ObjectiveTo explore the mechanisms of action of Ganlu Xiaodu Dan in treating viral pneumonia by combining network pharmacology and molecular docking with in vivo experimental validation. MethodsNetwork pharmacology and molecular docking were used to predict the core components， target genes， and major pathways of Ganlu Xiaodu Dan. Molecular docking was then applied to verify the interactions between the core components and key targets. Sixty male C57BL/6 mice were randomly divided into six groups （n = 10 per group）， including blank， model， dexamethasone， and Ganlu Xiaodu Dan low-， medium-， and high-dose groups. The blank and model groups were gavaged with physiological saline （10 mL·kg^-1） every 12 h. The dexamethasone group received intraperitoneal injections of dexamethasone （5 mg·kg^-1）. The low-， medium-， and high-dose groups of Ganlu Xiaodu Dan were gavaged with solutions at concentrations of 7.2， 14.4， and 21.6 g·kg^-1， respectively， every 12 h. Lung wet/dry weight ratio （W/D） was measured. Hematoxylin-eosin （HE） staining was used to observe pathological changes in lung tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the expression levels of tumor necrosis factor-α （TNF-α）， interleukin （IL）-17， and IL-1β in bronchoalveolar lavage fluid （BALF）. Western blot was performed to detect the expression of phosphoinositide 3-kinase （PI3K） and protein kinase B （Akt） in lung tissue for further validation. ResultsTwelve potential active components of Ganlu Xiaodu Dan were identified through network pharmacology. A total of 306 overlapping target genes were obtained between Ganlu Xiaodu Dan and viral pneumonia. PPI network analysis identified the top 20 key targets， and GO and KEGG enrichment analyses revealed the top 20 signaling pathways. An “active component–target–pathway” network was constructed. Molecular docking demonstrated strong affinity between the core components of Ganlu Xiaodu Dan and key targets related to viral pneumonia. In animal experiments， compared with the blank group， the model group showed severe bronchial epithelial damage， disordered alveolar structure， massive inflammatory cell infiltration， widened alveolar septa， and obvious interstitial edema. W/D， levels of IL-1β， TNF-α， and IL-17 in BALF， and protein expression of p-PI3K/PI3K and p-Akt/Akt in lung tissue were all significantly increased （P<0.05）. Compared with the model group， lung injury in the Ganlu Xiaodu Dan groups and the dexamethasone group was alleviated. W/D and TNF-α levels were significantly decreased （P<0.05）. IL-1β and IL-17 levels were significantly reduced in the medium- and high-dose groups and the dexamethasone group， and the protein expression levels of p-PI3K/PI3K and p-Akt/Akt in lung tissue were significantly decreased （P<0.05）. ConclusionGanlu Xiaodu Dan can alleviate lung injury in viral pneumonia by suppressing the inflammatory response， and its mechanism may be related to the inhibition of PI3K/Akt pathway activation.

ObjectiveTo explore the mechanisms of action of Ganlu Xiaodu Dan in treating viral pneumonia by combining network pharmacology and molecular docking with in vivo experimental validation. MethodsNetwork pharmacology and molecular docking were used to predict the core components， target genes， and major pathways of Ganlu Xiaodu Dan. Molecular docking was then applied to verify the interactions between the core components and key targets. Sixty male C57BL/6 mice were randomly divided into six groups （n = 10 per group）， including blank， model， dexamethasone， and Ganlu Xiaodu Dan low-， medium-， and high-dose groups. The blank and model groups were gavaged with physiological saline （10 mL·kg^-1） every 12 h. The dexamethasone group received intraperitoneal injections of dexamethasone （5 mg·kg^-1）. The low-， medium-， and high-dose groups of Ganlu Xiaodu Dan were gavaged with solutions at concentrations of 7.2， 14.4， and 21.6 g·kg^-1， respectively， every 12 h. Lung wet/dry weight ratio （W/D） was measured. Hematoxylin-eosin （HE） staining was used to observe pathological changes in lung tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the expression levels of tumor necrosis factor-α （TNF-α）， interleukin （IL）-17， and IL-1β in bronchoalveolar lavage fluid （BALF）. Western blot was performed to detect the expression of phosphoinositide 3-kinase （PI3K） and protein kinase B （Akt） in lung tissue for further validation. ResultsTwelve potential active components of Ganlu Xiaodu Dan were identified through network pharmacology. A total of 306 overlapping target genes were obtained between Ganlu Xiaodu Dan and viral pneumonia. PPI network analysis identified the top 20 key targets， and GO and KEGG enrichment analyses revealed the top 20 signaling pathways. An “active component–target–pathway” network was constructed. Molecular docking demonstrated strong affinity between the core components of Ganlu Xiaodu Dan and key targets related to viral pneumonia. In animal experiments， compared with the blank group， the model group showed severe bronchial epithelial damage， disordered alveolar structure， massive inflammatory cell infiltration， widened alveolar septa， and obvious interstitial edema. W/D， levels of IL-1β， TNF-α， and IL-17 in BALF， and protein expression of p-PI3K/PI3K and p-Akt/Akt in lung tissue were all significantly increased （P<0.05）. Compared with the model group， lung injury in the Ganlu Xiaodu Dan groups and the dexamethasone group was alleviated. W/D and TNF-α levels were significantly decreased （P<0.05）. IL-1β and IL-17 levels were significantly reduced in the medium- and high-dose groups and the dexamethasone group， and the protein expression levels of p-PI3K/PI3K and p-Akt/Akt in lung tissue were significantly decreased （P<0.05）. ConclusionGanlu Xiaodu Dan can alleviate lung injury in viral pneumonia by suppressing the inflammatory response， and its mechanism may be related to the inhibition of PI3K/Akt pathway activation.

Objective:To investigate the diagnostic value of density features of computed tomography(CT)of the fat around pericoronary artery of dual-source computer tomography angiography(CTA)combined with electrocardiogram(ECG)on the severity of disease condition in patients with coronary heart disease(CHD).Methods:A total of 120 CHD patients who admitted to Shanxi Bethune Hospital from March 2021 to March 2023 were selected,and they were grouped according to the New York Heart Association(NYHA).Among of them,86 cases at grade Ⅱ-Ⅲ were divided into grade Ⅱ-Ⅲ group,and 34 cases at grade Ⅳ were divided into grade Ⅳ group.A dual-source CT was used to detect the densities of different coronary branches of Pericardial Adipose Tissue(PCAT)of average coronary artery of proximal left anterior descending artery(pLAD),mid left anterior descending artery(mLAD),proximal left circumflex artery(pLCX),proximal right coronary artery(pRCA),mid right coronary artery(mRCA)and distal right coronary artery(dRCA)of all patients,and ECG was used to detect and record the value of QRS voltage,QRS time limit value and QTc interval of patients.The mean PCAT densities of pLAD,mLAD,pLCX,pRCA,mRCA and Drca,and the QRS voltage and QRS time limit,as well as QTc interval between the two groups were observed and compared.The receiver operating characteristics(ROC)curve was used to analyze the efficacies of the above indicators in single diagnosis and combined diagnosis for the severity of disease condition of CHD patients.Results:The mean PCAT density of pLAD,mLAD,pLCX,pRCA,mRCA,mRCA and dRCA,and QRS time limit and QTc interval of patients in grade Ⅱ-Ⅲ group were significantly lower than those in grade Ⅳ group,with statistically significant difference(t=58.681,5.097,5.902,13.513,P<0.05),respectively.The area under curve(AUC)values of ROC curves of ECG and CT density of the fat around pericoronary artery of CTA were larger than 0.5 for the severity of disease condition in CHD patients,and the highest AUC value of combined diagnosis was 0.966.The results of Pearson linear correlation analysis showed that there were correlations among mean PCAT density,QRS voltage,QRS time limit and QTc interval,and there were significantly negative correlations between QRS voltage and mean PCAT density,between QRS time limit and QTc interval(r=-0.754,-0.280,-0.452,P<0.05),and there were significantly positive correlations among mean PCAT density,QRS time limit,QTc interval and the severity of the disease condition of CHD patients(r=0.983,0.435,0.547,P<0.05),respectively.There was a significantly negative correlation between QRS voltage and severity of disease condition of CHD patients(r=-0.776,P<0.05).Conclusion:The combination of CT density features of the fat around pericoronary artery of coronary artery CTA and ECG QRS wave group detection is helpful to the diagnosis for the severity of disease condition of CHD patients,which can improve the accuracy of diagnosis and has a certain of application value.

Objective:To investigate the effect of mitochondrial division of GABAergic neurons in substantia nigra pars reticulata(SNr)on motor dysfunction in mice with acute hepatic encephalopathy(AHE).Methods:AHE mice model was established by intraperitoneal injection of thioacetamide(TAA).The changes of liver lobules in AHE mice were observed by hematoxylin-eosin(HE)staining.The changes of serum aspartate aminotransferase(AST),alanine aminotransferase(ALT)and blood ammonia in AHE mice were detected by biochemical detection kit.Then,the motor function of AHE mice was observed by rod fatigue test,elevated cross maze test and open field test.Furthermore,the changes of mitochondrial area,perimeter,roundness and other morphological indicators in SNr of AHE mice were ob-served and analyzed by transmission electron microscopy.The expression of mitochondrial division and fusion related molecules in SNr of AHE mice was observed by Western Blot.Then,the expression of mitochondrial dynamic related protein 1(DRP1)in SNr of AHE mice was targeted by AAV virus.The mitochondrial membrane potential(MMP),ATP and reactive oxygen species(ROS)in SNr were detected by fluorescence enzyme marker,and the changes of motor function of mice were observed.Results:Compared with the control group,the motor function of AHE mice was signifi-cantly decreased,the mitochondrial division of SNr was significantly enhanced,and the expression of mitochondrial divi-sion related proteins was significantly increased.The MMP in SNr of AHE mice was significantly decreased,the ATP of cells was decreased,and the ROS was increased.After targeted inhibition of DRP1 expression in SNr of AHE mice,the movement was improved;further observation found that after the mitochondrial division in SNr of AHE mice was inhibi-ted,the MMP was significantly increased,the ATP of cells was increased,and the ROS was decreased,which demon-strated that the mitochondrial function was significantly improved.Conclusion:Targeted inhibition of mitochondrial di-vision of GABAergic neurons in SNr of AHE mice can improve mitochondrial morphology and function,thus alleviating their movement disorders.

Objective:To investigate the value of ultrasonic measurement of the ratio of optic nerve sheath diameter (ONSD) to eyeball transverse diameter(ETD) in the diagnosis and prognosis of intracranial hypertension in patients with craniocerebral trauma.Methods:A total of 120 patients with craniocerebral trauma treated in the Xingtai General Hospital of North China Medical and Health Group from December 2021 to January 2023 were perspectively selected, and they were divided into normal intracranial pressure group (73 cases) and intracranial hypertension group (47 cases) according to the results of intracranial pressure measurements, and the intracranial hypertension group was divided into good prognosis group (20 cases) and poor prognosis group (27 cases) according to the follow-up prognosis. The efficacy of ONSD, ETD and ONSD/ETD in intracranial hypertension diagnosis and prognosis assessment were analyzed by receiver operating characteristic (ROC) curve. Kaplan-Meier method was used to evaluate the 6-month risk of adverse prognosis of patients, and the comparison was made by Log-rank test.Results:The levels of intracranial pressure, ONSD, ONSD/ETD in the normal intracranial pressure group were lower than those in the intracranial hypertension group: (130.73 ± 23.63) mmH 2O (1 mmH 2O = 0.009 8 kPa) vs. (270.11 ± 35.78) mmH 2O, (5.47 ± 0.29) mm vs. (5.78 ± 0.44) mm, 0.246 ± 0.018 vs. 0.263 ± 0.018, there were statistical differences ( P<0.05). The scores of Glasgow Coma Scale (GCS), intracranial pressure, ONSD, ONSD/ETD in the good prognosis group were lower than those in the poor prognosis group: (5.50 ± 1.24) scores vs. (6.41 ± 1.34) scores, (256.15 ± 30.23) mmH 2O vs. (280.44 ± 36.56) mmH 2O, (5.62 ± 0.40) mm vs. (5.90 ± 0.44) mm, 0.254 ± 0.014 vs. 0.270 ± 0.017, there were statistical differences ( P<0.05). ROC curve analysis results showed that the area under the curve (AUC) of ONSD and ONSD/ETD for diagnosing intracranial hypertension in patients with craniocerebral trauma were 0.718 and 0.765, respectively, and the critical values were 5.87 mm and 0.263, respectively. The AUC of ONSD and ONSD/ETD predicting prognosis of intracranial hypertension patients was 0.677 and 0.763, respectively, and the critical values were 5.90 mm and 0.267, respectively. Grouped by the threshold of ONSD/ETD for the prognosis of intracranial hypertension (0.267), the incidence of adverse prognosis in ONSD/ETD > 0.267 group was higher than that in the ONSD/ETD≤0.267 group, there was statistical difference ( P<0.05). Conclusions:ONSD/ETD can be used as an index for diagnosis and prognosis of intracranial hypertension.

Objective:To investigate the precipitating and aggravating factors in patients with fibromyalgia (FMS) compared to patients with rheumatoid arthritis (RA).Methods:This study was conducted from January 2015 to November 2021, using a cross-sectional survey research method, based on references to develop a patient-reported "onset and exacerbation triggers questionnaire", and surveyed patients with FMS and RA at the same time, and counted the types and proportions of onset and exacerbation triggers in the two groups of patients and used the chi-square test to make comparisons between the groups.Results:A total of 415 patients with FMS and 200 patients with RA participated the survey. 146 patients with FMS (35.2%) and 38 patients with RA (19.0%) reported morbidity triggers. Experiencing physical injury (71, 17.1%), wind-cold/cold-dampness (30 patients, 7.2%), mental stress (26, 6.2%), and exercise fatigue (10 patients, 2.4%) were the common morbidity triggers for FMS. More FMS patients reported to have experienced physical injuries and mental stress before the onset of the disease compared to RA patients [8.2%(17/200), χ2=5.41, P=0.020; 1.5%(3/200), χ2=6.82, P=0.009]. Exacerbation triggers were reported by 319 patients with FMS (76.9%) and 137 patients with RA (68.5%), in the order of weather changes (219 patients, 52.7%), physical labor (192 patients, 46.2%), mood swings (147 patients, 35.4%), sleep deprivation (145 patients, 34.9%), and mental stress (130 patients, 31.3%). The proportion of FMS patients with symptom exacerbation due to physical labor [46.2%(192/415)], mood swings[35.4%(147/415)], sleep deprivation[34.9%(145/415)], mental stress[31.3%(130/415)], and infection [9.3%(39/415)] was significantly higher than that of RA patients [35.0%(70/200), χ2=7.00, P=0.008; 19.5%(39/200), χ2=16.22, P<0.001; 13.5%(27/200), χ2=30.79, P<0.001; 17.5%(35/200), χ2=13.14, P<0.001; 3.0%(6/200), χ2=8.15, P=0.004). Conclusion:More than a third of FMS patients reported precipitating factors, and nearly four fifths FMS patients reported at least one aggravating trigger. FMS patients are likely to be more sensitive to environmental changes and perceived stress than RA patients.

Objective:To investigate the changes of mitochondria in the substantia nigra pars reticulata(SNr)in a mouse model of acute hepatic encephalopathy(AHE),and the effects of mitochondrial division inhibitor Mdivi-1 on the motor function and mitochondrial function of SNr in AHE mice.Methods:The mouse model of AHE was established by intraperitoneal injection of thioacetamide(TAA)and treated with Mdivi-1.The changes of serum aspartate aminotrans-ferase(AST),alanine aminotransferase(ALT),and blood ammonia were detected by biochemical detection kits.Open field test,rotor-rod fatigue test and elevated plus maze test were performed to observe the motor function of AHE mice.Mitochondrial membrane potential(MMP),cellular reactive oxygen species(ROS)and ATP of SNr were detected by commercial kits.Results:Compared with the control group,the levels of AST,ALT and blood ammonia in AHE mice were increased.The total movement distance of the mice in the open field was reduced,and the movement time of the rotor-rod fatigue test and the elevated plus maze test were shortened.In SNr,mitochondria became smaller and rounder,mitochondrial fission increased,MMP decreased,cellular ROS increased,and ATP production decreased.After treat-ment with Mdivi-1,the levels of AST,ALT and blood ammonia in AHE mice were decreased.In the open field,the total movement distance of mice increased,the movement time of rotorrod fatigue test and elevated plus maze test increased,the mitochondria of SNr were larger,with decreased roundness,decreased mitochondrial division,increased MMP,decreased cellular ROS,and increased ATP production.Conclusion:Mdivi-1 can improve movement disorders in AHE mice by repairing mitochondrial in the SNr.

End-stage liver diseases,such as cirrhosis and liver cancer caused by hepatitis B,are often combined with hepatic encephalopathy(HE);ammonia poisoning is posited as one of its main pathogenesis mechanisms.Ammonia is closely related to autophagy,but the molecular mechanism of ammonia's regulatory effect on autophagy in HE remains unclear.Sialylation is an essential form of glycosylation.In the nervous system,abnormal sialylation affects various physiological processes,such as neural development and synapse formation.ST3 β-galactoside α2,3-sialyltransferase 6(ST3GAL6)is one of the significant glycosyltransferases responsible for adding α2,3-linked sialic acid to substrates and generating glycan structures.We found that the expression of ST3GAL6 was upregulated in the brains of mice with HE and in astrocytes after ammonia induction,and the expression levels of α2,3-sialylated glycans and autophagy-related proteins microtubule-associated protein light chain 3(LC3)and Beclin-1 were upregulated in ammonia-induced astrocytes.These findings suggest that ST3GAL6 is related to autophagy in HE.Therefore,we aimed to determine the regulatory relationship between ST3GAL6 and autophagy.We found that silencing ST3GAL6 and blocking or degrading α2,3-sialylated glycans by way of Maackia amurensis lectin-Ⅱ(MAL-Ⅱ)and neuraminidase can inhibit autophagy.In addition,silencing the expression of ST3GAL6 can downregulate the expression of heat shock protein β8(HSPB8)and Bcl2-associated athanogene 3(BAG3).Notably,the overexpression of HSPB8 partially restored the reduced autophagy levels caused by silencing ST3GAL6 expression.Our results indicate that ST3GAL6 regulates autophagy through the HSPB8-BAG3 complex.

Objective To conduct a visual analysis of the current status, hotspots, and frontiers of research on renal cell carcinoma targeted therapy using VOSviewer software. Methods Literature related to renal cell carcinoma targeted therapy published between January 1, 2006 and December 31, 2023, from the Web of Science (WOS) Core Collection database were retrieved. Eligible articles were screened and subjected to bibliometric and visual analysis using VOSviewer software. Results A total of 1, 009 articles were selected, with an overall increasing trend in annual publication volume. The top three countries in terms of publication output were the United States, China, and Italy, while the top three institutions were Harvard University, The University of Texas, and France Uni-cancer Institute. The analysis of the core author collaboration network revealed close collaboration among researchers in the United States and the United Kingdom, whereas collaboration between China and foreign countries was limited, resulting in a relatively loose collaboration network. Through co-occurrence clustering analysis of high-frequency author keywords, nine clusters were generated, with hotspots focusing on targeted and immune combination therapy, efficacy, prognosis, drug resistance, targets, and biomarkers. Conclusion Remarkable progress has been made in renal cell carcinoma targeted therapy research over the past decade; however, drug resistance and adverse reactions to targeted therapies remain challenges in clinical treatment. Research related to targeted drug resistance mechanisms, novel targeted drugs, and effective predictive biomarkers has significantly increased. Grasping the developmental trends in this fieldis crucial, and VOSviewer's visual analysis can offer an intuitive representation of the current status, hotspots, and frontiers, thereby providing researchers with a valuable reference.

Objective:To study the genetic variation and distribution characteristics of thalassemia in people of childbearing age in Hubei Province, and to provide clinical basis for the local government decision-making departments to formulate and promote appropriate policies for prevention and control of thalassemia.Methods:Venous blood samples were collected from 44 849 people of childbearing age in hospitals in Hubei Province from May 13, 2019 to August 17, 2021. PCR-flow fluorescence hybridization and PCR+diversion hybridization were used to screen thalassemia genes. Spouses of those who tested positive were also tested for thalassemia genes. When both spouses carried the same type of thalassemia gene, the amniotic fluid of pregnant women was extracted for prenatal diagnosis and followed up.Results:Among the 44 849 people of childbearing age, 2 286 cases were diagnosed as thalassemia gene carriers through genetic testing, and the total detection rate was 5.10% (2 286/44 849). Among them, 1 488 cases were diagnosed as α-thalassemia, and the detection rate was 3.32% (1 488/44 849); 767 cases were diagnosed as β-thalassemia, and the detection rate was 1.71% (767/44 849); 31 cases were diagnosed as α-thalassemia combined with β-thalassemia, and the detection rate was 0.07% (31/44 849). The top three genotypes of α-thalassemia were -α 3.7/αα, -- SEA/αα, and -α 4.2/αα, accounting for 58.06% (864/1 488), 26.14% (389/1 488), and8.74% (130/1 488), respectively. The top three genotypes of β-thalassemia were β IVS-Ⅱ-654/β N, β CD41-42/β N, and β CD17/β N, accounting for 41.72% (320/767), 21.25% (163/767), and 16.04% (123/767), respectively. The main genotypes of α-thalassemia combined with β-thalassemia were -α 3.7/αα complex β IVS-Ⅱ-654/β N and -α 3.7/αα complex β CD41-42/β N, accounting for 29.03% (9/31) and 16.13% (5/31), respectively. A total of 59 people of childbearing age were conducted prenatal diagnosis, among fetus, there were 4 cases of severe thalassemia (2 cases of severe α-thalassemia, 2 cases of severe β-thalassemia), 5 cases of intermediate α-thalassemia, 5 cases of intermediate or severe β-thalassemia, 19 cases of mild thalassemia (8 cases of mild α-thalassemia, 11 cases of mild β-thalassemia), 13 cases of stationary α-thalassemia, and 1 case of stationary α-thalassemia combined with mild β-thalassemia, there were 12 cases without α-thalassemia or β-thalassemia genes. After follow-up, 4 cases of severe thalassemia, 2 cases of intermediate α-thalassemia, and 5 cases of intermediate or severe β-thalassemia were terminated pregnancy by the joint decision of both parents. Conclusions:In Hubei Province, the detection rate of thalassemia is high, and α-thalassemia is the main mutation type. The combination of thalassemia gene screening and prenatal diagnosis is of great significance in reducing the birth rate of children with thalassemia.