Metabolic associated fatty liver disease (MAFLD) is fundamentally driven by an imbalance in hepatic fatty-acid flux: the influx of fatty acids exceeds the liver’s capacity for disposal, resulting in excessive hepatic lipid accumulation, predominantly in the form of triglycerides (TGs). The occurrence and progression of MAFLD depend on disordered regulation across multiple metabolic steps, including fatty-acid uptake, de novo lipogenesis (DNL), fatty-acid oxidation (FAO), and very low-density lipoprotein (VLDL) export. Forkhead box protein O1 (FOXO1) is a key transcriptional regulator within the hepatic network coordinating glucose and lipid metabolism. Under metabolic stress and insulin resistance (IR), FOXO1 expression is frequently increased, whereas its inhibitory phosphorylation is reduced. These changes enhance FOXO1 nuclear localization and transcriptional activity, thereby reprogramming the expression of genes related to metabolism in the liver. Because hepatic lipid deposition is the central pathological feature of MAFLD, the functional status of FOXO1 directly influences hepatic lipid homeostasis. Growing evidence suggests that FOXO1 can exert bidirectional, environment-dependent effects on hepatic lipid accumulation; however, the molecular basis for this functional switch remains incompletely understood. This review systematically summarizes the biological functions and regulatory mechanisms of FOXO1 and its roles in hepatic lipid metabolism, with a particular focus on its crosstalk with insulin signaling. FOXO1 expression is shaped by RNA modifications and epigenetic regulation mediated by non-coding RNAs. Its transcriptional output is precisely governed by post-translational modifications—such as phosphorylation and acetylation—as well as by coordinated nucleocytoplasmic shuttling. Notably, these regulatory patterns vary markedly across nutritional states, degrees of insulin resistance, and stages of disease. In the fed state, insulin/IGF-1 signaling activates the PI3K-AKT pathway, promoting the inhibitory phosphorylation of FOXO1 and facilitating additional modifications, including acetylation, methylation, and ubiquitination. Together, these events drive FOXO1 export from the nucleus and dampen its transcriptional activity, suppressing gluconeogenesis and constraining lipogenic programs. Conversely, during fasting or when insulin signaling is weakened, FOXO1 inhibition is relieved. FOXO1 accumulates in the nucleus, binds to DNA, and regulates the transcription of downstream target genes. Mechanistically, FOXO1 can aggravate hepatic lipid accumulation by activating genes involved in TG synthesis while repressing FAO-related pathways, thereby favoring storage over oxidation. However, under specific conditions, FOXO1 may also alleviate the hepatic lipid burden by promoting TG hydrolysis and enhancing VLDL secretion, thereby reducing the net hepatic lipid load. In addition, lipotoxic signals mediated by ceramides and diacylglycerols (Cer/DAG) activate atypical protein kinase C (aPKC), further exacerbating the disruption of the AKT-FOXO1 axis. This vicious cycle ultimately produces a metabolic paradox in which increased hepatic glucose output coexists with persistent, insulin-independent lipogenesis, accelerating MAFLD progression. Importantly, FOXO1 regulation is not uniform: during early metabolic overload, insulin-mediated suppression may remain effective, whereas in advanced insulin resistance, the loss of AKT control permits sustained FOXO1 activity. Such stage-dependent dynamics may help explain why FOXO1 can either promote steatosis or, in certain contexts, support programs that facilitate lipid turnover. Accordingly, interventions should be liver-specific and tuned to the disease stage, aiming to curb maladaptive FOXO1 signaling while preserving its capacity to promote triglyceride hydrolysis and VLDL secretion when advantageous. Overall, this review offers an important perspective on MAFLD pathogenesis, emphasizing FOXO1 as a potential therapeutic target and providing a theoretical basis for developing liver-specific, disease-course-dependent precision interventions.

OBJECTIVE: To observe the effects of moxibustion at "Shenque" (CV8) on urodynamics and the expression of brain-derived neurotrophic factor (BDNF) and immediate early gene (c-fos) in pontine micturition center (PMC), periaqueductal gray (PAG), medial prefrontal cortex (mPFC) of neurogenic bladder (NB) rats after spinal cord injury. METHODS: Twenty-four SPF female SD rats were randomly divided into a sham-operation group (6 rats) and a modeling group (18 rats). In the modeling group, T₉ complete spinal cord transection method was used to establish a neurogenic detrusor overactivity model, and the 12 rats with successful modeling were randomized into a model group and a moxibustion group, with 6 rats in each group. The rats in the moxibustion group were treated with ginger/salt-insulated moxibustion at "Shenque" (CV8), and 4 consecutive moxa cones were delivered in one intervention. Moxibustion was operated once daily and for 14 days. After intervention completion, the urodynamic indexes of rats in each group were detected. Fluorescence quantitative PCR was used to detect the mRNA expression of BDNF and c-fos in PMC, PAG and mPFC in rats. Western blot was used to detect the protein expression of BDNF and c-fos in PMC, PAG and mPFC. RESULTS: The rats in the sham-operation group did not show phasic detrusor contraction during bladder filling. Compared with the model group, the frequency and amplitude of the phasic detrusor contraction were reduced 5 min before urine leakage in the rats of the moxibustion group (P<0.05), and the duration of the first phasic detrusor contraction during bladder filling was prolonged (P<0.05). Compared with the sham-operation group, the mRNA and protein expression of BDNF and c-fos in PMC, PAG and mPFC increased in the model group (P<0.05). Compared with the model group, the mRNA and protein expression of BDNF and c-fos in PMC, PAG and mPFC decreased in the moxibustion group (P<0.05). CONCLUSION Moxibustion at "Shenque" (CV8) can improve the phasic contraction during bladder filling in NB rats after spinal cord injury, possibly by down-regulating the mRNA and protein expression of BDNF and c-fos in PMC, PAG, and mPFC.
Animals ; Moxibustion ; Female ; Rats ; Brain-Derived Neurotrophic Factor/metabolism* ; Rats, Sprague-Dawley ; Acupuncture Points ; Spinal Cord Injuries/metabolism* ; Urinary Bladder, Neurogenic/etiology* ; Proto-Oncogene Proteins c-fos/metabolism* ; Humans ; Urinary Bladder/physiopathology* ; Brain/metabolism* ; Urination

As the longest and most widely distributed pair of nerves in the brain,the vagus nerve is involved in the regulation of many systems and organs.Recent studies have found that the vagus nerve may be involved in the occurrence of a variety of neuropsychiatric diseases by regulating the release of neurotransmitters(such as norepinephrine,5-hydroxytryptamine,gamma-aminobutyric acid and acetylcholine)and regulating the immune system and gut-brain axis.This article focuses on the regulatory mechanisms of the vagus nerve on neurotransmitters,immune system function,and the gut-brain axis,as well the therapeutic advances in vagus nerve stimulation for neurological and psychi-atric diseases such as epilepsy,depression and anxiety disorders.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

Objective To analyze the clinical trial projects of TCM treatment for psoriasis registered at the China Clinical Trial Registry(ChiCTR);To provide references for clinical research in this field.Methods Clinical trial studies on the TCM treatment for psoriasis were retrieved from the ChiCTR database from the establishment of the database to June 17,2024.Excel 2019 and GraphPad Prism 9.0 were used to organize and analyze the general characteristics included in registered clinical trials.Results Totally 65 TCM-related trials were included,of which 58(89.23%)were prospectively registered,and 55(84.62%)had undergone ethical review.The majority of trials were registered in Guangdong,Beijing and Shanghai,collectively accounting for 78.46%(n=51)of the total.The leading institution,Guangdong Provincial Hospital of Chinese Medicine,contributed 19 trials.Funding was predominantly sourced from governmental bodies,with 72.31%(n=47)supported by national or regional grants.Among the registered studies,interventional trials predominated(n=56),including 46 randomised parallel-controlled designs.Blinding was implemented in 23 trials,and biospecimen collection was reported in 48 studies.40 trials were single-centre studies,and a cumulative sample size was 17 695 participants.Common interventions included oral administration of classical TCM formulations or hospital-prepared remedies,alongside topical applications such as medicated baths and ointments.The primary outcome measure in most trials was the Psoriasis Area and Severity Index.Conclusion While the number of registered clinical trials on TCM for psoriasis in China demonstrates a fluctuating yet upward trend,the overall volume remains modest.Disparities in regional distribution,methodological variability,and incomplete trial registration details highlight areas for improvement.

Oropharyngeal squamous cell carcinoma(OPSCC)is a malignant tumor originating from the squamous epithelium of the oro-pharyngeal mucosa,accounting for more than 90％of oropharyngeal malignancies.In recent years,human papillomavirus(HPV)infec-tion has become one of the primary etiological factors of oropharyngeal squamous carcinoma.The incidence of HPV-associated oropharyn-geal squamous carcinoma has been rising annually,with a noticeable trend toward younger populations,posing a significant threat to hu-man health.Due to the distinct biological behavior and clinical characteristics of HPV-associated oropharyngeal squamous carcinoma com-pared to its non-HPV-related counterpart,the diagnostic and treatment strategies for oropharyngeal squamous carcinoma have undergone substantial changes.Prevention and screening for oropharyngeal squamous carcinoma are of critical importance.The diagnostic and treat-ment process involves multi-disciplinary collaboration,including oral and maxillofacial surgery,otolaryngology,head and neck surgery,oncology,radiology and pathology.Based on evidence from clinical practice,a comprehensive,integrated diagnostic and therapeutic ap-proach has been established,centered around the concept of"prevention,screening,diagnosis,treatment,and rehabilitation",covering the entire patient lifecycle and providing a valuable reference for clinical practice.

Primers and probes were designed based on the conserved regions of Senecavirus A(SVA),foot-and-mouth disease virus(FMDV),and porcine teschovirus(PTV)and used to devel-op a TaqMan fluorescent quantitative PCR method for detecting the above-mentioned three viru-ses.The triplex fluorescent quantitative PCR system was developed using recombinant positive plasmids containing conserved sequences of the three viruses as templates.After optimizing the conditions,the specificity,sensitivity,repeatability,standard curve,and mixed infection model were evaluated,and the constructed triplex fluorescent quantitative PCR was used for clinical detection.The results showed that this method could specifically detect SVA,FMDV and PTV without cross-reactivity with other pathogens with the minimal detection concentrations for SVA,FMDV,and PTV as low as 1X101 copies/μL,respectively.The coefficients of variation within and between groups were less than 5％.Furthermore,none of the three viruses were detected in 126 samples.The above results indicate that this method is highly specific,sensitive,and stable,making it suit-able for clinical detection.

Tovorafenib has been approved by the U.S.Food and Drug Administration(FDA)for the treatment of patients 6 months of age and older with relapsed or refractory pediatric low-grade glioma(LGGs)harboring the serine threonine kinae v-RAF murine sarcoma viral oncogene homologue B1(BRAF)fusion or rearrangement,or BRAV600E mutation.Tovorafenib is an oral,greater brain-penetrant,selective,type Ⅱ RAF inhibitor which has potent activity against both oncogenic BRAF fusions and BRAFV600E mutations.Most tumors have been showed some degree of shrinkage.The mechanism of action,pharmacodynamics,pharmacokinetics,clinical study and safety were introduced.

Objective Under the guidance of Zhuang medicine theory,this study aims to investigate the medicinal and compatibility rules of authentic medicinal pearls.Method This article focuses on the fourth national survey of traditional Chinese medicine resources—general survey of marine traditional Chinese medicine resources in Guangxi,led by Professor Lin Jiang's team from Guangxi University of Traditional Chinese Medicine and Guangxi Famous Traditional Chinese Medicine.The survey collected original prescriptions containing pearls,as well as data recorded in Zhuang medicine monographs containing pearls.The study integrated the efficacy,indications,pharmacology,and clinical research of pearl Zhuang medicine.Under the guidance of Zhuang medicine prescription compatibility theory,Zhuang medicine disease classification,and Zhuang medicine classification theory,this study explores the compatibility rules based on the data and functions of Zhuang medicine pearl formula.Result Zhuang medicine pearls taste sweet and salty,with a cold nature;It has the effects of activating the Qiao wu(brain),regulating Long lu(blood circulatory system)and Huo lu(nervous system),clearing heat and toxins,calming the mind,calming palpitations,relieving cough,promoting muscle growth,nourishing yin fluids,and Clearing eye mistiness;Indications:Nian nao nuo(Insomnia),Hen feng(Infantile Convulsions),Long lei(Epilepsy),Fright Palpitations,A rou tian(Diabetes),Huo yan ma(Sore throat),Bei ding(Deep-Rooted Boil),Bei nong(Sores and Ulcers),Redness and visual obstruction due to corneal opacity,Re Nong(Otitis media),Kou chuang(Oral ulcers),Da ning(Swelling and pain of eye).Based on the analysis of data on the formula of Zhuang medicine pearls,it was found that the topical use of Zhuang medicine pearls is concentrated in diseases of the ENT(Ear,Nose,and Throat),Ophthalmology,and diseases of the skin and subcutaneous tissue.When combined with drugs such as regulating Long lu,clearing heat toxin,and eliminating dampness-toxin,it is used to treat diseases such as Redness and visual obstruction due to corneal opacity,Oral ulcers,and Skin ulcers;For internal use,it is often combined with medicines that regulating Long lu,replenishing qi and blood,eliminating dampness-toxin,and nourishing the heart-mind,used in hypertension and palpitations.When paired with the medicines of clearing heat toxin,replenishing qi and blood,regulating Qiaowu,it is used to treat insomnia and epilepsy.Based on the analysis of pearl function,it is used in combination with airway and detoxifying drugs to treat airway diseases;Combination therapy with regulating Long lu and Qiao wu(brain)medicine for the treatment of Long lu disease;Combination treatment of gynecological diseases with regulating Long lu and Huo lu medicine and Bu xu medicine;Combination therapy with heat-clearing,detoxifying,and swelling-reducing medicines or astringents,for the treatment of persistent non-healing sores and ulcers;Used in combination with antipyretic drugs and yin tonifying drugs to treat ophthalmic diseases.Conclusion Zhuang medicine pearl has a wide range of therapeutic effects,and its efficacy can be enhanced by compatibility with different Zhuang medicines.Future research can combine modern compatibility methods of traditional Chinese medicine to optimize the compatibility scheme of pearls,study the specialized disease and prescription of Zhuang medicine pearls,combine Zhuang medicine with Western medicine to form prescriptions,and combine the pharmacological effects of pearls to form prescriptions.In depth exploration of the pharmacological substance basis and mechanism of action of pearl prescriptions can be conducted to develop new Zhuang medicine preparations for pearls.