ObjectiveTo investigate the neuroprotective effect of glycosides of cistanches （GCs） in 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine （MPTP）-induced Parkinson’s disease （PD） model mice and its potential mechanism. MethodsForty mice were randomly divided into control group， PD group， GCs group and levodopa （L-DOPA） group， with 10 mice in each group. The control group received intraperitoneal injection of normal saline， while the other groups were intraperitoneally injected with MPTP （30 mg/kg） once daily for 5 consecutive days. After model establishment， the control group and PD group were intragastrically administered normal saline， and the GCs group and L-DOPA group received intragastric administration once daily for 28 consecutive days， at doses of 100 mg/kg and 50 mg/kg， respectively. The open field test and rotarod test were used to evaluate motor function. Immunohistochemistry was performed to detect the number of tyrosine hydroxylase （TH）-positive neurons in the substantia nigra of the midbrain. Transmission electron microscopy was adopted to observe the ultrastructure of mitochondria in the substantia nigra. Biochemical assays were used to determine the levels of glutathione （GSH）， malondialdehyde （MDA）， total superoxide dismutase （T-SOD） and reactive oxygen species （ROS） in substantia nigra tissues. Western blot was applied to detect the protein expression of TH， nuclear factor erythroid 2-related factor 2 （Nrf2）， Kelch-like ECH-associated protein 1 （Keap-1） and heme oxygenase-1 （HO-1） in substantia nigra tissues. ResultsCompared with the control group， mice in the PD group exhibited markedly impaired motor function， significantly decreased T-SOD activity， obvious reductions in the number of TH-positive neurons and GSH content， as well as elevated MDA and ROS levels in the substantia nigra （P<0.01）. Compared with the PD group， mice in the GCs group showed improved motor function， increased T-SOD activity， higher number of TH-positive neurons and elevated GSH content， accompanied by decreased MDA and ROS levels （P<0.05）. In the control group， mitochondria in the substantia nigra displayed normal morphology without obvious blurred membrane structures or vacuolar degeneration. The PD group presented mitochondrial swelling， disordered cristae and vacuolar changes， whereas these mitochondrial pathological alterations were alleviated in the GCs group. Compared with the control group， the protein levels of TH， Nrf2 and HO-1 were significantly downregulated， while Keap-1 protein expression was markedly upregulated in the PD group （P<0.01）. Compared with the PD group， the GCs group showed significant upregulation of TH， Nrf2 and HO-1 protein levels and a notable reduction in Keap-1 protein level （P<0.05）. ConclusionGCs ameliorate motor dysfunction and attenuate dopaminergic neuronal and mitochondrial damage in MPTP-induced PD model mice. These effects may be associated with modulation of Nrf2/HO-1 pathway-related protein expression， enhancement of antioxidant capacity， and alleviation of oxidative stress.

ObjectiveTo evaluate the clinical efficacy of modified Zhishi Daozhi decoction in treating patients with metabolic associated fatty liver disease （MAFLD） due to dampness-heat and stasis obstruction. MethodsA randomized controlled trial design was adopted， with patients diagnosed with MAFLD due to dampness-heat and stasis obstruction treated in the Department of Endocrinology， Metabolism， and Gastroenterology at the Third Affiliated Hospital of Changchun University of Chinese Medicine between November 2023 and November 2024 as the study subjects. A total of 126 patients who met the inclusion criteria were randomized into an observation group and a control group， with 63 patients in each group. The observation group was administered the granule preparation of modified Zhishi Daozhi decoction， while the control group received Xuezhikang capsules orally. Both groups underwent a 12-week treatment course. The two groups before and after treatment were compared in terms of obesity indicators ［body weight， body mass index （BMI）， waist circumference （WC）， weight-adjusted waist circumference index （WWI）， and waist-to-hip ratio （WHR）］， lipid indicators ［total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C）］， liver function indicators ［alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and gamma-glutamyl transpeptidase （GGT）］， liver ultrasound imaging， traditional Chinese medicine （TCM） symptom scores， and Patient-Reported Outcome （PRO） scale scores at follow-up. Results① After treatment， the body weight， BMI， and levels of TC， TG， and LDL-C declined in both groups （P<0.05， P<0.01）， and the observation group demonstrated larger reductions in BMI， WC， LDL-C （P<0.05）， and WHR （P<0.01）. The levels of ALT， AST， and GGT declined in the observation group after treatment （P<0.05）， whereas no statistically significant differences in the three indicators were observed in the control group before and after treatment. Subgroup analysis based on normal vs. abnormal liver function revealed intergroup differences only in the abnormal liver function cohort. After treatment， the observation group demonstrated greater reductions in ALT （P<0.01） and AST （P<0.05） than the control group. ② The total response rate of liver ultrasound imaging was 79.24% （42/53） in the observation group and 62% （31/50） in the control group. Post-treatment comparison showed that the observation group （χ²=21.311， P<0.01） achieved greater alleviation of fatty liver disease severity. ③ The total response rate of TCM syndrome was 94.34% （50/53） in the observation group and 66% （33/50） in the control group， with the observation group demonstrating superior efficacy （χ²=26.78， P<0.01）. Compared with the control group post-treatment， the observation group showed enhanced reductions in the total TCM symptom score （P<0.01） and individual symptom scores of rib distension and pain， sticky and unsmooth stools， obesity with abdominal distension， sticky sensation in the mouth， and yellowish-red urine （P<0.01）. ④ After treatment， the PRO score improved in both groups （P<0.01）， and the increase was larger in the observation group （P<0.01）， primarily reflected in the physiological dimension （P<0.01）. ConclusionModified Zhishi Daozhi decoction shows definite efficacy in treating MAFLD patients with the syndrome of dampness-heat and stasis obstruction， with effects of alleviating abdominal obesity and regulating blood lipids. Additionally， it positively impacts patients quality of life， as evidenced by the changes in TCM symptom and PRO scores.

The epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutation is a rare subtype of mutations in non-small cell lung cancer (NSCLC). Patients with advanced NSCLC carrying the EGFR ex20ins mutation tend to have poor responses to traditional EGFR tyrosine kinase inhibitors (TKIs), chemotherapy, and immunotherapy, leading to a poor clinical prognosis. Significant progress has been made in the development of new drugs targeting the EGFR ex20ins mutation. The research on new drugs targeting EGFR ex20ins mutations has made significant progress. The main ones include new EGFR-TKIs (such as sunvozertinib, mobocertinib, and furmetinib, etc.), bispecific antibodies (such as amivantamab, JMT101, and GB263T, etc.), and emerging drugs such as AUY922. These agents have demonstrated promising efficacy in clinical trials, improving the objective response rate and progression-free survival of patients, and are expected to improve overall survival. An in-depth analysis of the mechanism of action and clinical trial progress of these novel targeted drugs for EGFR ex20ins-mutated NSCLC can offer new therapeutic strategies for patients with EGFR ex20ins-mutated NSCLC.

In recent years,a growing body of research has demonstrated that acupuncture can be used to effectively treat a diverse range of diseases,including functional gastrointestinal disorders,cardiovascular diseases,as well as anxiety and depression,through the modulation of the paraventricular hypothalamic nucleus(PVN).Acupuncture may exert its therapeutic effect either by modulating specific neurons within the PVN,such as corticotropin releasing hormone(CRH)neurons,or by regulating the release of hormones,such as oxytocin(OXT)and vasopressin(VP),and the activity of neural circuits associated with the PVN.This review summarizes the mechanisms by which PVN is involved in acupuncture treatment,including its regulatory mechanisms in gastrointestinal diseases,cardiovascular diseases,and negative emotions and pain.Future research should be conducted to further explore the precise mechanisms by which acupuncture regulates PVN to treat diseases,focusing on clarifying the specific processes of signaling pathway transduction,and exploring the specific effects of acupunture of different acupoint combinations and stimulation frequencies and intensity on PVN.

Forensic microbiology,a pivotal discipline within forensic science,focuses on microorganisms as the primary subject of study and applies life science technologies to analyze microbial evidence in criminal and civil investigations.Tissue source inference plays a crucial role in forensic investigations,facilitating case assessment and crime scene reconstruction.The application of microbiome analysis in tissue source inference benefits from the tissue specificity and spatiotemporal stability of human microbial communities.This article provides a systematic review of recent advances in tissue source inference based on microbiome analysis,covering technological development,research trends,and practical applications.Finally,the challenges confronted in practice in forensic microbiology and the future prospects for its development are summarized.

BACKGROUND:Previous studies have mostly performed biomechanical analysis of early fracture healing by ignoring muscle loading and using simplified femoral loading. Nevertheless,the biomechanical effects of muscle loading on early fracture healing are still uncertain.OBJECTIVE:To construct various femoral loading models allows for the study of the biomechanical effects of muscle loading on fracture healing,enabling clinicians to gain a deeper understanding of the biomechanical process of fracture healing and to optimize treatment protocols.METHODS:The AnyBody Modeling System software was employed to construct a personalized human musculoskeletal system,which was then analyzed by simulation in order to obtain the musculoskeletal loading model in vivo. This model,along with the femur loading model constructed using the improved simplified loading method and the simplified loading method,was utilized as boundary conditions for the finite element inputs,which were used to analyze the locking compression plate stress-strain and interfragmentary strain in the standing condition,respectively.RESULTS AND CONCLUSION:(1) The locking compression plate stresses and strains and interfragmentary strains obtained from the musculoskeletal method were,respectively,31.9％,38.9％,and 19.5％ smaller than those obtained from the simplified loading method. (2) A comparison of the musculoskeletal method with the modified simplified loading method revealed that the neglect of muscle loading resulted in an overestimation of locking compression plate stress and strain,as well as interfragmentary strain,by 16.8％,14.3％,and 19.5％,respectively. Muscle loading did not have a significant effect on the magnitude of the shear motion of the fracture block,whereas it did have a significant effect on the direction of motion. (3) The results indicated that the simplified femoral loading and the method of ignoring muscle loading exhibited some deviation from the musculoskeletal loading situation. Consequently,it is necessary to consider the biomechanical effects of muscle loading in the study of fracture healing.

OBJECTIVE To explore the therapeutic effect of human umbilical cord-derived mesenchymal stem cells(hUC-MSCs)in mouse model of allergic lung inflammation.METHODS hUC-MSCs were isolated and cultured from umbilical cord of healthy neonates.The expression of MSC cell surface markers were assessed by flow cytometry in the fifth generation of hUC-MSCs.Mice were sensitized by intraperitoneal injection of ovalbumin and challenged via inhalation of aerosolized ovalbumin to establish an allergic airway inflammation model.The same dose of normal saline was used in the control group.After 14 days of nebulization,lung tissues and bronchoalveolar lavage fluid(BALF)were collected from the mice.Hematoxylin and eosin staining and Luminex multiplex assay were performed to assess the levels of allergic inflammation.Lung tissues were minced,homogenized,and digested into single-cell suspensions for cell culture.hUC-MSCs or human nasal epithelial cells were co-cultured with mouse lung cells at a ratio of 1:5 or 1:10(cell number ratio).After 18 hours,the supernatants were collected,and Luminex multiplex assay was performed to assess the expression of inflammatory cytokines interleukin-5(IL-5)and IL-6.RESULTS Cultured hUC-MSCs showed an elongated spindle-shaped morphology.The positive markers CD105,CD73,and CD90 showed positive rates of>95%respectively,while the negative markers CD45,CD34,and CD11b exhibited positive rates of<2%respectively.Compared with the controls,the allergic mice showed significant infiltration of eosinophils in the peribronchial regions of lung tissues,and increased expression levels of IL-5(P<0.01)and IL-6(P<0.05)in BALF.Compared with the control group,mouse lung cells co-cultured with hUC-MSCs significantly decreased the levels of IL-5 and IL-6 in the supernatant(both P<0.05 in 1∶5 group and 1∶10 group).CONCLUSION Co-culture with hUC-MSCs can significantly ameliorate allergic inflammation in lung tissue of mouse model,indicating the therapeutic potential of hUC-MSCs in airway allergic inflammation.

As the field of oral pathology has evolved, the nomenclature and classification of oral mucosal diseases with a remarkable risk of malignant transformation have undergone several modifications. In 2005, the World Health Organization (WHO) introduced the concept of oral potentially malignant disorders (OPMDs) as an alternative to the terms for oral precancerous lesions and precancerous conditions. In the consensus report by the WHO Collaborating Center for Oral Cancer of 2021, OPMD is defined as "any oral mucosal abnormality that is associated with a statistically increased risk of developing oral cancer."This definition encompasses a range of conditions, in-cluding oral leukoplakia, oral submucous fibrosis, proliferative verrucous leukoplakia, oral lichen planus, and other lesions. In light of the complex etiology, unclear pathogenesis, and carcinogenesis of OPMDs, early and precise diagnosis and treatment can contribute to the secondary prevention of oral cancer. For this reason, this review, which aims to provide a basis for the precise clinical diagnosis of OPMDs, was performed. Its aim was achieved by reviewing the historical evolution and research progress of the nomenclature, classification, and histopathological diagnostic criteria of OPMDs.
Humans ; Mouth Neoplasms/diagnosis* ; Precancerous Conditions/diagnosis* ; Leukoplakia, Oral/diagnosis* ; Lichen Planus, Oral/pathology* ; Oral Submucous Fibrosis/pathology* ; Mouth Mucosa/pathology* ; World Health Organization

BACKGROUND:Previous studies have mostly performed biomechanical analysis of early fracture healing by ignoring muscle loading and using simplified femoral loading. Nevertheless,the biomechanical effects of muscle loading on early fracture healing are still uncertain.OBJECTIVE:To construct various femoral loading models allows for the study of the biomechanical effects of muscle loading on fracture healing,enabling clinicians to gain a deeper understanding of the biomechanical process of fracture healing and to optimize treatment protocols.METHODS:The AnyBody Modeling System software was employed to construct a personalized human musculoskeletal system,which was then analyzed by simulation in order to obtain the musculoskeletal loading model in vivo. This model,along with the femur loading model constructed using the improved simplified loading method and the simplified loading method,was utilized as boundary conditions for the finite element inputs,which were used to analyze the locking compression plate stress-strain and interfragmentary strain in the standing condition,respectively.RESULTS AND CONCLUSION:(1) The locking compression plate stresses and strains and interfragmentary strains obtained from the musculoskeletal method were,respectively,31.9％,38.9％,and 19.5％ smaller than those obtained from the simplified loading method. (2) A comparison of the musculoskeletal method with the modified simplified loading method revealed that the neglect of muscle loading resulted in an overestimation of locking compression plate stress and strain,as well as interfragmentary strain,by 16.8％,14.3％,and 19.5％,respectively. Muscle loading did not have a significant effect on the magnitude of the shear motion of the fracture block,whereas it did have a significant effect on the direction of motion. (3) The results indicated that the simplified femoral loading and the method of ignoring muscle loading exhibited some deviation from the musculoskeletal loading situation. Consequently,it is necessary to consider the biomechanical effects of muscle loading in the study of fracture healing.

Vernal keratoconjunctivitis is an allergic ocular surface disease mostly present with recurrent chronic inflammation, which usually affects children and adolescents and possibly results in corneal complications such as keratoconus. Keratoconus is a corneal disease characterized by a local cone-like corneal deformation. Previous studies have respectively put forward pathological mechanisms of vernal keratoconjunctivitis and keratoconus and the progressive risk factors, among which we find there's mutual mechanisms as well as cytokines' expression, including type I and IV hypersensitivity, inflammatory reaction, enzymatic changes, oxidative stress and mechanical injury. This review aims at summarizing the possible intrinsic mechanisms and cytokines exacerbating vernal keratoconjunctivitis patients corneas to keratoconus, so as to provide reference for the prevention and management in keratoconus caused by vernal keratoconjunctivitis.