The midgut epithelium of mosquitoes adjusts cell proliferation and endoreplication to respond to physiological challenges.

BACKGROUND: Hematophagous mosquitoes transmit many pathogens that cause human diseases. Pathogen acquisition and transmission occur when female mosquitoes blood feed to acquire nutrients for reproduction. The midgut epithelium of mosquitoes serves as the point of entry for transmissible viruses and parasites. RESULTS: We studied midgut epithelial dynamics in five major mosquito vector species by quantifying PH3-positive cells (indicative of mitotic proliferation), the incorporation of nucleotide analogs (indicative of DNA synthesis accompanying proliferation and/or endoreplication), and the ploidy (by flow cytometry) of cell populations in the posterior midgut epithelium of adult females. Our results show that the epithelial dynamics of post-emergence maturation and of mature sugar-fed guts were similar in members of the Aedes, Culex, and Anopheles genera. In the first three days post-emergence, ~ 20% of cells in the posterior midgut region of interest incorporated nucleotide analogs, concurrent with both proliferative activity and a broad shift toward higher ploidy. In mature mosquitoes maintained on sugar, an average of 3.5% of cells in the posterior midgut region of interest incorporated nucleotide analogs from five to eight days post-emergence, with a consistent presence of mitotic cells indicating constant cell turnover. Oral bacterial infection triggered a sharp increase in mitosis and nucleotide analog incorporation, suggesting that the mosquito midgut undergoes accelerated cellular turnover in response to damage. Finally, blood feeding resulted in an increase in cell proliferation, but the nature and intensity of the response varied by mosquito species and by blood source (human, bovine, avian or artificial). In An. gambiae, enterocytes appeared to reenter the cell cycle to increase ploidy after consuming blood from all sources except avian. CONCLUSIONS: We saw that epithelial proliferation, differentiation, and endoreplication reshape the blood-fed gut to increase ploidy, possibly to facilitate increased metabolic activity. Our results highlight the plasticity of the midgut epithelium in mosquitoes' physiological responses to distinct challenges.

Measurement of the Isolated Nuclear Two-Photon Decay in

The nuclear two-photon or double-gamma (2γ) decay is a second-order electromagnetic process whereby a nucleus in an excited state emits two gamma rays simultaneously. To be able to directly measure the 2γ decay rate in the low-energy regime below the electron-positron pair-creation threshold, we combined the isochronous mode of a storage ring with Schottky resonant cavities. The newly developed technique can be applied to isomers with excitation energies down to ∼100 keV and half-lives as short as ∼10 ms. The half-life for the 2γ decay of the first-excited 0^{+} state in bare ^{72}Ge ions was determined to be 23.9(6) ms, which strongly deviates from expectations.

Association of serum 25-hydroxyvitamin D with cardiovascular mortality and kidney outcome in patients with early stages of CKD.

PURPOSE: While serum 25-hydroxyvitamin D (25[OH]D) deficiency is prevalent in chronic kidney disease (CKD), the effects of 25(OH)D deficiency on cardiovascular mortality and kidney outcomes in patients with early-stage CKD remain incompletely understood. METHODS: This multicenter retrospective cohort study included adult patients with stages 1-3 CKD from 19 medical centers across China between January 2000 and May 2021. The primary outcome was cardiovascular mortality. The secondary study outcome included CKD progression (defined as a sustained > 40% eGFR decrease from baseline or progress to end-stage kidney disease), and annual percentage change of eGFR. RESULTS: Of 9229 adults with stages 1-3 CKD, 27.0% and 38.9% had severe (< 10 ng/mL) and moderate (10 to < 20 ng/mL) serum 25(OH)D deficiency, respectively. Compared with patients having 25(OH)D ≥ 20 ng/mL, a significantly higher risk of cardiovascular mortality (hazard ratio [HR] 1.90, 95% CI 1.37-2.63), CKD progression (HR 2.20, 95% CI 1.68-2.88), and a steeper annual decline in eGFR (estimate - 7.87%; 95% CI - 10.24% to - 5.51% per year) was found in those with serum 25(OH)D < 10 ng/mL. Similar results were obtained in subgroups and by sensitivity analyses. CONCLUSIONS: 25(OH)D deficiency is associated with increased risks of cardiovascular mortality and CKD progression in patients with early-stage CKD. Studies are needed to determine whether early intervention for 25(OH)D deficiency could improve the prognosis of patients with early-stage CKD.

[Cancer incidence and mortality in China, 2022].

Objective: The National Central Cancer Registry estimates the number of new cancer cases and deaths in China in 2022, using incidence and mortality data collected by the National Cancer Center. Methods: According to the data of 700 cancer registries in 2018 and the data of 106 cancer registries from 2010 to 2018, the age-period-cohort model was used to estimate the incidence rate and mortality rate of all cancers and 23 types of cancer in 2022, stratified by gender and urban and rural areas. We estimated the number of new cancer cases and deaths in China in 2022 based on the estimated rate and population data in 2022. Results: The estimated results showed that in 2022, there were approximately 4 824 700 new cancer cases in China (2 533 900 in males and 2 290 800 in females), with an age-standardized incidence rate of Chinese population (ASIR) of 208.58 per 100 000 (212.67 per 100 000 for males and 208.08 per 100 000 for females). Approximately 2 903 900 new cancer cases occurred in urban areas, with an ASIR of 212.95 per 100 000. It was estimated about 1 920 800 new cancer cases in rural areas, and the ASIR was 199.65 per 100 000. The top five cancers (lung cancer 1 060 600, colorectal cancer 517 100, thyroid cancer 466 100, liver cancer 367 700 and female breast cancer 357 200) accounted for 57.4% of all new cases. The estimated number of deaths from cancer in China in 2022 was 2 574 200 (1 629 300 in males and 944 900 in females), with an age-standardized mortality rate of Chinese population (ASMR) of 97.08 per 100 000 (127.70 per 100 000 in males and 68.67 per 100 000 in females). The number of deaths from cancer in urban and rural areas was about 1 400 600 and 1 173 400, with the ASMR of 92.37 and 103.97 per 100 000 in urban and rural areas, respectively. The top five leading cause of cancers death (lung cancer 733 300, liver cancer 316 500, gastric cancer 260 400, colorectal cancer 240 000 and esophageal cancer 187 500) accounted for 67.5% of all cancer deaths. Lung cancer ranked first in the incidence and mortality in men and women. The incidence rate in urban areas was higher than that in rural areas, while the mortality rate was lower than that in rural areas. Conclusions: The burden of cancer in China is still relatively heavy, with significant differences in cancer patterns in gender, urban-rural, and regional. The burden of cancer presents a coexistence of developed and developing countries, and the situation of cancer prevention and control is still serious in China.

[Effect of obstructive sleep apnea on the severity of acute coronary syndrome].

Objective: To investigate the effects of obstructive sleep apnea (OSA) on myocardial damage, coronary multi-vessel lesion and postoperative indexes in patients with acute coronary syndrome(ACS). Methods: The patients, admitted to the Second Affiliated Hospital of Soochow University from September 2022 to October 2023 due to chest tightness and pain, diagnosed with ACS and accompanied by emergency/elective percutaneous coronary intervention(PCI)at, were prospectively enrolled. Portable sleep monitor was used to monitor after stabilization of condition(postoperative day 2±1). The patients were divided into the OSA group (AHI≥15/h) and the control group (AHI<15/h) according to apnea-hypopnea index (AHI). The hematologic indices, echocardiographic parameters, coronary vascular scores and postoperative indicators between the groups were compared. Binary logistic regression model was used to analyze the risk factors for muti-vessel lesion in patients with ACS. Results: One hundred and four ACS patients who met the inclusion criteria were ultimately included, including 85 males (81.7%) and 19 females (18.3%), aged (57.3±10.8) years, of whom 48.1% (50/104) were complicated with OSA. Body mass index (BMI), prevalence of hypertension and diabetes, triglyceride (TG), glycosylated hemoglobin A1c (HbA1c) and D-dimer in the OSA group were higher than those in the control group (P<0.05). There were statistically significant differences in sleep parameters between the two groups (P<0.05). The patients in the OSA group exhibited higher troponin T (cTnT) [M(Q1,Q3),54.0 (9.3,343.8) ng/L vs 15.0 (7.8,38.8) ng/L, P<0.05], larger left atrial internal diameters [41.4 (39.3,45.2) mm vs 40.2 (37.1,42.0) mm, P<0.05], more diseased vessels [2 (1, 3) vs 1 (1, 2), P<0.001], a higher percentage of muti-vessel lesion[60.0%(30/50)vs 29.6%(16/54),P<0.05], and a higher incidence of cardiovascular complications during hospitalization[10.0%(5/50)vs 0(0/54), P=0.017]. The results of binary logistic regression analysis suggested that after adjusting for confounders, AHI (OR=1.035, 95%CI: 1.008-1.063, P=0.011) was independently associated with the development of muti-vessel lesion in patients with ACS. Conclusions: ACS patients with OSA suffer more severe myocardial damage, are more likely to develop structural abnormalities of left heart and multi-vessel lesion, and have a higher incidence of postoperative complications. High AHI is a risk factor for multi-vessel lesion in ACS patients.

[Comparison of the efficacy of gasless robotic surgery through transaxillary apporach and open surgery for papillary thyroid carcinoma].

Objective: To compare the efficacy of gasless robotic surgery through transaxillary approach and open surgery for papillary thyroid carcinoma (PTC). Methods: The data of patient undergoing robotic surgery through transaxillary approach and traditional open surgery for PTC at the Sun Yat-sen Memorial Hospital, Sun Yat-sen University, from November 2016 to June 2023 were retrospectively analyzed. A 1∶1 propensity score matching (PSM) was performed to balance age, sex, extent of surgery, tumor size, capsule invasion, and multifocality. Surgical data, postoperative pathological data, complications, postoperative 2-month visual analog scale (VAS) scores for aesthetics, and follow-up data were compared between the two groups. Results: A total of 728 PTC patients were included. There were 339 patients in the robotic group, among which 262 were female (77.3%) and 77 were male (22.7%), with the age of [M (Q1, Q3)] 39 (32, 46) years and a body mass index (BMI) of 22.8 (20.7, 25.0) kg/m². Meanwhile, 389 patients were in the open group, among which 290 were female (74.6%) and 99 were male (25.4%), with the age of 47 (38, 55) years and a BMI of 23.2 (21.3, 25.5) kg/m2. Further analysis after PSM (there were 264 cases in both groups) showed that in the subtotal thyroidectomy and central neck dissection (LT+CCND) subgroup, the robotic group had longer operative time, higher blood loss, and greater drainage volume compared with the open group [100 (80, 130) min vs 60 (50, 80) min; 10 (10, 20) ml vs 10 (10, 20) ml; 103 (69, 145) ml vs 75 (57, 98) ml; all P<0.001], and the central lymph node metastasis rate was higher in the robotic group [45.6% (57/125) vs 31.8% (47/148), P=0.019]. In the total thyroidectomy and central neck dissection (TT+CCND) subgroup, the robotic group also had longer operative time, higher blood loss, and greater drainage volume compared with the open group [150 (110, 180) min vs 85 (75, 100) min; 20 (10, 20) ml vs 10 (10, 20) ml; 155 (107, 206) ml vs 90 (70, 120) ml; all P<0.001]. The incidence of chest skin numbness at 3 months postoperatively was higher in the robotic group compared with the open group (12.9% vs 0, P<0.001), while there were no statistically significant differences in other postoperative complications (all P>0.05). The VAS score at 2 months postoperatively was higher in the robotic group compared with the open group [9 (9, 9) vs 8 (7, 9), P<0.001]. Three cases of contralateral lobe recurrence occurred in the open group, while there were no case of recurrence in the robotic group. The 5-year overall survival rate was 100.0% in both the robotic and open groups, and there was no statistically significant difference in the 5-year disease-free survival rate between the robotic and open groups (100.0% vs 98.6%, P=0.068). Conclusion: Gasless robotic surgery through transaxillary approach for total thyroidectomy or lobectomy in the treatment of PTC is safe, feasible, and effective, with good cosmetic outcomes and comparable efficacy to traditional surgery.

[A case of follicular lymphoma with recurrent fever and pulmonary infiltrates].

We reported a case of a 65-year-old male who had been treated with obinutuzumab and chemotherapy for follicular lymphoma. He was infected with SARS-CoV-2 after the second course of therapy. He developed fever, cough and bilateral pulmonary infiltrates. His nasopharyngeal swab became negative only temporarily after repeated courses of antiviral therapy, and the symptoms and pulmonary infiltrates waxed and waned. He presented to our hospital with exertional dyspnea and hypoxemia after his nasopharyngeal swab was positive for SARS-CoV-2 for the fourth time. He had an elevated serum lactate dehydrogenase and a positive 1, 3-ß-D-glucan test. The PCR test for Pneumocystis jirovecii in the sputum was positive. The patient was diagnosed with persistent COVID-19 and Pneumocystis jirovecii pneumonia. He responded well to the combination treatment of antiviral medication, convalescent plasma, trimethoprim-sulfamethoxazole and corticosteroids.

[Clinical research progress in non-invasive positive pressure ventilation in 2023].

Non-invasive positive pressure ventilation (NPPV) is a widely used method of providing respiratory support in a variety of clinical settings, including emergency departments, general wards, and intensive care units. The relevant research articles on NPPV published between 1st October 2022 and 30th September 2023 were retrieved from Medline and reviewed. In the management of acute respiratory failure (ARF) associated with COVID-19, studies have highlighted the significant influence of regional economic status on the choice of respiratory support strategies. It has been observed that NPPV is more suitable for patients with mild to moderate acute respiratory distress syndrome (ARDS) than for those with severe ARDS, as the latter group has an increased risk of delayed intubation. In addition, patients with severe dyspnea tended to benefit more from NPPV compared with high flow nasal cannula (HFNC) and conventional oxygen therapy, with a reduced risk of self-induced lung injury. For non-COVID-19-related ARF, research shows no significant differences in mortality and intubation rates between HFNC and NPPV in patients with hypercapnic ARF. The updated HACOR score and ROX score have been validated to have a high predictive value for clinical outcomes in patients receiving NPPV for hypoxemic ARF. With regard to weaning from invasive mechanical ventilation, immediate application of NPPV after extubation showed a lower mortality rate compared to continued invasive weaning. Moreover, NPPV with active humidification significantly decreased the reintubation rate within 7 days after extubation compared with HFNC. The choice between using NPPV and HFNC should be based on the specific etiology of the patient's condition. The potential effect of noninvasive high-frequency oscillatory ventilation on CO2 clearance was also investigated.

[Clinical analysis of COVID-19 in patients with preexisting interstitial lung abnormalities].

Objective: To describe the clinical characteristics of SARS-CoV-2 infected patients with interstitial lung abnormalities (ILA) during the COVID-19 pandemic. Methods: We respectively enrolled ILA patients who had been regularly followed up in Peking Union Medical College Hospital for more than six months since January 2021. Clinical data of these ILA patients were collected after the outbreak of COVID-19 pandemic (from December 2022 to January 2023), thirty-eight patients with preexisting ILA were enrolled. Among them, there were 34 ILA patients (20 males and 14 females) who were infected with SARS-CoV-2 during this period, with an average age of (64.0±8.8) years old (range: 41-80). There were 12 (35.3%) ILA patients who were suffered from COVID-19(pneumonia group) and others were the non-pneumonia group. The clinical characteristics, including vaccination status, features of COVID-19 and outcomes of the two groups were compared. Results: Regarding the subcategories of ILA, there were 7 cases of subpleural fibrotic ILA, 10 cases of subpleural non-fibrotic ILA, and 17 cases of non-subpleural ILA. Before SARS-CoV-2 infection, the average pulse oxygen saturation at rest was (97.38±0.87)% (range: 96%-99%); average forced vital capacity (FVC) was (97.6±18.1)% predicted (range: 65%-132%); and average diffusion capacity for carbon monoxide (DLCO) was (76.2±16.3)% predicted (range: 53%-108%). Nineteen patients had been vaccinated with 3 doses of SARS-CoV-2 vaccines, and 5 of them developed COVID-19. One patient had received one dose of vaccine and did not develop COVID-19. The other 14 patients had not been vaccinated, and seven of them developed COVID-19. Of the 12 patients with COVID-19, six were diagnosed with severe COVID-19, and the other 6 ILA patients were diagnosed with moderate COVID-19. Among them, 1 patient was complicated by deep vein thrombosis of left lower limb. All 6 patients with severe COVID-19 who were cured after systemic corticosteroids. As for the other six moderate COVID-19 patients, all were cured and/or improved greatly: two were treated with short-term oral corticosteroids, one was prescribed a dose of compound betamethasone, and the other two were not treated with systemic corticosteroids. Conclusion: Patients with ILA were predisposed to develop COVID-19 after infection with SARS-CoV-2, and more than half of them had severe COVID-19.

[Correlation between arousal threshold and occurrence of hypertension in patients with obstructive sleep apnea hypopnea syndrome].

Objective: To investigate the relationship between arousal threshold (ArTH) and hypertension in patients with obstructive sleep apnea hypopnea syndrome (OSA). Methods: This study recruited 648 patients diagnosed with OSA at the Sleep Center of the Second Affiliated Hospital of Soochow University from January 2020 to August 2021, including 569 males and 79 females, aged 42(35,52) years. The basic demographic information and clinical data of all patients were collected, including blood pressure measurement, and relevant questionnaire scores, and nocturnal polysomnography (PSG) parameters. A clinical predictive model based on sleep apnea hypopnea index (AHI), lowest pulse oxygen saturation (LSpaO2) and hypopnea ratio (FHypopneas) was used to access the arousal threshold of OSA patients. Patients were divided into OSA group and OSA with hypertension group according to whether they were combined with hypertension. The differences in the above indexes between the two groups were analyzed to explore the relationship between arousal threshold and hypertension in OSA patients, using a binary logistic stepwise regression analysis. Results: A total of 648 OSA patients were enrolled, including 415 in the OSA with hypertension group and 233 in the OSA group. Compared with OSA group, OSA with hypertension group had older age, higher body mass index (BMI), higher blood pressure at bedtime and at awakening, higher AHI and lower proportion of hypopnea (all P<0.05). There were no significant differences between other general data and PSG parameters (all P>0.05). The proportion of patients with low arousal threshold (AHI<30 events per hour, LSpO2>82.5%, Fhypopneas>58.3%) in OSA with hypertension group was lower, and the proportion of phenotypic patients with low arousal threshold was significantly lower (30.1% vs. 52.4% P<0.001). Binary logistic stepwise regression analysis showed that the high arousal threshold (OR=1.930, 95%CI:1.326-2.808, P=0.001) was an independent risk factor for OSA complicated with hypertension. Conclusion: The arousal threshold is associated with the development of hypertension in OSA patients, and OSA patients with a high arousal threshold have a higher risk of developing hypertension.

[Clinical features and prognostic analysis of checkpoint inhibitor pneumonitis in patients with non-small cell lung cancer].

Objective: To describe the clinical characteristics of patients with non-small cell lung cancer (NSCLC) who developed checkpoint inhibitor pneumonitis (CIP) and to explore potential prognostic factors. Methods: NSCLC patients who were complicated with CIP after immune checkpoint inhibitors (ICIs) therapy in our institute were enrolled in this study from 1 July 2018 to 30 November 2022. Clinical data of NSCLC-CIP patients were collected, including clinical and radiological features and their outcomes. Results: Among the 70 enrolled NSCLC-CIP patients, there were 57 males (81%) and 13 females (19%). The mean age at the diagnosis of CIP was (65.2±6.3) years. There were 46 smokers (66%), 26 patients (37%) with emphysema, 19 patients (27%) with previous interstitial lung disease, and 26 patients (37%) with a history of thoracic radiation. The mean interval from the first application of checkpoint inhibitor to the onset of CIP was (122.7±106.9) days (range: 2-458 days). The main chest CT manifestations were coincided with non-specific interstitial pneumonia (NSIP) pattern and organizing pneumonia (OP) pattern. Most patients had grade 2 (21 cases) or grade 3 (34 cases) CIP. Seventeen patients had been concurrent with other immune-related adverse events such as rash, hepatitis, colitis, and thyroiditis. Half of the enrolled patients (36 patients/51%) had fever, and most patients had elevated C-reactive protein (52 patients/72%) and all patients had elevated erythrocyte sedimentation rate (70 patients/100%). Serum lactate dehydrogenase was elevated in 34 CIP patients. Prednisone≥1 mg·kg-1·d-1 (or equivalent) was the most commonly used initial treatment in CIP patients (50 patients/71.4%). Complications with pulmonary infections (OR=4.44, P=0.03), use of anti-fungal drugs (OR=5.10, P=0.03) or therapeutic dose of sulfamethoxazole (OR=4.86, P=0.04), longer duration of prednisone≥1 mg·kg-1·d-1 (or equivalent) (Z=-2.33, P=0.02) were probable potential risk factors for poor prognosis. Conclusions: Older males with smoking history might be predisposed to develop NSCLC-CIPs after ICIs therapy. NSIP pattern and OP pattern were common chest CT manifestations. Complications with pulmonary infections (especially fungal infection or Pneumocystis jirovecii pneumonia), longer duration, longer duration of high-dose corticosteroids were likely potential risk factors for poor prognosis.

[A case of hypereosinophilia with diffuse pulmonary nodules].

We reported a case of a 36-year-old woman who presented with cough, dyspnea, hypereosinophilia, multiple pulmonary nodules and mediastinal lymphadenopathy. The percentage of eosinophils in bronchoalveolar lavage fluid (BALF) was as high as 65%. Pathogenic tests and cytologic examination of BALF were negative. Transbronchial lung biopsy and endobronchial ultrasound-guided transbronchial needle aspiration revealed only eosinophil infiltration. As the patient responded poorly to high-dose corticosteroids, a surgical lung biopsy was performed. The pathological diagnosis was angioimmunoblastic T-cell lymphoma. The patient received chemotherapy and achieved a partial response. Her eosinophil count returned to the normal range, and the pulmonary nodules on chest CT partially resolved.

[Surgical treatment and prognosis analysis of hilar cholangiocarcinoma].

Objective: To investigate the surgical treatment effect and prognostic factors of hilar cholangiocarcinoma. Methods: This is an ambispective cohort study. From August 2005 to December 2022,data of 510 patients who diagnosed with hilar cholangiocarcinoma and underwent surgical resection at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University were retrospectively collected. In the cohort,there were 324 males and 186 females,with an age of (M (IQR)) 63(13)years (range:25 to 85 years). The liver function at admission was Child-Pugh A (343 cases,67.3%) and Child-Pugh B (167 cases,32.7%). Three hundred and seventy-two(72.9%) patients had jaundice symptoms and the median total bilirubin was 126.3(197.6) µmol/L(range: 5.4 to 722.8 µmol/L) at admission. Two hundred and fourty-seven cases (48.4%) were treated with percutaneous transhepatic cholangial drainage or endoscopic nasobiliary drainage before operation. The median bilirubin level in the drainage group decreased from 186.4 µmol/L to 85.5 µmol/L before operation. Multivariate Logistic regression was used to identify the influencing factors for R0 resection,and Cox regression was used to construct multivariate prediction models for overall survival(OS) and disease-free survival(DFS). Results: Among 510 patients who underwent surgical resection,Bismuth-Corlett type Ⅲ-Ⅳ patients accounted for 71.8%,among which 86.1% (315/366) underwent hemi-hepatectomy,while 81.9% (118/144) underwent extrahepatic biliary duct resection alone in Bismuch-Corlett type Ⅰ-Ⅱ patients. The median OS time was 22.8 months, and the OS rates at 1-,3-,5-and 10-year were 72.2%,35.6%,24.8% and 11.0%,respectively. The median DFS time was 15.2 months,and the DFS rates was 66.0%,32.4%,20.9% and 11.0%,respectively. The R0 resection rate was 64.5% (329/510), and the OS rates of patients with R0 resection at 1-,3-,5-and 10-year were 82.5%, 48.6%, 34.4%, 15.2%,respectively. The morbidity of Clavien-Dindo grade Ⅲ-Ⅴ complications was 26.1%(133/510) and the 30-day mortality was 4.3% (22/510). Multivariate Logistic regression indicated that Bismuth-Corlett type Ⅰ-Ⅲ (P=0.009), hemi-hepatectomy and extended resection (P=0.001),T1 and T2 patients without vascular invasion (T2 vs. T1:OR=1.43 (0.61-3.35),P=0.413;T3 vs. T1:OR=2.57 (1.03-6.41), P=0.010;T4 vs. T1, OR=3.77 (1.37-10.38), P<0.01) were more likely to obtain R0 resection. Preoperative bilirubin,Child-Pugh grade,tumor size,surgical margin,T stage,N stage,nerve infiltration and Edmondson grade were independent prognostic factors for OS and DFS of hilar cholangiocarcinoma patients without distant metastasis. Conclusions: Radical surgical resection is necessary to prolong the long-term survival of hilar cholangiocarcinoma patients. Hemi-hepatectomy and extended resection,regional lymph node dissection and combined vascular resection if necessary,can improve R0 resection rate.

Observation of the Exotic 0_{2}

We report here the first observation of the 0_{2}^{+} state of ^{8}He, which has been predicted to feature the condensatelike α+^{2}n+^{2}n cluster structure. We show that this state is characterized by a spin parity of 0^{+}, a large isoscalar monopole transition strength, and the emission of a strongly correlated neutron pair, in line with theoretical predictions. Our finding is further supported by the state-of-the-art microscopic α+4n model calculations. The present results may lead to new insights into clustering in neutron-rich nuclear systems and the pair correlation and condensation in quantum many-body systems under strong interactions.

[Effects of obstructive sleep apnea syndrome on myocardial work and prognosis in patients with acute myocardial infarction].

Objective: To investigate the influence of obstructive sleep apnea syndrome (OSAS) on myocardial work and prognosis in patients with acute myocardial infarction (AMI). Methods: Patients with complete follow-up data diagnosed with AMI who were admitted to the Second Affiliated Hospital of Suzhou University due to chest pain within 24 hours attacks from February 2020 to January 2022 were retrospective enrolled in the study and were split into two groups based on sleep apnea hypoventilation index (AHI): OSAS group (AHI≥5/h) and non-OSAS group (AHI<5/h). Follow up for (12.4±0.1) months. There were finally 210 AMI patients including 130 males and 80 females with (69.6±9.4) years, ranging from 36 to 83 years. The general characteristics, haematological index, echocardiographic parameters, myocardial work (MW) and the occurrence of major adverse cardiac events (MACE) in 1 year between the two groups were quantified. Logistic regression analysis and receiver operating characteristic (ROC) curve were used to assess the risk of MACE in patients with AMI. Results: There were 50 cases in the OSAS group and 160 cases in the non-OSAS group. Compared with the non-OSAS group, OSAS group demonstrated higher BMI,neck circumference, Killip grade,GRACE score,ESS score,SYNTAX score, the number of diseased vessels and higher prevalence of hypertension, hyperlipidemia and smoking history. The differences were statistically significant (P<0.05). There were also statistically significant differences in sleep study result and hematological indexesof of cTnT, NT-ProBNP, and creatinine between the two groups (P<0.05). The general work index (GWI) of the OSAS group was lower than that of the non-OSAS group [(870.1±435.6) vs (1 005.0±313.6) mmHg% (1 mmHg=0.133 kPa), P=0.017]; The general myocardial active work (GCW) of the OSAS group was lower than that of the non-OSAS group [(1 046.7±472.2) vs (1 262.7±274.9) mmHg%, P=0.003]; The general work efficiency (GWE) of the OSAS group was lower than that of the non-OSAS group [(79.8±14.2)% vs (84.5±5.8)%, P=0.001]; The general reactive power (GWW) of the OSAS group was higher than that of the non-OSAS group [(312.2±163.2) vs (264.0±85.1) mmHg%, P=0.007]. There were 10 cases (20.0%) of MACE in the OSAS group and 13 cases (8.1%) in the non OSAS group, with a statistically significant difference (P=0.001).The combination of decreased OSAS (OR=4.039, 95%CI: 1.159-6.918), decreased myocardial work, including GCW [OR=0.850 (95%CI: 0.742-0.958)], GWE [OR=0.871 (95%CI: 0.818-0.924)], GWI (OR=0.862, 95%CI: 0.732-0.991), increased GWW (OR=2.425, 95%CI: 1.482-3.368), and increased GRACE score (OR=3.775, 95%CI: 2.314-5.236) increased the risk of MACE in AMI patients (all P<0.05). The area under the ROC curve (AUC) for predicting MACE in AMI using OSAS+myocardial work+GRACE score was 0.779 (95%CI: 0.717-0.834), with a sensitivity of 65.2% and a specificity of 84.5%. After the combination of the three, there were statistically significant differences compared to the AUC of combined OSAS, GRACE score, and myocardial work (all P<0.05). Conclusions: The MW of AMI patients with OSAS decreased compared to those without OSAS. The combination of OSAS and MW can improve the predictive value of MACE in patients with AMI.

[Analysis of dynamic functional connectivity states and influencing factors of brain network in male patients with obstructive sleep apnea].

Objective: To analyze dynamic functional connectivity (dFNC) states and influencing factors of brain network in male patients with obstructive sleep apnea (OSA). Methods: A total of 111 male patients diagnosed with obstructive sleep apnea or presenting with simple snoring, who visited the Sleep Clinic at the Second Affiliated Hospital of Soochow University between August 2020 and December 2021, were prospectively selected for this study. General information was collected, and polysomnography (PSG) was performed. Based on the oxygen desaturation index (ODI), the participants were divided into three groups: primary snoring group (ODI<5 events/hour, n=34), mild to moderate OSA group (5 events/hour≤ODI<30 events/hour, n=43), and sever OSA group (ODI≥30 events/hour, n=34). Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) scale, and daytime sleepiness was evaluated using the Epworth Sleepiness Scale (ESS). Resting-state functional magnetic resonance imaging (fMRI) data were collected and preprocessed. dFNC matrices were constructed using a sliding time window approach. The number of dFNC states was determined using k-means clustering analysis. Three parameters, namely, fractional time (FT), mean dwell time (MDT), and number of transitions (NT), were used to characterize the temporal properties of dFNC states. Differences in the temporal properties of dFNC states among the groups were compared. The correlations between temporal properties and PSG parameters, as well as MoCA and ESS scores, were further analyzed. Multiple stepwise linear regression analysis was performed to identify the influencing factors of the temporal properties of dFNC states. Results: The age of the patients was (40.2±8.6) years (range: 25-65 years). There were no significant differences in age, smoking history and alcohol history, and MoCA scores among the three groups (all P>0.05). Three dFNC states were extracted through k-means clustering analysis: state 1, characterized by strong connections within the visual and sensorimotor networks with a frequency of 31.7% (4 611/14 541); state 2, characterized by strong connections within the default mode network, attention network, and other cognitive networks, with the lowest frequency of 22.1% (3 213/14 541); state 3, characterized by weaker connections across the whole brain, with the highest frequency of 46.2% (6 717/14 541). The FT [0.28 (0.05, 0.35) vs 0.39 (0.26, 0.53)] and MDT [8.20 (4.35, 12.54) vs 11.68 (8.50, 16.69)] of state 2 in the sever OSA group were lower than those in the primary snoring group (both P<0.05), while there were no significant differences in the temporal properties of states 1 and 3 among the three groups (all P>0.05). The FT and MDT of state 2 were correlated with body mass index (BMI), apnea-hypopnea index (AHI), ODI, and minimum oxygen saturation (MinSaO2) (FT: r values were -0.218, -0.230, -0.249, 0.198, respectively; MDT: r values were 0.269, -0.253, -0.265, 0.209, respectively; all P<0.05). There were no significant correlations between the temporal properties and MoCA or ESS scores (all P>0.05). ODI was found to be an influencing factor for the temporal properties of state 2 (FT: ß=-0.225, 95%CI:-0.227 to -0.223; MDT: ß=-0.241, 95%CI:-0.289 to -0.195). Conclusions: Male patients with OSA exhibit alterations in specific temporal properties of brain network dynamic functional connectivity, which are associated with nocturnal oxygen parameters. This may be one of the mechanisms underlying brain functional damage in patients with OSA.

[The pulmonary toxicity of e-cigarette vaping exposure and the benefits of air cleaner application].

To evaluate e-cigarette vaping-induced respiratory toxicity and the interventional effects of air cleaners. A randomized controlled trial study of toxic vaping by the respiratory tract were conducted at the Key Laboratory of Environmental Medical Engineering, Ministry of Education, the School of Public Health, Southeast University from January to December 2022. 8-week-old male C57BL/6JGpt mice selected with a random number table method were used to establish a vaping-exposure model at different periods (0 d, 3 d, 7 d or 14 d), or exposed to clean air as a control group. Mice were exposed to regular heated vaping (200 ℃) and high-temperature heated vaping (280 ℃). Total lung RNA was extracted from control and e-cigarette exposed mice for transcriptome sequencing analysis. Reactive Oxygen Species (ROS) generation and mitochondrial membrane potential (MMP) were detected by flow cytometry. Total superoxide dismutase (SOD) and superoxide (O2-) were evaluated using a microplate reader. Real-Time Quantitative PCR (RT-qPCR) was used to detect gene expression. Air filter and ionizer were used to intervene the toxicity of vaping. Data were expressed as (x¯±s), differences between multiple groups were compared using one-way or two-way ANOVA. The results showed that, RNA sequencing assays suggested that the differential genes between the control and vaping exposure groups were significantly enriched in the oxidative stress (Fold Enrichment=3.18) and mitochondrial oxidative phosphorylation (OXPHOS) (Fold Enrichment=5.74) pathways. Both types of heated vaping exposure caused significantly increased the score of alveolitis (F=10.8, P<0.001), increased endogenous ROS generation (F=16.8, P<0.001), decreased MMP (F=13.6, P<0.01), and gene expression of mitochondrial complex I dysfunction. The toxic effects of high-temperature heated vaping were stronger compared to regular heated vaping (F=2.9, P<0.05). The filter demonstrated better protective effects against vaping than the ionizer by reducing pulmonary alveolitis (F=7.4, P<0.01). Air cleaners could partially alleviate oxidative stress and mitochondrial dysfunction. In conclusion, this study demonstrate that vaping brings potential health risks. Air cleaners could partially reverse mitochondrial dysfunction, but cannot completely prevent the toxic effects, effective interventions remain to be investigated.

The Effects of Different Exercise Interventions on Patients with Subjective Cognitive Decline: A Systematic Review and Network Meta-Analysis.

BACKGROUND AND OBJECTIVE: Exercise is a promising non-pharmacological therapy for subjective cognitive decline, but it is unclear which type of exercise is most effective. The objective was to assess the comparative effects and ranks of all exercise-based interventions on cognitive function in patients with subjective cognitive decline (SCD). METHOD: In this network meta-analysis, Online databases for Web of Science, PubMed, Embase, Medline, Cochrane Library and PsycINFO were searched from inception to April 30, 2023. The included studies are randomized controlled trials assessing the efficacy of exercise interventions for individuals with SCD. The primary outcome measure is memory, while secondary outcome measures encompass executive function, attention, verbal fluency, and global cognitive function. Represented using Standardized Mean Differences (SMDs) along with their 95% Confidence Intervals (CIs). Bias assessment was conducted in accordance with the 'Cochrane Risk of Bias Assessment Tool, 2nd Edition' (RoB 2). Pairwise meta-analysis was carried out using the 'meta-analysis' module within STATA 14.0, and network meta-analysis was performed using the 'mvmeta' and 'network' packages available in STATA 14.0. Registration number CRD42023289687. RESULT: This study included a total of 11 randomized controlled trials, encompassing 1,166 patients. Mind-body exercise was found to be efficacious in enhancing or sustaining memory (SMD: 0.58, 95%CI: 0.06 ~ 1.10) and executive function (SMD: 0.41, 95%CI: 0.09 ~ 0.73) in individuals with subjective cognitive decline. Furthermore, mind-body exercise exhibited the highest probability of being the most effective measures for improving or preventing the decline in memory (surface under cumulative ranking curve (SUCRA) value: 90.4) and executive function (SUCRA value: 91.8). The second-ranked moderate-intensity aerobic exercise has also shown a positive effect on the improvement of executive function in patients with subjective cognitive decline (SMD: 0.23, 95%CI: 0.03 ~ 0.43, SUCRA value: 68.2). However, we did not observe a significant effectiveness of exercise interventions on verbal fluency, attention, and overall cognitive function in subjective cognitive decline. CONCLUSION: Mind-body exercise may potentially be the optimal strategies for enhancing memory and executive function in individuals with subjective cognitive decline. Additionally, moderate-intensity aerobic exercise has shown a modest positive effect on executive function in subjective cognitive decline. When resources permit, practical application of these findings may be considered. Nevertheless, further support for the conclusions of this study is warranted through larger sample sizes and well-designed multicenter trials.

[Pristimerin enhances cisplatin-induced apoptosis in nasopharyngeal carcinoma cells via ROS-mediated deactivation of the PI3K/AKT signaling pathway].

OBJECTIVE: To explore the effect of pristimerin combined with cisplatin on proliferation and apoptosis of nasopharyngeal carcinoma cells. METHODS: CCK-8 assay was used to examine the survival rate of HNE-1 and CNE-2Z cells following treatment for 24 h with different concentrations of pristimerin, cisplatin or their combination. The changes in colony formation ability, apoptosis, and intracellular reactive oxygen species (ROS) levels of the treated cells were analyzed using colony formation assay and flow cytometry. Western blotting was performed to detect the changes in protein expressions in the cells. The effects of pre-treatment with NAC on proliferation, apoptosis, and PI3K/AKT signaling pathway were observed in pristimerin- and/or cisplatin-treated cells. RESULTS: Both pristimerin and cisplatin significantly lowered the survival rate of HNE-1 and CNE-2Z cells (P < 0.05). Compared with pristimerin or cisplatin alone, their combination more strongly inhibited survival and colony formation ability of the cells, increased cell apoptosis rate and intracellular ROS levels, upregulated the protein expressions of Bax, cleaved caspase-3, and cleaved PARP, and downregulated the protein expressions of Bcl-2, Mcl-1, PARP and p-PI3K and p-AKT (P < 0.05). NAC pretreatment significantly attenuated proliferation inhibition and apoptosis-promoting effects of pristimerin combined with cisplatin, and partially restored the downregulated protein expressions of p-PI3K and p-AKT in HNE-1 and CNE-2Z cells with the combined treatment (P < 0.05). CONCLUSION: Pristimerin can enhance cisplatin-induced proliferation inhibition and apoptosis in nasopharyngeal carcinoma cells, the mechanism of which may involve ROS-mediated deactivation of the PI3K/AKT signaling pathway.