes, indoor temperature, indoor relative humidity, and outdoor PM2.5 concentration are important factors that affect the indoor particulate removal rate. In the case of a certain amount of fresh air and indoor area, closing doors and windows and appropriately extending the operation time of the fresh air purification system can improve the air quality in the classroom to a certain extent and protect the health of students.

Cholesterol 24S-Hydroxylase overexpression increases the lipid droplet formation of human umbilical cord mesenchymal stem cells but does not affect adipocyte differentiation.

Dysregulation of the adipo-osteogenic differentiation balance of mesenchymal stem cells (MSCs), which are common progenitor cells of adipocytes and osteoblasts, has been associated with many pathophysiologic diseases, such as obesity, osteopenia, and several neurodegenerative disorders. Growing evidence suggests that lipid metabolism is crucial for maintaining stem cell homeostasis and cell differentiation, however, the detailed underlying mechanisms are largely unknown. In this study, we demonstrate that CYP46A1 genes are key determinants of MSC increasing lipid droplet formation. Brain cholesterol is synthesized in situ and cannot cross the blood-brain barrier: to be exported from the central nervous system into the blood circuit, excess cholesterol must be converted to 24S-hydroxycholesterol by the cholesterol 24-hydroxylase encoded by the CYP46A1 gene. To address this issue, we used an adenoassociated virus (AAV) gene transfer strategy to increase CYP46A1 expression in order to investigate the consequences on the human mesenchymal stem cell (hU-MSCs). CYP46A1 expression was assessed with Western blotting and quantitative reverse transcription PCR. We found that CYP46A1 expression was increased during adipogenesis, and treatment with exogenous CYP46A1 increased adipogenesis. Thus, we hypothesize that CYP46A1 overexpression in hU-MSCs would significantly enhance cholesterol turnover in the brain of hypoxic-ischemic encephalopathy (HIE). CYP46A1 can potentially serve as a specific target to modify the therapeutic and biological effects of hU-MSCs on HIE patients.

[The value of serum dehydroepiandrosterone sulfate in differential diagnosis of Cushing's syndrome].

Objective: To evaluate the changes and diagnostic value of serum dehydroepiandrosterone sulfate (DHEAS) in Cushing's syndrome (CS) with different etiologies. Methods: The study retrospectively recruited patients diagnosed as CS in Drum Tower Hospital affiliated to Nanjing University Medical School between January 2012 and June 2019, including 36 patients (8 males, 28 females, with an average age of 44 years) with Cushing disease (CD) and 64 patients (6 males, 58 females, with an average age of 39 years) with adrenal CS (ACS). Meanwhile, 97 patients diagnosed as nonfunctional adrenal adenoma (NFA) were also included as controls. Clinical characteristics, laboratory data, adrenocorticotropic hormone (ACTH), serum DHEAS level and sex-and age-adjusted DHEAS ratio of the three groups were collected. The sensitivity and specificity of DHEAS and its ratio in differential etiology diagnosis of CS were compared using receiver operating characteristic (ROC) curve analysis. Results: Compared to NFA group, ACS patients had lower DHEAS levels [0.39 (0.39, 0.63) µmol/L vs 2.96 (1.92, 4.60) µmol/L, P<0.01] and lower DHEAS ratio [0.58 (0.27, 0.98) vs 3.95 (3.08, 6.83), P<0.01]. DHEAS [6.49 (4.32, 11.63) µmol/L] and DHEAS ratio [9.17 (4.49, 15.41)] in CD patients were significantly higher compared to those in NFA and ACS patients (all P<0.01). There were 53 ACS patients (82.8%) with suppressed ACTH level (<2.2 pmol/L) and 11 patients (17.2%) with normal/high ACTH level (≥2.2 pmol/L). The level of 24 hour urine free cortisol in normal/high ACTH level group was lower than the suppressed ACTH group [(1 299±511) nmol/24 h vs (1 972±876) nmol/24 h, P=0.04]. No significant differences were found in the DHEAS and DHEAS ratio between the two groups. ROC analysis showed that the area under the curve of serum DHEAS and DHEAS ratio in diagnosing ACS from CD was 0.997 and 0.990, respectively. The optimal cut-off values for DHEAS and its ratio were 2.06 µmol/L and 2.10, respectively. The diagnostic sensitivity and specificity of DHEAS were 97.5% and 100%, and those of DHEAS ratio were 95.0% and 100%, respectively. Conclusion: There are significant differences in serum DHEAS level and DHEAS ratio between ACS and CD patients, which might be used as indicators for the identification of the two main CS etiologies, especially in the identification of ACS patients without plasma ACTH suppression from CD patients.

[Clinical features and outcomes of surgical versus conservative management in patients with subclinical Cushing's syndrome].

Objective: To examine the clinical characteristics and metabolic features of subclinical Cushing's syndrome (SCS), and determine the effects of surgical or conservative approaches on the hormone levels and metabolic comorbidities in patients with SCS, thereby providing the evidence for decision-making in SCS management. Methods: A total of 56 consecutive SCS patients were selected in Drum Tower Hospital Affiliated to Nanjing University Medical School between 2010 and 2018, with 41 patients undergoing surgical treatment and 15 patients receiving conservative therapy. Meanwhile, 56 and 68 cases of sex-and age-matched patients diagnosed as nonfunctional adrenal adenoma (NFA) and adrenal Cushing's syndrome (CS) were included respectively. Clinical characteristics of patients in different groups were compared. Hormone levels and metabolic comorbidities were also observed during follow-up. Results: There were 56 SCS patients, including 15 males and 41 females, with an age of (52.0±12.6) years. The circadian rhythms of adrenocorticotropic hormone (ACTH) and cortisol disappeared in CS and SCS groups. Compared to NFA group, patients with SCS were characterized by suppressed plasma ACTH level [2.40 (1.11, 4.33) pmol/L vs 4.23 (2.74, 6.26) pmol/L], elevated midnight cortisol level [(240±121) nmol/L vs (59±8) nmol/L] and increased cortisol level after 1 mg overnight dexamethasone suppression test [(241±130) nmol/L vs (34±12) nmol/L] (all P<0.01). The derangement of ACTH-cortisol axis was more obvious in CS patients compared to SCS patients. The prevalence of hypertension, glucose intolerance, dyslipidemia and osteopenia/osteoporosis were higher in SCS patients compared to NFA patients (75.0% vs 41.1%, 33.9% vs 12.5%, 62.5% vs 28.6%, 35.7% vs 8.9%, all P<0.05). The 24-hour urine free cortisol correlated positively with systolic blood pressure, glycated hemoglobin A1c (HbA1c) and fasting blood glucose in SCS patients (r=0.335, 0.562 and 0.463, respectively, all P<0.05). In the surgical group, body weight, body mass index (BMI) and blood pressure decreased significantly after surgery (all P<0.05). Glucose intolerance/diabetes mellitus improved in 6 of 9 patients, BMI of 4 of 11 overweight/obesity patients normalized, and hypertension in 54.5% of patients (12/22) showed improvement after surgery. However, no alterations of hormone levels and metabolic parameters were observed in conservatively-managed patients. Conclusions: Patients with SCS are characterized by mild autonomous cortisol secretion and increased risk of metabolic comorbidities. Compared with conservative management, hormone abnormalities were corrected and metabolic abnormalities were improved in some SCS patients after surgery.

Intratumoral IL17-producing cells infiltration correlate with antitumor immune contexture and improved response to adjuvant chemotherapy in gastric cancer.

BACKGROUND: Tumor IL17-producing (IL17A+) cells infiltration has different prognostic values among various cancers. The objective of this study was to assess the effect of IL17A+ cells in gastric cancer. PATIENTS AND METHODS: The study included two patient cohorts, the Cancer Genome Atlas cohort (TCGA, n = 351) and the Zhongshan Hospital cohort (ZSHC, n = 458). The TCGA and ZSHC were used for mRNA-related and cells infiltration-related analyses, respectively. The roles of IL17A mRNA and IL17A+ cells in overall survival (OS), response to adjuvant chemotherapy (ACT), and immune contexture were evaluated. Another independent cohort was included to identify the correlation between mRNA of IL17A and IL17A+ cells infiltration (the preliminary Zhongshan Hospital cohort, PZSHC, n = 21). RESULTS: The infiltration of IL17A+ cells was positively correlated with the expression of IL17A mRNA (Spearman's ρ = 0.811; P < 0.001). High IL17A mRNA expression and intratumoral IL17A+ cells were correlated with improved OS and remained to be significant after adjusted for confounders. Patients with TNM II/III disease whose tumor present higher intratumoral IL17A+ cells or lower peritumoral IL17A+ cells can benefit more from ACT. Elevated IL17A mRNA expression and increased intratumoral IL17A+ cells infiltration was associated with more antitumor mast cells and nature killer cells infiltration and less pro-tumor M2 macrophages infiltration. High IL17A mRNA expression represented a Th17 cells signature and immune response process and was correlated with increased cytotoxic GZMA, GZMB, IFNG, PRF1, and TNFSF11 expression. CONCLUSIONS: IL17A mRNA expression and intratumoral IL17A+ cells infiltration were correlated with antitumor immune contexture. IL17A+ cells infiltration could be used as an independent prognostic biomarker for OS and predictive biomarker for superior response to ACT, and further prospective validation needs to be conducted.

Association between remote diffusion-weighted imaging lesions and cerebral small vessel disease in primary intracerebral hemorrhage.

BACKGROUND AND PURPOSE: The aim of this study was to examine the association amongst remote diffusion-weighted imaging lesions (R-DWILs), imaging markers of cerebral small vessel disease (cSVD) and total cSVD burden in patients with primary intracerebral haemorrhage (ICH). METHODS: In total, 344 consecutive primary ICH patients were enrolled prospectively. R-DWILs on magnetic resonance imaging as well as four imaging markers of cSVD, including cerebral microbleeds (CMBs), white matter hyperintensities (WMHs), lacunes and enlarged perivascular spaces, were rated with validated scales. The total cSVD score was calculated by adding up these four markers. Univariate and multivariate analyses were performed. RESULTS: Remote DWI lesions were detected in 57 (16.6%) primary ICH patients. On multivariate logistic regression analysis, the presence of CMBs [odds ratio (OR) 5.26, 95% confidence interval (CI) 1.72-16.12], of high-grade WMHs (OR 4.68, 95% CI 2.01-10.90), the presence of lacunes (OR 2.69, 95% CI 1.20-6.06), mixed CMBs (OR 2.93, 95% CI 1.35-6.36), mixed lacunes (OR 3.60, 95% CI 1.25-10.37), periventricular WMHs (OR 2.19, 95% CI 1.40-3.44), deep WMHs (OR 1.92, 95% CI 1.24-2.97) and total WMHs (OR 1.52, 95% CI 1.20-1.94) were associated with the presence of R-DWILs. A significant association was also found between high-grade total cSVD score and R-DWILs (OR 1.97, 95% CI 1.36-2.84). This association remained significant in patients stratified by an age of 60 years or more than 60 years. CONCLUSIONS: Remote DWI lesions are correlated with the severity of each imaging marker of cSVD and with the total burden of cSVD.

[Influence of apatinib and VEGFR2-906T>C polymorphism on clinical outcomes of advanced non-small cell lung cancer patients].

Objective: To investigate the clinical outcomes of advanced non-small cell lung cancer (NSCLC) treated by apatinib regimens and the influence of VEGFR2-906T>C polymorphism. Methods: A total of 109 patients with advanced NSCLC who were treated by apatinib after three and more lines from March 2015 to December 2017 in the Department of Oncology of the First Affiliated Hospital of Zhengzhou University were included in this study. Overall response rates were evaluated after 2 cycles, then progression free survival (PFS) and overall survival (OS) were investigated, and safety data were recorded. Additionally, peripheral blood and the biopsy tissue specimens of some NSCLC patients were collected for the genotyping of genetic variation and VEGFR2 gene mRNA expression, respectively. The association between genotype and other characteristics and VEGFR2 gene mRNA expression were analyzed. The univariate analysis of genotypes and prognosis was carried out by Kaplan-Meier survival analysis, and multivariate analysis were adjusted by Cox regression analysis. Results: The treatment effect could be evaluated in all the 109 patients, among them, complete remission (CR) 0 case, partial remission (PR) 19 case, stable disease (SD) 58 case, progression disease (PD) 32 case. Overall response rate (ORR) was 17.43%, disease control rate (DCR) was 70.64%, median PFS was 4.35 months, median OS was 8.35 months. Of the polymorphisms analyzed, only -906T>C was of clinical significance. The prevalence of -906T>C in VEGFR2 among the study population were as follows: TT genotype 64 cases (58.72%), TC genotype 37 cases (33.94%), CC genotype 8 cases (7.34%), minor allele frequency of -906T>C was 0.24. The distribution of three genotypes was in accordance with Hardy-Weinberg Equilibrium (P=0.418). CC and TC genotype patients were merged in the comparison of clinical outcomes. The analysis of patients with different genotypes found that the ORR of CC/TC genotypes and TT genotypes were 13.33% and 20.31% (P=0.377), respectively. And the median PFS of patients with CC/TC genotype and TT genotype were 3.25 and 5.35 months, respectively, which was statistically significant (P=0.007). In terms of OS, the median OS of the two genotypes were 7.35 and 9.15 (P=0.014), respectively. Adjusted in multivariate Cox regression analysis of PFS, TC/CC genotypes were an independent factor for PFS (OR=1.83, P=0.015). The correlation between -906T>C and adverse reactions was not found in the safety analysis. Additionally, of the 69 biopsy tissue specimens, gene expression analysis was conducted. And the results show that the mRNA expression of VEGFR2 in cancer tissues of the patients with CC/TC genotypes were significantly higher than those of the TT genotype patients (P<0.001). Conclusions: Apatinib is safe and effective for patients with advanced non-small cell in multiline therapy. VEGFR2 -906T>C CC/TC genotype has a worse effect on apatinib multiline treatment in patients with advanced NSCLC.

[The effect of air test and methylene blue perfusion test on detecting the quality of anastomosis during laparoscopic rectal cancer excision (Dixon)].

Objective: To investigate the feasibility and safety of air test (AT) and methylene blue perfusion test (MBPT) to detect the quality of the anastomosis in laparoscopic rectal cancer excision (Dixon), and compare the two approaches. Methods: AT is performed by filling the pelvis with saline solution and insufflating the rectum with air through a size 22 G balloon catheter (Foley). MBPT is carried out by surrounding clean sponges around anastomosis and injecting methylene blue solution into the rectum as like as AT. The balloon catheter connected manometer,ensuring the pressure in rectum can reach 40 cmH(2)O during AT and MBPT. The presence of air bubbles and overt blue-stained spillage indicated anastomotic leaks which are were resolved during surgery. All 28 patients undergoing laparoscopic rectal excision received both AT and MBPT intraoperatively in a randomized fashion. The integrity of the anastomosis, postoperative vital signs, blood examination, drainage and postoperative imaging were analyzed. Results: All 28 patients received both tests successfully with no adverse event. MBPT Level 1 was detected in 15 cases, level 2 in 8 cases, level 3 in 5 cases. No MBPT level 4 was observed. AT level 1 was detected in 22 cases, level 2 in 5 cases, level 3 in 1 cases. No AT level 4 was founded. Three cases were diagnosed with postoperative anastomotic leakage (3/28, 10.71%), of which 2 cases were Grade B [definition and grading proposed by the international study group of rectal cancer (ISREC) in 2010]. One case was Grade C. The positive rate of MBPT was superior to AT (the McNemar testing, P<0.01). Conclusions: The two intraoperative tests are both technically feasible and safe. Compared to AT, MBPT has the advantage of localizing the leak site with a higher positive accuracy, and represents a promising standardized approach for intraoperative test of the anastomosis quality. Intraoperative repair is absolutely helpful for the level 3 and 4 intraoperative tests.

[Adrenal androgen measurement for assessing the selectivity of adrenal venous sampling in primary aldosteronism].

Objective: To investigate the usefulness of adrenal androgens for assessing the selectivity of adrenal venous sampling (AVS). Methods: Between January 2010 and December 2016, 37 consecutive patients [with an average age of (47±14) years, 16 males and 21 females] with primary aldosteronism (PA) who underwent AVS were enrolled. AVS procedures were performed with the bilateral simultaneous technique without cosyntropin stimulation. Cortisol, androstenedione, dehydroepiandrosterone (DHEA), and DHEA sulfate (DHEAS) concentrations were measured in adrenal venous (AV) and peripheral venous (PV) samples, respectively. Results: The selectivity index (SI) based on androstenedione and DHEA was higher than that of cortisol (SI-left: 13.9, 13.1 vs 6.05, P=0.006, 0.035; SI-right: 30.4, 18.5 vs 11.6, P=0.028, 0.051). However, the SI based on DHEAS was lower than that of cortisol (SI-left: 1.3 vs 6.0, P=0.002; SI-right: 1.5 vs 11.6, P=0.038). Plasma androstenedione and DHEA concentrations were positively correlated with cortisol and aldosterone in AV samples (all P<0.001). Compared to cortisol, the variation ratio of AV androstenedione and DHEA was lower from t(-15) to t(0) (0.23, 0.43 vs 0.52, both P<0.05). Using the receiver operating characteristic curve, a SI ≥ 3.0 for androstenedione or DHEA provided optimal sensitivity(97.7%, 91.9%) and specificity (93.8%, 93.8%) in AVS. Conclusion: Given the greater AV/PV ratios and reduced variability compared to cortisol, the adrenal androgens androstenedione and DHEA are useful for assessing the selectivity of AVS without cosyntropin stimulation and may be superior analytes in conditions with marked variability of cortisol levels or with adrenocortical tumors co-secreting cortisol and aldosterone.

[A study on alterations in mitochondrial biological characteristics during cellular senescence of human embryonic lung fibroblasts].

Objective: To study the alterations of mitochondrial biological characteristics during both cellular replicative and premature senescence induced by hydrogen peroxide in human embryonic lung fibroblasts (HEFs). Methods: The premature senescence was induced by 400 µmol/L H(2)O(2) once a day at the same time and with 2 hours each time, after four consecutive days the premature senescence models were classified into premature senescence initiation group (PSi) and premature senescence persistence group (PSp). Based on the life span of HEFs, the cell replicative senescence was divided into five groups included young-age (22 PDL), middle-age (35 PDL), replicative senescence (49 PDL), PSi and PSp. The mitochondrial distribution, relative content, adenosine triphosphate (ATP) contents, 8-hydroxydeoxyguanosine (8-OHdG) levels, the relative mitochondrial transcription factor A (TFAM) as well as mitochondrial DNA methyltransferase 1 (mtDNMT1) mRNA levels, mtDNA copy number, the relative TFAM protein level and the total enzyme activity of mitochondrial DNA methyltransferases (mtDNMTs) were detected in five senescence groups. Results: The mtDNA copy number, 8-OHdG contents, level of mtDNMT1 mRNA and mtDNMTs activity in 49 PDL group were higher than those in 22 PDL group (all P values <0.05); The level of 8-OHdG in PSi was higher than that in 22 PDL group (P<0.05); The ATP contents, mtDNA copy number, the mRNA and protein expression levels of TFAM and mtDNMTs activity of PSp were higher than those in 22 PDL group (all P values<0.05). Conclusion: During the cellular senescence of HEFs, the higher mtDNA copy number and mtDNMTs activity were common features regardless of replicative or premature senescence, with possibility that oxidative stress was involved in modifying the occurrence of premature senescence.

Forensic Analysis of 52 Corpses Found in Wells.

OBJECTIVES: To explore the forensic pathological characteristics of corpses in wells, and to summarize the differences in corpses between homicide and suicide, so as to provide references for forensic analysis of such cases. METHODS: Data of 52 corpses found in wells （51 cases） in Xuchang, Henan Province from 2004 to 2016 were retrospectively collected, and descriptive statistics were performed on the dead individuals, time of death, wells, autopsies, and diatom testings. RESULTS: The proportion of males and females in the 52 corpses was 1∶2.5, and 42 people were at the age of >20-50 years （80.8%）. The accuracy of the death time inference were 75.0% and 54.2% within 8 d and 8 d or more after the actual death time, respectively. Most of the wells （84.3%） were small ones with big wellhead diameters of 60-100 cm. The death causes in homicide cases were mainly mechanical injury and suffocation （90.3%） with heads downwards （58.1%）, but that in suicide cases was mostly drow-ning （85.0%） with heads upwards （65.0%） and body surface abrasions （95.0%）. CONCLUSIONS: Cases of corpses in wells should be comprehensively analyzed according to scene inspections, autopsies, and auxi-liary tests combined with inspection results.

Toward Scalable Boson Sampling with Photon Loss.

Boson sampling is a well-defined task that is strongly believed to be intractable for classical computers, but can be efficiently solved by a specific quantum simulator. However, an outstanding problem for large-scale experimental boson sampling is the scalability. Here we report an experiment on boson sampling with photon loss, and demonstrate that boson sampling with a few photons lost can increase the sampling rate. Our experiment uses a quantum-dot-micropillar single-photon source demultiplexed into up to seven input ports of a 16×16 mode ultralow-loss photonic circuit, and we detect three-, four- and fivefold coincidence counts. We implement and validate lossy boson sampling with one and two photons lost, and obtain sampling rates of 187, 13.6, and 0.78 kHz for five-, six-, and seven-photon boson sampling with two photons lost, which is 9.4, 13.9, and 18.0 times faster than the standard boson sampling, respectively. Our experiment shows an approach to significantly enhance the sampling rate of multiphoton boson sampling.

High-efficient catalytic reduction of 4-nitrophenol based on reusable Ag nanoparticles/graphene-loading loofah sponge hybrid.

Noble metal nanoparticles (NPs) such as Au and Ag have shown many applications in the field of catalysis, sensing etc. due to their excellent photoelectric properties. But agglomeration and a low recovery rate are big problems for their applications. In this research, a novel Ag NPs/graphene (reduced graphene oxide)-loading loofah sponge (Ag NPs/RGO-LS) was synthesized through a one-step reduction method. Where the RGO is used as a nano-support with the high specific surface area and the high conductivity to prevent the agglomeration of Ag NPs and provide a conductive layer. The natural, green, low-cost and high-yield LS is designed as a macro-support to reduce the loss of Ag NPs during recycling. The as-prepared Ag NPs/RGO-LS is stable, uniform, and exhibits high efficiency and reusability in the catalytic reduction of 4-nitrophenol (4-NP) with a high rate constant of 1.893 min-1 as well as an average conversion of 98% in 6 min during five cycles. The results have not only paved the way for the wide application of Ag NPs but also provide a new road for the application of other metal NPs.