OBJECTIVE: To investigate the therapeutic potential of pseudolaric acid B (PAB) on non-alcoholic fatty liver disease (NAFLD) and its underlying molecular mechanism in vitro and in vivo. METHODS: Eight-week-old male C57BL/6J mice (n=32) were fed either a normal chow diet (NCD) or a high-fat diet (HFD) for 8 weeks. The HFD mice were divided into 3 groups according to a simple random method, including HFD, PAB low-dose [10 mg/(kg·d), PAB-L], and PAB high-dose [20 mg/(kg·d), PAB-H] groups. After 8 weeks of treatment, glucose metabolism and insulin resistance were assessed by oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). Biochemical assays were used to measure the serum and cellular levels of total cholesterol (TC), triglycerides (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). White adipose tissue (WAT), brown adipose tissue (BAT) and liver tissue were subjected to hematoxylin and eosin (H&E) staining or Oil Red O staining to observe the alterations in adipose tissue and liver injury. PharmMapper and DisGeNet were used to predict the NAFLD-related PAB targets. Peroxisome proliferator-activated receptor alpha (PPARα) pathway involvement was suggested by Kyoto Encyclopedia of Genes and Genomes (KEGG) and search tool Retrieval of Interacting Genes (STRING) analyses. Luciferase reporter assay, cellular thermal shift assay (CETSA), and drug affinity responsive target stability assay (DARTS) were conducted to confirm direct binding of PAB with PPARα. Molecular dynamics simulations were applied to further validate target engagement. RT-qPCR and Western blot were performed to assess the downstream genes and proteins expression, and validated by PPARα inhibitor MK886. RESULTS: PAB significantly reduced serum TC, TG, LDL-C, AST, and ALT levels, and increased HDL-C level in HFD mice (P<0.01). Target prediction analysis indicated a significant correlation between PAB and PPARα pathway. PAB direct target binding with PPARα was confirmed through luciferase reporter assay, CETSA, and DARTS (P<0.05 or P<0.01). The target engagement between PAB and PPARα protein was further confirmed by molecular dynamics simulations and the top 3 amino acid residues, LEU321, MET355, and PHE273 showed the most significant changes in mutational energy. Subsequently, PAB upregulated the genes expressions involved in lipid metabolism and mitochondrial biogenesis downstream of PPARα (P<0.05 or P<0.01). Significantly, the PPARα inhibitor MK886 effectively reversed the lipid-lowering and PPARα activation properties of PAB (P<0.05 or P<0.01). CONCLUSION PAB mitigates lipid accumulation, ameliorates liver damage, and improves mitochondrial biogenesis by binding with PPARα, thus presenting a potential candidate for pharmaceutical development in the treatment of NAFLD.
Animals ; PPAR alpha/metabolism* ; Non-alcoholic Fatty Liver Disease/pathology* ; Male ; Mice, Inbred C57BL ; Lipid Metabolism/drug effects* ; Diterpenes/therapeutic use* ; Organelle Biogenesis ; Diet, High-Fat ; Humans ; Mice ; Liver/metabolism* ; Insulin Resistance ; Mitochondria/metabolism* ; Molecular Docking Simulation

OBJECTIVE: Cigarette smoking exacerbates the progression of pulmonary tuberculosis (TB). The role of tertiary lymphoid structures (TLS) in chronic lung diseases has gained attention; however, it remains unclear whether smoking-exacerbated lung damage in TB is associated with TLS. This study aimed to analyze the characteristics of pulmonary TLS in smokers with TB and to explore the possible role of TLS in smoking-related lung injury in TB. METHODS: Lung tissues from 36 male patients (18 smokers and 18 non-smokers) who underwent surgical resection for pulmonary TB were included in this study. Pathological and immunohistological analyses were conducted to evaluate the quantity of TLS, and chest computed tomography (CT) was used to assess the severity of lung lesions. The correlation between the TLS quantity and TB lesion severity scores was analyzed. The immune cells and chemokines involved in TLS formation were also evaluated and compared between smokers and non-smokers. RESULTS: Smoker patients with TB had significantly higher TLS than non-smokers ( P < 0.001). The TLS quantity in both the lung parenchyma and peribronchial regions correlated with TB lesion severity on chest CT (parenchyma: r = 0.5767; peribronchial: r = 0.7373; both P < 0.001). Immunohistochemical analysis showed increased B cells, T cells, and C-X-C motif chemokine ligand 13 (CXCL13) expression in smoker patients with TB ( P < 0.001). CONCLUSION Smoker TB patients exhibited increased pulmonary TLS, which was associated with exacerbated lung lesions on chest CT, suggesting that cigarette smoking may exacerbate lung damage by promoting TLS formation.
Humans ; Male ; Tuberculosis, Pulmonary/immunology* ; Middle Aged ; Tertiary Lymphoid Structures/pathology* ; Adult ; Lung/pathology* ; Smoking/adverse effects* ; Smokers ; Aged ; Tomography, X-Ray Computed

Objective:To explore the influence of different scanning positions based on chest phantom of computed tomography(CT)scan on chest on image quality and radiation dose.Methods:A thermoluminescent dosimeter(TLD)was placed at the breast area of simulating anthropoid chest phantom.GE Revolution evo CT was used to conduct scan on the conventional supine position(supine group)and prone position(prone group)for chest phantom.Different noise indexes(NI=10-23)were adjusted to control ration doses,and other parameters were fixed,and each group collected 12 sequence images.The average value(AV),standard deviation(SD)of the CT scan at region of interest(ROI)under different scanning positions were recorded to calculate the signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of the image.The radiation dose at the breast area was measured by TLD,and the volume CT dose index(CTDIvol)and dose-length product(DLP)were recorded.Results:Under different scanning positions,the radiation dose of breast organs in the prone group was lower than that in the supine group,there was a statistically significant difference between the two groups(t=6.57,P<0.05),while there were not statistically significant differences in CTDIvol and DLP between the two groups(P>0.05).There were not statistically significant differences in the CT values,SD,SNR,CNR of lung tissue,and the CT values of breast tissue between the two groups of images(P>0.05).The SD,SNR and CNR of breast tissue in the prone group were lower than those in the supine group,and the differences were statistically significant(t=-13.33,-10.59,6.70,P<0.05).There were no statistically significant differences in the subjective scores of the clarity of the edge of the tissue within lung,the layers of soft tissue of the breast,noise,and artifacts in the bone tissue between the two groups of images(P>0.05).Conclusion:When low-dose CT physical examination on chest is conducted in clinical practice,the scanning of prone position during undergoing CT scan on chest can obtain image quality that can meet the requirements in diagnosing lung,and reduce the radiation dose on the breast,and conform to the technical principle of optimal radiation protection.

Aim To explore the relationship between multiple cardiovascular and metabolic diseases and falls in middle-aged and elderly people.Methods Using the fifth dataset of the China Health and Retirement Longitudinal Study(CHARLS),18 968 middle-aged and elderly people aged 45 years and above were enrolled as study subjects.The relationship between multiple cardiovascular and metabolic diseases and falls was analyzed by Logistic regression model.Results The incidence rates of falls,severe falls and hip fractures in the study subjects were 17.3％,6.8％and 0.9％,respectively.Cardiovascular and metabolic diseases were positively associated with the risk of falls.Compared with study subjects without cardiovascular and metabolic diseases,those with 1,2,3 and 4 cardiovascular and metabolic disea-ses had a 13％,44％,69％and91％increased risk of falls,respectively,with OR(95％CI)of 1.13(1.02～1.25),1.44(1.29～1.61),1.69(1.48～1.93)and 1.91(1.56～2.32);the risk of serious falls increased by 22％,51％,69％and 102％,respectively,with OR(95％CI)of 1.22(1.05～1.42),1.51(1.27～1.78),1.69(1.38～2.05)and 2.02(1.54～2.66).The risk of hip fractures increased by 95％,147％and 157％in study subjects with2,3 and 4 cardiovascular and metabolic diseases,respectively,with OR(95％CI)of 1.95(1.24～3.05),2.47(1.50～4.07)and 2.57(1.26～5.20).Conclusion Multiple cardiovascular and metabolic diseases significantly increased the risk of falls in middle-aged and elderly people.

As one of the core theories of spleen governing transportation and transformation in the traditional Chinese medicine visceral manifestation theory,the modern biological basis of"spleen qi disperses essence"has not been fully elucidated.Lipids are one of the three major nutrients in the body,which are derived from exogenous absorption or endogenous transformation,and belong to the category of"grease"and"essence"substances in traditional Chinese medicine.Because of their hydrophobic nature,lipids require apolipoproteins to be transported in the bloodstream and used by the body;similarly,essence also needs spleen qi transformation to be distributed throughout the body and exert their nourishing effects,revealing a certain degree of inherent unity between the two.When the spleen qi functions properly,essence dispersal is orderly and lipid metabolism remains in homeostatic balance;if spleen deficient leads to impaired transportation,the essence will not be distributed,and the lipid turbidity will accumulate,causing disease.Classic strengthening spleen prescriptions such as Zexie Decoction,can reshape lipid homeostasis by regulating apolipoproteins.Based on apolipoprotein-mediated lipid metabolism,this paper explores the modern molecular biology basis of the theory of"spleen qi disperses essence,"which provides novel insights for enriching the modern research of traditional Chinese medicine visceral manifestation theory,and lays the foundation for clinical practice and theoretical innovation in the treatment of metabolic diseases from the spleen.

Objective:To evaluate the efficacy and safety of immunotherapy combined with chemotherapy as conversion therapy for initially unresectable locally advanced esophageal squamous cell carcinoma.Methods:This retrospective case series study analyzed clinical and pathological data of 32 patients with initially unresectable locally advanced esophageal squamous cell carcinoma who received immunotherapy combined with chemotherapy at the Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University, from June 2020 to December 2024. The cohort included 27 males and 5 females, with an age ( M(IQR)) of 61(9)years (range:46 to 73 years). Five patients were diagnosed with stage Ⅲ, 27 with stage ⅣA. All patients received PD-1 inhibitor sintilimab combined with nedaplatin and albumin-bound paclitaxel. Radiological evaluations were performed every two cycles, the multidisciplinary team evaluation was conducted to determine conversion to resectable status, and patients with successful conversion underwent radical esophagectomy. Follow-up was conducted via telephone or outpatient visits every 3 to 6 months after the last treatment. The primary endpoint was R0 resection rate, secondary endpoints included objective response rate (ORR), pathological complete response (pCR) rate, major pathological response (MPR) rate, event-free survival (EFS), disease-free survival (DFS) in patients with R0 resection, overall survival (OS) and safety. Kaplan-Meier method was used to plot survival curves and estimate median EFS, DFS, OS rates and their 95% CI. The 95% CI for ORR, pCR rate, MPR rate, and downstaging rate were calculated using the Clopper-Pearson method. Results:The median treatment cycle of 2(1) (range:2 to 8). As of June 2025, the median follow-up was 32.5(13.5)months (range:6.4 to 59.1 months). Among the 32 patients, 9 experienced progression or recurrence, including 2 with liver and lymph node metastases, 2 with lung metastases, 2 with thoracic vertebral metastases, and 3 with mediastinal lymph node metastases. After conversion therapy, 29 patients underwent surgery, achieving an R0 resection rate of 84.4% (95% CI:67.2% to 94.7%), a pCR rate of 27.6% (95% CI:12.7% to 47.2%), and an MPR rate of 55.2% (95% CI:35.7% to 73.6%). Grade 3 or higher surgical complications occurred in 6.9%(2/29) of patients, and grade 3 or higher treatment-related adverse events were observed in 15.6%(5/29). Among the 32 patients, the ORR was 56.3% (95% CI:37.7% to 73.6%),the 3-year EFS rate and OS rate was 59.4% (95% CI:40.8% to 86.4%) and 59.7% (95% CI:40.0% to 89.0%) respectively. Conclusion:Immunotherapy combined with chemotherapy demonstrates high conversion rates and favorable safety in the conversion therapy of initially unresectable locally advanced esophageal squamous cell carcinoma, representing a promising treatment strategy.

As one of the core theories of spleen governing transportation and transformation in the traditional Chinese medicine visceral manifestation theory,the modern biological basis of"spleen qi disperses essence"has not been fully elucidated.Lipids are one of the three major nutrients in the body,which are derived from exogenous absorption or endogenous transformation,and belong to the category of"grease"and"essence"substances in traditional Chinese medicine.Because of their hydrophobic nature,lipids require apolipoproteins to be transported in the bloodstream and used by the body;similarly,essence also needs spleen qi transformation to be distributed throughout the body and exert their nourishing effects,revealing a certain degree of inherent unity between the two.When the spleen qi functions properly,essence dispersal is orderly and lipid metabolism remains in homeostatic balance;if spleen deficient leads to impaired transportation,the essence will not be distributed,and the lipid turbidity will accumulate,causing disease.Classic strengthening spleen prescriptions such as Zexie Decoction,can reshape lipid homeostasis by regulating apolipoproteins.Based on apolipoprotein-mediated lipid metabolism,this paper explores the modern molecular biology basis of the theory of"spleen qi disperses essence,"which provides novel insights for enriching the modern research of traditional Chinese medicine visceral manifestation theory,and lays the foundation for clinical practice and theoretical innovation in the treatment of metabolic diseases from the spleen.

A retrospective analysis was made on clinical data of a child with osteopathia striata with cranial sclerosis (OS-CS) diagnosed in the Department of Neonatology, Children′s Hospital Affiliated to Shandong University in January 2024.The proband was admitted to hospital due to premature delivery at 30 + 2 weeks, shortness of breath and poor response for 13 days after resuscitation.After birth, the child had no spontaneous breathing with floppy limbs.Tracheal intubation was required for positive pressure ventilation.Cranial ultrasound showed right subventricular hemorrhage with bilateral intraventricular hemorrhage and bilateral parieto-occipital subdural hemorrhage; cardiac ultrasound showed patent ductus arteriosus and tricuspid regurgitation; scrotal ultrasound showed bilateral inguinal cryptorchidism with right testicular hydrocele; gastrointestinal ultrasound showed that the lumen of the transverse colon was filled with many fecal matters with strong echoes.Whole exome sequencing(WES) indicated that the proband carried a hemizygous variant of c. 1489C>T(p.Arg497 *) in the AMER1 gene, which was inherited from his mother, as verified by Sanger sequencing.The hemizygous variant of c. 1489C>T(p.Arg497 *) in the AMER1 gene was rated as likely pathogenic (PVS1+ PM2-Supporting) according to the American College of Medical Genetics and Genomics(ACMG) guidelines, which was not included in the Human Gene Mutation Database(HGMD) database.High-throughput sequencing identified the hemizygous variant of c. 1489C>T(p.Arg497 *) in the AMER1 gene as the genetic etiology of the proband.This was the first report of AMER1 gene variant leading to OS-CS in China.The study enriches the variation spectrum and clinical phenotype spectrum of the AMER1 gene, providing a valuable foundation for clinical diagnosis, treatment, and subsequent research of the disease.

Aim To explore the relationship between multiple cardiovascular and metabolic diseases and falls in middle-aged and elderly people.Methods Using the fifth dataset of the China Health and Retirement Longitudinal Study(CHARLS),18 968 middle-aged and elderly people aged 45 years and above were enrolled as study subjects.The relationship between multiple cardiovascular and metabolic diseases and falls was analyzed by Logistic regression model.Results The incidence rates of falls,severe falls and hip fractures in the study subjects were 17.3％,6.8％and 0.9％,respectively.Cardiovascular and metabolic diseases were positively associated with the risk of falls.Compared with study subjects without cardiovascular and metabolic diseases,those with 1,2,3 and 4 cardiovascular and metabolic disea-ses had a 13％,44％,69％and91％increased risk of falls,respectively,with OR(95％CI)of 1.13(1.02～1.25),1.44(1.29～1.61),1.69(1.48～1.93)and 1.91(1.56～2.32);the risk of serious falls increased by 22％,51％,69％and 102％,respectively,with OR(95％CI)of 1.22(1.05～1.42),1.51(1.27～1.78),1.69(1.38～2.05)and 2.02(1.54～2.66).The risk of hip fractures increased by 95％,147％and 157％in study subjects with2,3 and 4 cardiovascular and metabolic diseases,respectively,with OR(95％CI)of 1.95(1.24～3.05),2.47(1.50～4.07)and 2.57(1.26～5.20).Conclusion Multiple cardiovascular and metabolic diseases significantly increased the risk of falls in middle-aged and elderly people.

Objective:To construct a nursing norm for extracorporeal membrane oxygenation in adults, so as to provide a reference for improving the nursing care of adult extracorporeal membrane oxygenation.Methods:The first draft was developed through literature search and expert discussion. From September to October 2023, 16 experts were selected using the Delphi method to conduct two rounds of expert consultation on the first draft, and the final draft was revised with reference to the experts' comments. The expert positivity coefficient was expressed as the effective recovery rate of the questionnaire, and the degree of expert authority was evaluated with the authority coefficient, and the degree of harmonization of expert opinions was assessed with the Kendall's harmony coefficient.Results:Literature search screened a total of four guidelines and five expert consensus. In the two rounds of consultation, the effective recovery rates of the questionnaires were all 100% (16/16), and the expert authority coefficients were all 0.900, and the Kendall's harmony coefficients of the overall indicators were 0.581 and 0.666, respectively (both P<0.01). The final constructed nursing norm for extracorporeal membrane oxygenation in adults included five primary indicators, 27 secondary indicators, and 17 tertiary indicators. Conclusions:The constructed nursing norm for extracorporeal membrane oxygenation in adults is scientific, reliable and feasible, and can guide clinical nursing staff to carry out nursing care for extracorporeal membrane oxygenation.