OBJECTIVE To investigate the neuroprotective effect and mechanism of eleutheroside B （ELB） on Parkinson’s disease （PD） model mice by regulating the IκB kinase β （IKKβ）/nuclear factor-κB （NF-κB） signaling pathway. METHODS Fifty mice were randomly divided into normal control group， model group， positive control group （selegiline hydrochloride， 10 mg/kg）， and ELB low-dose and high-dose groups （80， 160 mg/kg）， with 10 mice in each group. Each group was given relevant medicine or normal saline intragastrically for 14 consecutive days. Starting from the 10th day of administration， the model group and all administration groups were intraperitoneally injected with 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine （MPTP） 30 mg/kg， for five consecutive days to establish the chronic PD model. After the last administration for 24 h， six mice were randomly selected from each group to test their behavioral abilities； detect the levels of interleukin-1β （IL-1β）， IL-10， tumor necrosis factor-α （TNF-α） in brain tissue and their mRNA expressions were measured， and positive expression of tyrosine hydroxylase （TH）， protein expressions of TH， α -synuclein （ α -syn）， ionized calcium-binding adaptor molecule 1 （Iba-1）， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in the brain tissue were detected. The ultrastructure of neurons in substantia nigra was observed. RESULTS Compared with the model group， rotarod endurance time and climbing score of each administration group （except for the ELB low-dose group） were increased significantly （ P ＜0.05）， while the levels and mRNA expressions of IL-1β， TNF-α， α -syn， and Iba-1， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in brain tissue were decreased significantly （except for TNF-α in the ELB low-dose group）. Conversely， the level and mRNA expression of IL-10 （except for the ELB low-dose group）， TH positive expression and protein expressions were significantly increased （ P ＜0.05）. Typical neurodegenerative pathological changes， such as neuronal karyopyknosis， mitochondrial swelling and vacuolization， and endoplasmic reticulum dilation， all showed varying degrees of improvement. CONCLUSIONS ELB may exert neuroprotective effects by inhibiting the activation of the IKKβ/NF-κB signaling pathway， alleviating inflammatory responses， reducing abnormal α -syn aggregation and neuronal loss， and further improving motor dysfunction in PD mice.

Spermatogenesis, the basis of male reproduction, is susceptible to internal and external environmental interferences that impair fertility. Heat-induced reproductive damage is one of the most important factors contributing to male infertility. The testes are located within the scrotum and need to be maintained 2-4 ℃ below the core body temperature, which is essential for normal spermatogenesis and sperm maturation. In the past 40 years, the global male sperm concentrations have consistently declined at an average annual rate of 1%-2%, accompanied by a sharp increase in the prevalence of sperm quality abnormalities such as oligozoospermia and azoospermia. In daily life, a variety of factors can elevate scrotal temperature, such as occupational exposure, lifestyle habits, and pathological conditions, resulting in varying degrees of reproductive injury. In this article, the effects of heat stress on male reproductive injury, the injury patterns associated with different hyperthermic modalities, as well as preventive and therapeutic treatments were described, aiming at a comprehensive and in-depth understanding of the mechanism underlying heat-induced reproductive injury, as well as providing theoretical guidance for the clinic prevention and therapy of male infertility.

Objective: To estimate the incidence and mortality of lung cancer in 2021 and their trends from 2014 to 2021 within cancer registration areas of Inner Mongolia Autonomous Region, so as to provide the basis for formulating localized strategies for lung cancer prevention and control. Methods: The data on lung cancer cases in cancer registration areas of Inner Mongolia Autonomous Region in 2021 were collected from the China Cancer Registration, encompassing data from 55 registries within the region. Crude incidence and crude mortality were calculated by genders, urban/rural rareas, and ages. The Chinese population-standardized rate was calculated using the age structure of the standard population from the Fifth National Population Census in 2000, while the world population-standardized rate was calculated using Segi's world standard population. To assess the trends in Chinese population-standardized incidence and mortality of lung cancer from 2014 to 2021, data from nine qualifying cancer registries were analyzed using the average annual percent change (AAPC). Results: In 2021, within Inner Mongolia Autonomous Region, the crude, Chinese population-standardized, and world population-standardized incidences of lung cancer were 58.96/100 000, 31.58/100 000, and 31.50/100 000, respectively. The crude, Chinese population-standardized, and world population-standardized mortalities were 46.48/100 000, 24.65/100 000, and 24.36/100 000 , respectively. The Chinese population-standardized incidence and mortality of lung cancer were 1.59-fold and 1.88-fold higher in males compared to females, and 1.08-fold and 1.10-fold higher in urban areas relative to rural areas. The crude incidence and mortality of lung cancer reached their peaks at age of 80-<85 years (379.91/100 000 and 474.31/100 000, respectively). From 2014 to 2021, the Chinese population-standardized incidence of lung cancer in Inner Mongolia Autonomous Region decreased from 43.28/100 000 to 31.41/100 000, showed a downward trend (AAPC=-3.312%, P<0.05), while the Chinese population-standardized mortality decreased from 31.55/100 000 to 24.11/100 000, showed no statistical significance (P>0.05). The Chinese population-standardized incidence of lung cancer in the group aged ≥75 years and the Chinese age-standardized mortality of lung cancer in the group aged 0-<45 years showed declining trends (AAPC=-4.307%, -7.355%, both P<0.05). Conclusions The disease burden of lung cancer in cancer registration areas of Inner Mongolia Autonomous Region has decreased, showing characteristics where the burden is higher in males than in females and slightly higher in urban areas than in rural areas. The elderly population represents a key group for lung cancer prevention and control.

Microwave thermochemotherapy (MTC) has been applied to treat lip squamous cell carcinoma (LSCC), but a deeper understanding of its therapeutic mechanisms and molecular biology is needed. To address this, we used single-cell transcriptomics (scRNA-seq) and spatial transcriptomics (ST) to highlight the pivotal role of tumor-associated neutrophils (TANs) among tumor-infiltrating immune cells and their therapeutic response to MTC. MNDA⁺ TANs with anti-tumor activity (N1-phenotype) are found to be abundantly infiltrated by MTC with benefit of increased blood perfusion, and these TANs are characterized by enhanced cytotoxicity, ameliorated hypoxia, and upregulated IL1B, activating T&NK cells and fibroblasts via IL1B-IL1R. In this highly anti-tumor immunogenic and hypoxia-reversed microenvironment under MTC, fibroblasts accumulated in the tumor front (TF) can recruit N1-TANs via CXCL2-CXCR2 and clear N2-TANs (pro-tumor phenotype) via CXCL12-CXCR4, which results in the aggregation of N1-TANs and extracellular matrix (ECM) deposition. In addition, we construct an N1-TANs marker, MX2, which positively correlates with better prognosis in LSCC patients, and employ deep learning techniques to predict expression of MX2 from hematoxylin-eosin (H&E)-stained images so as to conveniently guide decision making in clinical practice. Collectively, our findings demonstrate that the N1-TANs/fibroblasts defense wall formed in response to MTC effectively combat LSCC.
Humans ; Neutrophils/metabolism* ; Single-Cell Analysis ; Lip Neoplasms/genetics* ; Hyperthermia, Induced/methods* ; Microwaves/therapeutic use* ; Transcriptome ; Carcinoma, Squamous Cell/immunology* ; Tumor Microenvironment

Objective To observe the ultrasonic manifestations of aggressive angiomyxoma(AAM).Methods Four patients with newly diagnosed AAM and 3 with recurrent AAM confirmed by pathology were retrospectively enrolled,and the ultrasonic manifestations were analyzed.Results Among 7 cases of AAM,the lesions located in subcutaneous regions of perineum in 3 cases,in both perineum and pelvic cavity in 2 cases,in pelvic cavity and in cervix each 1 case,with a median maximum diameter of 7.6 cm.The lesions mainly manifested as heterogeneous hypoechoic,scattered cord-like moderate/moderate-hyperechoic inside,regular or lobulated shape with finger-like protrusions,with clear boundary or unclear boundary with adjacent vagina/rectum.Layered structure could be observed with gray-scale ultrasound and CDFI.Conclusion AAM mainly affected pelvis and perineal region,often manifested as large lesion tended to infiltrate surrounding areas and form finger-like protrusions,most with clear boundaries and interior heterogeneous hypoechoic regions,also the characteristic stratified structures.

Objective Jiedu Tongluo Tiaogan Formula(JTTF)is an effective formula for the clinical treatment of type 2 diabetes mellitus(T2DM).We used integrated pharmacology and in vitro experiments to explore the molecular mechanism of JTTF to improve insulin resistance(IR)in T2DM.Methods The drug targets of JTTF were obtained by identifying the key active ingredients of JTTF through UPLC-Q-TOF-MS.Multiple databases such as GeneCards,OMIM,and DrugBank were used to screen T2DM-IR related targets.Cytoscape software and String 11.0 database were used to construct the PPI network diagram of JTTF for T2DM-IR.GO and KEGG analyses were performed according to the Metascape platform to find the biological pathways related to the target proteins.AutoDock Tools software was used to simulate molecular docking.In vitro experiments were performed using palmitic acid(PA)-induced HepG2-IR cell model to detect the effect of JTTF on HepG2-IR.Results 28 effective active components of JTTF were screened.There were 857 gene targets of T2DM-IR,and 168 targets of drug-disease intersection.387 GO entries and 145 KEGG pathways were enriched.The molecular docking results showed that the main components of JTTF had good binding activities with PI3K and AKT-related proteins.The in vitro results showed that JTTF significantly alleviated PA-induced HepG2 cell injury,increased HepG2 glucose consumption,increased PI3K and AKT mRNA and protein expression,regulated the expression of GLUT2,GLUT4 and GSK3β,and improved cellular IR.Conclusion JTTF increases insulin sensitivity of HepG2-IR cells,promotes glucose uptake and intracellular glucose metabolism process,and its mechanism of action may be related to the up-regulation of PI3K/AKT signalling pathway.

Objective To analyze the molecular epidemiological characteristics of carbapenem-resistant Klebsiella pneumoniae(CRKP)in a hospital in Hainan Province,explore the differences in the distribution of resistance genes and virulence factors between hypervirulent CRKP(hv-CRKP)and non-hv-CRKP,analyze the clinical significance,and provide basis for optimizing treatment and prevention strategies.Methods CRKP strains isolated from a hospi-tal in Hainan Province from July 2023 to June 2024 were collected retrospectively.Their resistance phenotypes were detected by antimicrobial susceptibility testing.Carbapenemase genes(KPC-2,NDM-1,IPM)and virulence factors(rmpA/rmpA2,iucA,iroB,etc.)were detected by polymerase chain reaction(PCR).Department source,speci-men distribution,and resistance-virulence characteristics were analyzed.Results A total of 76 strains of CRKP were isolated,with an overall isolation rate of 7.7％(76/985).The strains were mainly distributed in the intensive care unit(ICU)(28.9％)and neurosurgery ICU(23.6％),with the highest proportion of strains isolated from re-spiratory tract specimens(60.5％).The resistance genes were mainly KPC-2(72.4％)and NDM-1(21.1％),and the virulence factors mrkD(type Ⅲ pili,85.5％)and fim H(type Ⅰ pili,84.2％)were commonly presented.Among 76 strains of CRKP,39 strains(51.3％)met the criteria for hv-CRKP and all carried KPC-2 gene(100％).The detection rates of resistance genes and virulence factors rmpA2(97.4％),iucA(100％),and iroB(89.7％)were all higher than those of non-hv-CRKP strains(KPC-2,43.2％;rmpA2,0;iucA,8.1％;iroB,13.5％).The main characteristics of hv-CRKP was the combination of KPC-2 resistance gene and rmpA2+iucA+iutA+iroB virulence factors(64.1％).Antimicrobial resistance phenotype of hv-CRKP was different from non-hv-CRKP.hv-CRKP presented higher susceptibility rates to aminoglycosides and compound sulfamethoxazole than non-hv-CRKP.Conclusion The proportion of hv-CRKP and non-hv-CRKP strains in this hospital is comparable.hv-CRKP is characterized by carrying the KPC-2 resistance gene in combination with rmpA2+iucA+iutA+iroB virulence factors,and the proportion of strains carrying multiple virulence factors is higher than that of non-hv-CRKP.Both are generally resistant to β-lactams and quinolones.hv-CRKP has lower resistance rates to aminoglycosides and com-pound sulfamethoxazole than non-hv-CRKP.Its advantage of aminoglycoside susceptibility provides a new treatment option.It is recommended to guide differential medication through molecular typing and strengthen infection control measures in ICU to curb the spread of antimicrobial-resistant bacteria.

The purpose of this study was to investigate the effect of medium-chain fatty acids(MC-FAs)caprylic acid(C8∶0)on lipid metabolism of calf hepatocytes.Primary calf hepatocytes were extracted and cultured,and 1.2 mmol/L nonesterified fatty acids(NEFAs)were added to the hep-atocytes to construct a model of hepatic lipid deposition in primary calf hepatocytes,Five process-ing groups have been set up:Control group(Ctrl),NEFA added group(NEFA),C8∶0 1.2 mmol/L treatment group(C8∶0 1.2),NEFA+C8∶0 0.2 mmol/L treatment group(NEFA+C8∶00.2),C8∶0 0.2 mmol/L treatment group(C8∶0 0.2).Stimulate calf liver cells for 12 hours,and the levels of triglyceride(TG),lipid oxidation(MDA),hydrogen peroxide(H2O2)and total SOD activity were detected by biochemical kit,and FAS,a protein related to lipid synthesis,was detec-ted by Western blot.The results showed that compared with the control group,the concentrations of TG,MDA and H2O2 in NEFA group increased significantly(P＜0.01),and the activity of SOD decreased significantly(P＜0.05).The protein expression levels of FAS,ACC1,DGAT2 and SREBP-1C were significantly up-regulated(P＜0.01),while the expression level of CPT1A was significantly down-regulated(P＜0.01).Compared with the NEFA group,the protein expression levels of SREBP-1C and DGAT2 in the NEFA+C8∶0(concentration 0.2 mmol/L)group de-creased significantly(P＜0.05),and the protein expression level of fatty acid β-oxidation related molecule CPT1A was slightly higher than that in the NEFA group,but there was no statistical sig-nificance(P＞0.05),and the MDA level in hepatocytes decreased significantly(P＜0.05).In a word,the results of this study show that C8∶0 has antioxidant effect,which can effectively reduce the liver injury caused by oxidative stress,regulate the expression of liver fat gene,and then pro-tect liver injury.

Objective To analyze the molecular epidemiological characteristics of carbapenem-resistant Klebsiella pneumoniae(CRKP)in a hospital in Hainan Province,explore the differences in the distribution of resistance genes and virulence factors between hypervirulent CRKP(hv-CRKP)and non-hv-CRKP,analyze the clinical significance,and provide basis for optimizing treatment and prevention strategies.Methods CRKP strains isolated from a hospi-tal in Hainan Province from July 2023 to June 2024 were collected retrospectively.Their resistance phenotypes were detected by antimicrobial susceptibility testing.Carbapenemase genes(KPC-2,NDM-1,IPM)and virulence factors(rmpA/rmpA2,iucA,iroB,etc.)were detected by polymerase chain reaction(PCR).Department source,speci-men distribution,and resistance-virulence characteristics were analyzed.Results A total of 76 strains of CRKP were isolated,with an overall isolation rate of 7.7％(76/985).The strains were mainly distributed in the intensive care unit(ICU)(28.9％)and neurosurgery ICU(23.6％),with the highest proportion of strains isolated from re-spiratory tract specimens(60.5％).The resistance genes were mainly KPC-2(72.4％)and NDM-1(21.1％),and the virulence factors mrkD(type Ⅲ pili,85.5％)and fim H(type Ⅰ pili,84.2％)were commonly presented.Among 76 strains of CRKP,39 strains(51.3％)met the criteria for hv-CRKP and all carried KPC-2 gene(100％).The detection rates of resistance genes and virulence factors rmpA2(97.4％),iucA(100％),and iroB(89.7％)were all higher than those of non-hv-CRKP strains(KPC-2,43.2％;rmpA2,0;iucA,8.1％;iroB,13.5％).The main characteristics of hv-CRKP was the combination of KPC-2 resistance gene and rmpA2+iucA+iutA+iroB virulence factors(64.1％).Antimicrobial resistance phenotype of hv-CRKP was different from non-hv-CRKP.hv-CRKP presented higher susceptibility rates to aminoglycosides and compound sulfamethoxazole than non-hv-CRKP.Conclusion The proportion of hv-CRKP and non-hv-CRKP strains in this hospital is comparable.hv-CRKP is characterized by carrying the KPC-2 resistance gene in combination with rmpA2+iucA+iutA+iroB virulence factors,and the proportion of strains carrying multiple virulence factors is higher than that of non-hv-CRKP.Both are generally resistant to β-lactams and quinolones.hv-CRKP has lower resistance rates to aminoglycosides and com-pound sulfamethoxazole than non-hv-CRKP.Its advantage of aminoglycoside susceptibility provides a new treatment option.It is recommended to guide differential medication through molecular typing and strengthen infection control measures in ICU to curb the spread of antimicrobial-resistant bacteria.

ObjectiveThis paper aims to verify the therapeutic effect of Cranial Painkiller pills' extract powder prepared by the new process on the rat's trigeminal neuralgia model caused by infraorbital injection of Talci Pulvis， evaluate its potential clinical application value， and compare the therapeutic effect with that of Cranial Painkiller granules， so as to provide data support for the application of the Cranial Painkiller pills' extract powder and precise treatment. MethodsThe rat's trigeminal neuralgia model was constructed by infraorbital injection of Talci Pulvis， and the rats were randomly divided into the normal group， model group， carbamazepine group （60 mg·kg^-1）， Cranial Painkiller granules group （2.70 g·kg^-1）， and low， medium， and high dosage groups of Cranial Painkiller pills' extract powder （1.35， 2.70， 5.40 g·kg^-1） according to the basal mechanical pain thresholds， and there were 10 rats in each group. The drug was administered by gavage to each group 2 h after modeling， and distilled water was given by gavage to the normal and model groups under the same conditions once a day for 10 d. Von Frey brushes were used to measure mechanical pain thresholds in rats. Hematoxylin-eosin （HE） staining was used to detect pathological changes in the trigeminal ganglion， and enzyme-linked immunosorbent assay （ELISA） was used to detect the inflammatory factors interleukin-1 （IL-1）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and tumor necrosis factor-α （TNF-α） levels in rat serum， as well as neuropeptide substance P （SP） and β-endorphin （β-EP） levels in rat brain tissue. Western blot technique was used to detect the levels of NLRP3， ASC， Caspase-1， and OTULIN proteins in rat brain tissue. ResultsCompared with the normal group， the pain threshold of rats in the model group showed a continuous significant decrease （P<0.01）. The pathological damage of brain tissue was significant （P<0.01）， and the inflammatory levels of IL-1， IL-6， IL-8， and TNF-α in serum were significantly elevated （P<0.01）. The level of the SP in the brain tissue was significantly elevated （P<0.01）， and the level of β-EP was significantly reduced （P<0.01）， while the level of OTULIN was significantly reduced， and NLRP3， ASC， and Caspase-1 protein levels were significantly elevated （P<0.01）. After administration of the drug， compared with the model group， the pain threshold of each dose group of the Cranial Painkiller pills' extract powder and the Cranial Painkiller granules group significantly increased （P<0.01）. The inflammatory levels of IL-1， IL-6， IL-8， and TNF-α and SP levels significantly decreased （P<0.01）， and the β-EP levels were significantly elevated （P<0.01）， while the levels of OTULIN protein were significantly elevated （P<0.05， P<0.01）， and the levels of NLRP3， ASC proteins were decreased （P<0.01）in high dose Cranial Painkiller pills' extract powder. Meanwhile， compared with those in the model group， the trigeminal ganglion lesions of rats in the Cranial Painkiller pills' extract powder and Cranial Painkiller granules groups showed different degrees of improvement （P<0.05， P<0.01）. ConclusionThe Cranial Painkiller pills' extract powder has significant therapeutic effects on the rat model of trigeminal neuralgia induced by infraorbital injection of Talci Pulvis， and its mechanism is related to the improvement of OTULIN-regulated neuroinflammation.