BACKGROUND:Choline kinase alpha is a key enzyme in phospholipid metabolism,involved in the synthesis of phosphatidylcholine,and plays an important role in maintaining cell membrane integrity and signal transduction.Research has shown that choline kinase alpha is highly expressed in various tumors and is closely related to cell proliferation,metabolic reprogramming,and tumor progression.As a potential therapeutic target,the role of choline kinase alpha in tumor metabolism and mitochondrial function still needs further exploration.OBJECTIVE:To evaluate the effects and the underlying mechanisms of choline kinase alpha on the proliferation and apoptosis of glioma U87MG and U251 cells.METHODS:Short hairpin RNA of choline kinase alpha and its empty vector control were transfected into U87MG and U251 glioma cells.Mitochondrial morphology was observed by transmission electron microscopy.Mitochondrial structure and functional protein levels were assessed by western blot assay.Reactive oxygen species levels in cells were measured using a reactive oxygen species fluorescent probe.Mitochondrial membrane potential was assessed with a JC-1 assay.Intracellular adenosine triphosphate levels were measured by chemiluminescence.Cell proliferation was evaluated using a CCK-8 assay.Apoptosis levels were analyzed by flow cytometry.The mitochondrial fission inhibitor Mdivi-1 was used to protect the mitochondrial function of the choline kinase α-silenced lentiviral cells.Finally,U87MG cells were subcutaneously injected to construct a subcutaneous tumor model in nude mice.The tumor growth in nude mice was observed before and after choline kinase alpha silencing and after the use of the mitochondrial fission inhibitor Mdivi-1.RESULTS AND CONCLUSION:(1)Compared with the empty control group,the mitochondria of U87MG and U251 cells in the choline kinase alpha silencing lentivirus group exhibited significant structural abnormalities in mitochondria,such as vacuolization and cristae disruption.The expressions of mitochondrial structure and function-related proteins TOM20,ACO2,and ATP5A were significantly decreased(P＜0.01,P＜0.001),the expression of SOD2 was significantly increased(P＜0.01,P＜0.000 1),the fluorescence intensity of reactive oxygen species was significantly increased(P＜0.01),the mitochondrial membrane potential and adenosine triphosphate level were significantly decreased(P＜0.01,P＜0.001),the cell proliferation ability was reduced(P＜0.01),and the apoptosis level was increased(P＜0.001).(2)Following Mdivi-1 treatment,the fluorescence intensity of reactive oxygen species in U87MG and U251 cells decreased(P＜0.05,P＜0.01),mitochondrial membrane potential and adenosine triphosphate levels were significantly restored(P＜0.05,P＜0.01,P＜0.001),cell proliferation ability was improved(P＜0.05,P＜0.01),and apoptosis level was decreased(P＜0.05).(3)In addition,the in vitro subcutaneous tumor formation experiment of nude mice showed that compared with the empty control group,the mass and growth rate of subcutaneous tumors formed by U87MG cells in the choline kinase alpha silencing lentivirus group were significantly reduced(P＜0.000 1).After Mdivi-1 treatment,the mass and growth rate of tumors were significantly increased(P＜0.000 1).(4)The results show that choline kinase alpha silencing affects the proliferation and apoptosis of glioma cells by inducing mitochondrial dysfunction.

BACKGROUND:Choline kinase alpha is a key enzyme in phospholipid metabolism,involved in the synthesis of phosphatidylcholine,and plays an important role in maintaining cell membrane integrity and signal transduction.Research has shown that choline kinase alpha is highly expressed in various tumors and is closely related to cell proliferation,metabolic reprogramming,and tumor progression.As a potential therapeutic target,the role of choline kinase alpha in tumor metabolism and mitochondrial function still needs further exploration.OBJECTIVE:To evaluate the effects and the underlying mechanisms of choline kinase alpha on the proliferation and apoptosis of glioma U87MG and U251 cells.METHODS:Short hairpin RNA of choline kinase alpha and its empty vector control were transfected into U87MG and U251 glioma cells.Mitochondrial morphology was observed by transmission electron microscopy.Mitochondrial structure and functional protein levels were assessed by western blot assay.Reactive oxygen species levels in cells were measured using a reactive oxygen species fluorescent probe.Mitochondrial membrane potential was assessed with a JC-1 assay.Intracellular adenosine triphosphate levels were measured by chemiluminescence.Cell proliferation was evaluated using a CCK-8 assay.Apoptosis levels were analyzed by flow cytometry.The mitochondrial fission inhibitor Mdivi-1 was used to protect the mitochondrial function of the choline kinase α-silenced lentiviral cells.Finally,U87MG cells were subcutaneously injected to construct a subcutaneous tumor model in nude mice.The tumor growth in nude mice was observed before and after choline kinase alpha silencing and after the use of the mitochondrial fission inhibitor Mdivi-1.RESULTS AND CONCLUSION:(1)Compared with the empty control group,the mitochondria of U87MG and U251 cells in the choline kinase alpha silencing lentivirus group exhibited significant structural abnormalities in mitochondria,such as vacuolization and cristae disruption.The expressions of mitochondrial structure and function-related proteins TOM20,ACO2,and ATP5A were significantly decreased(P＜0.01,P＜0.001),the expression of SOD2 was significantly increased(P＜0.01,P＜0.000 1),the fluorescence intensity of reactive oxygen species was significantly increased(P＜0.01),the mitochondrial membrane potential and adenosine triphosphate level were significantly decreased(P＜0.01,P＜0.001),the cell proliferation ability was reduced(P＜0.01),and the apoptosis level was increased(P＜0.001).(2)Following Mdivi-1 treatment,the fluorescence intensity of reactive oxygen species in U87MG and U251 cells decreased(P＜0.05,P＜0.01),mitochondrial membrane potential and adenosine triphosphate levels were significantly restored(P＜0.05,P＜0.01,P＜0.001),cell proliferation ability was improved(P＜0.05,P＜0.01),and apoptosis level was decreased(P＜0.05).(3)In addition,the in vitro subcutaneous tumor formation experiment of nude mice showed that compared with the empty control group,the mass and growth rate of subcutaneous tumors formed by U87MG cells in the choline kinase alpha silencing lentivirus group were significantly reduced(P＜0.000 1).After Mdivi-1 treatment,the mass and growth rate of tumors were significantly increased(P＜0.000 1).(4)The results show that choline kinase alpha silencing affects the proliferation and apoptosis of glioma cells by inducing mitochondrial dysfunction.

Objective:To comprehensively evaluate the clinical effectiveness with respect to a single dose of tranexamic acid (TXA) given preoperatively for blood loss control in perioperative patients accepted craniomaxillofacial plastic and cosmetic surgery.Methods:Embase, PubMed, WanFang Data, VIP, China National Knowledge Infrastructure (CNKI), the Chinese Clinical Trial Registry (ChiCTR) and Cochrane Central Register of Controlled Trials (CENTRAL) were electronically retrieved to collect randomized controlled trials (RCTs) related to appraise the efficacy in perioperative craniomaxillofacial plastic and cosmetic surgery patients used TXA from inception to August 2024. Based on the result of methodological heterogeneity, corresponding paired meta-analyses were carried out with a random-effects or fixed-effects model applying R 4.0.4 software. Subgroup analysis was performed based on type of surgery, patient age, regional distribution of patients, and sample size included in the studies. A meta-regression analysis was performed on studies that reported the effect of different doses of TXA on reducing perioperative bleeding. Sensitivity analysis was performed to verify the stability of the meta result. Egger’s test was used to analyze potential publication bias.Results:A total of 31 RCTs were included, involving 2 072 patients, with 1 051 in the TXA group and 1 021 in the placebo group. The paired meta-analysis random-effects model ( I2=90%) showed that compared with the control group, the use of TXA significantly reduced the amount of bleeding in perioperative patients[standardized mean difference ( SMD)=-1.13, 95% CI -1.47 to -0.80, P < 0.01]. Subgroup analysis revealed that TXA had a significant effect on reducing intraoperative bleeding in patients with different surgeries, ages, regions, and sample sizes. The most effective subgroups were cases in orthognathic surgery ( SMD=-1.44, 95% CI -2.07 to -0.80, P< 0.01), less than 30 year-old( SMD=-1.32, 95% CI -1.68 to -0.96, P< 0.01], Asian patients( SMD=-1.29, 95% CI -1.72 to -0.86, P< 0.01), less than 30 individuals ( SMD=-1.16, 95% CI -1.50 to -0.82, P< 0.01). The result of the meta regression showed there was no significant difference in the hemostatic effect of TXA on patients with increasing doses (5, 10, 15, 20, 25 mg/kg) ( P>0.05). Sensitivity analysis verified that the pooled values were stable and reliable. The Egger’s test indicated a certain degree of publication bias ( P < 0.01). Conclusion:Taken as a whole, existing evidence suggests that TXA can effectively reduce perioperative bleeding in patients undergoing craniofacial plastic surgery, regardless of its dosage administered. However, further clinical researches are still needed to provide more baselined data, transfusion-related indicators, and information on adverse events such as vascular embolism, in order to comprehensively evaluate and analyze the efficacy and safety of a single dose of TXA for perioperative blood loss control in patients treated with craniomaxillofacial plastic and cosmetic surgery.

[Purpose]To investigate the choice of medical institutions for the first-treatment of can-cer patients after diagnosis and the factors influencing it,so as to provide a reference basis for the rational allocation of health resources and the promotion of hierarchical diagnosis and treatment of cancer.[Methods]A total of 1 140 common cancer patients from 1 provincial,3 municipal and 6 county-level medical institutions in Shandong Province were included in the study,and a ques-tionnaire survey was conducted on their basic personal information and the selection of medical institutions.Chi-square test and Fisher exact test were used to compare different groups,and mul-ti-classification unordered Logistic regression were used to explore the factors influencing the se-lection of cancer patients.[Results]1 077 valid questionnaires were collected.The selection rates of first-treatment institutions for cancer patients were county hospitals(29.90％),city hospitals(35.28％),and provincial hospitals(34.82％),and the high level of medical care was the main reason for the selection of first-treatment institutions for cancer patients.The results of multi-clas-sification unordered Logistic regression showed that when choosing municipal and county medical institutions as the first treatment institution compared to choosing a county medical institution for the first treatment as a reference,compared to patients with stage Ⅰ tumors,patients with tumor stages at stage Ⅲ(OR=1.789,95％CI:1.014～3.158)and stage Ⅳ(OR=2.005,95％CI:1.179～3.409)were more likely to choose municipal medical institutions;and patients with annual house-hold income of 10 000～＜50 000 CNY(OR=0.625,95％CI:0.414～0.943)were less likely to choose mu-nicipal medical institutions compared to those with an annual household income of＜10 000 CNY.When choosing provincial and county medical institutions as the first treatment institution com-pared to patients in stage Ⅲ(OR=2.885,95％C1:1.549～5.372)and stage Ⅳ(OR=3.104,95％CI:1.724～5.586)compared to patients with stage Ⅰ tumors when choosing a county medical institu-tion for the first treatment was used as a reference;married(OR=2.248,95％CI:1.127～4.484)patients were more likely to choose provincial healthcare organizations than unmarried/divorced/widowed patients;patients with a family history of cancer compared to patients without a family history of cancer(OR=1.650,95％CI:1.115～2.441)were more inclined to choose provincial healthcare institutions;compared with patients＜45 years old,patients over 60 years old(OR=0.483,95％CI:0.242～0.962)were less inclined to choose provincial hospitals;and compared with patients who were not aware of knowledge related to cancer,those who were aware of knowledge related to cancer(OR=0.613,95％CI:0.441～0.852)patients were less inclined to choose provin-cial hospitals.[Conclusion]Vigorously carrying out publicity on cancer prevention and treatment knowledge,improving the cancer prevention and treatment literacy of cancer patients.strengthen-ing vertical cooperation among medical institutions at all levels,improving the provincial-munici-pal-county cancer prevention and treatment network,and promoting the sinking of high-quality medical resources are important ways to improve the cancer prevention and treatment capacity of counties and promote the work of hierarchical medical system.

To achieve the national objectives of improving medical quality and safety,the Shanghai Shenkang Hospital Development Center has formulated a list of major targets,tasks,and key results based onthe Objective and Key Results (OKR) method.The primary approaches adopted include establishing an organizational structure to advance medical quality and safety supervision,setting up a series of quantitative indicators for medical quality and safety targets,formulating standardized management systems,building an information platform,and strengthening supervision.It argues that the adoption of OKR can effectively promote the implementation of national target management for improving medical quality and safety,establish a cross-institutional management network for medical quality and safety,strengthen process management,and effectively drive continuous improvement in medical quality and safety.

[Purpose]To investigate the choice of medical institutions for the first-treatment of can-cer patients after diagnosis and the factors influencing it,so as to provide a reference basis for the rational allocation of health resources and the promotion of hierarchical diagnosis and treatment of cancer.[Methods]A total of 1 140 common cancer patients from 1 provincial,3 municipal and 6 county-level medical institutions in Shandong Province were included in the study,and a ques-tionnaire survey was conducted on their basic personal information and the selection of medical institutions.Chi-square test and Fisher exact test were used to compare different groups,and mul-ti-classification unordered Logistic regression were used to explore the factors influencing the se-lection of cancer patients.[Results]1 077 valid questionnaires were collected.The selection rates of first-treatment institutions for cancer patients were county hospitals(29.90％),city hospitals(35.28％),and provincial hospitals(34.82％),and the high level of medical care was the main reason for the selection of first-treatment institutions for cancer patients.The results of multi-clas-sification unordered Logistic regression showed that when choosing municipal and county medical institutions as the first treatment institution compared to choosing a county medical institution for the first treatment as a reference,compared to patients with stage Ⅰ tumors,patients with tumor stages at stage Ⅲ(OR=1.789,95％CI:1.014～3.158)and stage Ⅳ(OR=2.005,95％CI:1.179～3.409)were more likely to choose municipal medical institutions;and patients with annual house-hold income of 10 000～＜50 000 CNY(OR=0.625,95％CI:0.414～0.943)were less likely to choose mu-nicipal medical institutions compared to those with an annual household income of＜10 000 CNY.When choosing provincial and county medical institutions as the first treatment institution com-pared to patients in stage Ⅲ(OR=2.885,95％C1:1.549～5.372)and stage Ⅳ(OR=3.104,95％CI:1.724～5.586)compared to patients with stage Ⅰ tumors when choosing a county medical institu-tion for the first treatment was used as a reference;married(OR=2.248,95％CI:1.127～4.484)patients were more likely to choose provincial healthcare organizations than unmarried/divorced/widowed patients;patients with a family history of cancer compared to patients without a family history of cancer(OR=1.650,95％CI:1.115～2.441)were more inclined to choose provincial healthcare institutions;compared with patients＜45 years old,patients over 60 years old(OR=0.483,95％CI:0.242～0.962)were less inclined to choose provincial hospitals;and compared with patients who were not aware of knowledge related to cancer,those who were aware of knowledge related to cancer(OR=0.613,95％CI:0.441～0.852)patients were less inclined to choose provin-cial hospitals.[Conclusion]Vigorously carrying out publicity on cancer prevention and treatment knowledge,improving the cancer prevention and treatment literacy of cancer patients.strengthen-ing vertical cooperation among medical institutions at all levels,improving the provincial-munici-pal-county cancer prevention and treatment network,and promoting the sinking of high-quality medical resources are important ways to improve the cancer prevention and treatment capacity of counties and promote the work of hierarchical medical system.

To achieve the national objectives of improving medical quality and safety,the Shanghai Shenkang Hospital Development Center has formulated a list of major targets,tasks,and key results based onthe Objective and Key Results (OKR) method.The primary approaches adopted include establishing an organizational structure to advance medical quality and safety supervision,setting up a series of quantitative indicators for medical quality and safety targets,formulating standardized management systems,building an information platform,and strengthening supervision.It argues that the adoption of OKR can effectively promote the implementation of national target management for improving medical quality and safety,establish a cross-institutional management network for medical quality and safety,strengthen process management,and effectively drive continuous improvement in medical quality and safety.

The anterior cingulate cortex (ACC) has recently been proposed as a key player in the representation of itch stimuli. However, to date, little is known about the contribution of specific ACC interneuron populations to itch processing. Using c-Fos immunolabeling and in vivo Ca²⁺ imaging, we reported that both histamine and chloroquine stimuli-induced acute itch caused a marked enhancement of vasoactive intestinal peptide (VIP)-expressing interneuron activity in the ACC. Behavioral data indicated that optogenetic and chemogenetic activation of these neurons reduced scratching responses related to histaminergic and non-histaminergic acute itch. Similar neural activity and modulatory role of these neurons were seen in mice with chronic itch induced by contact dermatitis. Together, this study highlights the importance of ACC VIP⁺ neurons in modulating itch-related affect and behavior, which may help us to develop novel mechanism-based strategies to treat refractory chronic itch in the clinic.
Animals ; Pruritus/physiopathology* ; Vasoactive Intestinal Peptide/metabolism* ; Interneurons/metabolism* ; Gyrus Cinguli/metabolism* ; Mice ; Male ; Mice, Inbred C57BL ; Histamine ; Chloroquine ; Optogenetics ; Mice, Transgenic

Objective:To comprehensively evaluate the clinical effectiveness with respect to a single dose of tranexamic acid (TXA) given preoperatively for blood loss control in perioperative patients accepted craniomaxillofacial plastic and cosmetic surgery.Methods:Embase, PubMed, WanFang Data, VIP, China National Knowledge Infrastructure (CNKI), the Chinese Clinical Trial Registry (ChiCTR) and Cochrane Central Register of Controlled Trials (CENTRAL) were electronically retrieved to collect randomized controlled trials (RCTs) related to appraise the efficacy in perioperative craniomaxillofacial plastic and cosmetic surgery patients used TXA from inception to August 2024. Based on the result of methodological heterogeneity, corresponding paired meta-analyses were carried out with a random-effects or fixed-effects model applying R 4.0.4 software. Subgroup analysis was performed based on type of surgery, patient age, regional distribution of patients, and sample size included in the studies. A meta-regression analysis was performed on studies that reported the effect of different doses of TXA on reducing perioperative bleeding. Sensitivity analysis was performed to verify the stability of the meta result. Egger’s test was used to analyze potential publication bias.Results:A total of 31 RCTs were included, involving 2 072 patients, with 1 051 in the TXA group and 1 021 in the placebo group. The paired meta-analysis random-effects model ( I2=90%) showed that compared with the control group, the use of TXA significantly reduced the amount of bleeding in perioperative patients[standardized mean difference ( SMD)=-1.13, 95% CI -1.47 to -0.80, P < 0.01]. Subgroup analysis revealed that TXA had a significant effect on reducing intraoperative bleeding in patients with different surgeries, ages, regions, and sample sizes. The most effective subgroups were cases in orthognathic surgery ( SMD=-1.44, 95% CI -2.07 to -0.80, P< 0.01), less than 30 year-old( SMD=-1.32, 95% CI -1.68 to -0.96, P< 0.01], Asian patients( SMD=-1.29, 95% CI -1.72 to -0.86, P< 0.01), less than 30 individuals ( SMD=-1.16, 95% CI -1.50 to -0.82, P< 0.01). The result of the meta regression showed there was no significant difference in the hemostatic effect of TXA on patients with increasing doses (5, 10, 15, 20, 25 mg/kg) ( P>0.05). Sensitivity analysis verified that the pooled values were stable and reliable. The Egger’s test indicated a certain degree of publication bias ( P < 0.01). Conclusion:Taken as a whole, existing evidence suggests that TXA can effectively reduce perioperative bleeding in patients undergoing craniofacial plastic surgery, regardless of its dosage administered. However, further clinical researches are still needed to provide more baselined data, transfusion-related indicators, and information on adverse events such as vascular embolism, in order to comprehensively evaluate and analyze the efficacy and safety of a single dose of TXA for perioperative blood loss control in patients treated with craniomaxillofacial plastic and cosmetic surgery.

Abstract Family is the primary living place of children and adolescents, which has important impacts on children and adolescents physical activity. The article systematically reviews the research progress on potential mechanisms of family influence on physical activities of children and adolescents, focusing on the theoretical mechanism of intergenerational transmission on parent-child physical activities,which includes family s role in children s motivation and achievement for exercise behaviors, the integrative model of parental socialization influence and integrated model of physical activity parenting. It provides new perspectives for future research in related fields and gives more suggestions and reference for subsequent development of family enhancement programs and family-school collaborative programs.