OBJECTIVE To investigate the application and influencing factors of sodium-dependent glucose transporters 2 inhibitors（SGLT-2i） in patients with heart failure with preserved ejection fraction（HFpEF） in the real world. METHODS Data from 358 patients with HFpEF who were hospitalized at the First Affiliated Hospital of Chongqing Medical University from May 2023 to May 2024 were retrospectively collected. The patients were divided into the SGLT-2i group and the non-SGLT-2i group based on whether they were prescribed SGLT-2i upon discharge. Baseline characteristics， comorbidities， and differences in drug treatment were compared between the two groups. Based on univariate analysis， multivariate Logistic regression analysis was performed to identify independent influencing factors of SGLT-2i use in patients with HFpEF， followed by further stratified analysis. RESULTS Among 358 HFpEF patients， the overall utilization rate of SGLT-2i was 33.5%. Combined with type 2 diabetes [OR＝9.063，95%CI（4.924-16.679） ] ， atrial fibrillation [OR＝3.135，95%CI（1.590-6.178） ] ， coronary artery heart disease [OR＝1.888，95%CI（1.072-3.327） ] and the use of loop diuretics [OR＝3.822， 95%CI （1.588-9.200） ] were all independent influencing factors for the use of SGLT-2i in patients with HFpEF （ P ＜0.05）. The results of the stratified descriptive analysis were consistent with those of the multivariate analysis， showing a higher utilization rate of SGLT-2i among patients with concomitant T2DM，atrial fibrillation， coronary artery heart disease， and those receiving loop diuretics （ P ＜0.05）； whereas the utilization rate of SGLT-2i was comparable across patients with different levels of renal function （ P ＞0.05）. CONCLUSIONS In the real-world clinical practice， the utilization of SGLT-2i in patients with HFpEF remains suboptimal， and treatment coverage still needs to be improved. Their use of SGLT-2i is primarily influenced by the presence of type 2 diabetes， atrial fibrillation， coronary artery heart disease， and the use of loop diuretics.

ObjectiveTo investigate whether intestinal deficiency of lanosterol synthase （LSS）， a key enzyme in cholesterol synthesis， influences the progression of metabolic dysfunction-associated steatotic liver disease （MASLD） by regulating intestinal cholesterol absorption and immune response. MethodsLSS heterozygous knockout （LSS^+/-） mice and wild-type （WT） controls were generated using CRISPR/Cas9 technology and fed either a high-fat diet （HFD） or regular chow （CHOW）. The model was validated by genotyping. Hepatic steatosis was assessed by HE and oil red O staining. Immunohistochemistry was used to detect the localization and expression of NPC1L1 and CD36 proteins in the intestine. Western blot analysis was performed to measure JNK phosphorylation and TLR4 protein levels in intestinal tissues. Real-time quantitative polymerase chain reaction （qPCR） was employed to examine the mRNA expression of TLR4 and IL-6. ResultsLSS^+/- mice were successfully validated by genotyping and reduced intestinal LSS protein expression. HE and oil red O staining of liver sections showed that， compared with WT mice fed a CHOW diet， WT mice fed a HFD exhibited a marked increase in hepatic lipid vacuoles. In contrast， compared with HFD-fed WT mice， HFD-fed LSS^+/- mice displayed significantly attenuated hepatic lipid deposition and reduced serum ALT levels （P<0.05）. Immunohistochemical analysis revealed that， compared with WT mice， the expression of the cholesterol absorption protein NPC1L1 in the intestinal villi of LSS^+/- mice was downregulated under both CHOW and HFD conditions （P_HFD<0.001）. Conversely， the expression of the fatty acid transporter CD36 was upregulated in the intestines of LSS^+/- mice （P_CHOW<0.05， P_HFD<0.01）. Western blot analysis demonstrated that， compared with WT mice， TLR4 protein expression in the intestines of LSS^+/- mice significantly increased under both CHOW and HFD conditions （both P<0.05）. JNK phosphorylation level was significantly elevated in LSS^+/- mice under CHOW condition （both P<0.05）. Under HFD condition， total JNK protein expression increased， but its phosphorylation level showed no significant change. qPCR analysis showed that， compared with WT mice， the mRNA levels of TLR4 （P_CHOW<0.01， P_HFD<0.000 1） and IL-6 （P_CHOW<0.001， P_HFD<0.01） were significantly upregulated in the intestines of LSS^+/-mice. ConclusionLSS deficiency counteracts hepatic lipid deposition by orchestrating a synergistic reprogramming involving restricted intestinal cholesterol absorption， enhanced fatty acid utilization， and activation of immune pathways， suggesting intestinal LSS as a potential therapeutic target of MASLD.

ObjectiveTo investigate the effect of hypoxia on pemetrexed （PE）-mediated apoptosis in non-small cell lung cancer cells. MethodsA549 cells were cultured under 21% O₂ （normoxia） or 1% O₂ （hypoxia）， and treated with 8 μmol/L PE for 48 h. The cells were divided into normoxic control group， normoxic vehicle group， normoxic drug-treated group， hypoxic control group， hypoxic vehicle group and hypoxic drug-treated group. Trypan blue staining was used to observe cell death after PE intervention under normoxia and hypoxia. Flow cytometry was adopted to detect cell apoptosis rate. Wound healing assay was used to assess cell migration. Western blot was performed to detect the protein levels of MRP-1， Cleaved Caspase-3， E-Cadherin and N-Cadherin. ResultsTrypan blue staining results showed that the cell death rate was reduced in PE-treated cells under hypoxia compared with the normoxic PE group （P<0.001）. Flow cytometry results indicated that PE induced cell apoptosis under both normoxic and hypoxic conditions.However， the apoptosis rate of the normoxic PE group was significantly higher than that of the hypoxic PE group （P<0.000 1）. Wound healing assay showed that the migration distance of A549 cells decreased after PE treatment for 24 h and 48 h under normoxia and hypoxia when compared with the control group （P<0.05）， while no significant difference was found between the normoxic PE group and the hypoxic PE group. Western blot results revealed that MRP-1 expression was markedly higher in hypoxic PE-treated cells than in normoxic PE-treated cells （P<0.000 1）. Compared with the control group， Cleaved Caspase-3 expression was upregulated in A549 cells following PE intervention under normoxia （P<0.05）， whereas no obvious alteration in Cleaved Caspase-3 expression was detected in hypoxic PE-treated cells. Under both normoxic and hypoxic conditions， PE treatment downregulated the expression of E-Cadherin （P<0.000 1，P<0.001） and N-Cadherin （P<0.05，P<0.000 1）. In addition， the expression levels of E-Cadherin and N-Cadherin in the hypoxic PE group were significantly lower than those in the normoxic PE group （all P<0.000 1）. ConclusionHypoxia significantly attenuates the pro-apoptotic effect of PE on A549 cells and blocks Cleaved Caspase-3 activation. This mechanism may be related to hypoxia-induced MRP-1 overexpression and reduced drug accumulation. Interfering with MRP-1 or restoring the activity of the apoptosis pathway may serve as a novel strategy to overcome hypoxia-induced drug resistance.

BackgroundPatients with bipolar disorder exhibit persistent cognitive impairment across multiple domains， including executive function， memory， and attention. Furthermore， those with mixed features tend to have a poorer prognosis. Currently， research evidence regarding the characteristics of cognitive function and event-related potential P300， as well as their correlation， in patients with depressive episodes of bipolar disorder with mixed features remains limited. ObjectiveTo explore the correlation between cognitive function and event-related potential P300 in patients with depressive episodes of bipolar disorder with mixed features， analyze the influencing factors of cognitive function， so as to provide references for the improvement of cognitive function in this subtype of patients. MethodsA total of 73 patients who met the diagnostic criteria for depressive episodes of bipolar disorder in the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） were enrolled from the outpatient and inpatient departments of Tianjin Anding Hospital from November 2021 to April 2024. The Hamilton Depression Scale-17 item（HAMD-17） was used to assess the severity of depressive symptoms， and the Clinically Useful Depression Outcome Scale Supplemented with Questions for the DSM-5 Mixed Features Specifier （CUDOS-M） was used to evaluate whether patients presented with mixed features. Based on the CUDOS-M total scores， patients were divided into two groups： the mixed features group （n=34） and the non-mixed features group （n=39）. The MATRICS Consensus Cognitive Battery （MCCB） was used to assess cognitive function， and auditory event-related potential P300 testing was performed. Spearman correlation analysis was used to examine the correlations between P300 indicators and MCCB scores. Multiple linear regression analysis was conducted to investigate the influencing factors of cognitive function. ResultsPatients with depressive episodes of bipolar disorder with mixed features had a longer total illness duration than those without mixed features， and the difference was statistically significant （t=2.030， P<0.05）. Analysis of covariance showed that the MCCB scores for processing speed， attention/vigilance， and reasoning and problem solving were all lower in the mixed features group than those in the non-mixed features group （F=3.650， 3.520， 4.213， P<0.01）. However， no significant difference was found between the two groups in P300 latency or amplitude （P>0.05）. Correlation analysis revealed that the MCCB attention/vigilance score was negatively correlated with P300 latency in patients with depressive episodes of bipolar disorder with mixed features （r_s=-0.576， P<0.01）. Multiple linear regression analysis showed that， in the mixed features group， years of education positively predicted processing speed （β=0.378， P<0.05）， while P300 latency （β=-0.699， P<0.01） and age （β=-0.424， P<0.01） negatively predicted attention/vigilance function. ConclusionPatients with depressive episodes of bipolar disorder with mixed features have a longer illness duration and more severe impairment in three cognitive domains： processing speed， attention/vigilance， and reasoning and problem solving. P300 latency may be an influencing factor of attention/vigilance function in patients with depressive episodes of bipolar disorder with mixed features ［Funded by Tianjin Key Medical Discipline Construction Project （number， TJYXZDXK-3-015B）； Hospital-level Scientific Research Project of Tianjin Anding Hospital （number， ADYKHT2021010）］

Objective To evaluate the efficacy and safety of enteric-coated metformin hydrochloride capsules(Junlida?)in patients with T2DM and poor glycemic control under lifestyle interventions.Methods In this study,419 patients with T2DM were recruited from 15 research centers from July 2020 to March 2022,and randomly divided into observation(Obs)group(n=209)and control group(Con,n=210)using a multicenter,randomized,double-blind,non-inferiority trial design.Patients in the Obs group were treated with enteric-coated Metformin hydrochloride capsules(Junlida?),and patients in the Con group were treated with Metformin hydrochloride tablets(Glucophage?).The optimal effective dose of 2 g/d was achieved within 4 weeks,and the reasonable dose was maintained until the end of treatment.The treatment period was 24 weeks.HbA1c and its compliance rate,FPG,and body weight were compared between the two groups in full analysis set(FAS)and protocol set(PPS).Safety and adverse events(AE)were evaluated in safety set(SS).Results A total of 414 participants were randomized(207 cases in Obs group and 207 cases in Con group).414 cases in FAS population(207 cases in Obs group and 207 cases in Con group),and 328 cases in PPS population(164 cases in Obs group and 164 cases in Con group),and 414 cases in SS population(207 cases in Obs group and 207 cases in Con group).After treatment,HbA1c,FPG and body weight were lower in both groups(P<0.05)in FAS and PPS.HbA1c compliance rate was not significantly different between the two groups in FAS and PPS(P>0.05).The results of non-inferiority test showed that the lower limit was>-0.4%in both FAS(-0.154,95%CI-0.384～0.069)and PPS(-0.139,95%CI-0.390～0.112),and the Obs group reached non-inferiority end point.The achievement rate,compliance rate,safety index and incidence of AE were not significantly different between the two groups(P>0.05).Conclusions Junlida? demonstrated non-inferiority to Glucophage? in glycemic control and can be safely and effectively used in patients with diabetes.

In recent decades,the incidence of human papillomavirus(HPV)-associated oropharyngeal squamous cell carcinoma(OPSCC)has shown a marked increase.Significant changes have also occurred in the OPSCC diagnosis and treatment paradigm.Deter-mining HPV status prior to treatment is now essential,and radiotherapy/chemotherapy,immunotherapy,and minimally invasive surgical techniques have progressively emerged as key modalities for managing OPSCC.However,alongside these paradigm shifts,a comprehen-sive technical consensus guiding the entire diagnostic and therapeutic process for OPSCC patients is currently lacking.Given China's large population base and the rising incidence of OPSCC,an expert panel convened to develop a clinical technical consensus on OPSCC diagno-sis and management tailored to China's specific context.This consensus aims to further enhance and standardize understanding of OPSCC management techniques among relevant healthcare professionals.

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective:To explore the application value of the double-low technique of auto-prescription technique combined with iterative reconstruction algorithm in CT pulmonary angiography (CTPA).Methods:A total of 86 patients who were clinically suspected of having pulmonary embolism and underwent CTPA examination in the First Affiliated Hospital of Dalian Medical University were prospectively collected and randomly assigned to a control group ( n = 45) and an observation group ( n = 41) according to the random number table method. In the control group, a tube voltage of 120 kVp was used with a standard iodine contrast agent dose of 60 ml, and images were reconstructed using the 40% adaptive statistical iterative reconstruction algorithm (ASIR-V). In the observation group, the tube voltage was set by auto-prescription technique, and 0.4 ml/kg of personalized low iodine contrast agent was used. Images were reconstructed with 40%, 60%, and 80% ASIR-V, respectively, and designated as observation 1, observation 2, and observation 3 respectively. The volume CT dose index (CTDI vol), dose-length product (DLP), and effective dose ( E) were recorded and compared among the four groups. The CT values and standard deviation (SD) of the main pulmonary artery, left and right pulmonary arteries, as well as the left and right pulmonary lobe arteries were measured, and the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of these arteries were calculated. Additionally, the SD value at the contrast medium concentration in the superior vena cava was measured, and the artifact index (AI) was subsequently calculated. Two observers independently assessed the visibility of the pulmonary arteries, image noise, and sclerosis artifacts in the superior vena cava using a blinded method. Results:The E in the observation group was 3.28 (2.08, 3.93) mSv, which was significantly lower than that in the control group [5.03 (4.86, 5.20)] mSv, and the difference was statistically significant ( Z = 174.00, P < 0.05). The contrast agent dosage in the observation group was 28 (25, 30) ml, which was lower than that in the control group (60 ml), and the difference was statistically significant ( Z = 0, P < 0.05). The CT values for the main pulmonary artery and the left and right pulmonary lobe arteries in the observation group were higher than those in the control group, and the differences were all statistically significant ( t = -3.65 to -3.89, P < 0.05). The SNR and CNR of the observation groups 2 and 3 were greater than those of the control group ( t = -9.20 to -2.98, P < 0.05). The consistency of subjective evaluations between the two observers was good ( Kappa = 0.729 - 0.879, P < 0.05). There was no statistically significant difference in the subjective score of pulmonary artery visibility between the control and observation group ( P > 0.05). The subjective scores for image noise in observation group 2 and group 3 were higher than those in the control group ( U =598.50, 654.00, P < 0.05). The presence of artifacts due to sclerosis in the superior vena cava was significantly lower in the observation group compared to the control group ( χ2 = 46.09, P < 0.001). Conclusions:The combination of auto-prescription technique with ASIR-V reconstruction algorithm and low contrast agent imaging protocol can reduce the radiation dose and contrast agent dose without compromising image quality, and enable personalized double low CTPA imaging.

Objective To explore the application value of deep learning image reconstruction(DLIR)algorithm combined with a large reconstruction matrix in lung nodules screening using low-dose computed tomography(LDCT)of the chest.Methods Patients who underwent LDCT scans were prospectively enrolled.The control group(group A)used the iterative reconstruction(IR)algorithm(Karl)with a reconstruction level of Karl 5,reconstructed images of 512×512(group A1)matrix,and 1 024 × 1 024(group A2)matrix.The experimental group employed DLIR combined with 512×512(group B)matrix and 1 024 × 1 024(group C)matrix for image reconstruction at levels 1-5,which were recorded as groups B1-5 and groups C1-5.The CT values and standard deviation(SD)values of the lung parenchyma and tracheal air were measured,and the signal-to-noise ratio(SNR)was calculated.The overall lung image quality was scored on a Likert 5-point scale,and the subgroup with the best lung image quality was selected.The lung nodule detec-tion rate and clarity were compared with group A1.Results Under the same reconstruction matrix,the CT values of the tracheal air and lung parenchyma in the experimental group showed no significant difference compared to the control group,while the SD values were lower and SNR were higher(P＜0.05).Within groups B and C,as the DLIR level increased,the SD values of the tracheal air and lung paren-chyma gradually decreased,and SNR gradually improved(P＜0.05).Subjective scores for the image quality in groups B and C initially increased and then decreased,with group B3 and group C4 showed the best image quality.No difference was observed in objective eval-uation between the two groups,but the subjective image quality score of group C4 was superior to group B3(P＜0.05).Subjective eval-uation of lung nodule display in group C4 was better than in group A1(P＜0.05).Conclusion DLIR algorithm combined with a large reconstruction matrix is feasible for lung nodules screening in chest LDCT,reducing image noise while improving lung nodules clarity,demonstrating significant clinical value.