Microglia are the resident immune cells in the central nervous system(CNS),and play a dual role in maintaining brain homeostasis and mediating neuroprotection.Under normal conditions,microglia maintain brain homeostasis by monitoring environmental changes.When nerve damage or certain pathological stimuli occur,microglia are rapidly activated and initiate a series of complex immune responses to induce neuroinflammation.This proper activation of microglia can protect the brain by inhibiting or clearing various pathogens,but excessive neuroinflammation can lead to neuronal damage and even death.This imbalance of inflammatory response is one of the core features of pathological development of many CNS inflammatory diseases,such as Alzheimer's disease,Parkinson's disease,sepsis-associated encephalopathy,and ischemic strokes.In recent years,with the rapid development of frontier biotechnology such as single-cell sequencing,proteinomics and gene editing,important progress has been made in understanding the molecular mechanism by which microglia participate in CNS inflammatory diseases,especially in the activation of inflammatory corpuscles,epigenetic modifications,and metabolic reprogramming.However,due to the heterogeneity and duality of microglia under different pathological conditions,therapeutic methods targeting microglia have not yet been widely used in clinical practice.In summary,this article takes microglia as the starting point and introduces the molecular mechanisms of their involvement in the occurrence and development of CNS inflammatory diseases and its targeted regulatory treatment strategy,aiming to provide theoretical reference for the subsequent precise regulation of microglia function and the development of more targeted therapeutic drugs.

Microglia are the resident immune cells in the central nervous system(CNS),and play a dual role in maintaining brain homeostasis and mediating neuroprotection.Under normal conditions,microglia maintain brain homeostasis by monitoring environmental changes.When nerve damage or certain pathological stimuli occur,microglia are rapidly activated and initiate a series of complex immune responses to induce neuroinflammation.This proper activation of microglia can protect the brain by inhibiting or clearing various pathogens,but excessive neuroinflammation can lead to neuronal damage and even death.This imbalance of inflammatory response is one of the core features of pathological development of many CNS inflammatory diseases,such as Alzheimer's disease,Parkinson's disease,sepsis-associated encephalopathy,and ischemic strokes.In recent years,with the rapid development of frontier biotechnology such as single-cell sequencing,proteinomics and gene editing,important progress has been made in understanding the molecular mechanism by which microglia participate in CNS inflammatory diseases,especially in the activation of inflammatory corpuscles,epigenetic modifications,and metabolic reprogramming.However,due to the heterogeneity and duality of microglia under different pathological conditions,therapeutic methods targeting microglia have not yet been widely used in clinical practice.In summary,this article takes microglia as the starting point and introduces the molecular mechanisms of their involvement in the occurrence and development of CNS inflammatory diseases and its targeted regulatory treatment strategy,aiming to provide theoretical reference for the subsequent precise regulation of microglia function and the development of more targeted therapeutic drugs.

Objective:To describe the detail sampling design,weighting,instruments,filed procedures and quality control methods of the epidemiological survey on dementia among community residents in Tongliao City.Methods:A three-stage disproportionate probability sampling design was used to investigate the inhabitants aged 65 years and over in Tongliao City,Inner Mongolia Autonomous Region.The 10/66 Dementia Research Group(10/66 DRG)assessment instruments were used to diagnose dementia,using computer-assisted personal interview mode in the selected older people.Comprehensive quality control methods were implemented throughout the field-work.Results:A total of 166 villages or communities were sampled from nine counties or districts in Tongliao Cit-y.Totally 4 345 older people were interviewed with 96.2％response rate.By calculating sampling design weights,non-response adjustment weights and post-stratification adjustment weights,these weights were multiplied and per-formed trimming adjustment and standardization adjustment to generate final weights.The 171 interviewers were well-trained and qualified to carry out filed interview.Quality control methods included computer data check,audio record check,and telephone check in order to ensure the quality of the survey.Conclusion:This survey is imple-mented using a rigorous sampling design and timely quality control methods,and uses the 10/66 DRG assessment instruments with satisfactory international validity and reliability as survey instruments,which has international cross-cultural comparability.It provides a valid and feasible methodology of epidemiological survey on dementia for further studies in different regions in China.

Objective:To compare the curative effects between modified double-reverse traction technique and traditional open reduction in the treatment of tibial plateau fractures.Methods:A retrospective study was conducted to analyze the data of 70 patients with Schatzker type Ⅳ-Ⅴ tibial plateau fracture who had undergone surgical treatment at The Third Department of Orthopaedics, Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine from January 2017 to December 2022. The patients were divided into an observation group treated with modified double-reverse traction and a control group treated with traditional open reduction. In the observation group of 37 cases, there were 20 males and 17 females with an age of (44.6±13.5) years, and 9 cases of type Ⅳ and 28 cases of type V by the Schatzker classification; in the control group of 33 cases, there were 18 males and 15 females with an age of (45.9±13.7) years, and 10 cases of type Ⅳ and 23 cases of type Ⅴ by the Schatzker classification. The 2 groups were compared in terms of operation time, length of main incision, intraoperative blood loss, Rasmussen imaging score before discharge, and knee function score of American Hospital for Special Surgery (HSS), Visual Analogue Scale (VAS), fracture healing and complications at 6 months postoperatively.Results:There was no significant difference in the preoperative general data between the 2 groups, showing group comparability ( P>0.05). All patients were followed up for (14.3±1.4) months. The observation group was significantly better than the control group in operation time [(113.9±11.4) min versus (151.82±10.37) min], length of main incision [4 (4, 5) cm versus 6 (6, 7) cm], intraoperative blood loss [30 (20, 35) mL versus 55 (50, 65) mL], VAS [0 (0, 0) point versus 0 (0, 1) points] and HSS score [(89.8±3.1) points versus (86.0±3.5) points] ( P<0.05). There were no significant differences between the 2 groups in Rasmussen imaging score before discharge, or fracture healing rate or complication rate at 6 months postoperatively ( P>0.05). Conclusion:In the treatment of Schatzker type Ⅳ-Ⅴ tibial plateau fractures, modified double-reverse traction technique is worthy of clinical application and promotion, because it is advantageous over traditional open reduction in terms of shorter operation time, smaller surgical incision, less intraoperative blood loss, less postoperative pain and better knee function.

BACKGROUND:Epidemiologic studies have shown a correlation between type 2 diabetes mellitus and bone mineral density,but the causal association between the two and whether it is age-related remains unknown. OBJECTIVE:To study the correlation between type 2 diabetes mellitus and whole body bone mineral density at unspecified age and at all ages based on the Mendelian randomization technique. METHODS:The genome-wide association study(GWAS)data of type 2 diabetes mellitus and bone mineral density at all ages were selected from the IEU GWAS database of the University of Bristol.The exposure data were single nucleotide polymorphisms with significant correlation with type 2 diabetes mellitus as instrumental variables,and bone mineral density at all ages was selected as the outcome variable.Two-sample Mendelian randomization analysis of type 2 diabetes mellitus and bone mineral density was performed using inverse variance weighted method,weighted median estimator,and MR-Egger regression.The βvalue was used to evaluate the causal relationship between type 2 diabetes mellitus and bone mineral density at all ages. RESULTS AND CONCLUSION:A total of 118 single nucleotide polymorphisms were extracted from the GWAS summary data as instrumental variables.The MR-Egger regression results showed that there was no horizontal pleiotropy,but there was heterogeneity.Therefore,this study was based on the inverse variance weighted results.Inverse variance weighted results showed that type 2 diabetes mellitus may be a potential protective factor for bone mineral density and is associated with age:age-unspecified bone mineral density[β=0.038,95%confidence interval(CI):1.01-1.07,P=0.002],bone mineral density over 60 years old(β=0.052,95%CI:1.01-1.09,P=0.027),bone mineral density between 45-60 years old(β=0.049,95%CI:1.01-1.09,P=0.009),bone mineral density between 30-45 years old(β=0.033,95%CI:0.99-1.07,P=0.127).bone mineral density of 15-30 years old(β=0.025,95%CI:0.95-1.10,P=0.506),bone mineral density of 0-15 years old(β=0.006,95%CI:0.96-1.04,P=0.716).Similar results were obtained from the MR-Egger regression and weighted median estimator analyses.These findings indicate that type 2 diabetes mellitus may be one of the protective factors of bone mineral density,and there is a correlation with age.

Objective:To investigate the application value of laparoscopic-assisted total liver transplantation.Methods:The retrospective and descriptive study was conducted. The clinical data of 9 pairs of donors and recipients who underwent laparoscopic-assisted total liver transplanta-tion in People′s Hospital of Guangxi Zhuang Autonomous Region from January to April 2024 were collected. Of the donors, there were 8 males and 1 female, aged (39±18)years and with body mass index (BMI) of (20±4)kg/m 2. Of the recipients, there were 7 males and 2 females, aged (41±13)years and with BMI of (24±4)kg/m 2. Measurement data with normal distribution were represented as Mean± SD. Count data were described as absolute numbers. Results:(1) Surgical conditions. Of the 9 recipients, 7 recipients underwent laparoscopic-assisted total liver transplantation successfully, 1 recipient with severe portal hypertension converted to open surgery with reverse L-shaped incision due to the hemorrhage during the dissection of the first hepatic portal after completing liver mobilization under laparoscopy, and 1 recipient underwent trans-umbilical extension incision through the middle of the epigastric region due to the limited space for operation in the implantation of the donor liver. The total operation time for 7 recipients who successfully underwent laparoscopic-assisted total liver transplantation was (648±31)minutes, with a time of anhepatic phase of (57±5)minutes, the volume of intraoperative blood loss of (1 322±627)mL, the donor liver mass of (1 195±232)g, and the ratio of donor liver mass to recipient body mass of 1.86%±0.42%. The operation time for laparoscopic liver dissection and porta hepatis dissection in 8 recipients during surgery was (212±35)minutes. (2) Postoperative conditions. All 9 recipients recovered smoothly after surgery, without any vascular or biliary related complications, and the surgical incision recovered well. The duration of postoperative hospital stay of 7 recipients who successfully underwent laparoscopic-assisted total liver transplantation was (14.2±2.0)days. (3) Follow-up. All 9 recipients were followed up for 3 months after surgery. During the follow-up period, there was no vascular or bile duct related complication.Conclusion:Laparoscopic-assisted total liver transplantation can be applied to recipients who meet surgical conditions and achieve good short-term clinical efficacy.

Objective:To investigate the application value of laparoscopic-assisted total liver transplantation.Methods:The retrospective and descriptive study was conducted. The clinical data of 9 pairs of donors and recipients who underwent laparoscopic-assisted total liver transplanta-tion in People′s Hospital of Guangxi Zhuang Autonomous Region from January to April 2024 were collected. Of the donors, there were 8 males and 1 female, aged (39±18)years and with body mass index (BMI) of (20±4)kg/m 2. Of the recipients, there were 7 males and 2 females, aged (41±13)years and with BMI of (24±4)kg/m 2. Measurement data with normal distribution were represented as Mean± SD. Count data were described as absolute numbers. Results:(1) Surgical conditions. Of the 9 recipients, 7 recipients underwent laparoscopic-assisted total liver transplantation successfully, 1 recipient with severe portal hypertension converted to open surgery with reverse L-shaped incision due to the hemorrhage during the dissection of the first hepatic portal after completing liver mobilization under laparoscopy, and 1 recipient underwent trans-umbilical extension incision through the middle of the epigastric region due to the limited space for operation in the implantation of the donor liver. The total operation time for 7 recipients who successfully underwent laparoscopic-assisted total liver transplantation was (648±31)minutes, with a time of anhepatic phase of (57±5)minutes, the volume of intraoperative blood loss of (1 322±627)mL, the donor liver mass of (1 195±232)g, and the ratio of donor liver mass to recipient body mass of 1.86%±0.42%. The operation time for laparoscopic liver dissection and porta hepatis dissection in 8 recipients during surgery was (212±35)minutes. (2) Postoperative conditions. All 9 recipients recovered smoothly after surgery, without any vascular or biliary related complications, and the surgical incision recovered well. The duration of postoperative hospital stay of 7 recipients who successfully underwent laparoscopic-assisted total liver transplantation was (14.2±2.0)days. (3) Follow-up. All 9 recipients were followed up for 3 months after surgery. During the follow-up period, there was no vascular or bile duct related complication.Conclusion:Laparoscopic-assisted total liver transplantation can be applied to recipients who meet surgical conditions and achieve good short-term clinical efficacy.

Objective:To analyze the clinical characteristics and prognostic factors of high-risk neuroblastoma (HR-NB) patients with skeletal metastasis.Methods:The clinical features of 336 newly treated HR-NB patients with skeletal metastases admitted to the Department of Medical Oncology of Beijing Children′s Hospital, Capital Medical University from January 2007 to December 2018 were analyzed retrospectively.Kaplan-Meier method was used for the survival analysis, and Log- Rank test was used for univariate prognosis analysis.The Cox model was used to analyze the multifactorial prognostic analysis. Results:A total of 336 HR-NB patients were recruited, involving 188 males and 148 females with the median age of onset of at 43 (4-148) months.Skeletal metastases affected the viscerocranium (89 cases, 26.5%), neurocranium (193 cases, 57.4%), vertebrae (298 cases, 88.7%), sternum and ribs (183 cases, 54.5%), pelvis (270 cases, 80.4%), upper limbs (182 cases, 54.2%) and lower limbs (240 cases, 71.4%). The 5-year event-free survival (EFS) rate and overall survival (OS) rate were (30.4±2.7)% and (41.3±2.9)%, respectively.Univariate analysis showed a significantly lower 5-year OS rate in skeletal metastatic HR-NB patients with poor prognostic classification, the morphology of neuroblastoma (stroma-poor) and ganglioneuroblastoma (intermixed), high index of mitosis-karyorrhexis index, lactate dehydrogenase≥587 U/L, serum ferritin≥92 μg/L, MYCN amplification and 1p loss of heterozygosity, and metastases in the viscerocranium, neurocranium, vertebrae, sternum and ribs, pelvis, upper limbs and lower limbs (all P<0.05). The 5-year OS rate of HR-NB patients with all 7 regions of skeletal metastases was only (14.2±5.9)%, which was significantly lower than that in patients with a single region metastasis or multi-region metastases[(66.0±10.2)% vs.(43.6±3.4)%, χ2=45.722, P<0.05]. Cox multifactorial analysis showed that MYCN amplification ( HR=4.165, 95% CI: 2.356-7.363) and the viscerocranium metastasis ( HR=2.560, 95% CI: 1.519-4.315) were the independent risk factors affecting the prognosis of HR-NB patients with skeletal metastases (all P<0.05). Conclusions:The prognosis is extremely poor in HR-NB patients with multiple skeletal metastases at the initial diagnosis.The amplification of MYCN and the viscerocranium metastasis are the poor prognostic factors for HR-NB patients with skeletal metastases.

Objective:To investigate the expression of long non-coding RNA (Lnc RNA) RP5-919F19 in gastric cancer tissues and its correlation with gastric cancer invasion and metastasis.Methods:Non-tumor gastric mucosa (more than 3cm away from the cancer tissue) and gastric adenocarcinoma tissues were collected from Jan. 2020 to Jan. 2022 in our hospital. TRIzol kit was used to extract total RNA from cells and tissues, and reverse transcription kit was used to reverse transcribed RNA into cDNA. Quantitative real-time PCR kit was used for quantitative analysis. SGC-7901 and AGS human gastric cancer cells were used to construct RP5-919F19 knockdown and overexpression models. CCK-8 assay was used to confirm cell proliferation, and Transwell invasion assay was used to confirm the invasion ability of gastric cancer cells.Results:The expression of RP5-919F19 was detected in 79 cases of gastric cancer tissues and adjacent normal tissues, and it was found that the relative expression of RP5-919F19 in gastric cancer tissues was 1.51±0.05 significantly higher than that of 0.82±0.04 in adjacent normal tissues ( P<0.05) . The levels of RP5-919F19 in patients with different pathological conditions were compared and analyzed. The results showed that there were statistically significant differences in RP5-919F19 expression in patients with different TNM stages, distant metastasis, lymph node metastasis and different depth of invasion ( P<0.05) . There was no significant difference in RP5-919F19 expression among patients with different tumor sizes, ages and genders ( P>0.05) . AGS gastric cancer cells were transfected with RP5-919F19 overexpression plasmid and control plasmid, and the efficiency of RP5-919F19 was detected. The results showed that the expression level of RP5-919F19 in the overexpression group was 1.83±0.14 higher than that of 0.82±0.05 in the control group ( P<0.05) . SGC-7901 gastric cancer cells were transfected with RP5-919F19 knockout vector and control vector, and the efficiency of RP5-919F19 was detected. The results showed that the expression level of RP5-919F19 in the knockout group was 0.42±0.07 lower than that of 0.89±0.08 in the control group ( P<0.05) . CCK-8 was used to detect the proliferation ability of gastric cancer cells. The results showed that the proliferation ability of AGS cells in RP5-919F19 overexpression group was significantly increased compared with that of the control group at 24 and 48h after culture ( P<0.05) . However, the proliferation ability of SGC-7901 cells in RP5-919F19 knockdown group was lower than that in the control group at 24 h and 48 h ( P<0.05) . Transwell invasion assay showed that the invasion and migration abilities of AGS cells in RP5-919F19 overexpression group were higher than those in the control group ( P<0.05) , and the invasion and migration abilities of SGC-7901 cells in RP5-919F19 knockout group were lower than those in the control group ( P<0.05) . Western blot showed that compared with control cells, the expression of MMP-2 and MMP-9COPS7A proteins in down-regulated Lnc RNA RP5-919F19 SGC-7901 cells was decreased. Conclusion:The expression of LncRNA RP5-919F19 is abnormally increased in gastric cancer tissues, and the increased expression of RP5-919F19 can promote the proliferation and metastasis of gastric cancer cells.

OBJECTIVE To clarify the mecha-nism of Tou Tong Ning capsule(TTNC)and elu-cidate crosstalk between multi-components drug and trigeminal ganglia cells in migraine.METH-ODS We integrated single-cell RNA sequencing data and a quantitative evaluation algorithm of the disturbance of multi-target drugs on the dis-ease network to explore the specific pathology of TTNC for migraine.Cerebrovascular smooth muscle spasmolytic activity experiment was car-ried out to verify the results of bioinformatics analysis.RESULTS TTNC can effectively regu-late the functions of synaptic signaling,inflamma-tion and immune response,and cerebrovascular smooth muscle.For different cell subtypes of tri-geminal ganglia,TTNC can significantly disturb the robustness on neuronal cell networks and non-neural networks(fibroblast and vascular cells),indicating TTNC vasodilation activity of brain vessels and neural regulation activities of various neuro types.Contraction of cerebrovas-cular smooth muscle of mouse ex vivo confirmed the vasodilation activity of TTNC and active com-pounds(Emodin,Luteolin and Levistilide A).And literature mining confirmed the vasospasmolytic activity and neuroprotective effect activity of TTNC.CONCLUSIONS Integrating single-cell data and network disturbance tools provides a new strategy for the MoA of multi-components drug through cell subtyping.