Objective To explore the correlation of MET status in patients with advanced prostatic acinar adenocarcinoma with the clinical pathological parameters and prognosis. Methods The specimen from 135 patients with advanced prostatic acinar adenocarcinoma was included. The expression of c-MET protein was detected via immunohistochemistry, and MET gene amplification was assessed by fluorescence in situ hybridization. The relationships of c-MET expression and gene amplification with clinicopathological features and prognosis were analyzed. Results The positive expression rate of c-MET was 52.60% (71/135). Compared with the c-MET expression in adjacent tissues, that in tumor tissues showed lower heterogeneous expression. Among the cases, 1.71% (2/117) exhibited MET gene polyploidy, but no gene amplification was detected. Positive c-MET expression was significantly correlated with high Gleason scores and grade groups (P=0.0073). However, no significant relationship was found between c-MET expression and progression-free survival or post-treatment t-PSA levels. Conclusion c-MET protein is expressed at a relatively low level in advanced prostatic acinar adenocarcinoma, suggesting that c-MET may not be a viable target for ADC drug development in prostatic acinar adenocarcinoma.

OBJECTIVE: To observe the clinical efficacy of Daoqi (directing qi flowing) acupuncture technique in Huangdi Neijing (Yellow Emperor's Inner Classic) for moderate-to-severe obstructive sleep apnea-hypopnea syndrome (OSAHS). METHODS: Sixty patients with moderate-to-severe OSAHS were randomly divided into a Daoqi acupuncture group (30 cases) and a conventional acupuncture group (30 cases, 1 case dropped out). In the Daoqi acupuncture group, Daoqi acupuncture technique in Huangdi Neijing was applied at Shanglianquan (Extra), Fengfu (GV16), and bilateral Lieque (LU7), Zhaohai (KI6); in the conventional acupuncture group, conventional acupuncture was applied at Shanglianquan (Extra), Fengfu (GV16), Yamen (GV15), and bilateral Lieque (LU7), Zhaohai (KI6), Zusanli (ST36), Fenglong (ST40). The treatment was adopted once every other day, 3 times a week, 4 weeks as one course and 3 courses were required totally in both groups. Before and after treatment, the polysomnography (PSG) indexes [apnea-hypopnea index (AHI), hypopnea index (HI), apnea index (AI), longest apnea duration, lowest nocturnal SaO₂ (LSaO₂)], and scores of Epworth sleepiness scale (ESS), Pittsburgh sleep quality index (PSQI), World Health Organization quality of life-BREF (WHOQOL-BREF) were observed, and the clinical efficacy was evaluated after treatment in the two groups. RESULTS: After treatment, the AHI, HI, AI and longest apnea duration were reduced compared with those before treatment in the two groups (P<0.01), the LSaO₂ was increased in the Daoqi acupuncture group (P<0.01); in the Daoqi acupuncture group, the AHI, HI, AI and longest apnea duration were lower than those in the conventional acupuncture group (P<0.05), and the LSaO₂ was higher than that in the conventional acupuncture group (P<0.05). After treatment, the ESS and PSQI scores were decreased compared with those before treatment (P<0.01), while the WHOQOL-BREF scores were increased compared with those before treatment (P<0.01) in the two groups; in the Daoqi acupuncture group, the ESS and PSQI scores were lower than those in the conventional acupuncture group (P<0.05, P<0.01), and the WHOQOL-BREF score was higher than that in the conventional acupuncture group (P<0.05). The total effective rate was 93.3% (28/30) in the Daoqi acupuncture group, which was higher than 82.8% (24/29) in the conventional acupuncture group (P<0.01). CONCLUSION Daoqi acupuncture technique in Huangdi Neijing can effectively treat moderate-to-severe OSAHS patients, improve the clinical symptoms and quality of life, and has the advantages i.e. simpler acupoints selection and gentler stimulation.
Humans ; Sleep Apnea, Obstructive/physiopathology* ; Male ; Female ; Middle Aged ; Acupuncture Therapy ; Adult ; Acupuncture Points ; Treatment Outcome ; Aged ; Quality of Life

BACKGROUND: Alpha-glucosidase inhibitors or dipeptidyl peptidase-4 inhibitors are both hypoglycemia agents that specifically impact on postprandial hyperglycemia. We compared the effects of acarbose and sitagliptin add on to metformin on time in range (TIR) and glycemic variability (GV) in Chinese patients with type 2 diabetes mellitus through continuous glucose monitoring (CGM). METHODS: This study was a randomized, open-label, active-con-trolled, parallel-group trial conducted at 15 centers in China from January 2020 to August 2022. We recruited patients with type 2 diabetes aged 18-65 years with body mass index (BMI) within 19-40 kg/m 2 and hemoglobin A1c (HbA1c) between 6.5% and 9.0%. Eligible patients were randomized to receive either metformin combined with acarbose 100 mg three times daily or metformin combined with sitagliptin 100 mg once daily for 28 days. After the first 14-day treatment period, patients wore CGM and entered another 14-day treatment period. The primary outcome was the level of TIR after treatment between groups. We also performed time series decomposition, dimensionality reduction, and clustering using the CGM data. RESULTS: A total of 701 participants received either acarbose or sitagliptin treatment in combination with metformin. There was no statistically significant difference in TIR between the two groups. Time below range (TBR) and coefficient of variation (CV) levels in acarbose users were significantly lower than those in sitagliptin users. Median (25th percentile, 75th percentile) of TBR below target level <3.9 mmol/L (TBR 3.9 ): Acarbose: 0.45% (0, 2.13%) vs . Sitagliptin: 0.78% (0, 3.12%), P = 0.042; Median (25th percentile, 75th percentile) of TBR below target level <3.0 mmol/L (TBR 3.0 ): Acarbose: 0 (0, 0.22%) vs . Sitagliptin: 0 (0, 0.63%), P = 0.033; CV: Acarbose: 22.44 ± 5.08% vs . Sitagliptin: 23.96 ± 5.19%, P <0.001. By using time series analysis and clustering, we distinguished three groups of patients with representative metabolism characteristics, especially in GV (group with small wave, moderate wave and big wave). No significant difference was found in the complexity of glucose time series index (CGI) between acarbose users and sitagliptin users. By using time series analysis and clustering, we distinguished three groups of patients with representative metabolism characteristics, especially in GV. CONCLUSIONS: Acarbose had slight advantages over sitagliptin in improving GV and reducing the risk of hypoglycemia. Time series analysis of CGM data may predict GV and the risk of hypoglycemia. TRIAL REGISTRATION Chinese Clinical Trial Registry: ChiCTR2000039424.
Humans ; Metformin/therapeutic use* ; Sitagliptin Phosphate/therapeutic use* ; Acarbose/therapeutic use* ; Diabetes Mellitus, Type 2/blood* ; Middle Aged ; Male ; Female ; Adult ; Blood Glucose/drug effects* ; Hypoglycemic Agents/therapeutic use* ; Aged ; Glycated Hemoglobin/metabolism* ; Adolescent ; Young Adult ; China ; East Asian People

OBJECTIVES: The integrated endoplasmic reticulum stress inhibitor (ISRIB) is a selective inhibitor of the protein kinase R-like endoplasmic reticulum kinase (PERK) signaling pathway within endoplasmic reticulum stress (ERS) and can improve spatial and working memory in aged mice. Although ERS and oxidative stress are tightly interconnected, it remains unclear whether ISRIB alleviates cognitive impairment by restoring the balance between ERS and oxidative stress. This study aims to investigate the effects and mechanisms of ISRIB on lipopolysaccharide (LPS)-induced cognitive impairment in mice. METHODS: Eight-week-old male ICR mice were randomly divided into 3 groups: Normal saline (NS) group, LPS group, and ISRIB+LPS group. NS and LPS groups received daily intraperitoneal injections of normal saline for 7 days; on day 7, LPS group mice received intraperitoneal LPS (0.83 mg/kg) to establish a cognitive impairment model. ISRIB+LPS group received ISRIB (0.25 mg/kg) intraperitoneally for 7 days, with LPS injected 30 minutes after ISRIB on day 7. Cognitive ability was evaluated by the novel place recognition test (NPRT). Real-time fluorogenic quantitative PCR (RT-qPCR) was used to detect changes in nitric oxide synthase (NOS), superoxide dismutase-1 (SOD-1), and catalase (CAT) gene expression in the hippocampus and prefrontal cortex. Oxidative stress markers malondialdehyde (MDA), glutathione (GSH), and oxidized glutathione (GSSG), were measured in hippocampal and prefrontal cortex tissues. RESULTS: Compared with the NS group, mice in LPS group showed a significant reduction in novel place recognition ratio, upregulation of hippocampal NOS-1 and NOS-2 mRNA, downregulation of SOD-1 and CAT mRNA, increased MDA and GSSG, decreased GSH, and reduced GSH/GSSG ratio (all P<0.05). Compared with the LPS group, mice in ISRIB+LPS group exhibited significantly improved novel place recognition, downregulated NOS-1 and NOS-2 mRNA, upregulated SOD-1 and CAT mRNA, decreased MDA and GSSG, increased GSH, and an elevated GSH/GSSG ratio in the hippocampus (all P<0.05). No significant changes were observed in the prefrontal cortex. CONCLUSIONS ISRIB improves LPS-induced cognitive impairment in mice by restoring the oxidative/antioxidant balance in the hippocampus.
Animals ; Lipopolysaccharides ; Male ; Mice, Inbred ICR ; Cognitive Dysfunction/drug therapy* ; Mice ; Oxidative Stress/drug effects* ; Endoplasmic Reticulum Stress/drug effects* ; Hippocampus/drug effects* ; Nitric Oxide Synthase Type II/genetics* ; Guanidines/pharmacology* ; eIF-2 Kinase/antagonists & inhibitors* ; Signal Transduction/drug effects* ; Superoxide Dismutase/metabolism*

Traditional Chinese medicine (TCM) represents a paradigmatic approach to personalized medicine, developed through the systematic accumulation and refinement of clinical empirical data over more than 2000 years, and now encompasses large-scale electronic medical records (EMR) and experimental molecular data. Artificial intelligence (AI) has demonstrated its utility in medicine through the development of various expert systems (e.g., MYCIN) since the 1970s. With the emergence of deep learning and large language models (LLMs), AI's potential in medicine shows considerable promise. Consequently, the integration of AI and TCM from both clinical and scientific perspectives presents a fundamental and promising research direction. This survey provides an insightful overview of TCM AI research, summarizing related research tasks from three perspectives: systems-level biological mechanism elucidation, real-world clinical evidence inference, and personalized clinical decision support. The review highlights representative AI methodologies alongside their applications in both TCM scientific inquiry and clinical practice. To critically assess the current state of the field, this work identifies major challenges and opportunities that constrain the development of robust research capabilities-particularly in the mechanistic understanding of TCM syndromes and herbal formulations, novel drug discovery, and the delivery of high-quality, patient-centered clinical care. The findings underscore that future advancements in AI-driven TCM research will rely on the development of high-quality, large-scale data repositories; the construction of comprehensive and domain-specific knowledge graphs (KGs); deeper insights into the biological mechanisms underpinning clinical efficacy; rigorous causal inference frameworks; and intelligent, personalized decision support systems.
Medicine, Chinese Traditional/methods* ; Artificial Intelligence ; Humans ; Precision Medicine ; Decision Support Systems, Clinical

Objective Recent studies have indicated potential anti-inflammatory effects of glucagon-like peptide-1 receptor agonists(GLP-1RAs)on asthma,which is often comorbid with type 2 diabetes mellitus(T2DM)and obesity.Therefore,we conducted a meta-analysis to assess the association between the administration of glucagon-like peptide-1(GLP-1)receptor-based agonists and the incidence of asthma in patients with T2DM and/or obesity. Methods PubMed,Web of Science,Embase,the Cochrane Central Register of Controlled Trials,and Clinicaltrial.gov were systematically searched from inception to July 2023.Randomized controlled trials(RCTs)of GLP-1 receptor-based agonists(GLP-1RA,GLP-1 based dual and triple receptor agonist)with reports of asthma events were included.Outcomes were computed as risk ratios(RR)using a fixed-effects model. Results Overall,39 RCTs with a total of 85,755 participants were included.Compared to non-GLP-1 receptor-based agonist users,a trend of reduced risk of asthma was observed in patients with T2DM or obesity using GLP-1 receptor-based agonist treatments,although the difference was not statistically significant[RR=0.91,95%confidence interval(CI):0.68 to 1.24].Further Subgroup analyses indicated that the use of light-molecular-weight GLP-1RAs might be associated with a reduced the risk of asthma when compared with non-users(RR=0.65,95%CI:0.43 to 0.99,P=0.043).We also performed sensitivity analyses for participant characteristics,study design,drug structure,duration of action,and drug subtypes.However,no significant associations were observed. Conclusion Compared with non-users,a modest reduction in the incidence of asthma was observed in patients with T2DM or obesity using GLP-1 receptor-based agonist treatments.Further investigations are warranted to assess the association between GLP-1 receptor-based agonists and the risk of asthma.

Alzheimer's disease(AD) is a common neurodegenerative disease with increasing incidence rate. Up to now,there is no ideal treatment for AD. It has become a public health problem worldwide. Traditional Chinese medicine (TCM) believes that kidney deficiency is the key symptomatic element of deterioration and temporal progression symptoms,accompanied by the AD process. The treatment of tonifying kidneys,supplementing essence and replenishing marrow is the fundamental method for AD in TCM. Clinical studies have shown that kidney-tonifying formula can significantly improve the cognitive function and daily ability of patients with mild and moderate AD and have no obvious adverse reactions. Its mechanism of action may be related to the protection of nerves,reduction of β-amyloid (Aβ) level in the brain,inhibition of inflammatory factors activation and anti-oxidative stress. Besides reviewing the clinical and pharmacological research progress of kidney-tonifying formula for AD,this article also discusses the advantages and shortcomings of kidney-tonifying formula in the prevention and treatment of AD based on TCM theory and modern medical research. The aim of this study is to provide references of kidney nourishing therapy in TCM for the prevention and treatment of neurodegenerative diseases.

Objective:To investigate impacts of soy isoflavones(SIF)on alveolar bone resorption and inflammatory response in periodontitis rats based on Slit homologue 2(Slit2)/P38 mitogen-activated protein kinase(MAPK)signaling pathway.Methods:Rats were separated into Control group,Model group,SIF low-dose group(L-SIF,25 mg/kg)and SIF high-dose group(H-SIF,75 mg/kg),with 10 rats per group,and periodontitis model was established by ligating necks of maxillary first molars of rats with silk thread except for control group.Rats in L-SIF group and H-SIF group were given corresponding doses of SIF by gavage,Control group and Model group were given same amount of normal saline by gavage,once a day,for 4 consecutive weeks.After administration,serum Slit2,TNF-α,IL-6 and IL-1β levels were detected by ELISA;Micro-CT scan was performed to detect distance between cemen-tumenamel junction and alveolar ridge crest(CEJ-ABC),bone mineral density(BMD),bone volume fraction(BV/TV),and alveolar bone loss was evaluated;HE staining and tartrate-resistant acid phosphatase(TRAP)staining were performed to evaluate tissue inflam-mation,bone resorption and osteoclast activity;expressions of osteoprotegerin(OPG)and receptor activator of nuclear factor κB ligand(RANKL)in periodontal tissues were detected by immunohistochemistry(IHC);Western blot was performed to detect protein expressions of Slit2,P38 MAPK and p-P38 MAPK in periodontal tissues.Results:Compared with Control group,serum levels of Slit2,TNF-α,IL-1β,IL-6,CEJ-ABC distance,periodontal histopathological damage score,osteoclast number,positive expression of RANKL,protein level of Slit2 and p-P38 MAPK/P38 MAPK were greatly increased in Model group,BMD,BV/TV and positive ex-pression of periodontal tissues OPG were greatly decreased(all P<0.05);compared with Model group,serum levels of Slit2,TNF-α,IL-1β,IL-6,CEJ-ABC distance,periodontal histopathological damage score,osteoclast number,positive expression of RANKL,pro-tein levels of Slit2 and p-P38 MAPK/P38 MAPK were greatly decreased,BMD,BV/TV and OPG positive expression of periodontal tissues were greatly increased in L-SIF group and H-SIF group(P<0.05),the above indicators in H-SIF group changed greatly better than L-SIF group(P<0.05).Conclusion:SIF can inhibit alveolar bone resorption and inflammatory response in periodontitis rats and improve periodontitis,whose mechanism may be related to inhibition of Slit2/P38 MAPK signaling pathway.

ObjectiveTo explore the impact of Gegen Qinliantang（GQT） on the fecal short-chain fatty acids（SCFAs） metabolism in antibiotic-associated diarrhea（AAD） through targeted metabolomics. MethodA total of 240 SD rats were randomly divided into six groups（n=40， half male and half female）， including blank group， model group， bifidobiogen group（0.15 g·kg^-1）， and GQT high-， medium-， and low-dose groups（10.08， 5.04， 2.52 g·kg^-1）， except for the blank group， clindamycin（250 mg·kg^-1） was given to all groups by gavage for modeling every day for 7 d. After successful modeling， each administered group was gavaged with the corresponding dose of the drug， and the blank and model groups were gavaged with an equal volume of normal saline solution， 1 time/d， for 14 d. At 0， 3， 7， 14 d after the drug intervention， eight rats were randomly selected from each group， respectively. Gas chromatography-time-of-flight mass spectrometry（GC-TOF-MS） was used to perform targeted metabolomic analysis of SCFAs in the feces of rats， and partial least squares-discriminant analysis（PLS-DA） was applied to compare the differences in metabolic profiles between groups at different treatment times， and to compare the changes in the contents of SCFAs in rat feces between groups. ResultPLS-DA results showed that the blank group could be clearly distinguishable from the model group， with GQT exhibiting a closer proximity to the blank group after 7 d of treatment. After further analyzing the composition of SCFAs， it was found that the proportion of acetic acid increased and the proportions of butyric acid， valeric acid， hexanoic acid and isovaleric acid decreased in the model group compared with the blank group. After the treatment with GQT， the proportions of butyric acid， isobutyric acid， valeric acid， and isovaleric acid increased， and the proportions of acetic acid， propionic acid and caproic acid decreased. Subsequent differential analysis revealed that GQT could significantly improve the content of butyric acid， and had a certain retrogressive effect on the contents of valeric acid and hexanoic acid. ConclusionThe medium dose group of GQT can improve the contents of SCFAs in AAD feces after 7 days of treatment， which may be related to the improvement of the composition ratio of SCFAs and the contents of butyric acid， valeric acid and caproic acid.

ObjectiveTo clone the gene of Marmota himalayana type ‍Ⅰ interferon receptor β subunit （mhIFNAR2）， and to perform antibody preparation and functional identification. MethodsRT-PCR was used for amplification in the spleen tissue of Marmota himalayana to obtain the sequence， which was cloned to the prokaryotic expression vector pRSET-B to express the recombinant protein. Electrophoresis and Western blot were used for identification. BALB/c mice were immunized with the recombinant protein to prepare the polyclonal antibody of its extracellular domain； immunohistochemistry， immunofluorescence assay， and Western Blot were used for identification， and the method of siRNA blockade was used to investigate its function. An analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for comparison between two groups. ResultsA fragment of mhIFNAR2 （149‍ ‍—‍ ‍1 ‍300 bp） was obtained from spleen tissue， which showed the highest homology of 98.05% in marmot. A prokaryotic expression plasmid was successfully constructed for expression of the extracellular domain of the mhIFNAR2_{（50-181aa）} and was named pRSET-B.mhIFNAR2， and the recombinant protein expressed by this plasmid had a molecular weight of 27 kD， a purity of about 95% after purification， and a concentration of 160 μg/mL. After BALB/c mice were immunized with the purified recombinant protein， 1∶1 000 specific polyclonal antibodies were obtained， and immunohistochemistry and immunofluorescence assay showed the expression in cell membrane and cytoplasm. Among the three siRNAs synthesized， the siRNA starting from the 277 locus （siRNA277） could silence the expression of target genes and weaken the interferon signaling pathway compared with the blank control group and the negative control group （both P<0.05）. ConclusionThe fragment of mhIFNAR2 is obtained， and the polyclonal antibody for the extracellular domain of mhIFNAR2 is successfully prepared， with relatively high titer and specificity， and can be used for immunohistochemistry， immunofluorescence assay， and Western blot.