OBJECTIVE To explore a synergistic medication strategy integrating stage-specific modifications of Bushen huoxue decoction with hormone replacement therapy （HRT） for premature ovarian insufficiency （POI）. METHODS The connotation of Academician Tong Xiaolin’s “state-target differentiation and treatment” theory and the disease stage characteristics of POI were summarized. The latent stage， subclinical stage， clinical stage and exhaustion stage of POI were classified into corresponding core pathogenesis “states” and key objective indicator “targets”. Taking Bushen huoxue decoction as the basic prescription， its staged modification scheme and its sequential combination with HRT were analyzed. RESULTS & CONCLUSIONS The four stages of POI correspond to four pathogenic states respectively： kidney yin deficiency， kidney deficiency and blood stasis， heart-kidney disharmony， and deficiency of both yin and yang. Follicle-stimulating hormone （FSH）， anti-Müllerian hormone （AMH）， antral follicle count （AFC） and Kupperman score were taken as the evaluation targets of staging. Combined with the “state-target” characteristics of each stage， a medication principle based on Bushen huoxue decoction with syndrome differentiation modification and stage-adjusted administration was established： traditional Chinese medicine dominates in the latent stage， a sequential collaborative regimen is adopted in the subclinical stage， HRT is dominant supplemented by traditional Chinese medicine in the clinical stage， and integrated traditional Chinese and Western medicine is applied to consolidate the root cause in the exhaustion stage.

With the accelerating trend of population aging, the number of elderly patients with lung cancer continues to rise, and the disease burden is becoming increasingly heavy. The clinical management of these patients faces severe challenges due to their decreased physiological reserve, complex comorbidities, and significant individual heterogeneity. Consequently, under traditional diagnosis and treatment models, doctors often struggle to identify the individualized risks of elderly patients in a timely and comprehensive manner, which can easily lead to decision biases such as undertreatment or overtreatment. In view of this, this study advocates for the establishment of an umbrella decision-making model specifically tailored for elderly lung cancer patients. Grounded in a multidisciplinary team (MDT) platform, this model deeply integrates oncological indicators with the comprehensive geriatric assessment (CGA) system. By holistically considering multidimensional variables including tumor burden, organ function, frailty index, cognitive status, and social support, the model establishes an operational mechanism characterized by "single entry, precise stratification, and targeted selection". Accordingly, patients can be scientifically triaged into distinct intervention tiers, such as active surveillance, minimally invasive surgery, drug therapy, radiotherapy, and best supportive care, thereby achieving real-time alignment between treatment intensity and patient fitness. This article elaborates on the construction logic and key operational procedures of this novel decision-making framework, aiming to guide clinical practice beyond the limitations of a tumor-centric perspective toward a holistic, dynamic, whole-course management strategy. This transition seeks to ensure optimal quality of life and clinical net benefit for elderly patients alongside survival prolongation.

AIM To evaluate the quality of Croci Stigma from different producing areas.METHODS The analysis was performed on a 25 ℃ thermostatic Waters Acquity UPLC HSS T3 column(2.1 mm× 100 mm,1.8μm),with the mobile phase comprising of 0.1％phosphoric acid-acetonitrile flowing at 0.35 mL/min in a gradient elution manner,and the detection wavelengths were set at 254,440 nm.The UPLC fingerprints were established,after which orthogonal partial least squares discriminant analysis was performed,picrocrocin,crocin-Ⅰ,crocin-Ⅱ,crocin-Ⅲ,crocin-Ⅳ contents and chromaticity values(L*,a*,b*,E*ab)were determined,Pearson correlation analysis was adopted in the investigation of correlations between chromaticity values and internal constituent contents.RESULTS There were 14 common peaks in the fingerprints for 22 batches of medicinal materials with the similarities of more than 0.98.Various batches of medicinal materials were clustered into 2 types,7 quality difference components were screened.crocin-Ⅰ content in medicinal materials from different producing areas demonstrated significant differences(P＜0.05);the redder the color of medicinal material,the higher the contents of crocins.Picrocrocin,crocin-Ⅰ,crocin-Ⅱ,crocin-Ⅳ contents displayed highly significant correlations with colorimetric values(P＜0.01),while crocin-Ⅲ content exhibited no significant correlation with the latter(P＞0.05).CONCLUSION This accurate and reliable method can provide references for the quality control and color-quality relationship elucidation of Croci Stigma.

Objective:To explore the effects three of anesthetics(tribromoethanol,isoflurane,and pentobarbital so-dium)on the outcome of mice with post-stroke dysphagia(PSD)induced by photothrombosis(PT)method,and to e-valuate which anesthetic is more suitable for the preparation of this model.Methods:Sixty-six male C57BL/6J mice were divided into Tribromoethanol group,Isoflurane group,Pentobarbital sodium group and Sham group.The post-stroke dysphagia model was established by PT.Before and 5 min after modeling,a laser speckle imager was used to measure the regional cerebral blood flow(rCBF)decrease rate of mice and record the wake-up time of mice.Forty-eight hours after modeling,the mortality rate of PSD mice in three groups was recorded and the rCBF decrease rate was meas-ured again.The neurological function of mice was evaluated using the neurological deficit score,the water intake of mice was recorded using the 4-min drinking test,the infarct volume ratio was measured using the TTC staining method,and the swallowing counts induced by water administration was recorded using the multichannel physiological recorder MP160 and the myoelectric area of the swallowing muscle was calculated.Results:There was no statistical difference in the percentage of decrease in rCBF,infarct volume ratio,neurological deficit score,water intake,swallowing counts,and myoelectric area of swallowing muscle among the three groups of PSD mice 48 h after modeling(P＞0.05).Com-pared with the Tribromoethanol group and the Pentobarbital sodium group,the rCBF of the mice in the Isoflurane group decreased rapidly within 5 min(P＜0.05),and the mortality rate of the mice was lower and the awakening time was shorter.(P＜0.05).Conclusion:The use of different anesthesia will affect the mortality rate,wake-up time and the downward trend of rCBF within 48 h after modeling of PSD mice.Among the three anesthetics,isoflurane is more suit-able as an anesthetic for the PSD mouse model.

Objective:To explore the effects three of anesthetics(tribromoethanol,isoflurane,and pentobarbital so-dium)on the outcome of mice with post-stroke dysphagia(PSD)induced by photothrombosis(PT)method,and to e-valuate which anesthetic is more suitable for the preparation of this model.Methods:Sixty-six male C57BL/6J mice were divided into Tribromoethanol group,Isoflurane group,Pentobarbital sodium group and Sham group.The post-stroke dysphagia model was established by PT.Before and 5 min after modeling,a laser speckle imager was used to measure the regional cerebral blood flow(rCBF)decrease rate of mice and record the wake-up time of mice.Forty-eight hours after modeling,the mortality rate of PSD mice in three groups was recorded and the rCBF decrease rate was meas-ured again.The neurological function of mice was evaluated using the neurological deficit score,the water intake of mice was recorded using the 4-min drinking test,the infarct volume ratio was measured using the TTC staining method,and the swallowing counts induced by water administration was recorded using the multichannel physiological recorder MP160 and the myoelectric area of the swallowing muscle was calculated.Results:There was no statistical difference in the percentage of decrease in rCBF,infarct volume ratio,neurological deficit score,water intake,swallowing counts,and myoelectric area of swallowing muscle among the three groups of PSD mice 48 h after modeling(P＞0.05).Com-pared with the Tribromoethanol group and the Pentobarbital sodium group,the rCBF of the mice in the Isoflurane group decreased rapidly within 5 min(P＜0.05),and the mortality rate of the mice was lower and the awakening time was shorter.(P＜0.05).Conclusion:The use of different anesthesia will affect the mortality rate,wake-up time and the downward trend of rCBF within 48 h after modeling of PSD mice.Among the three anesthetics,isoflurane is more suit-able as an anesthetic for the PSD mouse model.

BACKGROUND:Buqi Huoxue Compounds have shown significant clinical effects on the treatment of ischemic stroke due to qi deficiency and phlegm stasis,but its specific mechanism of action needs to be further clarified.OBJECTIVE:To observe the effects of Buqi Huoxue Compounds on the neurological function,p-Akt and serum exosome expression in a rat model of cerebral ischemia-reperfusion injury.METHODS:Forty adult male SPF Sprague-Dawley rats,6 weeks old,were randomly divided into sham operation group,model group,Buqi Huoxue Compounds group,Buqi Huoxue Compounds+GW4869 group,with 10 rats in each group.In the latter three groups,a rat model of cerebral ischemia-reperfusion injury was established using thread technique.The sham operation group was given incision and separation without inserting a suture.The Buqi Huoxue Compounds group was intragastrically given Buqi Huoxue Compounds(6.49 g/kg,administered three times a day)2 hours after reperfusion;the GW4869+Buqi Huoxue Compounds group was intragastrically given Buqi Huoxue Compounds(6.49 g/kg,administered three times a day)2 hours after reperfusion and intraperitoneally given GW4869[2.5 mg/(kg·d)]2 hours before gavage with 3 days after modeling.Both the sham operation group and model group received equal amounts of saline via gavage,three times a day,for 7 consecutive days.Neurological function,cerebral infarct volume,brain tissue morphology,characterization of serum exosome,p-Akt in the cortical area and CD63 and TSG101 in serum exosome were detected after 7 days of administration.RESULTS AND CONCLUSION:(1)After modeling,compared with the sham operation group,the neurological function scores of the model group,Buqi Huoxue Compounds group,and Buqi Huoxue Compounds+GW4869 group were significantly increased(P＜0.01 or P＜0.05).After 7 days of intervention,the neurological function scores of the Buqi Huoxue Compounds group were significantly lower than those of the model group and Buqi Huoxue Compounds+GW4869 group(all P＜0.01).(2)The results of 2,3,5-triphenyltetrazolium chloride staining showed that cerebral infarct foci were observed in the model group,Buqi Huoxue Compounds group,and Buqi Huoxue Compounds+GW4869 group,and the cerebral infarct volume in the Buqi Huoxue Compounds group was smaller than that in the model group and the Buqi Huoxue Compounds+GW4869 group(P＜0.01).(3)The results of hematoxylin-eosin staining showed that the morphological and structural abnormalities of nerve cells in the Buqi Huoxue Compounds group and Buqi Huoxue Compounds+GW4869 group were less severe than those in the model group,but some cells still exhibited cytoplasmic agglutination and pyknosis in the Buqi Huoxue Compounds group and Buqi Huoxue Compounds+GW4869 group.(4)NanoSight analysis showed that the diameters of the isolated particles ranged from 60 nm to 300 nm,consistent with the characteristic size of exosomes.(5)Western blot results showed that the expression of p-Akt in the infarct zone and expression of CD63 and TSG101 in serum exosomes were significantly lower in the model group compared with the sham operation group(P＜0.05 or P＜0.01).Compared with the model group,the expression of p-Akt in the infarct zone and expression of CD63 and TSG101 in serum exosomes were significantly higher in the Buqi Huoxue Compounds group than in the model group(P＜0.05 or P＜0.01).However,the p-Akt expression in the infarct zone and CD63 expression in serum exosomes decreased significantly in the Buqi Huoxue Compounds+GW4869 group(P＜0.05),while TSG101 expression decreased without significant difference after the addition of GW4869.(6)To conclude,Buqi Huoxue Compounds attenuate cerebral ischemia-reperfusion injury and increase the expression of p-Akt in rats by promoting exosome secretion.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.