[Yigong San improves cognitive decline in a rat model of Alzheimer's disease by regulating intestinal microorganisms].

OBJECTIVE: To investigate the effect of Yigong San (YGS) on learning and memory abilities of rats with lipopolysaccharide (LPS)­induced cognitive decline and explore its possible mechanism in light of intestinal microbiota. METHODS: Forty SD rats were randomly divided into control group, model group, donepezil (1.3 mg/kg) group, and high-dose (5.25 g/kg) and low-dose (2.63 g/kg) YGS treatment groups. After 24 days of treatment with the corresponding drugs or water by gavage, the rats in the latter 4 groups received an intraperitoneal injection of LPS (0.5 mg/kg) to establish models of Alzheimer's disease (AD). Water maze test and HE staining were used to evaluate the changes in learning and memory abilities and pathomorphology of the hippocampus. The changes in gut microbial species of the rats were analyzed with 16S rRNA sequencing, and the levels of IL-6, TNF-α, and IL-1ß in the brain tissue and serum were detected using ELISA. RESULTS: Compared with the AD model group, the YGS-treated rats showed significantly shortened escape latency on day 5 after modeling, reduced neuronal degeneration and necrosis in the hippocampus, lowered pathological score of cell damage, and decreased levels IL-6, TNF-α and IL-1ß in the brain tissue and serum. The YGS-treated rats showed also obvious reduction of Alpha diversity indicators (ACE and Chao1) of intestinal microbiota with significantly increased abundance of Prevotellaceae species at the family level and decreased abundance of Desulfovibrionaceae, which were involved in such metabolic signaling pathways as cell community prokaryotes, membrane transport, and energy metabolism. CONCLUSION: YGS improves learning and memory abilities and hippocampal pathomorphology in AD rat models possibly by regulating the abundance of intestinal microbial species such as Prevotellaceae to affect the metabolic pathways for signal transduction, cofactors, and vitamin metabolism.

[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.

[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.

Cell-specific inhibitory modulation of sound processing in the auditory thalamus.

Inhibition along the auditory pathway is crucial for processing of acoustic information. Within the auditory thalamus, a key region in the central auditory pathway, inhibition is provided by the thalamic reticular nucleus (TRN), comprised of two large classes of inhibitory neurons, parvalbumin (PV TRN ) and somatostatin (SST TRN ) positive. In the auditory cortex, PV and SST neurons differentially shape auditory processing. We found that the ventral MGB, the thalamic region in the direct ascending auditory pathway, receives inputs predominantly from PV TRN neurons, whereas SST TRN neurons project to the dorso-medial regions of MGB. Consistently, inactivating PV TRN neurons increased sound-evoked activity in over a third of neurons in the vMGB, with another large fraction of neurons being suppressed. By contrast, inactivating SST TRN neuronal activity largely reduced tone-evoked activity in vMGB neurons. Cell type-specific computational models revealed candidate circuit mechanisms for generating the bi-directional effects of TRN inactivation on MGB sound responses. These differential inhibitory pathways within the auditory thalamus suggest a cell-specific role for thalamic inhibition in auditory computation and behavior.

[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.

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.

[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.

[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.

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.

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.

[Preliminary outcomes of neoadjuvant chemoimmunotherapy combined with transoral robotic surgery for locally advanced oropharyngeal squamous cell carcinoma].

Objective: To evaluate the efficacy of neoadjuvant chemoimmunotherapy (NACI) combined with transoral robotic surgery (TORS) in the treatment of locally advanced oropharyngeal squamous cell carcinoma (OPSCC). Methods: This was a retrospective study of 15 patients with locally advanced OPSCC who underwent TORS after neoadjuvant therapy (NAT) at the Department of Otolaryngology-Head and Neck Surgery of Sun Yat-sen Memorial Hospital of Sun Yat-sen University from April 2019 to February 2023. There were 12 males and 3 females, aged 31 to 74 years. Twelve cases were tonsil cancer, and 3 cases were tongue base cancer. There were 11 cases in stage Ⅲ and 4 cases in stage Ⅳ. Two patients received neoadjuvant chemotherapy and 13 patients received NACI, with 2 to 3 cycles, and all patients underwent TORS after multidisciplinary team consultation. The clinicopathological characteristics, surgical outcomes, and oncological results were summarized. Results: All surgeries were successfully completed with negative surgical margins, and no case was required conversion surgery. All patients were fed via nasogastric tubes postoperatively, with a median gastric tube stay of 7 days (range: 2-60 days). No tracheotomy was applied. There were no major complications such as postoperative bleeding. Pathological complete response (pCR) was found in 10 cases (76.9%) among the 13 patients with NACI. The follow-up time was 21 months (range: 10-47 months), and there was no death or distant metastasis. One patient with rT0N3M0 tonsil cancer had local recurrence 5 months after surgery. The 2-year overall survival and 2-year disease-free survival were respectively 100.0% and 93.3% in the 15 patients. Conclusion: NACI combined with TORS provides a safe, effective and minimally invasive treatment for patients with locally advanced oropharyngeal squamous cell carcinoma.

[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.

[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.

[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 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 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.

[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.

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.

Lacticaseibacillus rhamnosus GG Improves Periodontal Bone Repair via Gut-Blood Axis in Hyperlipidemia.

Periodontal bone regeneration remains a clinical challenge, and hyperlipidemia can aggravate alveolar bone resorption. Probiotics have recently been reported to improve bone mass. We aimed to determine the role of Lacticaseibacillus rhamnosus GG (LGG) in periodontal bone regeneration improvement within the context of periodontitis with hyperlipidemia. A Sprague Dawley rat model for periodontitis, hyperlipidemia, and periodontal fenestration defect was constructed (n = 36) and administered LGG gavage for 6 wk (the rats were subsequently sacrificed). Fecal microbiota from donor rats 3 wk after LGG gavage was transplanted into recipient rats to evaluate the role of LGG-modulated gut microbiota in periodontal bone regeneration. Regenerated bone mass was detected using micro-computerized tomography and hematoxylin and eosin stain. Gut microbiota was analyzed using 16S ribosomal RNA sequencing. Serum metabolites were detected by liquid chromatography-mass spectrometry (6 wk after LGG gavage). The pro-osteogenic effects of screened serum metabolite were verified in vitro on bone marrow mesenchymal stem cells (BMMSCs). We found that the bone mineral density, bone volume (BV), trabecular bone volume fraction (BV/TV), and trabecular thickness of the regenerated periodontal bone increased after LGG gavage (P < 0.05) but had little effect on oral flora. After LGG gavage, Staphylococcus, Corynebacterium, and Collinsella in the gut of donors were significantly changed, and these differences were maintained in recipients, who also showed increased trabecular thickness of the regenerated periodontal bone (P < 0.05). These key genera were correlated with BV/TV and BV (P < 0.05). In addition, LGG gavage significantly regulated bone-related blood metabolites, of which selenomethionine promoted BMMSC osteogenesis. Notably, selenomethionine was associated with key gut genera (P < 0.05). Collectively, LGG improved periodontal bone regeneration in the context of periodontitis with hyperlipidemia by modulating gut microbiota and increasing pro-osteogenic metabolites in the blood. These results reveal new insights into the use of probiotics to promote periodontal bone regeneration via the gut-blood-bone axis.