AIM:To investigate the effect of ranibizumab on blood flow density in different regions of the macula in patients with macular edema(ME)secondary to ischemic and non-ischemic branch retinal vein occlusion(BRVO).METHODS:This retrospective study enrolled patients with BRVO-ME who were treated at the hospital from September 2019 to March 2021. Patients were divided into ischemic and non-ischemic groups based on fundus findings. All patients received intravitreal injections of ranibizumab once monthly for three consecutive months. Best corrected visual acuity(BCVA), central macular thickness(CMT), and macular blood flow density were measured before treatment and at 1 d, 1 wk, 1 and 3 mo after treatment.RESULTS: A total of 46 patients(46 eyes)with BRVO-ME were included, comprising 21 eyes in the ischemic group(7 males, 14 females; mean age 55.81±10.36 y)and 25 eyes in the non-ischemic group(11 males, 14 females; mean age 54.84±9.81 y). At 3 mo after treatment, BCVA(LogMAR)in the non-ischemic group was superior to that in the ischemic group(0.19±0.19 vs 0.38±0.27, P=0.009). Analysis of CMT changes showed that the reduction amplitude in the ischemic group was significantly greater than that in the non-ischemic group at both 1 and 3 mo after treatment(all P<0.05). Blood flow densities in the whole, parafoveal, and perifoveal regions of the superficial capillary plexus(SCP), as well as in the whole and perifoveal regions of the deep capillary plexus(DCP), were significantly lower in ischemic patients than in non-ischemic patients, while blood flow density in the foveal region of DCP was significantly higher in the ischemic group(all P<0.05).CONCLUSION: Ranibizumab is effective for both types of patients. Non-ischemic patients have a better long-term visual prognosis, and the advantage may be related to better blood flow perfusion patterns in specific areas 3 mo after treatment. Monitoring changes in blood flow density in these areas can help provide personalized treatment for patients.

OBJECTIVE To form an expert consensus addressing clinical issues regarding the use of parenteral direct thrombin inhibitors （DTIs） in special populations. METHODS Led by the Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital（the Affiliated Hospital of UESTC）， a multidisciplinary working group was formed comprising experts from multiple fields， including clinical pharmacy， cardiac surgery， obstetrics， pediatrics and evidence-based medicine. Through literature review and the Delphi method， clinical questions regarding the efficacy and safety of parenteral DTIs used in special populations were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” （PICO） framework；systematic searches were conducted in CJFD， PubMed， Embase and other databases. Relevant evidence from randomized controlled trials，cohort studies and systematic reviews were included and synthesized. Evidence quality was assessed using the Grading of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through three rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven clinical questions were ultimately selected （with a consensus rate exceeding 90%）， resulting in the formulation of seven recommendations on the use of parenteral DTIs in special populations， including children， pregnant women， patients with hepatic or renal impairment， patients with mesenteric venous thrombosis， and individuals with thrombophilia. These recommendations clarify the preferred agents， dosing ranges， monitoring parameters， and safety management strategies for parenteral DTIs in these special populations. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in special populations.

The dried mature peel of Citrus reticulata, a plant in the Rutaceae family and its cultivated varieties, is a commonly used Chinese medicinal material known as Chenpi(Citri Reticulatae Pericarpium). It is rich in nutritional components and medicinal value, with pharmacological effects including relieving cough and eliminating phlegm, strengthening the spleen and drying dampness, protecting the liver and benefiting the stomach, tonifying Qi, and calming the mind. Huanglongbing(HLB), also known as Citrus Huanglongbing, is a destructive disease in citrus production that seriously threatens the development of the citrus industry. HLB causes symptoms such as the inability of Rutaceae plants to produce mature fruit, gradual weakening of the tree, and eventual death, posing a significant threat to the yield and quality of Chenpi. Due to the uneven distribution of the HLB pathogen in infected plants, accurate detection of the pathogen requires the collection of a large number of plant samples. Current sample pretreatment methods, such as traditional extraction methods and commercial extraction kits, are time-consuming and involve multiple steps, which significantly increase the difficulty and workload of HLB diagnosis and have become a bottleneck in HLB detection. In this study, a rapid high-throughput detection method combining alkali lysis and TaqMan qPCR was developed. This method allows the pretreatment of multiple samples within 5 min, and the entire detection process can be completed within 45 min, with a detection limit of 6.67 fg·μL~(-1). The alkali lysis method and commercial kits were used for parallel detection of field-collected citrus samples, and the results showed no significant difference. The sample pretreatment method established in this study is characterized by low cost, simplicity, and high efficiency. Combined with TaqMan qPCR, it can provide technical support for early and on-site diagnosis of HLB. This method is of great significance for disease prevention and control in the citrus industry and is expected to help improve the yield and quality of citrus medicinal materials.
Citrus/microbiology* ; Plant Diseases/microbiology* ; Rhizobiaceae/physiology* ; High-Throughput Screening Assays/methods* ; Liberibacter/physiology*

Heat stroke is a heat-related illness caused by an imbalance between the body's heat production and heat dissipation,which could lead to multiple organ dysfunction syndrome with a high mortality rate.Rapid and effective reduction of core body temperature is key to successful treatment.This article reviews recent progress in the treatment of heat stroke,including new understandings of organ injury mechanisms,the timing,velocity and goals of cooling treatment,evaluation and selection of traditional cooling techniques(such as cold water immersion),and scientific evaluation of new cooling technologies(such as blood purification technology and intravascular heat exchange cooling technology),aiming to promote understanding and treatment of heat stroke.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons and the accumulation of Lewy bodies, leading to motor and nonmotor symptoms. While both genetic and environmental factors contribute to PD, recent studies highlight the crucial role of lipid metabolism disturbances in disease progression. Altered lipid homeostasis promotes protein aggregation and oxidative stress, with significant changes in lipid classes such as sphingolipids and glycerolipids observed in patients with PD. These disturbances are involved in key pathological processes, such as α-synuclein aggregation, organelle dysfunction, lipid-mediated neuroinflammation, and impaired lipid homeostasis. This review examines the relationship between lipid species and PD progression, focusing on the physiological roles of lipids in the central nervous system. It explores the mechanistic links between lipid metabolism and PD pathology, along with lipid-related genetic risk factors. Furthermore, this review discusses lipid-targeting therapeutic strategies to mitigate PD progression, emphasizing the potential of lipid modulation for effective treatment development.
Humans ; Parkinson Disease/metabolism* ; Lipid Metabolism/physiology* ; Animals ; Oxidative Stress/physiology* ; alpha-Synuclein/metabolism*

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

Metabolic dysfunction-associated fatty liver disease (MAFLD), characterized by fatty acid overload, secondary chronic inflammation, and fibrosis, has become the most prevalent chronic liver disease globally. While no effective pharmacotherapy exists for MAFLD, mitigating inflammatory responses represents a promising approach to preventing the progression from steatosis to severe steatohepatitis. The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, which detects endogenous danger and stress signals, has emerged as a significant target for inflammatory disease treatment, as transcriptional inactivation of its components demonstrates the therapeutic potential for MAFLD. Natural products targeting NLRP3 inflammasome activation have shown promising efficacy in MAFLD therapy. This review synthesizes the current understanding of NLRP3 inflammasome activation and therapeutic targets for NLRP3 homeostasis. Additionally, natural products reported to inhibit NLRP3 inflammasome for MAFLD improvement are categorized according to their mechanisms of action. The review also addresses limitations and future directions regarding natural products targeting NLRP3 inflammasome in MAFLD treatment. Enhanced understanding of NLRP3 inflammasome activation mechanisms in MAFLD and the identification of novel natural products supported by mechanistic research will significantly advance MAFLD treatment.
Humans ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology* ; Inflammasomes/metabolism* ; Biological Products/therapeutic use* ; Animals ; Fatty Liver/immunology*

Dental treatments for children and adolescents have unique clinical characteristics that differ from dental care for adults in terms of children's physiology, psychology, and behavior. These differences impose specific requirements on the application of local anesthesia in pediatric dental procedures. This article presents expert consensus on the principles of local anesthesia techniques in pediatric dental therapies, including the use of common anesthetic drugs and dosage control, safety and efficacy evaluation, and prevention and management of complications. The aim is to improve the safety and quality of pediatric dental treatments and offer guidance for clinical application by dentists.
Humans ; Child ; Anesthesia, Local/methods* ; Consensus ; Anesthesia, Dental/methods* ; Adolescent ; Anesthetics, Local/administration & dosage* ; Dental Care for Children

Objective:To observe the clinical efficacy of gentle moxibustion at different temperatures in treating people with diarrhea-predominant bowel syndrome(IBS-D)due to spleen deficiency.Methods:A total of 108 IBS-D patients were divided into two groups using the random number table method,with 54 participants in each group.Moxibustion group 1 received gentle moxibustion at(43±1)℃at bilateral Tianshu(ST25)and Zusanli(ST36),lasting 30 min each session;moxibustion group 2 received gentle moxibustion at(37±1)℃at the same points.Both groups received the intervention 3 times weekly for a total of 18 sessions.Abdominal pain intensity,stool form,pattern-based efficacy,quality of life,and mental health assessments were performed at weeks 0,3,6,and 8.Results:The total effective rate for abdominal pain intensity was 87.8%in moxibustion group 1 versus 51.1%in moxibustion group 2,and the difference was statistically significant(P<0.05).When the treatment finished,abdominal pain intensity,the Bristol score,IBS-symptom severity scale(IBS-SSS)score,self-rating anxiety scale(SAS)score,and self-rating depression scale(SDS)score dropped significantly in both groups(P<0.05),and the IBS-quality of life(IBS-QOL)score increased markedly(P<0.05).Between-group comparisons demonstrated that abdominal pain intensity,the Bristol general score,IBS-SSS score,traditional Chinese medicine(TCM)pattern score,and SDS score were significantly lower in moxibustion group 1 than in moxibustion group 2 at treatment week 6(P<0.05),and the IBS-QOL score was notably higher in moxibustion group 1(P<0.05).Conclusion:Whether at 43℃or 37℃,gentle moxibustion at Tianshu(ST25)and Zusanli(ST36)can improve abdominal pain,stool form,and quality of life,reduce disease severity,and mitigate TCM pattern in IBS-D patients;43℃gentle moxibustion performs better than 37℃gentle moxibustion in improving abdominal pain,stool form,disease severity,TCM pattern,quality of life,anxiety,and depression in IBS-D.

Objectives:To investigate the incidence of tyrosine kinase inhibitor (TKI) withdrawal syndrome and psychological issues, and their associated factors, in patients with chronic-phase chronic myeloid leukemia (CML-CP) after TKI discontinuation.Methods:We retrospectively analyzed the clinical data of CML-CP patients who discontinued TKI therapy at Peking University People's Hospital after September 2012. Logistic regression models were used to identify independent factors associated with the occurrence of TKI withdrawal syndrome and psychological issues.Results:A total of 158 patients were included, of whom 92 (58%) were female. The median age at discontinuation was 50 ( IQR, 35-60) years. With a median follow-up of 25 ( IQR, 11-49) months, the 4-year rate of sustained major molecular response (MMR) was 60% (95% CI: 51%-70%) . Fifty-one (32%) patients experienced TKI withdrawal syndrome at a median of 1.3 ( IQR, 0.5-2.0) months after TKI discontinuation. Fifty-one (32%) patients reported psychological issues such as anxiety. These concerns stemmed from fears of fluctuating BCR::ABL1 levels or disease relapse, and, for those who discontinued TKI for pregnancy, worries about adverse fetal effects and/or the fetus inheriting CML. Multivariable analyses revealed that older age at discontinuation [ P=0.003 when adjusting for TKI therapy duration; P=0.002 when adjusting for deep molecular response (DMR) duration], longer TKI therapy duration ( P=0.010) , and longer DMR duration before discontinuation ( P=0.005) were significantly associated with a higher risk of TKI withdrawal syndrome; a university degree or higher ( P=0.010) and TKI discontinuation due to pregnancy or adverse events ( P=0.001) were significantly associated with psychological issues after discontinuation. The occurrence of TKI withdrawal syndrome or psychological issues had no impact on the probability of major molecular response loss after discontinuation. Conclusion:TKI withdrawal syndrome and psychological issues are common in CML patients who discontinue TKI therapy. Older age at discontinuation and longer TKI therapy duration or DMR duration are significantly associated with TKI withdrawal syndrome. Higher education level and TKI discontinuation due to pregnancy or adverse events are significantly associated with psychological issues.