Diabetic cardiomyopathy （DCM） is one of the most common complications of diabetes mellitus and is a major threat to global health. As a key mechanism in the occurrence and progression of DCM， the inflammatory response persists throughout the entire course of the DCM. The Gaozhuo theory suggests that the basic pathogenesis of inflammatory injury in DCM is the Qi deficiency of spleen and kidney and Gaozhuo invasion， and divides the pathological process into three phases： Gaozhuo invasion， turbid heat damage to the channels， and turbid blood stasis and heat junction. Among them， the Qi deficiency of spleen and kidney and the endogenous formation of Gaozhuo represent the process of inflammatory factor formation induced by glucose metabolism disorders. Turbid heat damage to the channels refers to the process of myocardial inflammatory injury mediated by inflammatory factors， and turbid blood stasis and heat junction are the process of myocardial injury developing toward myocardial fibrosis and ventricular remodeling. As the disease continues to progress， it eventually develops into a depletion of the heart Yang， leading to the ultimate regression of heart failure. According to the theory of Gaozhuo， traditional Chinese medicine （TCM） should regulate inflammatory injury in DCM by strengthening the spleen and tonifying the kidney to address the root cause， and resolving dampness and lowering turbidity to treat the symptoms. If the turbidity has been stored for a long time and turns into heat， strengthening the spleen and tonifying the kidney， and clearing heat and resolving turbidity should be the therapy. If the turbidity， stasis， and heat are knotted in the heart and collaterals， strengthening the spleen and tonifying the kidney， and resolving stasis and lowering turbidity should be the therapy. TCM compounds and monomers can regulate the inflammatory response in DCM. TCM compounds can be divided into the categories for benefiting Qi to resolve turbidity， benefiting Qi and clearing heat to resolve turbidity， and benefiting Qi and activating blood to reduce turbidity. The compounds can inhibit upstream signals of inflammation and expression of inflammatory factors， improve the inflammatory damage to myocardium and blood vessels， myocardial fibrosis， and cardiac systole and diastole， and thus slow down the onset and progression of DCM.

ObjectiveTo investigate the preventive and therapeutic effects of Qingfei Paidu decoction (QFPDD) on acute lung injury (ALI) in mice and its underlying molecular mechanisms based on miRNA sequencing technology. MethodsTwenty-four 4-week-old male KM mice were randomly divided into a control group, a model group, and a QFPDD group (n = 8 per group). After one week of acclimatization, mice in the control and model groups were intragastrically administered ultrapure water (0.2 mL per dose), whereas mice in the QFPDD group were intragastrically administered QFPDD (1.6 g crude drug/mL, 0.2 mL per dose), twice daily for 8 consecutive days. On days 2–8, mice in the model and QFPDD groups were exposed to aerosolized lipopolysaccharide (LPS) solution (2.5 g/L, 4 mL per exposure) for 7 consecutive days. On day 9, blood was collected via the retro-orbital venous plexus under deep anesthesia, and lung tissues were harvested. Body weight and lung weight were measured, and the lung coefficient was calculated. Serum levels of inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 were detected by ELISA. Lung histopathological changes were observed by HE staining of paraffin-embedded sections. miRNA expression profiles in lung tissues were analyzed using the Illumina HiSeq 2500 sequencing platform. Target genes of differentially expressed miRNAs were predicted using bioinformatics databases, and functional enrichment analysis of these target genes was performed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Differentially expressed miRNAs were validated by reverse transcription quantitative real-time PCR (RT-qPCR). ResultsCompared with the control group, the model group showed a consistent body weight growth trend but a significantly increased lung coefficient (P < 0.01). ELISA results showed that serum levels of TNF-α and IL-6 were significantly elevated in the model group compared with the control group (P < 0.01), whereas QFPDD treatment significantly reduced serum TNF-α and IL-6 levels compared with the model group (P < 0.05). HE staining showed that, compared with the control group, the model group exhibited widened alveolar septa, massive inflammatory cell infiltration, partial alveolar expansion, and mild capillary dilation with congestion. In contrast, the QFPDD group showed only slightly widened alveolar septa and mild inflammatory cell infiltration compared with the model group. Intersection analysis of miRNA sequencing data identified 13 differentially expressed miRNAs common to both the model vs. control and QFPDD vs. model comparisons. Among them, 6 miRNAs (mmu-miR-203-3p, mmu-miR-181b-5p_R-1, hsa-miR-4286_R+1, mmu-miR-1843b-5p_L+1R-1_2, mmu-miR-22-3p, and mmu-miR-1964-3p) were significantly up-regulated in the model group (P < 0.05) and significantly down-regulated after QFPDD treatment (P < 0.05), showing a therapeutic reversal trend. GO analysis revealed that the target genes of the differentially expressed miRNAs were mainly enriched in biological processes such as RNA polymerase Ⅱ transcriptional regulation. KEGG analysis indicated that target genes were mainly enriched in signaling pathways including the mitogen-activated protein kinase (MAPK) pathway. RT-qPCR validation result for mmu-miR-203-3p was consistent with the sequencing analysis results. ConclusionQFPDD may exert preventive and therapeutic effects against ALI by regulating the expression of mmu-miR-203-3p and other miRNAs, thereby modulating inflammatory responses and the MAPK signaling pathway and participating in the pathological process of lung injury.

Objective To compare the efficacy and tolerability of the novel bowel-cleansing agent TCIC-001 and the traditional polyethylene glycol (PEG) regimen for bowel preparation prior to colonoscopy. Methods Prospective inclusion of 62 patients who were scheduled to undergo colonoscopy at Zhongshan Hospital, Fudan University from July 2021 to July 2022. They were randomly divided into TCIC-001 group (n=31) and PEG group (n=31) using a random number table method. The TCIC-001 group took TCIC-001 orally, drinking water in stages, with a total liquid intake of 1 500 mL; the PEG group took PEG orally, taking it in 4 doses, with a total liquid intake of 3 000 mL. The primary endpoint indicator is the quality of intestinal hygiene evaluated by the Boston Bowel Preparation Scale (BBPS), the secondary endpoint indicators were medication adherence, medication duration, frequency of bowel movements, duration of bowel movements, and incidence of adverse events between two groups. Results No significant differences were observed in sex, age, or defecation frequency between the two groups. For efficacy, both groups achieved equivalent bowel cleanliness, with a “good preparation” rate of 93.55% and comparable BBPS score of each intestinal segment and total scores. For tolerability, the TCIC-001 group had a shorter medication duration compared to the PEG group ([48.8±25.9] min vs [82.8±28.4] min, P<0.001), a longer defecation duration ([288.6±74.0] min vs [236.5±74.3] min, P<0.001), and a lower incidence of first defecation before medication completion (9.68% vs 41.94%, P=0.004). Regarding safety, no significant differences were observed between the TCIC-001 group and the PEG group in incidences of chloride disturbances (0% vs 9.68%) and calcium disturbances (3.23% vs 6.45%), and no other adverse events. Conclusions TCIC-001 demonstrated comparable bowel-cleansing efficacy to PEG while significantly improving tolerability (reduced medication time and lower risk of premature defecation) and maintaining favorable safety.

Preeclampsia(PE)is a severe pregnancy complication that poses significant risks to maternal and fetal health,and its pathogenesis remains unclear.Recent studies have shown that lactate dehydrogenase(LDH),a key enzyme in glycolysis,plays a piv-otal role in the development and progression of PE.This article reviews the abnormal changes in the levels of LDH and its isozymes in serum and placental tissue and their impact on the pathogenesis of PE and analyzes the molecular mechanisms by which LDH subunits contribute to placental dysfunction through multiple pathways including hypoxia,inflammation,autophagy dysregulation,and cellular damage.In addition,this article discusses the role of lactate,a metabolic product of LDH activity,in the pathogenesis of PE.LDH can be used as a potential biomarker for PE,and the regulation of non-metabolic functions and metabolic reprogramming mediated by LDH provide new targets for the prevention and treatment of PE.

Objective To investigate the effect and mechanisms of celecoxib on right heart function in mice with acute high-altitude hypoxia exposure.Methods Male C57BL/6J mice(7 weeks old)were housed in a hypobaric chamber simulating an altitude of 5 800 m for 2 d to establish an animal model of acute hypobaric hypoxia.①Eighteen mice were randomly assigned to plain+saline(P+S),high-altitude hypoxia exposure+saline(H+S),and high-altitude hypoxia exposure+celecoxib(H+Cel).Body weight and routine blood indicators were measured,and cardiac ultrasound examination were performed for heart rate(HR),pulmonary artery acceleration time to ejection time ratio(AT/ET),tricuspid annular plane systolic excursion(TAPSE),tricuspid annular systolic velocity(S'),and left ventricular ejection fraction(LVEF)and fractional shortening(FS).Targeted metabolomic profiling was applied to detect the cardiac arachidonic acid(AA)metabolite levels.The contents of 12,13-dihydroxy-9Z-octadecenoic acid(12,13-diHOME)in the heart,liver,brown adipose tissue,and plasma were quantified by ELISA.② Eighteen mice were randomly assigned into plain+saline(P+S),high-altitude hypoxia exposure+saline(H+S)and high-altitude hypoxia exposure+12,13-diHOME(H+di)groups.Body weight,routine blood tests,and echocardiography were performed as above.③ Thirty-two mice were randomly divided into high-altitude hypoxia exposure+saline(H+S),high-altitude hypoxia exposure+celecoxib(H+Cel),high-altitude hypoxia exposure+soluble epoxide hydrolase inhibitor(sEHI)(H+sEHI),and high-altitude hypoxia exposure+sEHI+celecoxib(H+sEHI+Cel)groups.Body weight,routine blood tests,and echocardiography were performed as above.Cardiac and plasma contents of 12,13-diHOME and epoxyeicosatrienoic acids(EETs)were measured by ELISA.Results ① Compared to the P+S group,the H+S group exhibited significantly reduction of cardiac 12,13-diHOME level(P<0.001),increased counts of white blood cells(WBC)and neutrophils(P<0.01)and decreased TAPSE,S'and AT/ET both at resting state and under stress(P<0.01,P<0.001).Compared to the H+S group,the H+Cel group exhibited significantly increase of cardiac 12,13-diHOME level(P<0.05),reduced WBC and lymphocyte counts(P<0.01,P<0.05)and improved TAPSE and S'levels at resting state and under stress(P<0.01,P<0.001).② Compared to the H+S group,the H+di group demonstrated significantly improvement of TAPSE at basal and under stress(P<0.001)and a trend towards improved TAPSE at resting state(P=0.0532),but no obvious differences was observed in WBC and neutrophil counts between the H+di group and the H+S group.③ Compared to the H+Cel group,both the H+sEHI and H+sEHI+Cel groups exhibited significantly reduction of cardiac 12,13-diHOME level(P<0.01,P<0.05)though no statistical changes in cardiac function indicators.Compared to the H+S group,WBC counts and lymphocyte were decreased,and serum EETs level was incrased in the H+Cel group,H+sEHI group and H+sEHI+Cel group(P<0.01,P<0.001).Conclusion Celecoxib can elevate cardiac level of 12,13-diHOME and improves right heart function in mice after acute high-altitude hypoxia exposure through the CYP450-sEH metabolic pathway.

Objective To explore the diagnostic value of brain cord blood flow ultrasound combined with glucose metabolism indexes in the patients with preeclampsia(PE)complicated with fetal growth restriction(FGR).Methods This study was a prospective cohort case-control study.A total of 198 PE patients admitted to the hospital from January 2017 to January 2022 were collected and divided into group A(PE patients com-plicated with FGR,101 cases)and group B(PE patients without FGR,97 cases)according to whether they were complicated with FGR.45 pregnant women with healthy prenatal examination in the hospital were se-lected as group C,and the differences of brain cord blood flow ultrasound indexes and glucose metabolism inde-xes among the three groups and the efficiency for diagnosing PE complicated with FGR were analyzed.Results Fast-ing blood glucose and fasting insulin levels in group A,group B and group C were gradually decreased(P＜0.05).The peak systolic flow velocity/peak diastolic flow velocity(S/D),resistance index(RI)and pulsatility index(PI)of middle cerebral artery(MCA)of fetus in group A,group B and group C increased gradually(P＜0.05).The levels of umbilical artery(UA)of fetus in group A,group B and group C decreased gradually(P＜0.05).The area under the curve of fasting insulin,fasting blood glucose,S/D,RI and PI of MCA,S/D,RI,PI of UA and the combined detection were 0.782,0.748,0.765,0.836,0.805,0.758,0.811,0.795 and 0.895,respectively.The diagnostic efficiency of combined detection was higher than that of single diagnosis(Z=4.327,4.862,4.551,3.400,3.946,4.679,3.742,4.102,P＜0.05).Conclusion The combined detection of glucose metabolism indexes and brain cord blood flow ultrasound indexes is of great value in the differential diagnosis of patients with PE complicated with FGR,and has good clinical application value.

Objective To explore an epileptic seizure prediction method for patients with refractory epilepsy to improve the classification and prediction efficiency of epileptic electroencephalogram(EEG)signals.Methods The study used the long-term EEG database of patients with intractable epilepsy from Children's Hospital Boston(CHB-MIT).The EEG features of epileptic seizures and preictal periods were extracted from multiple dimensions such as EEG synchronization,complexity,and energy distribution,and then these features were input into the artificial neural network model for classification and identification,thereby achieving accurate prediction of epilepsy.The performance were optimized by adjusting the model parameters,and a comparative evaluation was conducted with existing deep learning models.Results The model proposed in this study showed an accuracy rate of 99.29％,a precision of 91.44％,a sensitivity of 96.46％,and a specificity of 99.46％.Compared with current epilepsy seizure prediction studies based on machine learning or deep learning frameworks,the model in this study improved its classification prediction capabilities and demonstrated higher prediction accuracy.Conclusion An effective prediction of epileptic seizures was achieved by manually extracting epileptic EEG features and constructing an artificial neural network model.The model demonstrated high accuracy and stability,providing reliable technique to support clinical treatment and prevention of epilepsy.

Female reproductive aging refers to the process that ovarian function gradually declines with age, leading to the decline of fertility and related physiological dysfunction. In recent years, the research on anti-female reproductive aging active molecules has become a hot spot in the medical field, aiming at delaying ovarian aging and improving reproductive health. In this paper, the main sources of anti-female reproductive aging molecules are reviewed, including natural products, endogenous molecules and synthetic small molecules, with emphasis on resveratrol, curcumin, soybean isoflavones, nicotinamide adenine dinucleotide precursors (such as nicotinamide mononucleotide) and mitochondrial targeting molecules. These molecules play an important role in delaying ovarian aging and maintaining ovarian function through various mechanisms such as antioxidant stress, regulating autophagy and apoptosis, anti-inflammatory and immunomodulation, and telomere protection. However, from laboratory research to clinical application, it still faces multiple challenges such as bioavailability, long-term safety and individual differences. Future research needs to further optimize the delivery system, carry out long-term clinical trials, and explore individualized treatment strategies to promote the clinical transformation and application of anti-female reproductive aging molecules.

This study aims to simultaneously detect three antibiotic resistance genes(blaNDM,mcr-1 and cfr).A triplex fluorescence quantitative PCR method was established.Plasmids,primers and probes were designed and optimized.The method could specifically detect blaNDM,mcr-1 and cfr,but not other antibiotic resistance genes.The R2 of the standard curves of the three antibiotic re-sistance genes were all greater than 0.999,and the coefficients of variation were all lower than 1％.The lowest detection limits of the plasmids were 1 × 102 copies/μL.This method was used to de-tect 800 bacterial samples.The results showed that 32 samples contained mcr-1 gene,40 samples contained blaNDM gene,2 samples contained cfr gene,8 samples contained both mcr-1 and blaNDM genes.There were no samples carrying three antibiotic resistance genes detected.The results indica-ted that the triplex fluorescence quantitative PCR method established in this experiment had the advantages of high sensitivity,specificity and stability.It was suitable for rapid detection of blaNDM,mcr-1 and cfr antibiotic resistance genes in clinical practice.It provided a convenient and quick method basis for the detection of antibiotic resistance genes.

Objective:To analyze the results of next generation sequencing (NGS) gene testing in liquid-based cytological specimens of lung adenocarcinoma cavity and evaluate the clinical efficacy of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment.Methods:Liquid based cytological specimens of 222 cases of lung adenocarcinoma with cavity effusion and 201 cases of metastatic lymph node biopsy were collected. Specimens were obtained from the Cytology Laboratory of the Cancer Hospital of the Chinese Academy of Medical Sciences. The collection period was from January 2018 to December 2022. The results of NGS gene detection were compared. The clinical efficacy of 91 patients treated with EGFR-TKI was evaluated, and the survival curve was analyzed by Kaplan-Meier and other statistical methods.Results:The mutation rates of cancer-related genes detected by NGS were 82.0% (182/222) vs 79.1% (159/201), ( P=0.455) in liquid-based cytological specimens and histological specimens of metastatic lymph node biopsy, respectively. However, the mutation rate of EGFR T790M was significantly higher in cavity effusion than in lymph node biopsy specimens [12.2%(27/222)＞3.5%(7/201), P=0.001]. The results of gene mutation were identical in 10 of the 13 cases with cavity effusion and metastatic lymph node biopsy, and the agreement rate of EGFR was 84.6%(11/13). In 3 inconsistent cases, EGFR mutations were detected in 2 cavity effusion cases that were not detected by lymph node biopsy. Results of genetic analysis of fluid-based cytological samples of 91 patients with cavity effusion were evaluated after drug treatment with EGFR-TKI. The mean progression-free survival (PFS) of the patients was 11.4 months (95% CI: 9.9-12.9). The mean PFS of patients harboring EGFR mutation was 12.3 months (95% CI: 10.8-13.9), and the mean PFS of EGFR wild type was 4.1 months (95% CI: 2.1-6.2). Conclusions:The results of NGS gene detection in liquid-based cytological specimens of lung adenocarcinoma patients with cavity effusion show that the PFS time is similar to that of histological specimens after clinical treatment with EGFR-TKI, which proves the reliability of NGS gene detection results in liquid cytological specimens. NGS gene testing appears higher sensitivity in cavity liquid-based samples than in metastatic lymph node samples.