Microglial functions are linked to Ca²⁺ signaling, with endoplasmic reticulum (ER) calcium stores playing a crucial role. Microglial abnormality is a hallmark of Alzheimer's disease (AD), but how ER Ca²⁺ receptors regulate microglial functions under physiological and AD conditions remains unclear. We found reduced ryanodine receptor 2 (Ryr2) expression in microglia from an AD mouse model. Modulation of RyR2 using S107, a RyR-Calstabin stabilizer, blunted spontaneous Ca²⁺ transients in controls and normalized Ca²⁺ transients in AD mice. S107 enhanced ATP-induced migration and phagocytosis while reducing ramification in control microglia; however, these effects were absent in AD microglia. Our findings indicate that RyR2 stabilization promotes an activation state shift in control microglia, a mechanism impaired in AD. These results highlight the role of ER Ca²⁺ receptors in both homeostatic and AD microglia, providing insights into microglial Ca²⁺ malfunctions in AD.
Animals ; Microglia/pathology* ; Alzheimer Disease/pathology* ; Phagocytosis/drug effects* ; Ryanodine Receptor Calcium Release Channel/metabolism* ; Disease Models, Animal ; Mice ; Cell Movement/drug effects* ; Mice, Transgenic ; Calcium Signaling/physiology* ; Calcium/metabolism* ; Mice, Inbred C57BL ; Male ; Endoplasmic Reticulum/metabolism*

Improving the prognosis of patients with colorectal cancer (CRC) holds important clinical and social significance. Immunotherapy is an emerging therapy approach for cancers, which mainly include immune checkpoint inhibitors (ICI), immune vaccine and adoptive cell therapy. ICI have achieved good clinical translation in treatment of metastatic CRC with deficient DNA mismatch repair/high microsatellite instability (dMMR/MSI-H) status. The application of some ICI, such as PD-1 inhibitors pembrolizumab and nivolumab, in this type patients have been approved by the FDA. In addition,numerous positive results are acquired in clinical trials of neoadjuvant therapy for resectable dMMR/MSI-H CRC. These results greatly bolstered the exploration enthusiasm of CRC immunotherapy. However, the proficient DNA mismatch repair/microsatellite stability (pMMR/MSS) CRC, which accounting for the vast majority in related patients, hardly benefit from ICI therapy. Various combination strategies, mainly including ICI combined with traditional chemotherapy, radiotherapy, or targeted therapy, have been attempted to alter the “cold tumors” microenvironment characteristics of pMMR/MSS CRC in clinical trials, whereas no breakthrough results were reached. Theoretically, tumor vaccines are ideal choice to break down the barrier of insufficient immune infiltration in solid tumors. However, the outcomes of related clinical trials in CRC patents are not satisfactory, and partially due to the weak specificity of the applied tumor-associated antigens. Clinical studies of adoptive cell therapy in CRC are also actively underway. The favorable efficacy of tumor-infiltrating lymphocyte, cytokine-induced killer (CIK) and dendritic cell-CIK in CRC have been confirmed, while the CAR-T and TCR-T therapies need more exploration based on screening more suitable antigens and optimizing engineering design. In this review, we made a summary based on the mainline of clinical studies related to diverse immunotherapies, so as to clarify the progress of CRC immunotherapy and provide bases for exploration of better treatment options.

Hyperkalemia is one of the common ion metabolism disorders in clinical practice. Hyperkalemia is defined as serum potassium higher than 5.0 mmol/L according to the guidelines at home and abroad. Acute severe hyperkalemia can cause serious consequences, such as flaccid paralysis, fatal arrhythmia, and even cardiac arrest. The use of renin-angiotensin- aldosterone system inhibitors, β-blockers and diuretics, low-sodium and high-potassium diets, and the presence of related comorbidities increase the occurrence of hyperkalemia. Hyperkalemia risk exist in all clinical departments, but there is a lack of a standardization in the management of multi- department cooperation in hospital. Therefore, a number of domestic nephrology and cardiology department experts have discussed a management model for multi-department cooperation in hyperkalemia, formulating the management standard on hospital evaluation, early warning, diagnosis and treatment, and process. This can promote each department to more effectively participate in nosocomial hyperkalemia diagnosis and treatment, as well as the long-term management of chronic hyperkalemia, improving the quality of hyperkalemia management in hospital.

Molecular Biology is a key basic professional course for all the students specializing in Biolo-gy,Biotechnology,and Bioengineering.With the promotion of double world-class project and first-class undergraduate construction,the development of English-taught course faces challenges.We started to teach the Molecular Biology course in English at the East China University of Science and Technology since 2019,the construction of Molecular Biology course has been reformed and practiced,including the combination of imagery,vividness and classroom teaching,the combination of advanced,cutting-edge and classical theories,and the comprehensive coverage of the teaching process,which has effectively pro-moted the construction and practice of Molecular Biology course.The Molecular Biology course taught in English greatly increased the students'professional and scientific research ability,international vision and English academic communication ability,comprehensive ability and satisfaction,and teachers'teaching and research ability.This course provides an effective reference for fostering innovative profes-sional first-class undergraduates and the construction of Molecular Biology course.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To study the application value of different transbronchial biopsies in the diagnosis of central lung cancer in elderly patients.Methods The clinical data of 97 elderly patients with central lung cancer diagnosed by pathology from June 2020 to June 2023 in the 923rd Hospital of Chinese People's Liberation Army Joint Logistic Support Force were retrospectively analyzed.According to the different initial transbronchial biopsy methods,the patients were divided into the endobronchial biopsy(EBB)group(n=51)and the conventional transbronchial needle aspiration(cTBNA)group(n=46).The histopathological results were statistically analyzed,and the first biopsy positive rates of EBB and cTBNA in the diagnosis of senile central lung cancer were calculated and compared.At the same time,the differences of biopsy tolerance and complications between the two groups were evaluated.Results The squamous cell carcinoma proportions in both groups were over 50%.There was no significant difference in the first biopsy positive rate between the two groups(P>0.05).The incidence of temporary retreat of the scope due to subjective tolerance in the EBB group was higher than that in the cTBNA group,and the difference was statistically significant(P<0.05).There was a statistically significant difference in the incidence of intraoperative complications of different grades between the two groups(P<0.001).Among them,the incidence of grade 2 and above complications during surgery in the EBB group was significantly higher than that in the cTBNA group(P<0.001).Conclusion For elderly patients with central lung cancer,the success rate of the first biopsy of EBB and cTBNA is roughly equivalent,but the incidence of postoperative complications of the latter is significantly lower than that of the former.cTBNA can be used as the first biopsy method for this population.

Objective:To construct a spatial radiomics model based on the spatial distribution characteristics of supratentorial pilocytic astrocytoma (PA) and ganglioglioma (GG) and to evaluate its differential diagnosis efficiency.Methods:The study was a cross-sectional study. A retrospective collection of 244 patients with episodic PA and GG who attended Beijing Tiantan Hospital of Capital Medical University (Center 1) from June 2016 to June 2022 and 116 patients with episodic PA and GG who attended General Hospital of Eastern Theater Command (Center 2) from March 2019 to October 2022 was performed. The patients in Center 1 were divided into a training set (171 patients) and a validation set (73 patients) in a 7∶3 ratio according to the random number table method, and the patients in Center 2 as a whole were regarded as test sets. All patients underwent MRI. Segmentation of tumor based on enhanced T 1WI and T 2WI images, alignment to standard space to generate a statistical parametric mapping of tumor locations and intergroup comparison was conducted. The Johns Hopkins University template was used to extract 189 tumor location features to construct a spatial model of tumor location; PyRadiomic 3.0.1 software was used to extract tumor radiomics features to construct a radiomics model; and the two models were fused to construct a spatial radiomics model. The efficacy of spatial radiomics model, spatial model, and radiomics model to discriminate PA from GG was analyzed using receiver operating characteristic curves and area under the curve (AUC). The generalization ability of the model was assessed by the difference in accuracy between the test sets and the validation sets (ΔACC). The clinical utility of the model was compared using clinical decision curves and calibration curves. Results:The statistical parametric mapping of lesions showed that supratentorial PA was vulnerable to medial structure areas such as suprasellar region, thalamus, basal ganglia and frontal lobe, temporal lobe, parietal lobe. GG was mainly distributed in bilateral temporal lobes, as well as frontal lobe, occipital lobe and parietal lobe. The AUCs of spatial radiomics model, radiomics model and spatial model to identify PA and GG in the test set were 0.876, 0.785, and 0.819, with accuracies of 77.59%, 72.41%, and 77.14%, respectively, and ΔACCs in the test set and validation set were 11.6%, 15.43%, and 6.94%, respectively. The clinical decision curves showed an overall greater clinical benefit of the spatial radiomics model compared with the conventional radiomics model and spatial model.Conclusion:Spatial radiomics model containing spatial information on lesion location can improve the diagnostic efficacy of supratentorial PA and GG, and enhance the generalization of the prediction model.

Objective: To understand the knowledge, attitude and behavior of adult residents on influenza, pneumococcus, human papillomavirus (HPV), herpes zoster (HZ), COVID-19, hepatitis B and rabies vaccination in Shandong Province. Methods: From August to September 2022, a multi-stage stratified random sampling method was used to investigate community-dwelling residents aged 18 years old and above in 12 counties (cities and districts) of Shandong Province. A questionnaire survey was used to collect the basic information of the respondents, such as knowledge, attitude and vaccination behavior of influenza, pneumococcus, HPV, HZ, COVID-19, hepatitis B and rabies vaccine. Analysis of variance was used to compare the differences in the respondents' knowledge and attitude scores of different vaccines. The Chi-square test was conducted to compare the differences in vaccination reasons among different characteristics, and a logistic regression model was used to analyze the influencing factors of vaccination behavior. Results: The median age (Q₁, Q₃) of the 2 754 respondents was 39 (29, 57) years ranging from 18 to 94 years, with a number of 1 234 (44.81%) males. The average score of the respondents' understanding of various knowledge about adult vaccines was less than 4 points, with the highest score for understanding which diseases can be prevented by adult vaccines. The average score of consent and necessity for adult vaccines to prevent diseases was greater than 3.6 points. In terms of knowledge demand and trust in information channels, there was a high level of trust in the recommendations of vaccination outpatient staff and clinical doctors [with scores of (4.15±0.79) and (4.02±0.80), respectively]. The highest demand for information on vaccination safety knowledge was (4.18±0.84) points. In recent two years, 52.11% of the population had been vaccinated with other vaccines in addition to the COVID-19 vaccine and rabies vaccine, and 45.44% of the population felt it was necessary to be vaccinated through media publicity. Women, age growth, high education level, and high-income level were the promoting factors for adopting vaccination behavior. Conclusion: Adult residents in Shandong Province have a basic understanding and supportive attitude towards vaccination, but the vaccination behavior rate is still relatively low, with significant differences in sex, age, education level, and income level. It is necessary to further increase efforts in the breadth and depth of adult vaccination promotion and education, as well as promotion strategies targeting different populations.
Adult ; Male ; Female ; Humans ; Adolescent ; COVID-19 Vaccines ; Health Knowledge, Attitudes, Practice ; Influenza, Human ; Papillomavirus Infections ; Rabies Vaccines ; Influenza Vaccines ; COVID-19/prevention & control* ; Hepatitis B ; Herpes Zoster

Objective: To understand the knowledge, attitude and behavior of adult residents on influenza, pneumococcus, human papillomavirus (HPV), herpes zoster (HZ), COVID-19, hepatitis B and rabies vaccination in Shandong Province. Methods: From August to September 2022, a multi-stage stratified random sampling method was used to investigate community-dwelling residents aged 18 years old and above in 12 counties (cities and districts) of Shandong Province. A questionnaire survey was used to collect the basic information of the respondents, such as knowledge, attitude and vaccination behavior of influenza, pneumococcus, HPV, HZ, COVID-19, hepatitis B and rabies vaccine. Analysis of variance was used to compare the differences in the respondents' knowledge and attitude scores of different vaccines. The Chi-square test was conducted to compare the differences in vaccination reasons among different characteristics, and a logistic regression model was used to analyze the influencing factors of vaccination behavior. Results: The median age (Q₁, Q₃) of the 2 754 respondents was 39 (29, 57) years ranging from 18 to 94 years, with a number of 1 234 (44.81%) males. The average score of the respondents' understanding of various knowledge about adult vaccines was less than 4 points, with the highest score for understanding which diseases can be prevented by adult vaccines. The average score of consent and necessity for adult vaccines to prevent diseases was greater than 3.6 points. In terms of knowledge demand and trust in information channels, there was a high level of trust in the recommendations of vaccination outpatient staff and clinical doctors [with scores of (4.15±0.79) and (4.02±0.80), respectively]. The highest demand for information on vaccination safety knowledge was (4.18±0.84) points. In recent two years, 52.11% of the population had been vaccinated with other vaccines in addition to the COVID-19 vaccine and rabies vaccine, and 45.44% of the population felt it was necessary to be vaccinated through media publicity. Women, age growth, high education level, and high-income level were the promoting factors for adopting vaccination behavior. Conclusion: Adult residents in Shandong Province have a basic understanding and supportive attitude towards vaccination, but the vaccination behavior rate is still relatively low, with significant differences in sex, age, education level, and income level. It is necessary to further increase efforts in the breadth and depth of adult vaccination promotion and education, as well as promotion strategies targeting different populations.
Adult ; Male ; Female ; Humans ; Adolescent ; COVID-19 Vaccines ; Health Knowledge, Attitudes, Practice ; Influenza, Human ; Papillomavirus Infections ; Rabies Vaccines ; Influenza Vaccines ; COVID-19/prevention & control* ; Hepatitis B ; Herpes Zoster

Background:Complete colonoscopy is key to the diagnosis and treatment of colorectal disease,its role in reducing the morbidity and mortality of colorectal cancer is well known.Nonetheless,there are numerous factors,not just from the endoscopist's perspective but also from the patient's,that can potentially increase the difficulty of completing a colonoscopy.Aims:To identify patient-related factors that influenced the difficulty of a colonoscopy.Methods:Through two rounds of expert consultation,the factors that might affect the difficulty of colonoscopy were selected.A total of 1621 consecutive painless colonoscopies from Jan.2021 to Jan.2022 at the endoscopy center of The Affiliated Wuxi People's Hospital of Nanjing Medical University were evaluated in a retrospective manner.Factors including demographic data,cecal insertion time,adenoma detection rate and so on were recorded.These factors were analyzed to determine their association with difficulty by using Logistic regression model.Results:A total of 29 patient-related factors affecting the difficulty of colonoscopy were selected.Through retrospective analysis,the mean age of 1621 cases was(47.45±13.27)years,of which 45.8%were male and the mean body mass index was(23.32±3.11)kg/m2.Logistic regression analysis revealed that age≥60 years(OR=2.890,95%CI:1.957-4.269,P<0.001),female gender(OR=0.324,95%CI:0.217-0.484,P<0.001),history of gynecological surgery(OR=14.895,95%CI:9.741-22.776,P<0.001),constipation for 20-30 years(OR= 1.412,95%CI:0.925-2.156,P=0.010)were independent risk factors for difficult colonoscopy.Conclusions:This retrospective study identified several patient-related factors that influence the technical difficulty of colonoscopy.These findings had implications for practice and teaching of colonoscopy.