ObjectiveTo investigate the effects of Astragali Radix polysaccharides （APS） on the polarization of BV2 microglial cells in an oxygen-glucose deprivation/reoxygenation （OGD/R） model through regulation of the Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） signaling pathway. MethodsThe OGD/R injury model of BV2 microglia was established and divided into blank group， OGD/R group and APS group （0.4 g·L^-1 APS）. Neuroinflammatory injury was induced by lipopolysaccharide （LPS） and treated with APS. The cells were divided into blank group， LPS group （1 mg·L^-1 LPS） and APS group （0.4 g·L^-1 APS+1 mg·L^-1 LPS）. Cell viability was detected using the cell counting kit-8 （CCK-8） assay. Cell morphology was observed under an inverted microscope. Nitric oxide （NO） content in the cell supernatant was determined by the Griess assay. The secretion levels of tumor necrosis factor-α （TNF-α）， interleukin （IL）-6， IL-10， and IL-4 were measured by enzyme-linked immunosorbent assay （ELISA）. Immunofluorescence （IF） was used to detect the double-positive rates of ionized calcium-binding adapter molecule-1/inducible nitric oxide synthase （Iba-1⁺/iNOS⁺） and ionized calcium-binding adapter molecule-1/arginase 1 （Iba-1⁺/Arg1⁺）， as well as the nuclear translocation rate of nuclear factor-κB p65 （NF-κB p65）. Protein expression levels of Iba-1， iNOS， Arg1， TLR4， and NF-κB p65 were detected by Western blot. ResultsIn the OGD/R injury model， compared with the blank control group， BV2 microglial cells in the OGD/R group were activated and exhibited amoeboid morphological changes. The secretion levels of NO， TNF-α， and IL-6 were significantly increased （P<0.01）. The double-positive expression rate of Iba-1⁺/iNOS⁺ and the protein expression of Iba-1 and iNOS were significantly increased （P<0.01）. The nuclear translocation rate of NF-κB p65 and the protein expression levels of TLR4 and NF-κB p65 were significantly increased （P<0.01）. The levels of IL-10 and IL-4 were significantly decreased （P<0.01）， and the double-positive expression rate of Iba-1⁺/Arg1⁺ and Arg1 protein expression were significantly decreased （P<0.01）. Compared with the OGD/R group， the APS group （0.4 g·L^-1） showed reduced cell activation， significantly decreased secretion levels of NO， TNF-α， and IL-6 （P<0.01）， significantly decreased double-positive expression rate of Iba-1⁺/iNOS⁺ and relative protein expression of Iba-1 and iNOS （P<0.01）， significantly decreased nuclear translocation rate of NF-κB p65 and protein expression levels of TLR4 and NF-κB p65 （P<0.01）， significantly increased levels of IL-10 and IL-4 （P<0.01）， and significantly increased double-positive expression rate of Iba-1⁺/Arg1⁺ and Arg1 protein expression （P<0.01）. In the LPS-induced neuroinflammation model， compared with the blank control group， the LPS group showed increased cell activation， significantly increased levels of NO， TNF-α， and IL-6， significantly increased Iba-1⁺/iNOS⁺ double-positive expression rate， NF-κB p65 nuclear translocation rate， and protein expression levels of Iba-1， iNOS， TLR4， and NF-κB p65 （P<0.01）， while IL-10 and IL-4 levels， Iba-1⁺/Arg1⁺ double-positive expression rate， and Arg1 protein expression were significantly decreased （P<0.01）. Compared with the LPS group， the APS group showed reduced cell activation， significantly decreased levels of NO， TNF-α， and IL-6， Iba-1⁺/iNOS⁺ double-positive expression rate， NF-κB p65 nuclear translocation rate， and protein expression levels of Iba-1， iNOS， TLR4， and NF-κB p65 （P<0.01）， while IL-10 and IL-4 levels， Iba-1⁺/Arg1⁺ double-positive expression rate， and Arg1 protein expression were significantly increased （P<0.01）. ConclusionAPS may reduce microglial activation and promote their polarization toward the M2 phenotype by inhibiting activation of the TLR4/NF-κB signaling pathway， thereby alleviating the neuroinflammatory response induced by OGD/R.

OBJECTIVE: To explore the improvement effect of electroacupuncture (EA) based on Xingnao Kaiqiao acupuncture (acupuncture for regaining consciousness and opening orifices) on cognitive impairment in mice with Parkinson's disease (PD), and to explore its regulatory mechanisms on the kinesin family member 5A (KIF5A)/mitochondrial Rho GTPase 1 (Miro1) pathway and mitophagy in prefrontal cortical neurons. METHODS: A total of 70 male C57BL/6J mice of clean grade were randomly divided into a normal group (12 mice), a sham operation group (12 mice), and a model pre-screening group (46 mice). Unilateral stereotaxic injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle was adopted to establish the PD model in the model pre-screening group. Twenty-four mice after successful modeling were randomly selected and divided into a model group and an EA group, 12 mice in each one. In the EA group, acupuncture was applied at "Shuigou" (GV26) and bilateral "Sanyinjiao" (SP6) and "Neiguan" (PC6), ipsilateral "Sanyinjiao" (SP6) and "Neiguan" (PC6) were connected to EA respectively, with disperse-dense wave, 5 Hz/20 Hz in frequency, 0.5 mA in current intensity, 20 min a time, 6 times a week for 30 days. Cognitive function was assessed by Y-maze and Morris water maze tests; morphology of prefrontal cortex was observed by H.E. staining; reactive oxygen species (ROS) level in prefrontal cortex was detected by fluorescence probe method; mitochondrial morphology and autophagosome ultrastructure were observed by transmission electron microscopy; the mRNA expression of tyrosine hydroxylase (TH) was detected by quantitative real-time PCR; the protein expression of TH, KIF5A, Miro1, p62, Parkin and PTEN induced kinase 1 (PINK1) was detected by Western blot. RESULTS: Compared with the sham operation group, both the model group and the EA group exhibited increased rotation number of per minute (P<0.001). Compared with the sham operation group, in the model group, the novel arm exploration time of Y-maze test was shortened (P<0.001), the escape latency of Morris water maze test was prolonged (P<0.05) and the platform crossing number of Morris water maze test was reduced (P<0.01); in the prefrontal cortex, the number of cellular vacuole and neurons with karyopyknosis was increased (P<0.001), and mitochondrial autophagosomes could be observed; in the prefrontal cortex, the relative expression of ROS was increased (P<0.001), the protein and mRNA expression of TH was decreased (P<0.001), the protein expression of Miro1, PINK1, Parkin was increased (P<0.001, P<0.01), the protein expression of KIF5A and p62 was decreased (P<0.001). Compared with the model group, in the EA group, the novel arm exploration time of Y-maze test was prolonged (P<0.01), the escape latency of Morris water maze test was shortened (P<0.05) and the platform crossing number of Morris water maze test was increased (P<0.05); in the prefrontal cortex, the number of cellular vacuole and neurons with karyopyknosis was decreased (P<0.001), and the number of mitochondrial autophagosomes reduced and the mitochondrial morphology was improved; in the prefrontal cortex, the relative expression of ROS was decreased (P<0.01), the protein and mRNA expression of TH was increased (P<0.001, P<0.01), the protein expression of Miro1, PINK1, Parkin was decreased (P<0.001, P<0.01, P<0.05), the protein expression of KIF5A and p62 was increased (P<0.01, P<0.05). CONCLUSION Xingnao Kaiqiao electroacupuncture effectively alleviates cognitive impairment and damage of neuronal function in PD mice, its mechanism may be related to the regulation of KIF5A/Miro1 pathway, hence reducing the mitophagy in prefrontal cortical neurons.
Animals ; Electroacupuncture ; Male ; Mice ; Parkinson Disease/physiopathology* ; Cognitive Dysfunction/psychology* ; Kinesins/genetics* ; Humans ; Mitophagy ; Mice, Inbred C57BL ; rho GTP-Binding Proteins/genetics* ; Mitochondria/genetics* ; Prefrontal Cortex/metabolism*

Acute symptomatic osteoporotic thoracolumbar compression fracture (ASOTLF) can lead to chronic low back pain, kyphosis deformity, pulmonary dysfunction, loss of mobility, and even life-threatening complications. Vertebral augmentation is currently the mainstream treatment method for this condition. In 2019, the Editorial Board of Chinese Journal of Trauma and the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association collaboratively led the development of Clinical guideline for vertebral augmentation for acute symptomatic osteoporotic thoracolumbar compression fractures. Six years later, with advances in clinical diagnosis and treatment techniques as well as accumulating evidence in related fields, the 2019 guideline requires updating. To this end, the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association, the Spinal Health Professional Committee of China Human Health Science and Technology Promotion Association, and the Minimally Invasive Orthopedics Professional Committee of Shaanxi Medical Doctor Association have organized experts in the field to develop the Clinical guideline for vertebral augmentation of acute symptomatic osteoporotic thoracolumbar compression fractures ( version 2025) , based on the latest evidence-based medical researches. This guideline incorporates 3 recommendations retained from the 2019 version with updated strength of evidence, along with 12 new recommendations. It provides recommendations from six aspects of diagnosis, pain management, treatment option selection, prevention of postoperative complications, anti-osteoporosis therapy, and postoperative rehabilitation, aiming to provide a reference for standard treatment of vertebral augmentation for ASOTLF in hospitals at all levels.

Objective:To explore the efficacy and safety of B-Raf proto-oncogene, serine/threonine kinase (BRAF) inhibitor and epidermal growth factor receptor (EGFR) inhibitor combined with immune checkpoint inhibitor in microsatellite stable (MSS) BRAF V600E metastatic colorectal cancer (mCRC) patients.Methods:The data and outcomes of mCRC patients with MSS BRAF V600E who received BRAF inhibitor, EGFR inhibitor combined with immune checkpoint inhibitor in Tianjin Medical University Cancer Hospital from May 2022 to April 2024 were retrospectively collected.Results:A total of 12 mCRC patients were included in this study, the objective response rate was 50.0%, the disease control rate was 66.7%, and the median disease control time of patients who achieved objective response was 8.0 months. The median progression-free survival was 6.8 months and the median overall survival was 8.4 months. Overall adverse reactions were controllable, the most common treatment-related adverse events were fatigue (8 cases), fever (5 cases), and rash (4 cases). There were no grade 4 adverse event, serious adverse event, and treatment-related death.Conclusion:BRAF inhibitor and EGFR inhibitor combined with immune checkpoint inhibitor show good efficacy and controllable safety in BRAF V600E mCRC patients.

Objective To investigate the impact of individualized medical nutrition therapy on the weight loss effect and metabolic related indicators in the patients with moderate to severe obesity.Methods Seventy-six adult patients with diagnosed moderate to severe obesity in this hospital from June 2019 and June 2022 were enrolled as the study subjects.The changes in body compositions and metabolic related in-dicators before and after treatment were analyzed.Results The body fat,body fat ratio and visceral fat area in the body compositions before treatment all exceeded the normal range.Among the metabolism-related indica-tors,ALT,UA,FINS,TC and TG all exceeded the normal range.After treatment,the levels of ALT,AST,FBG,FINS,TC,TG and LDL-C all were decreased(P＜0.05).All achieved the target values of weight loss after 2-month treatment,and the body weight after 6 months still continued to reduce.Conclusion The pa-tients with moderate to severe obesity exhibit complicating multiple metabolic disorders.The personalized medical nutrition therapy not only continuously reduces the body weight,but can also improves the levels of metabolism-related indicators.

Objective:To explore the role of chemokine CX3CL1/CX3CR1 in intraperitoneal metastasis of ovarian cancer in nude mice.Methods:Fifty SPF SD female nude mice were selected and randomly divided into normal group ( n=10) , ovarian cancer model group ( n=20) and CX3CL1 group ( n=20) by random number table method. Ovarian cancer model was not established in normal group, and ovarian cancer model was established in both ovarian cancer model group and CX3CL1 group. CX3CL1 group was given intraperitoneal injection of 20 μl CX3CL1 with a concentration of 10 ng/μl to observe the survival status of nude mice. Tumor mass, tumor volume, tumor inhibition rate, ascites rate and peritoneal metastasis rate were recorded. The pathological morphology of ovarian tissue was examined by HE staining, the expression of CX3CL1/CX3CR1 in ovarian tissue was detected by Western blotting, and the correlation between the expression of CX3CL1/CX3CR1 and peritoneal metastasis rate was analyzed by point two-column correlation. Results:During the administration, the mental state, activity, food and water intake of nude mice in the normal group were good with sensitive responses. The nude mice in the ovarian cancer model group showed signs of mental fatigue, reduced activity, less food and water intake, delayed response, as well as and a hard and gradually enlarged abdomen. The mental state, activity, food and water intake of nude mice in CX3CL1 group were better than those in ovarian cancer model group, and the abdominal hardness volume was smaller compared with that in ovarian cancer model group. The survival time of normal group, ovarian cancer model group and CX3CL1 group were (14.00±0.00) , (9.24±0.67) and (12.05±0.82) d, respectively, with a statistically significant difference ( F=22.27, P<0.001) . Further pair-to-pair comparisons showed that the normal group had the longest survival time, followed by the CX3CL1 group and the ovarian cancer model group (all P<0.05) . The tumor mass of ovarian cancer model group and CX3CL1 group was (1.31±0.21) and (0.62±0.13) g, respectively, with a statistically significant difference ( t=12.49, P<0.001) . The tumor volumes were (130.47±13.45) and (70.02±7.52) mm 3, respectively, with a statistically significant difference ( t=17.54, P<0.001) . The tumor suppression rates were (0.00±0.00) % and (48.96±4.74) %, respectively, with a statistically significant difference ( t=46.19, P<0.001) , the ascites rates were 60.00% (12/20) and 25.00% (5/20) , respectively, with a statistically significant difference ( χ2=5.01, P=0.025) . The abdominal metastasis rates were 80.00% (16/20) and 50.00% (10/20) , respectively, with a statistically significant difference ( χ2=3.96, P=0.047) . The results of HE staining showed that in the normal group, the ovarian tissue structure was complete, the follicles and oocytes developed normally with good shape, and no cancerous cells were found. The ovarian structure of the ovarian cancer model group was obviously destroyed, and a large number of cancerous cells could be seen. The nucleolus were deeply stained and the number increased. Compared with the ovarian cancer model group, the pathological structure was significantly improved, and the number of cancer cells was significantly decreased in the CX3CL1 group. The CX3CL1 protein relative expression levels in normal group, ovarian cancer model group and CX3CL1 group were 2.05±0.22, 1.33±0.11 and 2.41±0.24, respectively, with a statistically significant difference ( F=9.26, P<0.001) . The CX3CR1 protein relative expression levels were 1.99±0.21, 1.34±0.14, 2.73±0.31, respectively, with a statistically significant difference ( F=8.14, P<0.001) . Further pair-to-pair comparisons showed that compared with the normal group, the relative expression levels of CX3CL1 and CX3CR1 protein in ovarian cancer model group were significantly decreased, and the relative expression levels of CX3CL1 and CX3CR1 protein were higher in CX3CL1 group (all P<0.05) . Compared with ovarian cancer model group, the relative expression levels of CX3CL1 and CX3CR1 protein in ovarian tissue of CX3CL1 group were significantly increased (both P<0.05) . Correlation analysis showed that CX3CL1 and CX3CR1 expressions were negatively correlated with peritoneal metastasis rate ( r=-0.50, P=0.024; r=-0.58, P=0.012) . Conclusions:The expression of chemokine CX3CL1/CX3CR1 is down-regulated in ovarian cancer, and CX3CL1/CX3CR1 expression is negatively correlated with peritoneal metastasis of ovarian cancer. Activation of CX3CL1/CX3CR1 can significantly inhibit peritoneal metastasis of ovarian cancer.

Objective To analyze risk factors of hypokalemia after treatment with piperacillin-tazobactam(PTZ)and to provide a reference for safe clinical medication.Methods A retrospective collection of 1 355 inpatients treated with PTZ was conducted.Patients were assigned to the hypokalemia group(serum potassium<3.5 mmol/L,374 cases)and the non-hypokalemia group(serum potassium≥3.5 mmol/L,981 cases)based on whether they suffered from hypokalemia after PTZ treatment.Clinical data were collected and compared in both groups of patients.Multifactorial Logistic regression analysis was used to identify the influencing factors of hypokalemia induced by PTZ.Results In the hypokalemia group,there were 308 cases of mild hypokalemia(82.3%),63 cases of moderate hypokalemia and 3 cases of severe hypokalemia.The incidence of moderate to severe hypokalemia was 4.9%,with the lowest serum potassium concentration recorded at 2.1 mmol/L.The proportion of females,treatment duration,cumulative dosage,age-adjusted Charlson Comorbidity Index(aCCI),the percentage of patients with platelets(PLT)<100×109/L and the proportion of patients using glucocorticoids were all higher in the hypokalemia group than those of the non-hypokalemia group(P＜0.05).Conversely,baseline serum potassium levels and red blood cell(RBC)were lower in the hypokalemia group than those of the non-hypokalemia group(P＜0.05).Multivariate Logistic regression analysis indicated that female,increased cumulative dosage,elevated aCCI and lower baseline serum potassium concentration were risk factors for PTZ induced hypokalemia(P＜0.05).Conclusion Female,lower basline serum potassium level,long-term high-dose use of PTZ and high comorbidity index are risk factors for the occurrence of PTZ-induced hypokalemia.The changes in serum potassium during the medication period of this type of patients should be closely monitored to ensure the safety of drug use for patients.

Objective:To explore the efficacy and safety of B-Raf proto-oncogene, serine/threonine kinase (BRAF) inhibitor and epidermal growth factor receptor (EGFR) inhibitor combined with immune checkpoint inhibitor in microsatellite stable (MSS) BRAF V600E metastatic colorectal cancer (mCRC) patients.Methods:The data and outcomes of mCRC patients with MSS BRAF V600E who received BRAF inhibitor, EGFR inhibitor combined with immune checkpoint inhibitor in Tianjin Medical University Cancer Hospital from May 2022 to April 2024 were retrospectively collected.Results:A total of 12 mCRC patients were included in this study, the objective response rate was 50.0%, the disease control rate was 66.7%, and the median disease control time of patients who achieved objective response was 8.0 months. The median progression-free survival was 6.8 months and the median overall survival was 8.4 months. Overall adverse reactions were controllable, the most common treatment-related adverse events were fatigue (8 cases), fever (5 cases), and rash (4 cases). There were no grade 4 adverse event, serious adverse event, and treatment-related death.Conclusion:BRAF inhibitor and EGFR inhibitor combined with immune checkpoint inhibitor show good efficacy and controllable safety in BRAF V600E mCRC patients.

Objective To analyze risk factors of hypokalemia after treatment with piperacillin-tazobactam(PTZ)and to provide a reference for safe clinical medication.Methods A retrospective collection of 1 355 inpatients treated with PTZ was conducted.Patients were assigned to the hypokalemia group(serum potassium<3.5 mmol/L,374 cases)and the non-hypokalemia group(serum potassium≥3.5 mmol/L,981 cases)based on whether they suffered from hypokalemia after PTZ treatment.Clinical data were collected and compared in both groups of patients.Multifactorial Logistic regression analysis was used to identify the influencing factors of hypokalemia induced by PTZ.Results In the hypokalemia group,there were 308 cases of mild hypokalemia(82.3%),63 cases of moderate hypokalemia and 3 cases of severe hypokalemia.The incidence of moderate to severe hypokalemia was 4.9%,with the lowest serum potassium concentration recorded at 2.1 mmol/L.The proportion of females,treatment duration,cumulative dosage,age-adjusted Charlson Comorbidity Index(aCCI),the percentage of patients with platelets(PLT)<100×109/L and the proportion of patients using glucocorticoids were all higher in the hypokalemia group than those of the non-hypokalemia group(P＜0.05).Conversely,baseline serum potassium levels and red blood cell(RBC)were lower in the hypokalemia group than those of the non-hypokalemia group(P＜0.05).Multivariate Logistic regression analysis indicated that female,increased cumulative dosage,elevated aCCI and lower baseline serum potassium concentration were risk factors for PTZ induced hypokalemia(P＜0.05).Conclusion Female,lower basline serum potassium level,long-term high-dose use of PTZ and high comorbidity index are risk factors for the occurrence of PTZ-induced hypokalemia.The changes in serum potassium during the medication period of this type of patients should be closely monitored to ensure the safety of drug use for patients.