ObjectiveTo investigate the effects of Schisandrae Chinensis Fructus lignans on schizophrenia induced by dizocilpine maleate （MK-801） in mice and to clarify its mechanism. MethodsMale mice of 4-6 weeks old were randomized into blank， model， positive drug， and low-， medium-， and high-dose （40， 80， 160 mg·kg^-1， respectively） Schisandrae Chinensis Fructus lignans groups. The blank group was administrated with distilled water， and the other groups were injected with 0.5 mg·kg^-1 MK-801 to induce schizophrenia symptoms. Meanwhile， risperidone was injected at 0.2 mg·kg^-1 in the positive drug group， and mice in the intervention groups were injected with corresponding drugs for 14 consecutive days. The behavioral changes of mice were observed by autonomous activity test， open field test， forced swimming test， and water maze test. The levels of dopamine （DA） and 5-hydroxytryptamine （5-HT） in the brain and tumor necrosis factor-α （TNF-α） and nuclear factor-κB （NF-κB） in peripheral blood were quantified by enzyme-linked immunosorbent assay （ELISA）. The changes in the prefrontal lobe of mice were observed by hematoxylin-eosin staining， and the changes of the hippocampal tissue were observed by Nissl staining. The protein levels of silencing information regulatory factor 1 （SIRT1） and forkhead box protein O3a （FoxO3a） in the hippocampus of mice were determined by Western blot. ResultsCompared with the model group， low， medium， and high doses of Schisandrae Chinensis Fructus lignans reduced the total number of autonomous activities， total distance in the open field test， immobile time in the forced swimming test， and levels of TNF-α and NF-κB in peripheral blood （P<0.05）， while increasing the number of platform crossings in the water maze test and DA and 5-HT levels in the brain tissue （P<0.05）. Compared with the model group， risperidone and low， medium， and high doses of Schisandrae Chinensis Fructus lignans improve the neural cell morphology in the CA1 region， with full cells in neatly dense arrangement and exhibiting clear membrane boundary. Schisandrae Chinensis Fructus lignans inhibited the expression of SIRT 1 and FoxO3a in the hippocampus （P<0.05）. ConclusionTo sum up， Schisandrae Chinensis Fructus lignans may improve the behavior of schizophrenic mice by activating the SIRT1/FoxO3a signaling pathway to exert neuroprotective effects.

This paper summarizes Professor WANG Xixing's clinical experience in treating immune checkpoint inhibitor-related pneumonitis （CIP） based on the theory of "cough attributed to the five zang （脏） organs". Cough is a common predominant symptom of CIP. According to the theory of "cough attributed to the five zang organs"， drug toxicity triggers cancer toxin， leading to disharmony among the five zang organs， and then lung failing to diffuse and govern descent as the core pathogenesis. Therefore， treatment should focus on harmonizing the five zang organs to restore the normal function of lung qi to diffuse and govern descent. In clinical practice， CIP can be classified into four syndrome patterns， including lung yin depletion， deficiency of both the lung and the spleen with phlegm-dampness， liver fire harassing the lung， and lung-kidney yin deficiency. Correspondingly， Chaimai Jinluo Runfei Decoction （柴麦金络润肺汤） is used to nourish yin and moisten the lung； Qigui Peitu Huayin Decoction （芪桂培土化饮汤） is used to fortify the spleen and tonify the lung， resolve dampness and dispel phlegm； Chaidan Shuyu Runjin Decoction （柴丹疏郁润金汤） is used to drain liver and clear the lung； and Dimai Jinshui Xiangsheng Decoction （地脉金水相生汤） is used to nourish the kidney and moisten the lung.

Objective To investigate the epidemiological characteristics and changing trend of typhus in Shaanxi Province from 2005 to 2023 to provide a scientific basis for its prevention and control. Methods Excel 2007, SPSS 25.0, Joinpoint 4.9.1.0, and Geoda 1.6 were used for data collection and statistical analysis. Super Map was used for data visualization to describe the changing characteristics of the disease. Results A total of 394 typhus cases were reported in Shaanxi Province from 2005 to 2023. The average annual incidence of typhus was 0.054/100 000, showing a dynamic fluctuation trend(AAPC=-3.3, t=-0.3, P>0.05). The cases were mainly concentrated in Baoji, Hanzhong and Xi′an, accounting for 78.68%. The incidence peak was from May to October, accounting for 64.21% of annual incidence. The epidemic season was from May to October and December. The incidence of the disease was concentrated in the 40-69 age group, accounting for 58.88%, and the sex was 1.07:1. The main occupation was farmers, accounting for 72.08%. The median time from onset to diagnosis was 7 days. Global spatial autocorrelation analysis showed that there were significant spatial autocorrelations in 11 years from 2005 to 2023(P<0.05). Local spatial autocorrelation analysis detected a total of 43“high-high”clustering areas, mainly concentrated in Baoji City. Conclusions The overall incidence of typhus in Shaanxi Province showed a dynamic fluctuation trend, with notable seasonal and regional aggregation. The incidence of typhus was higher in middle-aged and elderly people in rural areas. Surveillance should be strengthened in typhus endemic areas in summer and autumn, and health education should be conducted for key population to form good health habits and reduce the incidence of typhus.

ObjectiveCell adhesion is a critical process that regulates cellular physiological functions. Quantitative characterization of adhesion dynamics is essential for elucidating the intrinsic mechanical mechanisms underlying cellular activities. Although atomic force microscopy-based single-cell force spectroscopy is widely used for single-cell adhesion measurements, it requires complex chemical modifications for preparation of live-cell probes, leading to limitations such as cumbersome operation, low throughput, and potential impacts on cell viability. Fluidic force microscopy, which combines atomic force microscopy with microfluidic probes, is a technique allowing the operation of force-controlled nanopipettes in aqueous environments. By applying negative or positive pressure via a pressure controller, a single living cell can be captured onto or released from the cantilever under physiological conditions. This procedure offers a simple workflow and high assay throughput for single-cell adhesion measurements without the need for chemical functionalization. In this study, fluidic force microscopy-based single-cell force spectroscopy was adopted to achieve long-term quantitative characterization of single-cell adhesion dynamics in a simpler and more efficient manner, comparing the dynamic differences in adhesion establishment between two cell lines with different differentiation levels. MethodsHEK 293T and hTERT RPE-1 cells were non-invasively captured on the cantilever of a fluidic force microscope via its integrated microfluidic system during 40 h of adhesion culture. Cell-substrate detachment assays were performed, and force-distance curves were recorded to extract key mechanical adhesion parameters, including adhesion force, adhesion energy, and maximum detachment distance. These measurements were combined with real-time monitoring of cell spreading area to systematically characterize the dynamic evolution of single-cell adhesion. ResultshTERT RPE-1 cells rapidly entered a stable adhesion phase within 1 h after seeding, with both area-normalized adhesion force and area-normalized adhesion energy reaching peak values. In contrast, HEK 293T cells required 4 h to achieve stable adhesion. Subsequently, the adhesion force, adhesion energy and maximum detachment distance of hTERT RPE-1 and HEK 293T cells stabilized at approximately 240 nN vs. 30 nN, 2.2 pJ vs. 0.12 pJ and 6 μm vs. 4 μm, respectively. hTERT RPE-1 cells reached the peak of area-normalized adhesion parameters earlier than HEK 293T cells, with their peak area-normalized adhesion force and area-normalized adhesion energy being substantially elevated relative to HEK 293T cells. HEK 293T cells presented stronger linear correlations among adhesion energy, maximum detachment distance and adhesion force compared with hTERT RPE-1 cells. For both cell lines, cell spreading area exhibited a weak correlation with adhesion force. Whereas the area-normalized adhesion parameters of HEK 293T cells remained relatively constant throughout the adhesion process, hTERT RPE-1 cells exhibited elevated values in the early phase, followed by a gradual decline. These results indicated distinct dynamic adhesion patterns between the two cell types, with hTERT RPE-1 cells exhibiting stronger adhesion strength and higher adhesion efficiency. ConclusionIn this study, fluidic force microscopy-based single-cell force spectroscopy was successfully applied to perform long-term in situ quantitative measurement of the adhesion dynamics in single adherent cells. The approach revealed divergent adhesion patterns between HEK 293T and hTERT RPE-1 cells, suggesting a close association between cell differentiation and adhesion behaviors. These findings provide quantitative mechanical evidence for further understanding the underlying mechanisms of cell adhesion.

Objective Patients with lung cancer often experience interrelated symptoms such as fatigue, pain, and sleep disturbances during chemotherapy, forming a core symptom cluster that significantly impacts daily functioning, treatment experience, and quality of life. Currently, evidence on non-pharmacological management of this core symptom cluster is scattered, and there is a lack of standardized, patient- and caregiver-friendly guidance tools that are easy to understand and implement. This patient guideline aims to provide decision support for self-management of the core symptom cluster in patients undergoing chemotherapy for lung cancer. Methods Guided by evidence-based methodology, qualitative interviews and on-site questionnaire surveys were conducted to identify the health-related needs of stakeholders. Domestic and international guideline websites, relevant professional association websites, and comprehensive databases were systematically searched according to the inclusion and exclusion criteria. The included literature was evaluated for quality, and recommendations were extracted, integrated, and graded to form a summary of the best evidence. Based on the identified health issues and evidence summary, preliminary recommendations for the patient guideline were developed. The recommendations were then revised through two rounds of Delphi expert consultation, and consensus was reached on the strength of recommendations, forming the final version of the patient guideline. Results The patient guideline covered four major sections: screening and assessment of core symptom clusters, daily management, intervention measures, and timing of referral. The core content included nine aspects: screening of core symptom clusters, assessment, lifestyle habits, dietary interventions, sleep environment, exercise interventions, psychological interventions, Traditional Chinese Medicine interventions, and referral indications. In total, the guidelines addressed 16 health issues and provided 25 recommendations. Conclusion The development process of this patient guideline is rigorous and fully considered the needs of patients. Expert review concludes that the recommendations are highly feasible and appropriate.

ObjectiveTo observe the inhibitory effect of the Weiliuan mixture （WLAHJ） on the subcutaneous xenograft tumor of MKN-74 gastric cancer cells， and explore the potential anti-gastric cancer mechanism of WLAHJ by using transcriptomic sequencing technology to reveal related genes and pathways. Methods30 Balb/c nude mice were randomly divided into model， low-， medium-， and high-dose（15，30，45 g·kg^-1） WLAHJ and 5-FU （0.025 g·kg^-1） groups to build a subcutaneous xenograft tumor model with MKN-74 human gastric cancer cells. After modeling，each group was continuously treated with the corresponding drugs for 28 days. During the treatment period， the body weight and tumor size of the mice were observed and recorded every 2 days. At the end of the treatment， the mice were sacrificed， and required samples were collected to calculate the tumor inhibition rate of WLAHJ on the subcutaneous xenograft tumor. High-throughput transcriptomic sequencing （RNA-seq） technology was used to analyze the differentially expressed genes in the subcutaneous tumor tissues of the model group and the medium-dose WLAHJ group， thus exploring the potential mechanism of WLAHJ in gastric cancer intervention. Immunofluorescence experiments were conducted to detect the protein expression levels of glutathione peroxidase 4 （GPX4）， solute carrier family 7 member 11 （SLC7A11）， transferrin receptor protein-1 （TFR-1）， and acyl-CoA synthetase long-chain family member 4 （ACSL4） in subcutaneous xenograft tumors of each group. Cell counting kit-8（CCK-8） and colony formation assays were used to detect the viability and anti-proliferative ability of human gastric cancer AGS and MKN-74 cells at different concentrations of WLAHJ. Kits were used to detect the levels of Fe²⁺， reactive oxygen species （ROS）， malondialdehyde （MDA）， and superoxide dismutase （SOD） activity in cells. Western blot was used to detect the expression levels of GPX4， SLC7A11， TRF-1， ACSL4， spermidine/spermine N1-acetyltransferase 1 （SAT1）， arachidonic acid 15-lipoxygenase （ALOX15）， and key proteins in the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway. ResultsThe mechanism of WLAHJ in gastric cancer intervention may be related to ferroptosis and the PI3K/Akt /mTOR signaling pathway. The growth of subcutaneous xenograft tumors in nude mice of the WLAHJ and 5-FU groups（P<0.05，P<0.01）， GPX4， and SLC7A11 dropped significantly（P<0.01）， while TFR-1， ACSL4， SAT1， and ALOX15（P<0.05，P<0.01）increased significantly compared with those in the model group. The levels of ROS， Fe²⁺， and MDA increased in the WLAHJ and 5-FU groups and the proliferation of gastric cancer cells， SOD activity， the ratios of phosphorybation （p）-mTOR/mTOR， p-PI3K/PI3K， and p-Akt/Akt protein expressions（P<0.05，P<0.01）decreased compared with those in the blank group. ConclusionThe mechanism of WLAHJ in treating gastric cancer may be related to the regulation of the PI3K/ Akt /mTOR signaling pathway to intervene in ferroptosis.

In recent years, there has been a growing interest in the research on NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome inhibitors in the treatment of inflammatory diseases. The NLRP3 inflammasome is integral to the innate immune response, and its abnormal activation can lead to the release of pro-inflammatory cytokine, consequently facilitating the progression of various pathological conditions. Therefore, investigating the pharmacological inhibition pathway of the NLRP3 inflammasome represents a promising strategy for the treatment of inflammation-related diseases. Currently, the Food and Drug Administration(FDA) has not approved drugs targeting the NLRP3 inflammasome for clinical use due to concerns regarding liver toxicity and gastrointestinal side effects associated with chemical small molecule inhibitors in clinical trials. Natural small molecule compounds such as polyphenols, flavonoids, and alkaloids are ubiquitously found in animals, plants, and other natural substances exhibiting pharmacological activities. Their abundant sources, intricate and diverse structures, high biocompatibility, minimal adverse reactions, and superior biochemical potency in comparison to synthetic compounds have attracted the attention of extensive scholars. Currently, certain natural small molecule compounds have been demonstrated to impede the activation of the NLRP3 inflammasome via various action mechanisms, so they are viewed as the innovative, feasible, and minimally toxic therapeutic agents for inhibiting NLRP3 inflammasome activation in the treatment of both acute and chronic inflammatory diseases. Hence, this study systematically examined the effects and potential mechanisms of natural small molecule compounds derived from traditional Chinese medicine on the activation of NLRP3 inflammasomes at their initiation, assembly, and activation stages. The objection is to furnish theoretical support and practical guidance for the effective clinical application of these natural small molecule inhibitors.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Inflammasomes/metabolism* ; Inflammation/drug therapy* ; Anti-Inflammatory Agents/therapeutic use* ; Humans ; Animals ; Disease Models, Animal ; Biological Products/therapeutic use* ; Drug Discovery ; Medicine, Chinese Traditional/methods*

This study employed the "disease-medicine-dose" pattern to mine the medication rules of traditional Chinese medicine(TCM) prescriptions containing Astragali Radix in ancient Chinese medical books, aiming to provide a scientific basis for the clinical application of Astragali Radix and the development of new medicines. The TCM prescriptions containing Astragali Radix were retrieved from databases such as Chinese Medical Dictionary and imported into Excel 2020 to construct the prescription library. Statical analysis were performed for the prescriptions regarding the indications, syndromes, medicine use frequency, herb effects, nature and taste, meridian tropism, dosage forms, and dose. SPSS statistics 26.0 and IBM SPSS Modeler 18.0 were used for association rules analysis and cluster analysis. A total of 2 297 prescriptions containing Astragali Radix were collected, involving 233 indications, among which sore and ulcer, consumptive disease, sweating disorder, and apoplexy had high frequency(>25), and their syndromes were mainly Qi and blood deficiency, Qi and blood deficiency, Yin and Yang deficiency, and Qi deficiency and collateral obstruction, respectively. In the prescriptions, 98 medicines were used with the frequency >25 and they mainly included Qi-tonifying medicines and blood-tonifying medicines. Glycyrrhizae Radix et Rhizoma, Angelicae Sinensis Radix, Ginseng Radix et Rhizoma, Atractylodis Macrocephalae Rhizoma, and Citri Reticulatae Pericarpium were frequently used. The medicines with high frequency mainly have warm or cold nature, and sweet, pungent, or bitter taste, with tropism to spleen, lung, heart, liver, and kidney meridians. In the treatment of sore and ulcer, Astragali Radix was mainly used with the dose of 3.73 g and combined with Glycyrrhizae Radix et Rhizoma to promote granulation and heal up sores. In the treatment of consumptive disease, Astragali Radix was mainly used with the dose of 37.30 g and combined with Ginseng Radix et Rhizoma to tonify deficiency and replenish Qi. In the treatment of sweating disorder, Astragali Radix was mainly used with the dose of 3.73 g and combined with Glycyrrhizae Radix et Rhizoma to consolidate exterior and stop sweating. In the treatment of apoplexy, Astragali Radix was mainly used with the dose of 7.46 g and combined with Glycyrrhizae Radix et Rhizoma to dispell wind and stop convulsions. Astragali Radix can be used in the treatment of multiple system diseases, with the effects of tonifying Qi and ascending Yang, consolidating exterior and stopping sweating, and expressing toxin and promoting granulation. According to the manifestations of different diseases, when combined with other medicines, Astragali Radix was endowed with the effects of promoting granulation and healing up sores, tonifying deficiency and Qi, consolidating exterior and stopping sweating, and dispelling wind and replenishing Qi. The findings provide a theoretical reference and a scientific basis for the clinical application of Astragali Radix and the development of new medicines.
Drugs, Chinese Herbal/history* ; Humans ; Medicine, Chinese Traditional/history* ; History, Ancient ; Astragalus Plant/chemistry* ; China ; Astragalus propinquus

Objective To report the genetic analysis of a family with a fetus suspected of Ellis-van Creveld(EVC)syndrome based on ultrasound findings such as ventricular septal defect(VSD),short long bones in the limbs and polydactyly,and to conduct a literature review to clarify the pathogenic cause.Methods A 27-year-old pregnant woman,who was pregnant for the first time and had no prior deliveries,was admitted to the prenatal diagnosis center of Shijiazhuang Obstetrics and Gynecology Hospital in October 2021.At 17 weeks of gestation,ultrasound detected multiple fetal malformations.The genomic DNA of the fetal proband's amniotic fluid cells and the parents'peripheral blood samples were sequentially subjected to chromosomal karyotype analysis,chromosomal microarray analysis(CMA),and whole exome sequencing(WES).Suspected pathogenic mutations were verified by Sanger sequencing in the proband and its parents.Subsequently,a Minigene in vitro experiment was used to analyze one splicing mutation.Meanwhile,databases such as PubMed were searched,and literature reports were combined for genetic analysis.Results Chromosomal karyotype analysis of the fetus showed no abnormalities,and CMA did not detect any copy number variation(CNV)with clinical significance.WES results revealed two mutations in the EVC gene(NM_153717.2)of the fetus:a nonsense mutation c.1405G>T(p.E469X)in exon 10 and a splicing mutation c.1886+5G>A in intron 13.Family verification using Sanger sequencing showed that the father was a carrier of the c.1405G>T(p.E469X)mutation in exon 10,and the mother was a carrier of the c.1886+5G>A mutation in intron 13.The compound heterozygous mutation of the fetus was inherited from the parents.According to the guidelines of the American College of Medical Genetics and Genomics(ACMG)for classifying genetic variations,c.1405G>T(p.E469X)was classified as likely pathogenic mutation(PVS1+PM2),and c.1886+5G>A was classified as likely pathogenic mutation(PM2+PM3_Strong).The Minigene experiment results showed that the c.1886+5G>A mutation caused a 115-bp segment retention in intron 13,further supporting its pathogenicity.Review of the literature showed that the typical clinical manifestations of EVC syndrome include short limbs,short ribs,postaxial polydactyly,nail and tooth dysplasia,and congenital heart defects.Gene mutations in EVC/EVC2 were found to be the main pathogenic cause through whole exome sequencing,with mutation types including missense mutations,large-scale duplications/deletions,in-frame microdeletions,nonsense mutations,frameshift mutations,and splicing mutations.Conclusions The compound heterozygous mutations in the EVC gene are the pathogenic cause of the fetus.The detection of these mutations expands the genetic variation spectrum of Ellis-van Creveld syndrome.

Under the trend of increasing aging， integrated elderly care and medical services is an important measure to optimize the supply of elderly care services and promote the good death of the elderly. Using the cooperative production theory and the classical grounded theory， a qualitative analysis was conducted on 38 cases of elderly palliative care and 25 cases of hospital-based palliative care under the integrated elderly care and medical services model from a hospital in Nanning City using Nvivo 20.0 software. This paper found that the integrated elderly care and medical services mode emphasized the deep integration of medical and elderly care services by integrating resources and improving service efficiency， to achieve the basic experience of comprehensive health care for the elderly. The promotion of these experiences has a positive significance for building a multi-agent cooperative production system， strengthening personnel training， perfecting the performance distribution mechanism， and further promoting the development of the national palliative care pilot.