ObjectiveTo observe the effect of Huayu Mingmu prescription on retinal angiogenesis and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR）-hypoxia inducible factor-1α/vascular endothelial growth factor A （HIF-1α/VEGFA） signaling pathway in diabetic retinopathy （DR） rats. MethodsSixty-four SPF-grade male SD rats were used in the study. Eleven rats were randomly selected as the normal group， while the remaining 53 rats were fed a high-sugar， high-fat diet combined with low-dose streptozotocin （STZ） intraperitoneal injection to establish a type 2 diabetes mellitus （T2DM） rat model. DR model evaluation was performed after 12 weeks of diabetes. The rats were then divided into model， low-dose， medium-dose， and high-dose groups of Huayu Mingmu prescription （9.29， 18.57， 37.14 g·kg^-1）， and a calcium dobesilate group （0.16 g·kg^-1）， with 10 rats in each group. The rats were orally administered the corresponding doses of Huayu Mingmu prescription and calcium dobesilate. The normal and model groups received equal volumes of physiological saline via gavage for 8 consecutive weeks. Retinal vascular changes were observed through fundus photography， and pathological changes in retinal tissue were evaluated using hematoxylin-eosin （HE） staining. Retinal microvascular pathological changes were examined through retinal vascular network preparation and periodic acid-Schiff （PAS） staining. Immunofluorescence （IF） was used to detect the expression of VEGFA and angiopoietin-2 （Ang-2） in retinal tissue. Western blot was employed to detect the protein expression of PI3K， Akt， mTOR， HIF-1α， VEGFA， and VEGFR2 in retinal tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to assess the mRNA expression of PI3K， Akt， mTOR， HIF-1α， VEGFA， and VEGFR2 in retinal tissue. ResultsCompared with the normal group， the model group exhibited significant pathological changes in retinal tissue， including the appearance of acellular capillaries， as well as significant endothelial cell （E） proliferation and pericyte （P） loss （P<0.01）. The E/P was significantly elevated （P<0.01）. Protein and mRNA expression levels of PI3K， Akt， mTOR， HIF-1α， VEGFA， and VEGFR2 in retinal tissue were significantly increased （P<0.01）， and the expression of Ang-2 protein was significantly elevated （P<0.01）. In contrast， retinal tissue in the treatment groups showed alleviated pathological changes， with reduced endothelial cell proliferation and pericyte loss （P<0.05， P<0.01）. Among the treatment groups， the high-dose Huayu Mingmu prescription and the calcium dobesilate group exhibited a decreased E/P （P<0.01）. Protein and mRNA expression levels of PI3K， Akt， mTOR， HIF-1α， VEGFA， and VEGFR2 in retinal tissue were significantly reduced （P<0.05， P<0.01）， and the expression of Ang-2 protein was significantly decreased （P<0.01）. ConclusionHuayu Mingmu prescription can intervene in retinal neovascularization in DR rats， delay the progression of DR， and its mechanism may be related to antagonizing the PI3K/Akt/mTOR-HIF-1α/VEGFA signaling pathway.

OBJECTIVE To evaluate the long-term cost-effectiveness of canagliflozin or semaglutide in patients with type 2 diabetes mellitus（T2DM）poorly controlled with metformin. METHODS Based on the perspective of China’s health system， a Markov model was used to calculate the long-term costs and utilities of canagliflozin or semaglutide combined with metformin for T2DM patients in China for 30 years based on the data from SUSTAIN 8 study. The incremental cost-effectiveness ratio（ICER） and incremental net monetary benefit （INMB） were calculated using one time the 2024 per capita gross domestic product（GDP） as the willingness-to-pay（WTP） threshold. One-way sensitivity analysis， probability sensitivity analysis and scenario analysis were conducted to confirm the stability of the conclusions. RESULTS Compared with canagliflozin + metformin， ICER of semaglutide combined with metformin was 260 485.67 yuan/quality-adjusted life year （QALY），which was higher than the WTP threshold set in this study （95 749 yuan/QALY），and the corresponding INMB was －61 576.24 yuan，indicating that the canagliflozin + metformin regimen was more cost-effective. The cost of diabetes without complications treatment in the semaglutide + metformin group had the greatest influence on INMB，but changes in parameters within the selected range did not drive decision reversal. With the increasing of WTP threshold，the economic acceptability of semaglutide + metformin regimen increased. Under the current WTP threshold，the annual cost of semaglutide should be reduced by 42.95% to make the semaglutide + metformin regimen more cost- effective. CONCLUSIONS From the perspective of China’s health system， canagliflozin + metformin is more cost-effective than semaglutide + metformin for T2DM patients yueru. with poor glycemic control with metformin alone.

Objective:To evaluate the utility of the Rapid Axial Roll Test （RART）, Supine Roll Test （SRT）, and Lying-Down Test （LDT） in determining the affected semicircular canal in cases of horizontal semicircular canal benign paroxysmal positional vertigo （HSC-BPPV）. Methods:A total of 330 patients diagnosed with HSCBPPV from September 2022 to September 2023 were collected and divided into three groups based on the different positional tests received: ①SRT Group, ②LDT+SRT Group, ③RART+SRT Group. The trial was divided into two stages: LDT/RART for patients in the first stage, and SRT for patients in the second stage. The elicitation rate of nystagmus among the three groups was compared to evaluate the accuracy in determining the affected semicircular canal in HSCBPPV. Results:Nystagmus was elicited in 84.55% （279/330） of the patients by positional tests. The elicitation rate of nystagmus in the RART+SRT/LDT group was 94.55% （104/110）, in the LDT+SRT group it was 84.11% （90/107）, and in the SRT group it was 69.91% （79/113）. The differences among the three groups were statistically significant （χ²= 23.88, P<0.001）. In the ② and ③ groups, there was a statistically significant difference in the elicitation rate of nystagmus between stage Ⅰ （patients with LDT or RART） （χ²=43.842, P<0.001）. SRT was performed in the stage Ⅱ, and there was a statistically significant difference in nystagmus extraction rate between the two groups （χ² =4.690, P=0.030）. The difference in the proportion of agreement between stage Ⅰ（LDT or RART） and stageⅡ （SRT） in determining the affected side of the semicircular canal was also statistically significant （χ² =40.502, P<0.001）. For patients with a consistent diagnosis of the affected semicircular canal, the difference in cure rate was not significant （P=0.149）. The Kappa statistic indicated substantial agreement between RART and SRT in terms of eliciting nystagmus （agreement 96.36%, Kappa = 0.730, P<0.001）. Conclusion:RART and SRT show a high degree of agreement regarding the elicitation rate of nystagmus. RART is simple and safe, and it can effectively induce the characteristic nystagmus of HSC-BPPV, accurately identify the responsible semicircular canal and provide a more optimized examination protocol for clinical practice in HSCBPPV.
Humans ; Semicircular Canals/physiopathology* ; Benign Paroxysmal Positional Vertigo/diagnosis* ; Female ; Male ; Middle Aged ; Nystagmus, Pathologic/diagnosis* ; Vestibular Function Tests/methods* ; Aged ; Vertigo/diagnosis* ; Adult

OBJECTIVE To evaluate the safety， efficacy， and cost-effectiveness of sodium-glucose co-transporter 2 （SGLT-2） inhibitors for treating type 2 diabetes mellitus （T2DM）. METHODS Retrieved databases such as PubMed， Cochrane Library， Embase， CNKI， as well as relevant health technology assessment （HTA） official websites， HTA reports， systematic review/meta- analysis and pharmacoeconomic studies about SGLT-2 inhibitors （including 12 types such as canagliflozin， dapagliflozin， and empagliflozin） in the treatment of T2DM were collected from the inception to January 28， 2025. After literature screening data extraction and quality assessment， a descriptive analysis was conducted on the results of the included studies. RESULTS A total of 38 articles were included， comprising 30 systematic reviews/meta-analyses， 4 pharmacoeconomic studies， and 4 HTA reports. In terms of effectiveness， most research results showed that canagliflozin was effective in controlling blood glucose， reducing body weight， and lowering blood pressure compared to other SGLT-2 inhibitors， while empagliflozin could effectively reduce all-cause mortality. In terms of safety， compared with other SGLT-2 inhibitors， empagliflozin has a lower overall adverse event rate and cardiovascular death risk， canagliflozin presented a higher risk of hypoglycemia， and dapagliflozin had a higher risk of urinary tract infections. In terms of economics， empagliflozin possessed greater economic advantages over both dapagliflozin and canagliflozin， while canagliflozin offered more benefits than dapagliflozin. CONCLUSIONS The selection of SGLT-2 inhibitors for the treatment of T2DM should be individualized. Canagliflozin is recommended for patients with high cardiovascular risk. Empagliflozin boasts the best overall safety profile. Dapagliflozin should be used with caution in patients at high risk of urinary tract infections. Based on foreign economic evidence， empagliflozin has economic advantages. In the future， drug economic studies under the Chinese health system need to be conducted.

Diabetic cardiomyopathy (DCM) is a medical condition characterized by cardiac remodeling and dysfunction in individuals with diabetes mellitus. Sarcoplasmic reticulum (SR) and mitochondrial Ca²⁺ overload in cardiomyocytes have been recognized as biological hallmarks in DCM; however, the specific factors underlying these abnormalities remain largely unknown. In this study, we aimed to investigate the role of a cardiac-specific long noncoding RNA, D830005E20Rik (Trdn-as), in DCM. Our results revealed the remarkably upregulation of Trdn-as in the hearts of the DCM mice and cardiomyocytes treated with high glucose (HG). Knocking down Trdn-as in cardiac tissues significantly improved cardiac dysfunction and remodeling in the DCM mice. Conversely, Trdn-as overexpression resulted in cardiac damage resembling that observed in the DCM mice. At the cellular level, Trdn-as induced Ca²⁺ overload in the SR and mitochondria, leading to mitochondrial dysfunction. RNA-seq and bioinformatics analyses identified calsequestrin 2 (Casq2), a primary calcium-binding protein in the junctional SR, as a potential target of Trdn-as. Further investigations revealed that Trdn-as facilitated the recruitment of METTL14 to the Casq2 mRNA, thereby enhancing the m⁶A modification of Casq2. This modification increased the stability of Casq2 mRNA and subsequently led to increased protein expression. When Casq2 was knocked down, the promoting effects of Trdn-as on Ca²⁺ overload and mitochondrial damage were mitigated. These findings provide valuable insights into the pathogenesis of DCM and suggest Trdn-as as a potential therapeutic target for this condition.
Animals ; Diabetic Cardiomyopathies/pathology* ; RNA, Long Noncoding/genetics* ; Myocytes, Cardiac/metabolism* ; Mice ; Calsequestrin/genetics* ; Calcium/metabolism* ; Male ; Sarcoplasmic Reticulum/metabolism* ; Methyltransferases/metabolism* ; Mice, Inbred C57BL ; Mitochondria, Heart/metabolism* ; Disease Models, Animal ; Mitochondria/metabolism*

Saponins associated with Panax notoginseng (P. notoginseng) demonstrate significant therapeutic efficacy across multiple diseases. However, certain high-yield saponins face limited clinical applications due to their reduced pharmacological efficacy. This study synthesized and evaluated 36 saponin-1,2,3-triazole derivatives of ginsenosides Rg1/Rb1 and notoginsenoside R1 for anti-adipogenesis activity in vitro. The research revealed that the ginsenosides Rg1-1,2,3-triazole derivative a17 demonstrates superior adipogenesis inhibitory effects. Structure-activity relationships (SARs) analysis indicates that incorporating an amidyl-substituted 1,2,3-triazole into the saponin side chain via Click reaction enhances anti-adipogenesis activity. Additionally, several other derivatives exhibit general adipogenesis inhibition. Compound a17 demonstrated enhanced potency compared to the parent ginsenoside Rg1. Mechanistic investigations revealed that a17 exhibits dose-dependent inhibition of adipogenesis in vitro, accompanied by decreased expression of preadipocytes. Peroxisome proliferator-activated receptor γ (PPARγ), fatty acid synthase (FAS), and fatty acid binding protein 4 (FABP4) adipogenesis regulators. These findings establish the ginsenoside Rg1-1,2,3-triazole derivative a17 as a promising adipocyte differentiation inhibitor and potential therapeutic agent for obesity and associated metabolic disorders. This research provides a foundation for developing effective therapeutic approaches for various metabolic syndromes.
Adipogenesis/drug effects* ; Triazoles/chemical synthesis* ; Ginsenosides/chemical synthesis* ; Saponins/chemical synthesis* ; Animals ; Mice ; Structure-Activity Relationship ; PPAR gamma/genetics* ; 3T3-L1 Cells ; Adipocytes/metabolism* ; Panax notoginseng/chemistry* ; Drug Design ; Molecular Structure ; Humans ; Cell Differentiation/drug effects* ; Fatty Acid-Binding Proteins/genetics*

2-substituted quinolines are the building blocks for the synthesis of natural products and pharmaceuticals. In comparison with classical methods, dehydroaromatization of 2-substituted-1,2,3,4-tetrahydroquinolines has emerged in recent years as an efficient and straightforward method to synthesize quinolines due to its high atom economy and sustainability. However, existing chemical methods need transition metal catalysts and harsh reaction conditions. Biocatalysis with high efficiency, high selectivity, and mild reaction conditions has become an important method of organic synthesis. We mined a strain Pseudomonas monteilii ZMU-T06 capable of producing monoamine oxidase for the dehydroaromatization of 2-substituted-1,2,3,4-tetrahydroquinolines to synthesize 2-substituted quinolines (8 substrates, yields of 45.7%-48.4%) and then hypothesized the catalytic mechanism, providing a new method for green synthesis of 2-substituted quinolines.
Quinolines/chemistry* ; Pseudomonas/classification* ; Oxidation-Reduction ; Monoamine Oxidase/biosynthesis* ; Biocatalysis

Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.

Objective:To investigate the clinical features and genetic variant of a child with West syndrome due to a variant of NEXMIF gene. Methods:A child who was admitted to Department of Pediatrics, the First Medical Center of Chinese PLA General Hospital in March 2021 was selected as the study subject. Clinical data of the patient was collected. The child and his parents were subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing and pathogenicity analysis.Results:The child, a 4-month-old boy, had presented with spastic seizures with no obvious cause. Abnormal EEG, severe hypsarrhythmia, and multiple spastic seizures were discovered. Cranial MRI revealed widening of the extracerebral space at the top of the frontal lobe. Physical examination revealed that he could not hold his head up, and could not respond to sounds or follow objects with eyes. He also has microcephaly, with height < 1 s. The child was diagnosed with West syndrome at a local hospital, and given prednisone orally for 3 months, with seizures under control. Topiramate tablets were taken orally for maintenance treatment, and he has been seizure-free for 7 months. DNA sequencing revealed that he has harbored a de novo nonsense variant of c. 982_c.983delTT (p.L328Dfs*23) in the NEXMIF gene. Conclusion:For children with West syndrome with severe developmental delay or even regression as the first symptoms, uncontrollable seizures and abnormal facial appearance, mutations in the NEXMIF gene should be suspected, and genetic testing can facilitate early diagnosis and treatment.

Objective·To investigate the imaging features of computed tomography(CT)and magnetic resonance imaging(MRI)in the patients with Kimura disease(KD)in the head and neck.Methods·Sixty-four cases of KD in the head and neck comfirmed by histopathology were retrospectively collected from 2009 to 2023 in Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine.All patients completed CT and/or MRI enhancement imaging before surgery.Clinical and imaging characteristics were collected,recorded and analyzed,including age,gender,peripheral blood eosinophilic ratio,serum IgE level,the lesion location,shape,size,CT density and degree of enhancement,MRI signal intensity and degree of enhancement,apparent diffusion coefficient(ADC),time-signal intensity curve(TIC)patterns,wash-in rate,and time to peak(TTP).Results·The average age of the 64 KD patients was(40±19)years,and 92.2%were males.A total of 73.5%of the patients showed an elevated ratio of peripheral blood eosinophil,and all 10 tested patients exhibited increased serum IgE levels.There were 82 extranodal(subcutaneous and glandular)lesions and 144 lymph node lesions detected by CT and MRI.Among the extranodal lesions,80.5%were subcutaneous or glandular patchy lesions with unclear boundaries,and the rest were nodular lesions with clear boundaries.All lesions exhibited isodensity on CT scans and showed isointensity on T1-weighted imaging(T1WI)and hyperintensity on T2-weighted imaging(T2WI)in MRI.Most extranodal lesions tended to show heterogeneous enhancement,while most lymph node lesions showed homogeneous enhancement.The median ADCs of the extranodal lesions and the lymph node lesions were 1.04×10-3 mm2/s and 0.67×10-3 mm2/s,respectively,which were significantly different(P=0.000).The dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)results showed that the TIC patterns of extranodal lesions were predominantly type Ⅰ andⅡ,accounting for 57.5%and 42.5%,respectively;while the TIC patterns of lymph node lesions were predominantly type Ⅱ(96.6%).The difference in the TTP and the wash-in rate between the extranodal lesions and the lymph node lesions were both statistically significant(P=0.000).Conclusion·Extranodal lesions and lymph node lesions of KD both show isodensity on CT,and isointensity on T1WI and hyperintensity on T2WI in MRI.Extranodal lesions often show high ADC,TIC type Ⅰ or Ⅱ,and mostly heterogeneous enhancement;lymph node lesions often show low ADC,TIC type Ⅱ,and mostly homogenous enhancement.