Diabetic cardiomyopathy is a distinct form of cardiomyopathy that can lead to heart failure, arrhythmias, cardiogenic shock, and sudden death. It has become a major cause of mortality in diabetic patients. The pathogenesis of diabetic cardiomyopathy is complex, involving increased oxidative stress, activation of inflammatory responses, disturbances in glucose and lipid metabolism, accumulation of advanced glycation end products (AGEs), abnormal autophagy and apoptosis, insulin resistance, and impaired intracellular Ca²⁺ homeostasis. Recent studies have shown that adenosine monophosphate-activated protein kinase (AMPK) plays a crucial protective role by lowering blood glucose levels, promoting lipolysis, inhibiting lipid synthesis, and exerting antioxidant, anti-inflammatory, anti-apoptotic, and anti-ferroptotic effects. It also enhances autophagy, thereby alleviating myocardial injury under hyperglycemic conditions. Consequently, AMPK is considered a key protective factor in diabetic cardiomyopathy. As part of diabetes prevention and treatment strategies, both pharmacological and exercise interventions have been shown to mitigate diabetic cardiomyopathy by modulating the AMPK signaling pathway. However, the precise regulatory mechanisms, optimal intervention strategies, and clinical translation require further investigation. This review summarizes the role of AMPK in the prevention and treatment of diabetic cardiomyopathy through drug and/or exercise interventions, aiming to provide a reference for the development and application of AMPK-targeted therapies. First, several classical AMPK activators (e.g., AICAR, A-769662, O-304, and metformin) have been shown to enhance autophagy and glucose uptake while inhibiting oxidative stress and inflammatory responses by increasing the phosphorylation of AMPK and its downstream target, mammalian target of rapamycin (mTOR), and/or by upregulating the gene expression of glucose transporters GLUT1 and GLUT4. Second, many antidiabetic agents (e.g., teneligliptin, liraglutide, exenatide, semaglutide, canagliflozin, dapagliflozin, and empagliflozin) can promote autophagy, reverse excessive apoptosis and autophagy, and alleviate oxidative stress and inflammation by enhancing AMPK phosphorylation and its downstream targets, such as mTOR, or by increasing the expression of silent information regulator 1 (SIRT1) and peroxisome proliferator-activated receptor‑α (PPAR‑α). Third, certain anti-anginal (e.g., trimetazidine, nicorandil), anti-asthmatic (e.g., farrerol), antibacterial (e.g., sodium houttuyfonate), and antibiotic (e.g., minocycline) agents have been shown to promote autophagy/mitophagy, mitochondrial biogenesis, and inhibit oxidative stress and lipid accumulation via AMPK phosphorylation and its downstream targets such as protein kinase B (PKB/AKT) and/or PPAR‑α. Fourth, natural compounds (e.g., dihydromyricetin, quercetin, resveratrol, berberine, platycodin D, asiaticoside, cinnamaldehyde, and icariin) can upregulate AMPK phosphorylation and downstream targets such as AKT, mTOR, and/or the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), thereby exerting anti-inflammatory, anti-apoptotic, anti-pyroptotic, antioxidant, and pro-autophagic effects. Fifth, moderate exercise (e.g., continuous or intermittent aerobic exercise, aerobic combined with resistance training, or high-intensity interval training) can activate AMPK and its downstream targets (e.g., acetyl-CoA carboxylase (ACC), GLUT4, PPARγ coactivator-1α (PGC-1α), PPAR-α, and forkhead box protein O3 (FOXO3)) to promote fatty acid oxidation and glucose uptake, and to inhibit oxidative stress and excessive mitochondrial fission. Finally, the combination of liraglutide and aerobic interval training has been shown to activate the AMPK/FOXO1 pathway, thereby reducing excessive myocardial fatty acid uptake and oxidation. This combination therapy offers superior improvement in cardiac dysfunction, myocardial hypertrophy, and fibrosis in diabetic conditions compared to liraglutide or exercise alone.

Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.

Objective To investigate the expression level and clinical application value of G-protein coupled receptor 15 ligand (GPR15L) in patients with systemic lupus erythematosus (SLE). Methods In a retrospective cohort, real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression levels of G-protein coupled receptor 15 (GPR15) mRNA and GPR15L mRNA in peripheral blood from 63 SLE patients (SLE group) and 57 healthy controls (control group). Enzyme-linked immunosorbent assay was employed to measure the serum GPR15L protein expression levels in the SLE group, control group, and 50 rheumatoid arthritis (RA) patients (disease control group). The relationship between serum GPR15L and laboratory indicators as well as therapeutic efficacy in SLE patients was analyzed. Receiver operating characteristic (ROC) curves were used to assess the diagnostic efficacy of serum GPR15 alone and combination with common autoantibody indicators for SLE. Multivariate Logistic regression analysis was conducted to explore the independent risk factors for SLE onset. Results Compared with the control group, the SLE group exhibited increased levels of GPR15 mRNA and GPR15L mRNA in peripheral blood (P=0.016 4, P < 0.000 1, respectively). The serum GPR15L expression in the SLE group was higher than that in the disease control group (P < 0.000 1). The serum GPR15L protein expression level in SLE patients was positively correlated with GPR15L mRNA and disease activity (r=0.301 3, P=0.016 4; r=0.361 7, P=0.003 6) and negatively correlated with complement C3 and C4 levels (r=-0.341 2, P=0.006 2; r=-0.338 4, P=0.006 7). The ROC curves showed that the area under the curve (AUC) for serum GPR15L in distinguishing the SLE group from the control group was 0.870 8, and the AUC for distinguishing the SLE group from the control group was 0.765 5. The diagnostic efficacy of serum GPR15L combined with anti-SSA for SLE was significantly improved, with an AUC of 0.895 2. Multivariate Logistic regression analysis revealed that elevated GPR15L protein and GPR15L mRNA were independent risk factors for SLE onset (P < 0.05). Conclusion The significant increase in serum GPR15L protein levels in SLE patients is closely related to SLE disease activity, and abnormal expression of GPR15L may play an important role in the pathogenesis of SLE.

The post-translational modification of proteins is a key mechanism that imparts physiological functions to proteins,among which reversible phosphorylation modifications play a pivotal role in many biological processes.Aberrant changes in phosphorylation are often closely associated with various major disease processes.In recent years,with the aid of proteomic technologies and methods,high-throughput,high-precision qualitative and quantitative approaches for phosphorylated proteins have rapidly advanced.This article reviews the research progress of phosphorylated protein quantification and chemical proteomics analysis methods based on the"bottom-up"strategy,including phosphopeptide enrichment methods,mass spectrometry fragmentation methods,quantification analysis methods and phosphorylation site stoichiometry,and discusses the development trend of quantification and stoichiometric analysis methods for phosphorylated proteins.

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

AIM: To evaluate retinal vascularization caused by the intravitreal injection of Conbercept in the treatment of a series of retinopathy of prematurity(ROP)cases in Type Ⅰ(threshold and pre-threshold period)and aggressive ROP(A-ROP).METHODS: The data of 34 ROP cases(67 eyes)treated by intravitreal injection of Conbercept(IVC)in the ophthalmology department of the Xiamen Children's Hospital from July 2017 to March 2020 were retrospectively analyzed. Reactivation, which refers to recurrence of acute phase features, occurred at any stage of the disease in the presence or absence of other diseases. RESULT: The average gestational age of the 34 children was 28.82±2.32wk. The average birth weight was 1155.18±398.22g. The lesion zone of 19 cases(37 eyes)was Zone Ⅰ. In 10 cases(20 eyes), the lesion was in Zone Ⅱ, and in 5 cases(10 eyes), the lesion was in the posterior Zone Ⅱ. The total effective rate of disease control in ROP children treated with once IVC was 73.1%(49/67), and the vascularization of Zone Ⅱ was completed. The patients showed variable changes in the vascularization in Zone Ⅲ. For the patients who received one treatment and did not reactivate, the average rate of Type Ⅰ vascularization of ROP was 9.11±2.49wk, and the A-ROP was 13.40±4.04wk. The rate of A-ROP vascularization in Zone Ⅱ was significantly longer compared to Type Ⅰ.CONCLUSION: IVC effectively completes vascularization in Zone Ⅱ.

Humans ; Mpox (monkeypox) ; China

OBJECTIVE: To assess the effect and safety of Reyanning Mixture (RYN) in treating asymptomatic or mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents. METHODS: This is a prospective, open-label, randomized controlled trial. Patients aged 1-17 years and diagnosed with asymptomatic or mild coronavirus disease-2019 (COVID-19) were assigned to an intervention group (RYN plus standard care) and a control group (standard care) according to a randomization list. The primary outcomes were SARS-CoV-2 negative conversion time. Secondary outcomes included negative conversion rate on days 3 and 7, hospital length of stay, symptom relief rate, new-onset symptoms of asymptomatic infected patients, and progressive disease rate. The cycle threshold (Ct) values of ORF1ab or N genes were also tested. RESULTS: A total of 214 patients in the intervention group and 217 in the control group were analyzed. The SARS-CoV-2 negative conversion time was significantly shortened in the intervention group [5 days (interquartile range (IQR): 5-6) vs. 7 days (IQR: 6-7), P<0.01]. By days 3 and 7, the negative conversion rates were significantly higher in the intervention group (day 3: 32.7% vs. 21.2%, P=0.007; day 7: 75.2% vs. 60.8%, P=0.001). Ct values significantly increase on day 2 [ORF1ab gene: 35.62 (IQR: 29.17-45.00) vs. 34.22 (IQR: 28.41-39.41), P=0.03; N gene: 34.97 (IQR: 28.50-45.00) vs. 33.51 (IQR: 27.70-38.25), P=0.024] and day 3 [ORF1ab gene: 38.00 (IQR: 32.72-45.00) vs. 35.81 (IQR: 29.96-45.00), P=0.003; N gene: 37.16 (IQR: 32.01-45.00) vs. 35.26 (IQR: 29.09-45.00), P=0.01]. No significant difference was found in hospital length of stay between the two groups (P>0.05). Symptoms of cough were significantly improved (82.2% vs. 70.0%, P=0.02) and wheezing was significantly reduced (0.7% vs. 12.9%, P<0.01) in the intervention group compared with the control group. During the trial, no disease progression or serious adverse events were reported. CONCLUSION Adding RYN to standard care may be a safe and effective treatment for children with asymptomatic and mild SARS-CoV-2 infection. (Registration No. ChiCTR2200060292).

Seven compounds were isolated from fermentation extract of cave-derived Metarhizium anisopliae NHC-M3-2 by silica gel, semi-preparative HPLC and other chromatographic methods. Their structures were elucidated by UV, IR, MS and NMR methods as 2,3-dehydroindigotide G (1), (-)-regiolone (2), naphtho-γ-pyrone (3), indigotide G (4), indigotide B (5) destruxin A (6) and destruxin B (7). Compound 1 is a new glycoside naphthopyranone compound. The anti-hepatitis B virus (HBV) activity of these compounds was evaluated. The EC₅₀ and CC₅₀ of compound 3 against HBV were 4.5 μmol·L^-1 and 92.3 μmol·L^-1, respectively. This is the first report of the antiviral activity of compound 3.

Abstract:Objective　To investigate the clinical characteristics and early diagnostic methods of patients with Talaromyces marneffei infection, so as to reduce the mortality of patients. Methods The clinical characteristics and microbiological analysis data including fungal culture, smear examination and mass spectrometry were collected from 18 patients with Talaromyces marneffei infection in the Department of Respiratory Medicine, Department of Tuberculosis, and Department of Critical Respiratory Medicine in Fuzhou Pulmonary Hospital from January 2017 to December 2021, and descriptive analysis was conducted. Results　All the 18 patients were confirmed to be infected with Talaromyces marneffei by conventional culture and matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry (MS). The main infection sites of 18 patients with Talaromyces marneffei infection were lungs and lymph nodes, and the patients were accompanied by clinical manifestations such as cough, sputum and fever. The imaging features such as patchy shadows, mediastinal lymph node shadows and nodular shadows were common. Microbiological testing showed a statistically significant difference between smear and culture with a higher positive culture rate (χ2=13.74, P<0.05). The positive rate of blood culture in microbiological test was 60.0% (9/15), the positive rate of bronchial lavage fluid culture was 26.7% (4/15), the positive rate of sputum culture was 5.6% (1/18), one case each of pus, bone marrow, pleural fluid and cerebrospinal fluid was positive for culture and the other cases were negative, one case of sputum and one case of pus were positive for smear and the rest were negative. Colony characteristics showed that the colony morphology was mycelial phase at 25 ℃, producing red pigment, and the branching pattern of the penicillus was seen microscopically as monoverticillate or biverticillate; At 35 ℃, the yeast phase appeared at the initial stage, and then the mycelium phase changed after 5-6 days; the yeast phase was observed at 37 ℃, and yeast-like cells were seen under the microscope. All 18 patients with Talaromyces marneffei infection got better after using antifungal drugs. Compared with non-HIV patients with Talaromyces marneffei infection, leukopenia and anemia were common in HIV patients with Talaromyces marneffei infection, and the differences were statistically significant (P<0.05). 　Conclusions The infection of Talaromyces marneffei can be divided into localized type and disseminated type, which usually invade the lungs, skin, lymph nodes and other places. The main manifestations of patients are fever, cough, phlegm and other atypical symptoms. At present, the diagnosis of Talaromyces marneffei infection is mostly based on the fungal culture test, and the application of MALDI-TOF MS method can effectively shorten the diagnosis time of Talaromycosis marneffei. Clinical characteristics combined with microbiological analysis provide an objective basis for early diagnosis of patients with Talaromyces marneffei infection, and timely use of antifungal therapy can improve the prognosis of patients.