[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.

[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.

[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.

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.

Changes in menopausal symptoms comparing oral estradiol versus transdermal estradiol.

OBJECTIVE: This study aimed to compare the efficacy and safety of oral and transdermal estradiol in alleviating menopausal symptoms. METHOD: A total of 257 recently menopausal women were randomized into two groups. The t-E2 group received transdermal estradiol (2.5 g per day) (n = 128) and the o-E2V group received oral estradiol valerate (2 mg per day) (n = 129) for 24 weeks; both groups received micronized progesterone (200 mg per day). The primary outcome measure is the change in the modified Kupperman Menopausal Index (KMI) after 24 weeks of treatment. Menopausal symptoms were recorded at screening and at 4, 12 and 24 weeks using both the KMI and the Menopause Rating Scale (MRS). RESULTS: Significant amelioration was observed by KMI and MRS scores for both groups after treatment (p < 0.001). The mean KMI scores showed no difference between the two groups. The mean MRS scores were similar between the two groups at baseline and after 4 weeks of treatment. The results showed statistical differences after 12 weeks and 24 weeks of treatment (p = 0.005 and p = 0.011). Both the after-treatment scores minus the baseline scores of KMI and MRS and the incidence of adverse effects showed no difference between the two groups. CONCLUSIONS: This study shows that both transdermal and oral estradiol are effective in relieving menopausal symptoms, with little difference in treatment efficacy and safety. CLINICAL TRIAL NUMBER: ChiCTR2300073146.

Comparison of conventional and endoscope-assisted partial clretain-->superficial parotidectomy for benign neoplasms of the parotid gland: a matched case-control study.

Long-term tumour recurrence rates and complications of endoscope-assisted partial superficial parotidectomy (PSP) are rarely reported compared to traditional open approaches. This retrospective study included 306 patients with superficial parotid benign neoplasms who were divided into an endoscopy group (endoscope-assisted PSP, n = 102) and a control group (conventional PSP, n = 204). There were no significant differences in clinical and pathological characteristics between the two groups, except age (P = 0.001). Three patients had confirmed recurrence during a mean follow-up duration of 125.1 months. Ten (9.8%) patients in the endoscopy group and 22 (10.8%) in the control group developed transient facial nerve palsy (P = 0.792), and recovered 6 months after the operation. Nine (8.8%) and 19 (9.3%) patients, respectively, suffered from Frey syndrome (P = 0.889). A sensory deficit of the auricle occurred in 24 (23.5%) and 57 (27.9%) patients respectively (P = 0.410). Patients in the endoscopy group were more satisfied with the postoperative scar than those in the control group (P < 0.001). This study demonstrated that the endoscope-assisted PSP can be curative, with better cosmetic outcomes than the conventional approach, and does not increase the incidence of postoperative complications or the local recurrence rate.

[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.

[Efficacy and safety of endoscopic submucosal dissection with additional radiotherapy for T1a-MM/T1b-SM esophageal squamous cell carcinoma].

Objective: To clarify the efficacy and safety of endoscopic submucosal dissection (ESD) with additional radiotherapy in T1a-MM/T1b-SM esophageal squamous cell carcinoma (ESCC). Methods: A retrospective analysis was conducted on 71 patients with T1a-MM/T1b-SM ESCC admitted to Southeast University Affiliated Zhongda Hospital from January 2015 to December 2019. The patients were divided into two groups based on the treatment method: the ESD group (ESD therapy alone) and the ESD-radiotherapy group (ESD combined radiotherapy). The follow-up duration after ESD was (44±17) months. The difference of disease-free survival (DFS) rate and overall survival (OS) rate between the two groups was compared by survival analysis, and the occurrence of complications was compared. Baseline variables of the two groups were compared and the influencing factors of DFS rate were analyzed by Cox proportional risk regression model. Results: There were 44 patients in the ESD-radiotherapy group [28 males, 16 females, aged (65±7) years] and 27 patients in the ESD group [18 males, 9 females, aged (67±9) years]. The results of survival analysis show that the 1, 3 and 5-year DFS rates of ESD-radiotherapy group were 95.5%, 92.9% and 77.4%, respectively, which were higher than those of ESD group 85.2%, 73.2% and 62.7% (all P<0.05). The 1, 3 and 5-year OS rates of the ESD-radiotherapy group were 100%, 94.7% and 94.7%, while those of the ESD group were 96.3%, 96.3% and 79.4%, respectively. The difference was not statistically significant (all P>0.05). Cox proportional hazard regression model analysis showed that ESD combined with radiotherapy (HR=0.19, 95%CI: 0.04-0.90, P=0.037), complete tumor resection (HR=0.25, 95%CI: 0.07-0.86, P=0.027), and vascular invasion (HR=12.06, 95%CI: 1.61-90.26, P=0.015) were the influencing factors of DFS rates. The most common complication of ESD was esophageal stenosis, and no grade 3 or higher radiation adverse reactions occurred after combined radiotherapy. Conclusion: ESD combined radiotherapy is an effective and safe therapeutic strategy for patients with T1a-MM/T1b-SM ESCC.

[Analysis of the serum bile acid profile to facilitate diagnosis and differential diagnosis of NA(+)-taurocholate cotransporting polypeptide deficiency].

Objective: This study focuses on Na(+)-taurocholate cotransporting polypeptide (NTCP) deficiency to analyze and investigate the value of the serum bile acid profile for facilitating the diagnosis and differential diagnosis. Methods: Clinical data of 66 patients with cholestatic liver diseases (CLDs) diagnosed and treated in the Department of Pediatrics of the First Affiliated Hospital of Jinan University from early April 2015 to the end of December 2021 were collected, including 32 cases of NTCP deficiency (16 adults and 16 children), 16 cases of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), 8 cases of Alagille syndrome, and 10 cases of biliary atresia. At the same time, adult and pediatric healthy control groups (15 cases each) were established. The serum bile acid components of the study subjects were qualitatively and quantitatively analyzed by ultra-high performance liquid chromatography-tandem mass spectrometry. The data were plotted and compared using statistical SPSS 19.0 and GraphPad Prism 5.0 software. The clinical and bile acid profiles of children with NTCP deficiency and corresponding healthy controls, as well as differences between NTCP deficiency and other CLDs, were compared using statistical methods such as t-tests, Wilcoxon rank sum tests, and Kruskal-Wallis H tests. Results: Compared with the healthy control, the levels of total conjugated bile acids, total primary bile acids, total secondary bile acids, glycocholic acid, taurocholic acid, and glycochenodeoxycholic acid were increased in NTCP deficiency patients (P < 0.05). Compared with adults with NTCP deficiency, the levels of total conjugated bile acids and total primary bile acids were significantly increased in children with NTCP deficiency (P < 0.05). The serum levels of taurochenodeoxycholic acid, glycolithocholate, taurohyocholate, and tauro-α-muricholic acid were significantly increased in children with NTCP deficiency, but the bile acid levels such as glycodeoxycholic acid, glycolithocholate, and lithocholic acid were decreased (P < 0.05). The serum levels of secondary bile acids such as lithocholic acid, deoxycholic acid, and hyodeoxycholic acid were significantly higher in children with NTCP deficiency than those in other CLD groups such as NICCD, Alagille syndrome, and biliary atresia (P < 0.05). Total primary bile acids/total secondary bile acids, total conjugated bile acids/total unconjugated bile acids, taurocholic acid, serum taurodeoxycholic acid, and glycodeoxycholic acid effectively distinguished children with NTCP deficiency from other non-NTCP deficiency CLDs. Conclusion: This study confirms that serum bile acid profile analysis has an important reference value for facilitating the diagnosis and differential diagnosis of NTCP deficiency. Furthermore, it deepens the scientific understanding of the changing characteristics of serum bile acid profiles in patients with CLDs such as NTCP deficiency, provides a metabolomic basis for in-depth understanding of its pathogenesis, and provides clues and ideas for subsequent in-depth research.

[Application of novel non-endoscopic device in the screening and early diagnosis of esophageal cancer].

Esophageal cancer (EC) is a dreadful disease with a poor prognosis and poses heavy health burden worldwide. Developing effective methods to identify high-risk individuals is urgently needed for preliminary screening before endoscopy. The novel non-endoscopic device has the potential advantages of low cost, simple operation, and minimal invasiveness. Approximately 90% of participants can swallow the device successfully with high safety profiles, and sufficient esophageal exfoliated cells can be collected for cytological examination and biomarker detection. Cytological examination based on the device combined with trefoil factor 3 (TFF3) protein or DNA methylation examinations could effectively screen Barrett's esophagus-associated dysplasia and early esophageal adenocarcinoma, but large prospective studies are needed to further validate the diagnostic value of this device to improve the quality of evidence. Although the device-based cytological examination in combination with biomarker detection holds promise in the early screening of esophageal squamous dysplasia and early esophageal squamous cell carcinoma, related research is still in its infancy, and there is still a lack of sufficient evidence for population screening in China. Active research into the application of this novel non-endoscopic device in EC screening and early diagnosis is of great significance for optimizing EC screening strategies and improving the early diagnosis of EC.

[Diagnostic values of nuclear score combined with cyclin D1 immunocytochemistry in indeterminate thyroid follicular nodules in preoperative fine needle aspiration].

Objective: To assess the feasibility of nuclear score combined with cyclin D1 immunocytochemistry in classifying indeterminate thyroid nodules with fine-needle aspiration (FNA) cytological diagnosis of Bethesda category Ⅲ-Ⅴ. Methods: A consecutive cohort of 118 thyroid FNA specimens with indeterminate diagnosis (TBSRTC category Ⅲ-Ⅴ) and available histopathologic follow-up data were collected between December 2018 and April 2022 at the Department of Pathology, Beijing Hospital, China. These cases were subjected to cytological evaluation and cyclin D1 immunocytochemistry. The optimal cut-off points of a simplified nuclear score and the percentage of cyclin D1-positive cells for the diagnosis of malignancy or low-risk neoplasm were determined using the receiver operating characteristic (ROC) curves and area under the ROC curve (AUC). The specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of nuclear score and cyclin D1 immunostaining were evaluated from the crosstabs based on cut-off points. The diagnostic accuracy of simplified nuclear score combined with cyclin D1 immunostaining was estimated using ROC curve analysis. Results: Nuclear grooves, intra-nuclear inclusions and chromatin clearing were more commonly found in malignancy/low-risk neoplasms than benign lesions (P=0.001, P=0.012 and P=0.001 respectively). A cut-off point of≥2 for the simplified nuclear score was sensitive for defining malignancy/low-risk neoplasm, and its PPV, NPV, sensitivity and specificity were 93.6%, 87.5%, 99.0% and 50.0% respectively. A positive cut-off point of 10% positive thyroid cells in cyclin D1 immunostaining demonstrated sensitivity of 88.5%, specificity of 100%, PPV of 100% and NPV of 53.8% for correctly detecting thyroid malignancy or low-risk neoplasm. The sensitivity and PPV of simplified nuclear score combined with cyclin D1 immunostaining were 93.3% and 100%, respectively. Both specificity and NPV were maintained at high levels (100% and 66.7%, respectively). The diagnostic accuracy of simplified nuclear score combined with cyclin D1 immunostaining in detecting thyroid malignancy/low-risk neoplasm was increased to 94.1% compared to using either of them alone. Conclusions: Combing simplified nuclear score and cyclin D1 immunostaining on FNA cytology specimens can increase the diagnostic accuracy in classifying thyroid nodules of indeterminate cytological categories. Thus, this supplementary approach provides a simple, accurate, and convenient diagnostic method for cytopathologists so that may reduce unnecessary thyroidectomies.

Diagnostic accuracy of magnifying chromoendoscopy in the assessment of tumor invasion depth in early colorectal cancer: a systematic review and meta-analysis.

PURPOSE: The aim of the study was to evaluate the ability of magnifying chromoendoscopy (MCE) to correctly differentiate early colorectal cancer (CRC) lesions with massively invasive submucosal cancer (SMm) from lesions without submucosal massive invasion (polyp, adenoma, dysplasia, intramucosal cancer, slightly invasive submucosal cancer (SMs)). METHODS: We searched PubMed, Embase, the Cochrane Library from the time of the establishment of each database to 5 April 2023. Stata 15 software was used to perform the meta-analysis for sensitivity, specificity, positive likelihood ratio (LR), and negative LR, diagnostic odds ratio, and 95% CI. A summary receiver-operating characteristic (SROC) curve was constructed, the area under the curve (AUC) was calculated, and the diagnostic value was evaluated. Furthermore, to explore the potential sources of heterogeneity, we used meta-regression to estimate the influencing factors of these studies and their impact on the diagnostic accuracy. MCE was used to evaluate the diagnostic accuracy in differentiating CRC lesions with SMm from lesions without submucosal massive invasion (polyp, adenoma, dysplasia, intramucosal cancer, SMs). Subgroup analysis was conducted as well. Deeks' funnel plots were also used to assess publication bias. RESULTS: A total of 11,387 colorectal lesions were included in 19 articles, including polyp, adenoma, dysplasia, and early cancer (intramucosal cancer, SMs, and SMm). The aggregate sensitivity, specificity, positive LR, negative LR, and diagnostic advantage scores of MCE in the diagnosis of differentiating CRC lesions with SMm from lesions without submucosal massive invasion (polyp, adenoma, dysplasia, intramucosal cancer, SMs) were 0.78 (95% CI 0.72-0.83), 0.95 (0.95% CI 0.91-0.97), 15.4 (0.95% CI 8.7-27.4), 0.23 (0.95% CI 0.18-0.30), and 66 (0.95% CI 32-136), respectively. The AUC of the SROC curve was 0.91 (0.95% CI 0.88-0.93). No significant publication bias was found with Deeks' funnel plot. The results showed significant heterogeneity due to the different objects included. CONCLUSION: MCE can differentiate CRC lesions with SMm from lesions without submucosal massive invasion (polyp, adenoma, dysplasia, intramucosal cancer, SMs) with high accuracy and it can guide assessment of invasion depth of SMm in T1 early CRCs to help us select the most appropriate treatment.

[Alertness and task processing speed impairment status and influencing factors of young-middle aged men with obstructive sleep apnea hypopnea syndrome].

Objective: To investigate the alertness and task processing speed impairment status in young-mild aged men with obstructive sleep apnea hypopnea syndrome (OSAHS), and analyze its influencing factors. Methods: This prospective study recruited 251 snoring patients aged 18 to 59 (38.9±7.6) years in the Sleep Center of the Second Affiliated Hospital of Soochow University from July 2020 to September 2021 and all patients were diagnosed by polysomnography (PSG). Clinical information, Epworth Sleepiness Scale (ESS) and PSG date were collected. All patients were assessed with the Montreal Cognitive Assessment (MoCA) questionnaires, Mini-mental State Examination (MMSE) and Computerized Neurocognitive Assessment System which includes the reaction time of Motor Screening Task (MOT) for alertness, the reaction time of pattern recognition memory (PRM), spatial span (SSP) and spatial working memory (SWM) for task processing speed. Based on AHI tertiles, all patients were divided into Q1 group (AHI<15 times/h, n=79), Q2 group (15 times/h≤AHI<45 times/h, n=88), and Q3 group (AHI≥45 times/h, n=84). The characteristics of clinical information, ESS, PSG parameters and cognitive scores among three groups were compared. Multiple linear stepwise regression was conducted to analyze the influencing factors of cognitive impairment. Results: There were no statistically significant differences in age, years of education, history of smoking and drinking, and past disease history (except for the prevalence of hypertension) among the 3 groups (P>0.05). There were statistically significant among-group differences in the body mass index (BMI), ESS, prevalence of hypertension and complaints of daytime sleepiness (P<0.05). Compared with Q1 and Q2 group, the arousal index (ArI), oxygen desaturation index (ODI),the proportion of non-rapid eye movement phase 1 and 2 (N1+N2) and percentage of total sleep time with oxygen saturation level<90% (TS90) of Q3 group were higher (all P<0.05). In the cognitive assessment, there was no statistically significant difference in the MoCA total and individual scores and MMSE scores among the three groups (P>0.05). Compared with the Q1 group, the task processing speed and alertness were worse in Q3 group, as shown by slower PRM immediate and delayed reaction time, SSP reaction time and MOT reaction time (all P<0.05). The total time of SWM in Q2 group was slower than that in Q1 group (P<0.05). Multiple linear stepwise regression showed that years of education (ß=-40.182, 95%CI:-69.847--10.517), ODI (ß=3.539, 95%CI: 0.600-6.478) were the risk factors of PRM immediate reaction time. Age(ß=13.303,95%CI: 2.487-24.119), years of education(ß=-32.329, 95%CI:-63.162--1.497), ODI (ß=4.515, 95%CI: 1.623-7.407) were the risk factors of PRM delayed reaction time. ODI was the risk factor of SSP reaction time (ß=1.258, 95%CI: 0.379-2.137). TS90 was the risk factor of MOT reaction time (ß=1.796, 95%CI: 0.664-2.928). Conclusions: The early cognitive impairment in young-mild aged OSAHS patients was manifested in decreased alertness and task processing speed, and intermittent nocturnal hypoxia was its influencing factor in addition to age and years of education.

[Preliminary experience of gasless transoral vestibular robotic thyroidectomy].

Objective: To explore the feasibility and safety of the gasless transoral vestibular robotic thyroidectomy using skin suspension. Methods: The clinical data of 20 patients underwent gasless transoral vestibular robotic thyroidectomy in the Department of Otorhinolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University from February 2022 to May 2022 were retrospectively analyzed. Among them, 18 were females and 2 were males, aged (38.7±8.0) years old. The intraoperative blood loss, operation time, postoperative hospital stay, postoperative drainage volume, postoperative pain visual analogue scale (VAS) score, postoperative swallowing function swallowing impairment score-6 (SIS-6), postoperative aesthetic VAS score, postoperative voice handicap index-10 (VHI-10) voice quality, postoperative pathology and complications were recorded. SPSS 25.0 was used for statistical analysis of the data. Results: The operations were successfully completed without conversion to open surgery in all patients. Pathological examination showed papillary thyroid carcinoma in 18 cases, retrosternal nodular goiter in 1 case, and cystic change in goiter in 1 case. The operative time for thyroid cancer was 161.50 (152.75, 182.50) min [M (P25, P75), the same below] and the average operative time for benign thyroid diseases was 166.50 minutes. The intraoperative blood loss 25.00 (21.25, 30.00) ml. In 18 cases of thyroid cancer, the mean diameter of the tumors was (7.22±2.02) mm, and lymph nodes (6.56±2.14) were dissected in the central region, with a lymph node metastasis rate of 61.11%. The postoperative pain VAS score was 3.00 (2.25, 4.00) points at 24 hours, the mean postoperative drainage volume was (118.35±24.32) ml, the postoperative hospital stay was 3.00 (3.00, 3.75) days, the postoperative SIS-6 score was (4.90±1.58) points at 3 months, and the postoperative VHI-10 score was 7.50 (2.00, 11.00) points at 3 months. Seven patients had mild mandibular numbness, 10 patients had mild cervical numbness, and 3 patients had temporary hypothyroidism three months after surgery and 1 patient had skin flap burn, but recovered one month after surgery. All patients were satisfied with the postoperative aesthetic effects, and the postoperative aesthetic VAS score was 10.00 (10.00, 10.00). Conclusion: Gasless transoral vestibular robotic thyroidectomy using skin suspension is a safe and feasible option with good postoperative aesthetic effect, which can provide a new treatment option for some selected patients with thyroid tumors.

Recombinant Treponema pallidum protein Tp47 promoted the phagocytosis of macrophages by activating NLRP3 inflammasome induced by PKM2-dependent glycolysis.

BACKGROUND: Glycolysis is a critical pathway in cellular glucose metabolism that provides energy and participates in immune responses. However, whether glycolysis is involved in NOD-like receptor family protein 3 (NLRP3) inflammasome activation and phagocytosis of macrophages in response to Treponema pallidum infection remains unclear. OBJECTIVES: To investigate the role of glycolysis in activating the NLRP3 inflammasome for regulating phagocytosis in macrophages in response to T. pallidum protein Tp47 and its associated mechanisms. METHODS: Interactions between activation of the NLRP3 inflammasome and phagocytosis and the role of glycolysis in Tp47-treated macrophages were investigated through experiments on peritoneal macrophages and human monocytic cell line-derived macrophages. RESULTS: Activation of phagocytosis and NLRP3 inflammasome were observed in Tp47-treated macrophages. Treatment with NLRP3 inhibitor MCC950 or si-NLRP3 attenuated Tp47-induced phagocytosis. Glycolysis and glycolytic capacity were enhanced by Tp47 stimulation in macrophages, and a change in the levels of glycolytic metabolites (phosphoenolpyruvate, citrate and lactate) was induced by Tp47 in macrophages. Inhibition of glycolysis with 2-deoxy-D-glucose, a glycolysis inhibitor, decreased the activation of NLRP3. Expression of M2 isoform of pyruvate kinase (PKM2), an enzyme catalysing a rate-limiting reaction in the glycolytic pathway, was upregulated in Tp47-stimulated macrophages. Inhibition of PKM2 with shikonin or si-PKM2 decreased glycolysis and NLRP3 activation. CONCLUSION: Tp47 promotes phagocytosis in macrophages by activating the NLRP3 inflammasome, which is induced by the enhancement of PKM2-dependent glycolysis.

[Endovascular therapy accompanied by spontaneous portosystemic shunts for overt hepatic encephalopathy].

Objective: To preliminarily evaluate the safety and efficacy of shunt-related interventional therapy accompanied with spontaneous portosystemic shunts (SPSS) in patients with hepatic encephalopathy (HE). Methods: Case data on six patients who underwent interventional therapy accompanied by SPSS for HE from January 2017 to March 2021 were collected to evaluate the efficacy and postoperative complications. Results: All six patients underwent SPSS. Four patients had hepatitis B cirrhosis; one had alcoholic cirrhosis; and one had hepatic arterioportal fistula-induced portal hypertension. Child-Pugh liver function scores were C and B in three and three cases, respectively. The SPSS type was gastrorenal shunt in two cases; portal-thoracic-azygos venous in two cases; portal-umbilical-iliac venous in one case; and portal-splenic venous - inferior vena cava in one case. Two of them had previously had a transjugular intrahepatic portosystemic shunt (TIPS), and there were SPSS prior to TIPS. Five cases (5/6) successfully underwent shunt embolization, and one case (1/6) underwent stent implantation for flow restriction (portal-umbilical-iliac vein). The technical success rate was 100%. HE did not recur during hospitalization or the three-month follow-up period. However, one case had a recurrence of HE within a year after surgery and was treated symptomatically, while another experienced gastrointestinal bleeding a year after surgery.. Conclusion: SPSS embolization or flow restriction is effective and safe for improving HE patients' symptoms.

[Neoadjuvant therapy in locally advanced esophageal squamous cell carcinoma].

The efficacy of surgery alone for locally advanced esophageal squamous cell carcinoma (ESCC) is limited. In-depth studies concerning combined therapy for ESCC have been carried out worldwide, especially the neoadjuvant treatment model, including neoadjuvant chemotherapy (nCT), neoadjuvant chemoradiotherapy (nCRT), neoadjuvant chemotherapy combined with immunotherapy (nICT), neoadjuvant chemoradiotherapy combined with immunotherapy (nICRT), etc. With the advent of the immunity era, nICT and nICRT have attracted much attention from researchers. An attempt was thus made to take an overview of the evidence-based research advance regarding the neoadjuvant therapy of ESCC.