Spatial mapping of hepatic ER and mitochondria architecture reveals zonated remodeling in fasting and obesity.

The hepatocytes within the liver present an immense capacity to adapt to changes in nutrient availability. Here, by using high resolution volume electron microscopy, we map how hepatic subcellular spatial organization is regulated during nutritional fluctuations and as a function of liver zonation. We identify that fasting leads to remodeling of endoplasmic reticulum (ER) architecture in hepatocytes, characterized by the induction of single rough ER sheet around the mitochondria, which becomes larger and flatter. These alterations are enriched in periportal and mid-lobular hepatocytes but not in pericentral hepatocytes. Gain- and loss-of-function in vivo models demonstrate that the Ribosome receptor binding protein1 (RRBP1) is required to enable fasting-induced ER sheet-mitochondria interactions and to regulate hepatic fatty acid oxidation. Endogenous RRBP1 is enriched around periportal and mid-lobular regions of the liver. In obesity, ER-mitochondria interactions are distinct and fasting fails to induce rough ER sheet-mitochondrion interactions. These findings illustrate the importance of a regulated molecular architecture for hepatocyte metabolic flexibility.

Elevated venous lactate level as an early predictive marker of organ failure in acute pancreatitis: a retrospective study.

OBJECTIVE: The aim of this study was to elucidate the relationship between venous lactate levels and the severity of acute pancreatitis (AP). PATIENTS AND METHODS: Retrospective data analysis was conducted on patients diagnosed with acute pancreatitis. The comparative assessment encompassed baseline characteristics, laboratory data, illness severity, local consequences, and organ failure instances. This comparison was performed between patients exhibiting normal serum lactic acid levels (HL) and those displaying elevated HL levels. The association between serum HL levels and other pertinent clinical markers was investigated using linear regression. Logistic regression analysis was employed to evaluate the utility of elevated serum lactate levels in identifying high-risk groups. RESULTS: Significantly elevated serum HL levels were observed in patients with moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP) in contrast to those with mild acute pancreatitis (MAP) (p<0.01). Multivariate logistic analysis demonstrated that higher lactate levels independently predicted organ failure (95% CI 0.738-0.902, p<0.05). Receiver operating characteristic (ROC) curve analysis indicated that the lactate (LAC) cut-off value of 2.45 mmol/L yielded sensitivity and specificity values of 76.5% and 79.1%, respectively, for predicting AP-associated organ failure. The corresponding area under the curve (AUC) was 0.820. CONCLUSIONS: In AP patients, elevated serum HL levels signify disease severity and hold predictive potential for assessing the risk of organ failure.

Multi-center Dose Prediction Using Attention-aware Deep learning Algorithm Based on Transformers for Cervical Cancer Radiotherapy.

AIMS: Accurate dose delivery is crucial for cervical cancer volumetric modulated arc therapy (VMAT). We aimed to develop a robust deep-learning (DL) algorithm for fast and accurate dose prediction of cervical cancer VMAT in multicenter datasets and then explore the feasibility of the DL algorithm to endometrial cancer VMAT with different prescriptions. MATERIALS AND METHODS: We proposed the AtTranNet algorithm for three-dimensional dose prediction. A total of 367 cervical patients were enrolled in this study. Three hundred twenty-two cervical patients from 3 centers were randomly divided into 70%, 10%, and 20% as training, validation, and testing sets, respectively. Forty-five cervical patients from another center were selected for external testing. Moreover, 70 patients of endometrial cancer with different prescriptions were further selected to test the model. Prediction precision was evaluated by dosimetric difference, dose map, and dose-volume histogram metrics. RESULTS: The prediction results were all clinically acceptable. The mean absolute error within the body in internal testing was 0.66 ± 0.63%. The maximum |δD| for planning target volume was observed in D98, which is 1.24 ± 2.73 Gy. The maximum |δD| for organs at risk was observed in Dmean of bladder, which is 4.79 ± 3.14 Gy. The maximum |δV| were observed in V40 of pelvic bones, which is 4.77 ± 4.48%. CONCLUSION: AtTranNet showed the feasibility and reasonable accuracy in the dose prediction for cervical cancer in multiple centers. The model can also be generalized for endometrial cancer with different prescriptions without any transfer learning.

[Clinical efficacy of induction chemoimmunotherapy for locally advanced hypopharyngeal carcinoma: a prospective phase â ¡ study].

Objective: To evaluate the objective response rate (ORR) of induction chemoimmunotherapy with camrelizumab plus TPF (docetaxel, cisplatin, and capecitabine) for locally advanced hypopharyngeal squamous cell carcinoma (LA HSCC) and potential predictive factors for ORR. Methods: A single-center, prospective, phase 2 and single-arm trial was conducted for evaluating antitumor activity of camrelizumab+TPF(docetaxel+cisplatin+capecitabine) for LA HSCC between May 21, 2021 and April 15, 2023, patients admitted to the Eye & ENT Hospital affiliated with Fudan University. The primary endpoint was ORR, and enrolled patients with LA HSCC at T3-4N0-3M0 received induction chemoimmunotherapy for three cycles: camrelizumab 200 mg day 1, docetaxel 75 mg/m2 day 1, cisplatin 25 mg/m2 days 1-3, and capecitabine 800 mg/m2 days 1-14. Patients were assigned to radioimmunotherapy when they had complete response or partial response (PR)>70% (Group A), or assigned to surgery plus adjuvant radiotherapy/chemoradiotherapy when they had PR≤70% (Group B), and the responses were defined by using tumor volume evaluation system. Tumor diameter was also used to assess the treatment responses by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Use SPSS 23.0 software was used to analyze the data. Results: A total of 51 patients were enrolled who underwent the induced chemoimmunotherapy for three cycles, and all were males, aged 35-69 years old. After three cycles of induction immunochemotherapy, 42 (82.4%) patients existed in Group A (complete response or PR>70%) and 9 patients (17.6%) in Group B (PR≤70%), the ORR was 82.4%. The primary endpoint achieved expected main research objectives. Compared to the patients of Group A, the patients of Group B showed the higher T stage and the larger volume of primary tumor before induced immunochemotherapy, and also had the less regression of tumor volume after induced immunochemotherapy (all P<0.05). The optimal cutoff value of pre-treatment tumor volume for predicting ORR was 39 cm3. The T stage (OR=12.71, 95%CI: 1.4-112.5, P=0.022) and the volume (OR=7.1, 95%CI: 1.4-36.8, P=0.018) of primary tumor were the two main factors affecting ORR rate of induction chemoimmunotherapy. Conclusion: The induction chemoimmunotherapy with camrelizumab plus TPF shows an encouraging antitumor efficacy in LA HSCC.

COPII with ALG2 and ESCRTs control lysosome-dependent microautophagy of ER exit sites.

Endoplasmic reticulum exit sites (ERESs) are tubular outgrowths of endoplasmic reticulum that serve as the earliest station for protein sorting and export into the secretory pathway. How these structures respond to different cellular conditions remains unclear. Here, we report that ERESs undergo lysosome-dependent microautophagy when Ca2+ is released by lysosomes in response to nutrient stressors such as mTOR inhibition or amino acid starvation in mammalian cells. Targeting and uptake of ERESs into lysosomes were observed by super-resolution live-cell imaging and focus ion beam scanning electron microscopy (FIB-SEM). The mechanism was ESCRT dependent and required ubiquitinated SEC31, ALG2, and ALIX, with a knockout of ALG2 or function-blocking mutations of ALIX preventing engulfment of ERESs by lysosomes. In vitro, reconstitution of the pathway was possible using lysosomal lipid-mimicking giant unilamellar vesicles and purified recombinant components. Together, these findings demonstrate a pathway of lysosome-dependent ERES microautophagy mediated by COPII, ALG2, and ESCRTS induced by nutrient stress.

[Analysis of epidemiological characteristics and risk factors of catheter-associated urinary tract infections in patients with perineal and/or hip burns].

Objective: To explore the epidemiological characteristics and risk factors of catheter-associated urinary tract infections in patients with perineal and/or hip burns. Methods: This study was a retrospective case series study. From January 2018 to December 2022, 260 patients with perineal and/or hip burns and urinary catheters indwelling who met the inclusion criteria were admitted to the Department of Burns and Wound Repair of the Second Affiliated Hospital of Zhejiang University School of Medicine, including 192 males and 68 females, aged 20-93 years. The total incidence of catheter-associated urinary tract infections in patients with perineal and/or hip burns, the detection of pathogenic bacteria, and the resistance of major Gram-negative and Gram-positive bacteria to commonly used antimicrobial drugs in clinic were recorded. According to whether catheter-associated urinary tract infection occurred or not, the patients were divided into infection group (43 cases) and non-infection group (217 cases). The basic conditions including gender, age, total burn area, depth of perineal burn, depth of hip burn, and burn site on admission, complications of diabetes mellitus, inhalation injury, and hypoproteinaemia, invasive operations including tracheotomy and non-perineal/hip debridement/skin transplantation surgery, duration of catheter retention, number of urethral catheterization, and bladder irrigation of patients between the two groups were compared, and the independent risk factors influencing the occurrence of catheter-associated urinary tract infections in patients with perineal and/or hip burns were screened. Results: The total incidence of catheter-associated urinary tract infections in patients with perineal and/or hip burns in this study was 16.5% (43/260). The pathogens detected were predominantly Gram-negative, followed by fungi; the main Gram-negative bacterium was Klebsiella pneumoniae, and the main Gram-positive bacterium was Enterococcus faecalis. The resistance rates of Klebsiella pneumoniae to amoxicillin/clavulanic acid, amitraz, amikacin, ciprofloxacin, ceftriaxone, and levofloxacin were higher than 70.0%, the resistance rates of Klebsiella pneumoniae to cefoxitin, cefoperazone/sulbactam, cefepime, meropenem, imipenem, and piperacillin/tazobactam ranged from 56.3% to 68.8%, and the resistance rates of Klebsiella pneumoniae to ceftazidime and tigecycline were lower than 50.0%. The resistance rates of Enterococcus faecalis to ciprofloxacin and penicillin were both 85.7%, the resistance rates of Enterococcus faecalis to erythromycin, clindamycin, moxifloxacin, and tetracycline ranged from 14.3% to 57.1%, and the resistance rates of Enterococcus faecalis to linezolid, tigecycline, and vancomycin were all 0. The differences were statistically significant between the two groups in terms of gender, status of complication of hypoproteinaemia, depth of perineal burn, status of non-perineal/hip debridement/skin transplantation surgery, status of bladder irrigation, number of urethral catheterization, and duration of catheter retention of patients (with χ2 values of 7.80, 4.85, 10.68, 9.11, and 16.48, respectively, and Z values of -4.88 and -5.42, respectively, P<0.05). There were no statistically significant differences in the age, total burn area, complications of diabetes mellitus and inhalation injury, burn site, depth of hip burns, and status of tracheotomy of patients between the two groups (P>0.05). Multifactorial logistic regression analysis showed that gender, deep partial-thickness perineal burns, non-perineal/hip debridement/skin transplantation surgery, bladder irrigation, and duration of catheter retention were the independent risk factors for catheter-associated urinary tract infections in patients with perineal and/or hip burns (with odds ratios of 2.86, 2.63, 2.79, 2.34, and 1.04, respectively, with 95% confidence intervals of 1.21-6.73, 1.03-6.71, 1.03-7.59, 1.05-5.22, and 1.02-1.06, respectively, P<0.05). Conclusions: The incidence of catheter-associated urinary tract infections is high in patients with perineal and/or hip burns, with Klebsiella pneumoniae as the predominant pathogenic bacteria having a high resistance rate to commonly used antimicrobial drugs in clinic. Gender, deep partial-thickness perineal burns, non-perineal/hip debridement/skin transplantation surgery, bladder irrigation, and duration of catheter retention are the independent risk factors for catheter-associated urinary tract infections in patients with perineal and/or hip burns.

[Differentiation of temporal lobe epilepsy and temporal plus epilepsy using radiomics nomogram based on MPRAGE images].

A total of 82 patients with temporal lobe epilepsy (TLE) and temporal plus epilepsy (TPE)admitted in Xuanwu Hospital from January 1, 2019, to January 1, 2021 were restrospectively analyzed, including 41 males and 41 females, aged 2 to 52 (24±10) years. The patients were randomly divided into the training set (58 cases) and test set (24 cases) by Python. FreeSurfer software was used to segment the cortex of the affected hemisphere, defining 33 regions of interest (ROIs), and radiomics features were extracted by Python. After selecting features using the filter-based feature selection method, a radiomics model was constructed with a logistic regression classifier, and radiomics scores were calculated. Combining clinical characteristics with radiomics scores, a nomogram model was constructed using R software, the predictive accuracy of the model was assessed with the concordance index (C-index), and the model's goodness-of-fit was tested with the Hosmer-Lemeshow method. The results showed statistically significant differences between TLE and TPE patients in disease duration, intracranial electrode implantation, and hippocampal sclerosis (both P<0.05). The accuracy of the radiomics model in the training set and the test set was 91.4% and 87.5%, respectively. The nomogram model uses C-index to predict accuracy. Hosmer-Lemeshow method was used to test the goodness of fit, with AUCs of 0.95 (95%CI: 0.853-0.991) in the training set and 0.84 (95%CI: 0.676-0.999) in the test set. The study indicates that the radiomics nomogram model based on MPRAGE sequences can effectively differentiate TLE from TPE, providing reference for the development of personalized treatment plans in clinical practice.

[Predictive value of whole brain perfusion on admission for shunt-dependent hydrocephalus fllowing aneurysmal subarachnoid hemorrhage].

Objective: To explore the value of predicting shunt-dependent hydrocephalus (SDHC) in patients with aneurysmal subarachnoid hemorrhage (aSAH) based on whole brain CT perfusion(CTP) and clinical data within 24 hours at admission. Methods: The clinical and imaging data of aSAH patients who received interventional embolization in our hospital were retrospectively collected from March 2018 to August 2022. All patients underwent one-stop whole brain CT examination within 24 hours after symptom onset, and the qualitative and quantitative CTP parameters were obtained after post-processing. Follow-up was conducted once every 2 months by consulting electronic medical records or by telephone for 6 months. According to whether SDHC occurred or not, the patients were divided into SDHC group and non-SDHC group. The differences between the two groups were compared. Logistic regression model was used to analyze and determine the predictive factors of SDHC, and the SDHC predictive model was established. The effectiveness of the predictive model was evaluated by drawing the receiver operating characteristic (ROC) curve of the subjects. Results: A total of 414 patients were included, including 132 males and 282 females, aged (59±11) years. 17.6%(73/414) patients had SDHC. There were significant differences in the occurrence of acute hydrocephalus, the World Neurosurgical League Scale (WFNS), the Hunt-Hess scale, the modified Fisher score (mFS), and the qualitative and quantitative parameters of CTP between the two groups (both P<0.001). Multivariate logistic regression analysis showed that acute hydrocephalus (OR=8.621, 95%CI: 4.237-17.542),old age (OR=1.107, 95%CI: 1.068-1.148), high mFS and high Hunt-Hess classification (OR=3.740, 95%CI: 1.352-10.342) were the risk factors of SDHC in aSAH patients, and high mean cerebral blood flow (mCBF) (OR=0.931, 95%CI: 0.885-0.980) was a protective factor of SDHC.The area under ROC curve (AUC) of the prediction model constructed by these five variables was 0.923(95%CI: 0.89-0.95), with 84.5% sensitivity and 87.7% specificity. Conclusion: The mCBF and acute hydrocephalus, age, mFS and Hunt-Hess classification within 24 hours at admission can be used to predict SDHC for aSAH patients.

[Modified reverse puncture technique for esophagojejunostomy during totally laparoscopic total gastrectomy for gastric cancer].

Objective: To evaluate the value of implementing a modified reverse puncture procedure for esophagojejunostomy during totally laparoscopic total gastrectomy. Methods: This was a descriptive case series. Relevant clinical data, including the operative procedure, recovery, and pathological findings of 35 patients with gastric cancer who had undergone esophagojejunostomy with a modified reverse puncture technique during totally laparoscopic total gastrectomy in the Department of Gastrointestinal Surgery, Fujian Provincial Hospital, from June 2022 to January 2023, were prospectively collected and retrospectively analyzed. The age of all patients in the group was (64.9±8.0) years old, with 22 males (62.9%) and a body mass index of (23.2±2.4) kg/m2. The tumors were located in the upper and middle parts of the stomach in 24 cases (68.6%) and in the junction of the esophagus and stomach in 11 cases (31.4%). Important technical aspects of the modified reverse puncture procedure are as follows. (1) Site of the esophageal incision: a transverse incision is made across the right lateral wall of the esophagus at the expected site of esophageal disjunction. (2) Technique for inserting an anvil: after threading a silk thread through the tip of anvil, the end of the thread is knotted and fixed as the traction thread, after which an anvil is inserted into the esophagus through the esophageal incision, leaving the end of the traction line exposed. Next, a 60-mm linear cutter is placed through the right midclavicular trocar to straighten the opened esophagus vertically, after which the rod of the anvil is pulled out of a small incision that has been made in the esophagus by pulling the traction thread, thus completing anvil placement. (3) Jejunal binding: the jejunum on the central bar of the stapler is fastened with silk thread to the stump of the jejunum, and then tied to the output loop of the jejunum with a gauze strip. Results: All 35 surgeries were successful, with no mortality or conversion to laparotomy. The operation time, anvil insertion time, and digestive tract reconstruction time were (232.7±34.4), (8.5±1.4), and (40.5±4.8) minutes, respectively. The intraoperative blood loss was 100 (20-250) mL and the incision was (5.3±0.9) cm long. The upper surgical margin was negative in all patients and the mean distance between the upper and tumor margins was (3.5±1.2) cm. The mean number of lymph nodes dissected per patient was 33.9±7.1. The times to initial ambulation, initial passage of flatus , postoperative fluid intake, and length of postoperative hospital stay were (3.2±1.1), (3.7±1.5), (4.6±2.3), and (9.8±3.2) days, respectively. Postoperative complications occurred in five patients: one case of anastomotic leak, two of anastomotic stenosis, one of pulmonary infection, and one of incomplete intestinal obstruction, all of which were successfully managed conservatively. Conclusion: Esophagojejunostomy using a modified reverse puncture technique during totally laparoscopic total gastrectomy is safe and feasible for gastric cancer, requiring only a small incision and achieving higher upper esophageal resection margins and good postoperative recovery, and therefore warrants further implementation.

[Clinicopathological features of gastric alpha-fetoprotein-producing adenocarcinoma with SWI/SNF complex deletion].

Objective: To investigate the clinicopathological features and treatment of gastric alpha-fetoprotein (AFP)-producing adenocarcinoma with SWI/SNF complex deletion. Methods: Four cases of gastric AFP-producing adenocarcinoma with SWI/SNF complex deletion diagnosed in Zhongshan Hospital of Fudan University from January 2021 to December 2022 were collected, and their histomorphological characteristics, immunohistochemical (IHC), in situ hybridization of Epstein-Barr virus-encoded RNA (EBER), next-generation sequencing results, clinicopathological features and treatment were summarized, and literature review was conducted. Results: Among the 4 patients, there were three males and one female. They presented with abdominal pain, belching and melena. Serum AFP was significantly elevated in three patients, and endoscopy showed ulcerative lesions. Microscopically, the tumor cells showed mainly diffuse flaky or nest-like growth and typical characteristics of hepatoid adenocarcinoma. In two cases there were adenoid growth, and the tumor cells in these areas possessed clear cytoplasm, suggesting enteroblastic differentiation. The tumor cell nuclei were pleomorphic with large nucleoli and brisk mitoses. The IHC results showed that the tumor cells expressed AFP, GPC3 and SALL4, and there was retained expression of broad-spectrum keratin (CKpan) and E-cadherin. IHC detection of SWI/SNF complex subunits, namely INI1 (SMARCB1), BRG1 (SMARCA4), BRM (SMARCA2), ARID1A protein was performed. In all four cases the hepatoid adenocarcinoma region and enteroblastic differentiation region showed SMARCA2 deletion, and one case with enteroblastic differentiation also showed ARID1A deletion. SMARCB1 and SMARCA4 deletions were not seen. All the four cases were diffusely positive for p53 protein, and the Ki-67 proliferation index was 80%-90%. There were no mismatch repair deletion detected; one cases showed HER2 was strongly positive (3+), and EBER was negative. None of the four cases had mutations in the SWI/SNF complex-related subunits detected by next-generation sequencing. Among the four patients, two underwent palliative surgery due to distant metastasis at the time of surgery, two underwent radical resection. Postoperative adjuvant chemotherapy was given to three patients. Conclusions: AFP-producing adenocarcinoma is a rare subtype of gastric cancer, which can be combined with SWI/SNF complex deletion, and the pathomorphological manifestations are different from the classical SWI/SNF complex deletion of undifferentiated carcinoma with rhabdoid phenotype.

[Reappraisals of biological behaviors of PDGFRA mutant gastrointestinal stromal tumor].

Objective: To investigate the biological behavior spectrum of platelet-derived growth factor alpha receptor (PDGFRA)-mutant gastrointestinal stromal tumor (GIST), and to compare the clinical values of the Zhongshan method of benign and malignant evaluation with the modified National Institutes of Health (NIH) risk stratification. Methods: A total of 119 cases of GIST with PDGFRA mutation who underwent surgical resection at Zhongshan Hospital, Fudan University from 2009 to 2020 were collected. The clinicopathological data, follow-up records, and subsequent treatment were reviewed and analyzed statistically. Results: There were 79 males and 40 females. The patients ranged in age from 25 to 80 years, with a median age of 60 years. Among them, 115 patients were followed up for 1-154 months, and 13 patients progressed to disease. The 5-year disease-free survival (DFS) and overall survival (OS) were 90.1% and 94.1%, respectively. According to the modified NIH risk stratification, 8 cases, 32 cases, 38 cases, and 35 cases were very-low risk, low risk, intermediate risk, and high risk, and 5-year DFS were 100.0%, 95.6%, 94.3%, and 80.5%, respectively. There was no significant difference in prognosis among the non-high risk groups, only the difference between high risk and non-high risk groups was significant (P=0.029). However, the 5-year OS was 100.0%, 100.0%, 95.0% and 89.0%, and there was no difference (P=0.221). According to the benign and malignant evaluation Zhongshan method, 43 cases were non-malignant (37.4%), 56 cases were low-grade malignant (48.7%), 9 cases were moderately malignant (7.8%), and 7 cases were highly malignant (6.1%). The 5-year DFS were 100.0%, 91.7%, 77.8%, 38.1%, and the difference was significant (P<0.001). The 5-year OS were 100.0%, 97.5%, 77.8%, 66.7%, the difference was significant (P<0.001). Conclusions: GIST with PDGFRA gene mutation shows a broad range of biological behavior, ranging from benign to highly malignant. According to the Zhongshan method, non-malignant and low-grade malignant tumors are common, the prognosis after surgery is good, while the fewer medium-high malignant tumors showed poor prognosis after surgical resection. The overall biological behavior of this type of GIST is relatively inert, which is due to the low proportion of medium-high malignant GIST. The modified NIH risk stratification may not be effective in risk stratification for PDGFRA mutant GIST.

[A multi-dimensional analysis of pollen broadcasting concerns in Chinese population: a large-scale multi-center cross-sectional survey].

Objective: To investigate the concern about pollen broadcasting in Chinese population from multiple dimensions and to understand the information about allergic rhinitis (AR) in China by analyzing related factors. Methods: From March 1 to September 30, 2022, a large-scale multi-center cross-sectional survey was conducted based on the Questionnaire Star platform in 21 Chinese hospitals. A total of 7 056 subjects from 7 regions in China: Northeast, North, East, Central, South, Southwest, and Northwest China were included. Basic characteristics (including social demographic characteristics and disease characteristics of AR patients), concern about pollen broadcasting, the willingness of pollen-induced AR (PiAR) patients to receive pollen broadcasting, and the treatment satisfaction rate of AR patients were collected. The chi-square test, multivariate linear regression model, and Logistic regression analysis were used to analyze the concern about pollen broadcasting in the Chinese population and related factors from multiple dimensions. Results: Among 7 056 subjects, 23.02% were concerned about pollen broadcasting. Among 3 176 self-reported AR and 1 019 PiAR patients, 25.60% and 39.16% were concerned about pollen broadcasting, respectively, which was higher than that of non-AR or non-PiAR subjects (χ2 value was 21.74 and 175.11, respectively, both P<0.001). Among AR patients, the proportion of spring and autumn allergen-positive patients concerned about pollen broadcasting was higher than that in perennial allergen-positive patients (χ2 value was 20.90 and 19.51, respectively, both P<0.001). The proportion of AR patients with asthma, sinusitis, allergic conjunctivitis, and cardiovascular and cerebrovascular diseases was higher than those without complications (χ2 value was 50.83, 21.97, 56.78, 7.62, respectively, all P<0.05). The proportion of AR patients in North China who could find pollen broadcasting locally was 31.01%, significantly higher than those in other regions (all P<0.05). Multivariate linear regression model analysis showed that among PiAR patients, those with higher per capita household income and higher AR disease cognition levels had been concerned about pollen broadcasting in the past, and those complicated with allergic conjunctivitis had stronger intention to receive pollen broadcasting (B value was 0.24, 0.13, 0.66, 0.47, respectively, all P<0.05). The higher the disease cognition level of PiAR patients, the stronger their willingness to actively participate in treatment (R2=0.72, P<0.001). Only 18.89% of AR patients felt satisfied with the treatment effect. Logistic regression analysis showed that in AR patients, the treatment satisfaction rate was significantly higher among those concerned about pollen broadcasting compared to those who were not (OR=1.83, P<0.001). Conclusions: Currently, the dissemination of pollen broadcasting in China is hindered by various factors such as disease cognition level. The treatment satisfaction among AR patients remains unsatisfactory.

Motion of VAPB molecules reveals ER-mitochondria contact site subdomains.

To coordinate cellular physiology, eukaryotic cells rely on the rapid exchange of molecules at specialized organelle-organelle contact sites1,2. Endoplasmic reticulum-mitochondrial contact sites (ERMCSs) are particularly vital communication hubs, playing key roles in the exchange of signalling molecules, lipids and metabolites3,4. ERMCSs are maintained by interactions between complementary tethering molecules on the surface of each organelle5,6. However, due to the extreme sensitivity of these membrane interfaces to experimental perturbation7,8, a clear understanding of their nanoscale organization and regulation is still lacking. Here we combine three-dimensional electron microscopy with high-speed molecular tracking of a model organelle tether, Vesicle-associated membrane protein (VAMP)-associated protein B (VAPB), to map the structure and diffusion landscape of ERMCSs. We uncovered dynamic subdomains within VAPB contact sites that correlate with ER membrane curvature and undergo rapid remodelling. We show that VAPB molecules enter and leave ERMCSs within seconds, despite the contact site itself remaining stable over much longer time scales. This metastability allows ERMCSs to remodel with changes in the physiological environment to accommodate metabolic needs of the cell. An amyotrophic lateral sclerosis-associated mutation in VAPB perturbs these subdomains, likely impairing their remodelling capacity and resulting in impaired interorganelle communication. These results establish high-speed single-molecule imaging as a new tool for mapping the structure of contact site interfaces and reveal that the diffusion landscape of VAPB at contact sites is a crucial component of ERMCS homeostasis.

Association between infarct location and haemorrhagic transformation of acute ischaemic stroke after intravenous thrombolysis.

AIM: To evaluate the association between computed tomography (CT)-based imaging variables at the time of admission and haemorrhagic transformation (HT) after intravenous thrombolysis (IVT). MATERIALS AND METHODS: One hundred and eight patients who were treated with IVT for acute ischaemic stroke (AIS) during January 2021 to July 2023 were analysed retrospectively. The infarct location was classified as cortical or subcortical in accordance with the Alberta Stroke Program Early CT Score (ASPECTS) system. Logistic regression and receiver operating characteristic curve analyses were performed to determine the relationship between ischaemic variables and HT. RESULTS: Of the total, 18 (16.7%) patients had HT and seven (6.5%) had symptomatic intracerebral haemorrhage (sICH). Multivariate analysis revealed that cortical ASPECTS was independently associated with HT (odds ratio [OR], 0.197; 95% confidence interval [CI], 0.076-0.511; p=0.001) and cortical ASPECTS was independently associated with sICH (OR, 0.066; 95% CI, 0.009-0.510; p=0.009). To predict HT and sICH, cortical ASPECTS (HT area under the curve [AUC] = 0.881, sICH AUC = 0.971) provided a higher AUC compared with ASPECTS (HT AUC = 0.850, sICH AUC = 0.918). CONCLUSION: Cortical ASPECTS seen on CT at the time of admission is associated with HT and sICH after IVT.

[Influence of disposable diaper dependence on emotional behavior and related factors of preschool-aged children].

Objective: To investigate the influence of disposable diaper dependence (DDD) on emotional behavior and related factors of preschool-aged children. Methods: A total of 3 000 preschool-aged children from 16 kindergartens in Zhengzhou of Henan Province from October 2019 to March 2020 were selected and their parents were investigated by using a basic information questionnaire (including usage of disposable diapers), Strengths and Difficulties Questionnaire (SDQ) and Children's Sleep Questionnaire (PSQ). The differences in baseline and clinical data were compared between the DDD children and normal children, and multiple linear regression models were used to analyze the factors associated with emotional behavior in DDD children. Results: A total of 3 000 questionnaires were distributed and 2 775 (92.50%) were valid. The children ranged in age from 3 to 5 years, including 1 438 boys (51.82%) and 1 337 girls (48.18%). There were 98 (3.53%) children in DDD group and 2 677 (96.47%) children in normal group. The proportion of children living in cities in the DDD group was 58.16%, significantly higher than that of 41.84% in the normal children group (P<0.001). The abnormal detection rate of various factors in SDQ in DDD children, from high to low, were hyperactivity (n=14, 14.29%), peer communication problems (n=12, 12.24%), prosocial behavior (n=11, 11.22%), emotional symptoms (n=10, 10.20%) and conduct problems (n=7, 7.14%). The detection rates of abnormal total difficulty scores in DDD group and normal children were 7.14% (7 cases) and 0.78% (21 cases), respectively, with statistically significant differences (P<0.001). The proportions of emotional symptoms and hyperactivity disorder in DDD group were higher than those in normal group, and the differences were statistically significant (P<0.05). The PSQ score of children in DDD group was 3.01±2.02 which was not significantly different from the PSQ score of the normal group (2.71±2.10, P=0.157). The multi-factor analysis showed that caregiver's education level (ß=-1.135,95%CI:-1.910 to -0.359), urinary incontinence (ß=2.222, 95%CI: 1.105-3.339), fecal incontinence (ß=3.833, 95%CI: 2.691-4.975), urinary and fecal incontinence (ß=5.522, 95%CI: 4.145-6.899), and recurrent urinary tract infections(ß=3.523,95%CI: 1.798-5.248)were the independent influencing factors of emotional behavioral problems in DDD children (P<0.05). Conclusions: Children with DDD are more likely to have emotional behavioral problems than normal children. Caregiver's education level, urinary incontinence and recurrent urinary tract infections were influencing factors of emotional behavioral problems in DDD children.

[TRPS1 expression in salivary gland-type breast carcinoma and its clinical application].

Objective: To investigate the expression of TRPS1 in salivary gland-type breast carcinoma and its clinical application. Methods: A total of 30 cases of salivary gland-type breast carcinoma diagnosed from May 2015 to November 2022 at the Department of Pathology of the First Affiliated Hospital of Nanjing Medical University were collected. The expression of TRPS1 was detected by immunohistochemistry and compared with that of GATA3. TRPS1 and GATA3 expression in 24 cases of primary salivary gland carcinoma. Results: There were 10 cases of breast secretory carcinoma, aged 21-61 years (median 53.5 years), with the size ranging from 0.9-2.2 cm (median 1.6 cm), 2 of which were accompanied by axillary nodal macrometastasis. All patients were alive after 2-55 months of follow-up (median 29.5 months, mean 29.7 months). There were 20 cases of breast adenoid cystic carcinoma, aged 36-77 years (median 53.5 years), with the size ranging from 1.2-5.5 cm (median 2.5 cm), 3 of which were accompanied by axillary nodal macrometastasis. All patients were alive after 3-92 months of follow-up (median 22.5 months, mean 31.7 months), and 1 patient had lung metastasis 15 months after surgery. The medium/high expression ratio of TRPS1 in breast secretory carcinoma was 10/10, which was higher than that of GATA3 (7/10). TRPS1 was also positive in the 2 cases with lymph node metastases. The medium/high expression rate of TRPS1 in breast adenoid cystic carcinoma was 20/20, which was significantly higher than that of GATA3 (2/20). TRPS1 was highly expressed in both classic and solid subtypes, while GATA3 was only expressed in a few cases of the classic subtype. TRPS1 was also positive in 3 cases with lymph node metastases and 1 case of the pulmonary metastases. The expression level of TRPS1 was the same in 1 case before and after neoadjuvant chemotherapy. In addition, TRPS1 was positive in parotid secretory carcinoma and adenoid cystic carcinoma. The medium/high expression rate of TRPS1 in parotid secretory carcinoma (6/6) was higher than that of GATA3 (2/6), and the medium/high expression rate of TRPS1 in parotid adenoid cystic carcinoma (17/18) was higher than that of GATA3 (2/18). Conclusions: The expression of TRPS1 is highly sensitive to salivary gland-type breast carcinoma, especially in GATA3-negative solid subtype of adenoid cystic carcinoma, which plays an important role in clinical practice.

[Research progress of phage therapy in orthopedic implant-related infection].

The widespread application of implantable materials has brought about a corresponding increase in implant-related complications, with implant-associated infections being the most critical. Biofilms, which often form on these implants, can significantly impede the effectiveness of traditional antibiotic therapies. Therefore, strategies such as surgical removal of infected implants and prolonged antibiotic treatment have been acknowledged as effective measures to eradicate these infections. However,the challenges of antibiotic resistance and biofilm persistence often result in recurrent or hard-to-control infections, posing severe health threats to patients. Recent studies suggest that phages, a type of virus, can directly eliminate pathogenic bacteria and degrade biofilms. Furthermore, clinical trials have demonstrated promising therapeutic results with the combined use of phages and antibiotics. Consequently, this innovative therapy holds significant potential as an effective solution for managing implant-associated infections. This paper rigorously investigates and evaluates the potential value of phage therapy in addressing orthopedic implant-associated infections, based on a comprehensive review of relevant scientific literature.

[Current status and prospects of non-surgical treatment for fecal incontinence].

Fecal incontinence is a refractory disease in colorectal surgery. The main clinical manifestation is that patients cannot control the discharge of gas, solid or liquid feces in the rectum autonomously. It is easy to bring shame to patients and seriously affect their physical and mental health. Reducing the frequency of fecal incontinence, restoring anal sphincter function, and improving patient quality of life are important goals for treating fecal incontinence. With the development of medical technology and the improvement of treatment plans for fecal incontinence, patients with fecal incontinence usually undergo conservative treatment first, and if conservative treatment is ineffective, surgery can be chosen. Non-surgical treatment methods commonly used in clinical practice include biofeedback therapy, magnetic stimulation therapy, pelvic floor muscle training, anal sphincter training, Kegel training, and other rehabilitation treatments. This article discusses the non-surgical treatment methods for fecal incontinence, hoping to provide a choice for clinical treatment of fecal incontinence.