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*

Antiviral drug research and development is an important research direction in the current and future biomedical field. The research and development of antiviral drugs not only requires the application of new strategies and new technologies, but also requires the complementary advantages and close cooperation of project teams. Based on the latest progress in this field and the author's drug research practice, this paper summarizes the underlying logic, innovative thinking and research paradigm of antiviral medicinal chemistry.

Objective To compare the effects of two arc(TA)and dual arc(DA)techniques on the dose distribution to the planning target volume(PTV)and organs at risk(OAR)in volumetric modulated arc therapy(VMAT)for lower mid-thoracic esophageal cancer.Methods Ten patients with lower mid-thoracic esophageal cancer who received radiation therapy at some hospital from July 2020 to June 2022 were selected retrospectively.A TA radiation therapy plan and a DA radiation therapy plan were developed for each patient using the Ray Arc module of RayStation 4.7.5.4 planning system,and the two kinds of radiation plans were compared in terms of dosimetric parameters including D2,D5,D50,D95,D98,homogeneity index(HI),conformity index(CI),beam-on time and total monitor unit for PTV and lung V5,V10,V20,V30 and Dmean and heartV30,V40 and Dmean and spine cord Dmax for OAR.SPSS 22.0 was used for statistical analysis.Results TA and DA radiation therapy plans had no significant differences in PTV CI,HI,D2,D5,D50,D95 and beam-on time(P＞0.05),and DA plan had D98 and total monitor unit higher obviously than those of TA plan(P＜0.05).In terms of OARs protection,DA plan had heart V30,V40 and Dmean slightly lower than those of TA plan with non-significantly differences(P＞0.05),while lung V5,V30 and Dmean and spine cordDmax significantly lower(P＜0.05).Conclusion DA technique gains advantages over TA technique in PTV dose distribution and dose to OAR,and the involvement of DA technique in preparing the VMAT plan for esophageal cancer contributes to enhancing the treatment efficacy.[Chinese Medical Equipment Journal,2024,45(1):62-66]

Currently, clinically used drugs for the treatment of gout inflammation, such as colchicine, nonsteroidal anti-inflammatory drugs, and glucocorticoids, can only relieve the pain of joint inflammation and have severe hepatorenal toxicity and multiple organ adverse reactions. The NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome is a key complex that induces the onset of gout inflammation and has become a crucial target in the development of anti-gout drugs. This article reviews the research progress of anti-gout small molecules targeting the NLRP3 inflammasome and their bioactivity evaluation methods in the past five years, in order to provide information for the development of specific drugs for the treatment of gout inflammation.

AIM To establish a UPLC-MS/MS method for the simultaneous content determination of liquiritin apioside,alibiflorin,swertiamarin,methyl gallate,benzoylpaeoniflorin,sweroside,6′-O-β-D-glucosylgentiopicroside,isoliquiritigenin,loganic acid,liquiritigenin,gallic acid,paeoniflorin,oxypaeoniflorin,gentiopicroside,glycyrrhizic acid,isoliquiritoside and liquiritin in Yangxue Ruanjian Capsules.METHODS The analysis was performed on a 40℃thermostatic Waters BEH C18column(2.1 mm×100 mm,1.7 μm),with the mobile phase comprising of 2 mmol/L ammonium acetate(containing 0.1%formic acid)-acetonitrile flowing at 0.3 mL/min in a gradient elution manner,and electron spray ionization source was adopted in negative ion scanning with multiple reaction monitoring mode.RESULTS Seventeen constituents showed good linear relationships within their own ranges(r>0.999 6),whose average recoveries were 91.33%-104.03%with the RSDs of 1.58%-3.50%.CONCLUSION This rapid,accurate and stable method can be used for the quality control of Yangxue Ruanjian Capsules.

Objective:To investigate the clinicopathological characteristics and prognostic factors of gastrointestinal stromal tumor (GIST) with initial surgical resection.Methods:The retro-spective cohort study was conducted. The clinicopathological data of 847 GIST patients who under-went initial surgical resection in Tianjin Medical University Cancer Institute & Hospital from January 2011 to December 2020 were collected. There were 405 males and 442 females, aged (60±10)years. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the nonparameter rank sum test. The Kaplan-Meier method was used to calculate survival rates. Univariate analysis was conducted using the Log-rank test. Multivariate analysis was conducted using the COX regression model. Results:(1) Clinicopatholo-gical characteristics. Of 847 patients, the tumor primary location was stomach in 585 cases, jejunum and ileum in 142 cases, duodenum in 76 cases, colorectum in 10 cases, esophagus in 3 cases, and extra-gastrointestinal in 31 cases. There were 13 cases with liver metastasis and 22 cases with abdominal metastasis. The tumor maximum diameter was (7±5)cm, and the number of nuclear divisions was 4(range, 0-60) cells/50 high-power field or 5 mm 2. According to risk classification of National Institutes of Health (NIH), 31 cases were of extremely low risk, 238 cases were of low risk, 213 cases were of moderate risk, 365 cases were of high risk. There were 839 of 847 patients positive for CD117, 788 cases positive for Dog-1, 710 cases positive for CD34, respectively. There were 272 cases with Ki-67 <5%, 214 cases with Ki-67 of 5%- 9%, 198 cases with Ki-67 ≥10%, 163 cases with missing data. R 0 resection was in 814 cases and non-R 0 resection was in 33 cases. (2) Gene testing and postoperative adjuvant therapy of GIST patients. ① Gene testing. Of 847 patients, 424 underwent genetic testing. The proportion of genetic testing was 1.89%(1/53) in 2011, 9.76%(8/82) in 2012, 8.45%(6/71) in 2013, 15.66%(13/83) in 2014, 50.00%(40/80) in 2015, 55.26%(42/76) in 2016, 73.86%(65/88) in 2017, 68.27%(71/104) in 2018, 80.65%(75/93) in 2019, 88.03%(103/117) in 2020, respectively. Of 424 with genetic testing, 338 cases had KIT mutation, 31 cases had PDGFRA mutation, 55 cases were wild type. ② Adjuvant therapy. Of 847 patients, 253 patients underwent postoperative adjuvant therapy. The proportions of postoperative adjuvant therapy were 8.82%(21/238), 41.78%(89/213), 39.18%(143/365) in patients of low risk, moderate risk, high risk. Of 578 patients with moderate to high risk, the proportion of postoperative adjuvant therapy was 15.15%(5/33) in 2011, 14.71%(10/68)in 2012, 22.45%(11/49) in 2013, 29.09%(16/55) in 2014, 41.38%(24/58) in 2015, 46.15%(24/52) in 2016, 32.81%(21/64)in 2017, 60.00%(45/75) in 2018, 60.42%(29/48) in 2019, 61.84%(47/76) in 2020, respectively. Of 253 patients underwent postoperative adjuvant therapy, 247 cases received imatinib had 6 cases received sunitinib. (3) Comparison of clinicopathological characteristics of GIST with non-gastric origin and gastric origin. Of 847 patients, 262 cases had non-gastric origin and 585 cases had gastric origin. There were significant differences in gender, the number of tumor, tumor maximum diameter, Ki-67 index, risk classification of NIH, and R 0 resection between the two groups ( χ2=8.62, 8.40, 12.97, 6.57, Z=-6.15, χ2=17.19, P<0.05). (4) Analysis of influencing factors for recurrence-free survival rate in GIST patients. Results of multivariate analysis showed that the year of initial diagnosis, primary site, tumor maximum diameter, mitotic image, risk classification of NIH, R 0 resection, genetic testing and postoperative adjuvant therapy were independent factors influencing recurrence-free survival rate in GIST patients with initial surgical resection ( hazard ratio=0.58, 0.61, 2.00, 1.71, 5.81, 2.56, 0.65, 0.38, 95% confidence interval as 0.39-0.85, 0.45-0.83, 1.46-2.74, 1.24-2.35, 3.16-10.69, 1.63-4.02, 0.46-0.94, 0.25-0.56, P<0.05). Conclusions:GIST with initial surgical resection is common located in stomach, with high positive rate in CD117 and Dog-1. The number of people undergoing genetic testing and targeted therapy for GIST is increasing year by year. There are significant differ-ences in clinicopathological characteristics between GIST with non-gastric origin and gastric origin. The year of initial diagnosis, primary site, tumor maximum diameter, mitotic image, risk classifica-tion of NIH, R 0 resection, genetic testing and postoperative adjuvant therapy are independent factors influencing recurrence-free survival rate in GIST patients with initial surgical resection.

Objective To investigate the patterns of traditional Chinese medicine(TCM)syndrome differentiation and treatment for dengue fever by using R language data visualization technology,so as to provide reference for TCM syndrome differentiation and treatment of dengue fever.Methods The related literature of dengue fever treated by Chinese medicine was retrieved from CNKI,Wanfang Data,and VIP.R-Studio software was used to conduct descriptive statistical analysis of the TCM syndromes,treatment methods,prescriptions and Chinese medicine in the literature of dengue fever treated by oral use of Chinese medicine.Based on Apriori algorithm,association rule mining and cluster analysis were carried out to explore the TCM syndrome and treatment patters of dengue fever.Results A total of 176 prescriptions for effective cases were extracted,and the included literature involved 29 syndromes,73 TCM treatment methods,56 classical prescriptions and 35 self-formulated prescriptions,and 179 Chinese medicinals.The syndrome of comorbidity of defense phase and qi phase and the syndrome of blazing of both qi phase and nutrient phase were the high-frequency syndromes of dengue fever treated by oral use of Chinese medicine.The high-frequency treatment methods covered heat-clearing therapy,toxin-removing therapy,blood-cooling therapy and dampness-resolving therapy.Qingwen Baidu Decoction was the most frequently-used prescription.Glycyrrhizae Radix et Rhizoma,Forsythiae Fructus,Scutellariae Radix,Gypsum Fibrosum,and Lonicerae Japonicae Flos were the frequently-used Chinese medinals.There were three drug combinations containing Paeoniae Radix Rubra,Moutan Cortex,and Rehmanniae Radix,and their correlation of association rules was the highest.Bubali Cornu,Moutan Cortex,Paeoniae Radix Rubra,Rehmanniae Radix,Lonicerae Japonicae Flos,Forsythiae Fructus,Gypsum Fibrosum,Scutellariae Radix,Anemarrhenae Rhizoma,and Glycyrrhizae Radix et Rhizoma were the core Chinese medicinals for the treatment of dengue fever.Conclusion The TCM syndromes of dengue fever are predominated by the syndrome of comorbidity of defense phase and qi phase and the syndrome of blazing of both qi phase and nutrient phase.The treatment of dengue fever with TCM is based on the principle of clearing heat toxin from the qi phase,cooling the nutrient-blood excess heat,resolving pathogenic dampness,and nourishing qi and yin.The treatment focuses on clearing qi phase and blood phase,and the application of removing stasis in febrile diseases should be stressed,thus to block the progression of the disease in time.

Objective:To analyze the clinical efficacy of three-dimensional(3D) reconstruction guided uniportal fluorescence thoracoscopic subsegmentectomy for the pulmonary nodules.Methods:We retrospectively analyzed 50 patients with nodules who underwent uniportal fluorescence thoracoscopic subsegmentectomy from December 2021 to February 2024. All patients underwent thin-slice CT scanning and 3D reconstruction preoperatively. 12 patients were given CT-guided hookwire localization preoperatively.The intersegmental plane was identified by fluorescence method.Results:One patient was converted to right upper lobectomy due to no lesion found in S1b. The mean blood loss was(23.4±16.5)ml and the mean operative time was(126.5±38.5)min. The mean duration of postoperative drainage was(2.6±0.8)days. Mean postoperative hospitalization was(4.8±1.8)days. There were 2 cases with postoperative pulmonary infections, including one with encapsulated pleural effusion. There was no air leakage over 3 days, and no death within 30 days after surgery.Conclusion:3D reconstruction guided uniportal fluorescence thoracoscopic subsegmentectomy is a safe and feasible technique for resection of pulmonary nodules in lung subsegments, and surgical indications must be strictly controlled.

The gallium-based liquid metals were introduced in terms of the advantages when applied in medical field,application status in medical imaging,drug delivery,antibiosis and tumor therapy and cutting-edge application in flexible e-skin,wearable sensor and flexible medical device.The deficiencies of the gallium-based liquid metals in durability,potential toxicity,high cost of preparation and difficulty of process control were analyzed when applied in medical fields.The future development directions of the gallium-based liquid metals were pointed out.[Chinese Medical Equipment Journal,2024,45(11):97-102]

Objective To establish and evaluate a talent training system for hospital information pharmacists based on a competency model,thereby enhancing refined management of pharmaceutical affairs in hospitals and promoting high-quality development of pharmacy services.Methods The current development status of hospital information pharmacists at home and abroad was examined.A competency model for hospital information pharmacist positions was established using methods such as behavioral event interviews.In conjunction with this model,training course outlines addressing knowledge and capability requirements were developed.National skill training classes for hospital information pharmacists were conducted using innovative teaching methods like scenario simulation and case discussion.Training effectiveness was evaluated by tracking participants'work performance and scientific research achievements in the field of pharmaceutical information through questionnaire surveys before and after the training.Results The hospital information pharmacist positions competency model was constructed in four parts:knowledge,experience,skills,and personal traits.Based on this model,a training system for hospital information pharmacists was established,which included setting job responsibilities and performance indicators,establishing a pharmacy information department system,designing a series of training courses and publishing textbooks,founding national training classes,creating a specialized question bank,and developing a digital pharmacy network platform.The project team tracked the work performance and scientific research achievements of participants before and after training,using the national hospital information pharmacist training class hosted by the Guangdong Pharmaceutical Association as an example.From 2018 to 2024,a total of 465 information pharmacists from 298 hospitals across 28 provinces and cities were trained over seven sessions.Questionnaires were sent to participants who had completed at least one year since graduation,and 236 valid responses were received.Of these,169(71.6% )participants reported playing a major role in pharmacy informatization projects after the training,and 65(27.5% )participants published papers,applied for projects,or filed for patents after the training,with the majority related to pharmacy automation and informatization.Conclusion A competency model for hospital information pharmacist positions was constructed and applied nationwide,achieving favorable results.