BACKGROUND:Spondylolisthesis is a common disease,and there is a lack of effective drugs to treat it.There is still a need to further define the pathogenesis and screen out more suitable therapeutic targets for spondylolisthesis.Mendelian randomization analysis can be used to explore the drugable genes associated with spondylolisthesis and provide valuable guidance for the development of more effective and targeted therapeutic drugs.OBJECTIVE:To explore potential therapeutic targets and effective drugs for spondylolisthesis by means of pharmaceutically available genome-wide Mendelian randomization analysis.METHODS:Using the Finnish database,eQTLGen consortium,drug signature database,drug-gene interaction database,protein-protein interaction database,organic small molecule biological activity database and protein structure database,which contains genome and health information of half a million Finns,data on druggable genes were subjected to two-sample Mendelian randomization analysis and co-localization analysis with data from genome-wide association studies of spondylolisthesis to identify genes highly associated with spondylolisthesis.In addition,GO and KEGG enrichment analysis,protein network construction,drug prediction and molecular docking were performed to provide valuable guidance for the development of more effective and targeted therapeutic agents.RESULTS AND CONCLUSION:In this study,we identified 34 potential drug target genes that were significantly associated with spondylolisthesis,particularly the gene APOBEC3G.This gene showed a significant association with spondylolisthesis outcomes through Mendelian analysis and co-localization analysis,suggesting that APOBEC3G may be a priority therapeutic target.As for other potential mechanisms and drugs,we still need to conduct more in-depth research to determine their roles.This study used a database from a European population,which can be used as a reference for the study of population genetics in China.

ObjectiveTo investigate the characteristics and potential mechanisms of Luotong Xianrong Yin （LTXRY） in improving lung injury in rats with idiopathic pulmonary fibrosis （IPF） by regulating glycolysis. MethodsForty specific pathogen-free （SPF） Sprague-Dawley （SD） rats were randomly divided into a sham-operated group （10 mL·kg^-1）， model group （10 mL·kg^-1）， LTXRY group （15.18 g·kg^-1）， and nintedanib group （0.1 g·kg^-1）， with 10 rats in each group. The IPF rat model was established by intratracheal instillation of bleomycin. After 28 days of gavage intervention， pulmonary function was assessed. Lung pathological changes were observed by hematoxylin-eosin （HE） and Masson staining. Enzyme-linked immunosorbent assay （ELISA） was used to determine the levels of inflammatory factors， including tumor necrosis factor-α （TNF-α）， interleukin （IL）-1β， and IL-6， in lung tissue. Chemiluminescence assays were employed to detect lactate content and lactate dehydrogenase activity in lung tissue. Western blot was used to measure the protein expression of transforming growth factor-β₁ （TGF-β₁）， CollagenⅠ and CollagenⅢ to evaluate collagen deposition， as well as hexokinase 2 （HK2）， pyruvate kinase M2 （PKM2）， and 6-phosphofructo-2-kinase/fructose-2，6-bisphosphatase 3 （PFKFB3） to assess glycolysis levels. Network pharmacology was applied to analyze the potential targets and signaling pathways of LTXRY in IPF， and molecular docking was conducted to evaluate the binding energy between active components and potential targets. Western blot was further used to detect the expression of target- and pathway-related proteins. ResultsCompared with the sham-operated group， rats in the model group showed significantly increased main airway resistance （Rn） and respiratory system resistance （Rrs）， and significantly decreased respiratory system compliance （Crs）. Inflammatory infiltration and collagen deposition were observed in lung tissue， with significantly increased levels of TNF-α， IL-1β， and IL-6， as well as elevated protein expression of TGF-β₁， CollagenⅠ and CollagenⅢ. Lactate content， lactate dehydrogenase activity， and the protein expression of HK2， PKM2， and PFKFB3 in lung tissue were significantly increased. Network pharmacology analysis indicated that signal transducer and activator of transcription 3 （STAT3） was a key target of LTXRY in IPF， and hypoxia-inducible factor-1 （HIF-1） was a critical signaling pathway. The expression levels of phosphorylated STAT3 （p-STAT3） and HIF-1α in lung tissue were significantly higher than those in the sham-operated group. Compared with the model group， rats in the LTXRY group showed significantly decreased Rn and Rrs and significantly increased Crs. Lung inflammatory infiltration and collagen deposition were markedly alleviated， with significantly reduced levels of TNF-α， IL-1β， and IL-6， and decreased protein expression of TGF-β₁， CollagenⅠ and CollagenⅢ. Lactate content， lactate dehydrogenase activity， and the protein expression of HK2， PKM2， and PFKFB3 were significantly decreased， accompanied by markedly reduced expression of p-STAT3 and HIF-1α. ConclusionLTXRY alleviates lung tissue injury in IPF rats by regulating glycolysis mediated by the STAT3/HIF-1α signaling pathway.

BACKGROUND:Spondylolisthesis is a common disease,and there is a lack of effective drugs to treat it.There is still a need to further define the pathogenesis and screen out more suitable therapeutic targets for spondylolisthesis.Mendelian randomization analysis can be used to explore the drugable genes associated with spondylolisthesis and provide valuable guidance for the development of more effective and targeted therapeutic drugs.OBJECTIVE:To explore potential therapeutic targets and effective drugs for spondylolisthesis by means of pharmaceutically available genome-wide Mendelian randomization analysis.METHODS:Using the Finnish database,eQTLGen consortium,drug signature database,drug-gene interaction database,protein-protein interaction database,organic small molecule biological activity database and protein structure database,which contains genome and health information of half a million Finns,data on druggable genes were subjected to two-sample Mendelian randomization analysis and co-localization analysis with data from genome-wide association studies of spondylolisthesis to identify genes highly associated with spondylolisthesis.In addition,GO and KEGG enrichment analysis,protein network construction,drug prediction and molecular docking were performed to provide valuable guidance for the development of more effective and targeted therapeutic agents.RESULTS AND CONCLUSION:In this study,we identified 34 potential drug target genes that were significantly associated with spondylolisthesis,particularly the gene APOBEC3G.This gene showed a significant association with spondylolisthesis outcomes through Mendelian analysis and co-localization analysis,suggesting that APOBEC3G may be a priority therapeutic target.As for other potential mechanisms and drugs,we still need to conduct more in-depth research to determine their roles.This study used a database from a European population,which can be used as a reference for the study of population genetics in China.

The high comorbidity and heterogeneity of obsessive-compulsive disorder (OCD) underscore the importance of better understanding its transdiagnostic features. Intolerance of uncertainty (IU), a transdiagnostic negative psychological trait, has been consistently linked to a variety of psychiatric disorders, including OCD. IU is hierarchically structured, comprising general IU, inhibitory IU and prospective IU, each of them potentially relating differently to OCD symptom dimensions. For example, inhibitory IU has shown specific associations with procrastination behaviors. Neuroimaging studies indicate that OCD patients demonstrate abnormal neural activity within the fronto-limbic circuit and salience network, including anterior insula, amygdala and ventromedial prefrontal cortex, during IU-related psychological processes. This review synthesizes findings across three key areas: symptom presentation, neurobiological mechanisms and intervention strategies, aiming to clarify the role of IU in OCD. Furthermore, the potential of targeting IU therapeutically to complement first-line treatment is discussed, ultimately enhancing clinical intervention outcomes.

The high comorbidity and heterogeneity of obsessive-compulsive disorder (OCD) underscore the importance of better understanding its transdiagnostic features. Intolerance of uncertainty (IU), a transdiagnostic negative psychological trait, has been consistently linked to a variety of psychiatric disorders, including OCD. IU is hierarchically structured, comprising general IU, inhibitory IU and prospective IU, each of them potentially relating differently to OCD symptom dimensions. For example, inhibitory IU has shown specific associations with procrastination behaviors. Neuroimaging studies indicate that OCD patients demonstrate abnormal neural activity within the fronto-limbic circuit and salience network, including anterior insula, amygdala and ventromedial prefrontal cortex, during IU-related psychological processes. This review synthesizes findings across three key areas: symptom presentation, neurobiological mechanisms and intervention strategies, aiming to clarify the role of IU in OCD. Furthermore, the potential of targeting IU therapeutically to complement first-line treatment is discussed, ultimately enhancing clinical intervention outcomes.

Objective:To investigate the clinical characteristics and treatment of patients with perianal necrotizing fasciitis.Methods:This study was a retrospective cohort study. Twenty patients with perianal necrotizing fasciitis who met the inclusion criteria were admitted to the Department of Burn and Plastic Surgery of the First Affiliated Hospital of Guangxi Medical University (hereinafter referred to as our department) from August 2013 to September 2023, including 19 males and 1 female, aged 24-74 (56±11) years. Based on the spreading route of perianal infection to the lower abdomen, the patients were divided into perianal-inguinal-lower abdominal wall group (12 cases) and perianal-pelvic cavity-retroperitoneal group (8 cases). The following clinical data were compared between the two groups of patients: general data, including gender, age, combined underlying diseases, blood glucose level and acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score when admitted to our department, and laboratory risk indicator for necrotizing fasciitis (LRINEC) score when admitted to our department and at 14 d after admitted to our department; infection indicators when admitted to our department, including C-reactive protein level, white blood cell count, lymphocyte count, procalcitonin level, and lactic acid level; clinical outcome-related indicators, including time from onset to definite infection range, number of surgery, treatment in intensive care unit (ICU), length of hospital stay, treatment outcome, and recurrence of necrotizing fasciitis during follow-up; detection of pathogen and bacterial drug resistance in wound necrotic tissue specimen when admitted to our department.Results:Compared with those in perianal-inguinal-lower abdominal wall group, the APACHE Ⅱ score and lactic acid level when admitted to our department and LRINEC score at 14 d after admitted to our department (with t values of -5.98, -5.01, and -2.86, respectively, P<0.05) and ICU treatment ratio ( P<0.05) were significantly increased, the time from onset to definite infection range was significantly prolonged ( Z=-3.75, P<0.05), and the number of surgery was significantly increased ( Z=2.80, P<0.05) in patients in perianal-pelvic cavity-retroperitoneal group. There were no statistically significant differences in other data between the two groups of patients ( P>0.05). Eighteen patients were cured, and no recurrence of perianal necrotizing fasciitis was observed during follow-up of 6 months in 18 cured patients. The main bacteria were Escherichia coliand Klebsiella pneumoniae, and the fungui were Aspergillus and Candida albicans detected in wound necrotic tissue specimens in two groups of patients when admitted to our department. The ratio of multiple drug resistance of bacteria in wound necrotic tissue specimens in perianal-pelvic cavity-retroperitoneal group of patients was significantly higher than that in perianal-inguinal-lower abdominal wall group ( P<0.05). Conclusions:Perianal necrotizing fasciitis can spread to the lower abdomen through two routes: the perianal-inguinal-lower abdominal wall route and the perianal-pelvic cavity-retroperitoneal route. The latter is more insidious in disease progression and more challenging in treatment. Establishing a mechanism of multi-disciplinary team diagnosis and treatment can achieve the goal of early diagnosis and precise treatment of perianal necrotizing fasciitis.

Objective To explore the predictive value of glucose metabolism and lipid metabolism indexes for in-stent restenosis(ISR)in patients with arteriosclerosis obliterans(ASO)of lower limbs after surgery.Methods A total of 160 patients with ASO of lower limbs admitted to the Second Affiliated Hospital of Zhengzhou University and Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine from January 2018 to October 2021 were selected as the research subjects.All patients were treated with percutaneous transluminal angioplasty combined with stent implantation and were followed up for 1 year.Patients were divided into the ISR group(n=59)and the non-ISR group(n=101),according to the incidence of ISR during the follow-up period.General clinical data of patients in the two groups were collected.Univariate analysis was performed to preliminarily screen out the influencing factors for ISR,and the selected indexes were further analyzed by multivariate logistic regression to analyze the influencing factors for the occurrence of ISR in patients with ASO of lower limbs after surgery.The receiver operating characteristic(ROC)curve was used to analyze the value of the glucose metabolism and lipid metabolism indexes one day before discharge alone and their combination in predicting the occurrence of ISR in patients with ASO of lower limbs after surgery.The net benefit rate of predicting the occurrence of ISR in patients with ASO of lower limbs by the levels of glucose metabolism and lipid metabolism indexes one day before discharge alone and their combination was analyzed through the decision curve.Results Among the 160 patients,59 developed ISR,with an incidence rate of 36.88％.There was no significant difference in age,gender,alcohol consumption,complications,affected side,Fontaine stage,fasting plasma glucose,and serum triglycerides of patients between the ISR group and the non-ISR group(P＞0.05);the proportion of smokers and the levels of glycosylated hemoglobin A1c(HbA1c)in peripheral blood and low-density lipoprotein(LDL)in serum of patients in the ISR group were significantly higher than those in the non-ISR group,while the level of high-density lipoprotein(HDL)in serum was significantly lower than that in the non-ISR group(P＜0.05).Multivariate logistic regression analysis showed that the elevated levels of HbA1 c in peripheral blood and LDL in serum were risk factors for ISR in patients with ASO of lower limbs after surgery(odds ratio＞1.00,P＜0.05),and the increased level of HDL in serum was the protective factor for ISR in patients with ASO of limbs after surgery(odds ratio＜1.00,P＜0.05).The ROC curve showed that the area under the curve of peripheral blood HbA1c,serum LDL and HDL levels alone and their combination in predicting the occurrence of ISR in patients with ASO of lower limbs after surgery was 0.717,0.761,0.654,and 0.824,respectively;the specificity was 0.861,0.792,0.851,and 0.663,respectively;and the sensitivity was 0.525,0.678,0.424,and 0.864,respectively.The decision curve showed that the net benefit rate for the combination of peripheral blood HbA1c,serum LDL and HDL levels one day before discharge in predicting the occurrence of ISR in patients with ASO of lower limbs after surgery was higher than that of prediction by the said indexes alone.Conclusion Glucose metabolism index peripheral blood HbA1c and lipid metabolism indexes serum LDL and HDL have certain predictive values for the occurrence of ISR in patients with ASO of lower limbs after surgery,and the net benefit rate of the joint prediction of the three indexes is higher.

[Objective]To comb the origin and flow of the Sachet therapy,chasing the past and thinking of the present,summarize the application characteristics in contemporary Zhejiang school of TCM pediatric fragrance therapy.[Methods]Using the methods of textual research of historical materials,study ancient books,literature analysis and questionnaire survey,trace the origin and development of Sachet therapy,analyze the characteristics of contemporary Zhejiang school of TCM pediatricians using Sachet therapy.[Results]Sachet therapy originated in pre-Qin,Tang,Song and Yuan Dynasties was rapidly improved and developed,and reached its peak in Ming and Qing Dynasties. Zhejiang is located in the southeast coast,the climate is humid,and people like wetland walking and water bath,easy to be invaded by external dampness,so the successive Zhejiang school doctors attach importance to the application of aromatic drugs to wake up the spleen and relieve dampness. After Lin 'an,the capital of the Southern Song Dynasty,Sachet therapy was widely used in court and folk,and had been passed down to the present.The contemporary TCM pediatricians of Zhejiang school inherited the experience of their ancestors,followed the changes of the times,fully integrated the regional characteristics,physical characteristics and humanistic feelings of Zhejiang,and formed the clinical application characteristics of adapting to local conditions,suiting measures according to the time and applying medicine according to the disease.[Conclusion]Sachet therapy has a long history,and contemporary Zhejiang school of TCM pediatricians have formed the characteristics of "three basis" in the long-term clinical application:adapting to local conditions,suiting measures according to the time and applying medicine according to the disease.

Compared with the global average, the incidence rate of nasopharyngeal carcinoma (NPC) in China is higher, particularly in the southern regions where the mortality rate has remained persistently high. Nimotuzumab, a targeted therapy that acts on the epidermal growth factor receptor, has prompted continuous progress in NPC treatment. The combination of nimotuzumab with traditional radiotherapy and chemotherapy can enhance treatment efficacy, reduce adverse reactions, and improve patients’ quality of life. This article summarizes current research findings from this perspective to provide diagnostic and therapeutic strategies for NPC treatment.

Background It is a research hotspot to study the changes of metabolites and metabolic pathways in the process of coal worker's pneumoconiosis (CWP) by metabonomics and to explore its pathogenesis. Objective To study the change of metabolites in bronchoalveolar lavage fluid (BALF) of patients with CWP and explore the metabolic regulation mechanism of the disease. Methods Patients with CWP who met the national diagnostic criteria according to Diagnosis of occupational pneumoconiosis (GBZ 70-2015) and underwent massive whole lung lavage were selected as the case group, and patients with tracheostenosis who underwent bronchoscopy were selected as the control group. BALF samples were collected from the cases and the controls. After filtering out large particles and mucus, the supernatant was stored in a −80 ℃ refrigerator. The samples were detected and analyzed by liquid chromatography-mass spectrometry after adding extraction solution, cold bath ultrasonication, and high-speed centrifugation, and the metabolic profiles and related data of CWP patients were obtained. The differential metabolites related to the occurrence and development of CWP were screened by multiple statistical analysis; furthermore, we searched the Kyoto Encyclopedia of Genes and Genomes (KEGG) database for potential metabolic pathways involved in the progression. Results There was no significant difference in the general conditions of the subjects, such as weight, height, age, and length of service among the stage I group, the stage II group, the stage III group, and the control group (P˃0.05). When comparing the CWP stage I group with the control group, 48 differential metabolites were screened out, among which 14 were up-regulated and 34 were down-regulated. A total of 66 differential metabolites were screened out between the patients with CWP stage II and the controls, 14 up-regulated and 52 down-regulated differential metabolites. Compared with the control group, 63 differential metabolites were screened out in the patients with CWP stage III, including 11 up-regulated and 52 down-regulated differential metabolites. There were 36 differential metabolites that may be related to the occurrence of CWP, among which 11 differential metabolites were up-regulated, and 25 were down-regulated. Four significant differential metabolic pathways were identified through KEGG database query: linoleic acid metabolic pathway, alanine metabolic pathway, sphingolipid metabolic pathway, and glycerophospholipid metabolic pathway. Conclusion The metabolomic study of BALF show that there are 36 different metabolites in the occurrence and development of CWP, mainly associating with linoleic acid metabolism, alanine metabolism, sphingolipid metabolism, and glycerophospholipid metabolism pathways.