ObjectiveTo investigate the relationship between the vasodilation and hydrogen sulfide （H₂S） mechanism of total flavonoids of chrysanthemum （TFCC） and the large conductance Ca²⁺- activated K⁺ （BK_Ca） channels on vascular smooth muscle cells （VSMCs） of the middle cerebral artery in rats. In addition， this study will also investigate the effect of TFCC on the expression of BK_Ca channel alpha protein in rat middle cerebral artery VSMCs. MethodsThe primary method employed was acute digestion to isolate VSMCs from the middle cerebral artery of rats； whole-cell patch-clamp techniques were used to measure BK_Ca channel currents； primary tissue adherence culture was utilized to cultivate VSMCs from the middle cerebral artery of rats； Western blot were employed to determine protein expression levels. ResultsIn whole-cell patch-clamp experiments， both the H₂S donor NaHS （100 μmol/L） and endogenous H₂S enhanced BK_Ca channel currents. TFCC （30， 90， and 270 mg/L） also activatedBK_Ca channels and exhibited a certain concentration-dependent effect. Even after blocking endogenous H₂S production， TFCC （270 mg/L） still activated BK_Ca channels in VSMCs of the middle cerebral artery in rats. In Western blot experiments， the α-subunit of BK_Ca channel proteins was expressed in all groups of cells， but TFCC （30， 90， and 270 mg/L） and inhibitor IBTX group did not affect the expression of channel protein content.Conclusion TFCC can promote the opening of BK_Ca channels by promoting the generation of endogenous H₂S， or directly activate BK_Ca channels， thereby playing a role in relaxing cerebral blood vessels. However， TFCC had no significant effect on the expression of BK_Ca channel proteins.

In December 2025， American Gastroenterological Association released the expert review of clinical practice update on the management of ascites， volume overload， and hyponatremia in cirrhosis. The expert review proposes 13 best practice recommendations based on available evidence. This article gives an excerpt of the main recommendations from the expert review.

OBJECTIVE To evaluate the long-term efficacy of intra-articular injection of hyaluronic acid （HA）， platelet-rich plasma （PRP）， and micro-fragmented adipose tissue （MFAT） in treatment of knee osteoarthritis （KOA）. METHODS Randomized controlled trials （RCTs） of KOA patients receiving intra-articular injection of the three agents were collected from PubMed， Web of Science， Embase， Cochrane Library， CNKI， Wanfang Data， VIP， Chinese Biomedical Literature Service System，and clinical trial registration platforms. The retrieval time limit was from January 2016 to December 2025. After screening the literature， extracting the data，and evaluating the quality of the literature， network meta-analysis was performed using RevMan 5.3 and Stata MP 16.0 software. RESULTS A total of 31 RCTs involving 2 964 patients were included. For pain relief， after 6 months of treatment， the Visual Analogue Scale （VAS） scores in the PRP+HA and PRP groups were significantly lower than those in the saline and HA groups （ P ＜0.05）， PRP+HA and PRP were ranked as the top two by surface under the cumulative ranking curve （SUCRA）. After 12 months of treatment， the VAS scores in the PRP group were significantly lower than those in the HA and saline groups （ P ＜0.05）， PRP and PRP+HA were ranked as the top two by SUCRA. For functional recovery， after 6 months of treatment， the Western Ontario and McMaster Universities Osteoarthritis Index （WOMAC） scores in the PRP group were significantly lower than those in the HA or saline groups （ P ＜0.05）. After 12 months of treatment， the WOMAC scores in the MFAT， PRP and PRP+HA groups were significantly lower than those in the HA or saline groups （ P ＜0.05）. After 6 and 12 months of treatment， International Knee Documentation Committee （IKDC） scores in the MFAT and PRP groups were significantly higher than the saline group （ P ＜0.05）， and after 12 months of treatment， the PRP group was significantly higher than the HA group （ P ＜0.05）. MFAT and PRP were ranked as the top two by SUCRA for both the WOMAC and IKDC scores. CONCLUSIONS For pain relief， PRP+HA showed a significant advantage at 6 months after treatment， whereas PRP alone demonstrated a notable superiority at 12 months after treatment. For functional recovery， MFAT exhibited a marked advantage at both 6 and 12 months after treatment.

ObjectiveTo investigate the effect of Gardeniae Fructus-Salviae Miltiorrhizae Radix et Rhizoma on ferroptosis in the rat model of myocardial infarction and further elucidate its role in myocardial remodeling. MethodsThe rat model of myocardial infarction was established by ligation of the left anterior descending coronary artery. The 50 successfully modeled rats were randomly divided into model group， ferroptosis inhibitor group （2 mg·kg^-1）， enalapril group （2.1 mg·kg^-1）， and low- and high-dose （4 g·kg^-1 and 8 g·kg^-1， respectively） Gardeniae Fructus-Salviae Miltiorrhizae Radix et Rhizoma， with 10 rats in each group. The rat model of myocardial infarction was established by ligation of the left anterior descending coronary artery. After 4 weeks of treatment， echocardiography was used to assess the cardiac structure and function. Hematoxylin-eosin （HE） staining and Masson staining were employed to observe pathological morphology and fibrosis of the myocardial tissue. Serum levels of N-terminal pro-B-type natriuretic peptide （NT-proBNP）， transforming growth factor-β （TGF-β）， and myosin heavy chain-β （MHC-β） were measured by enzyme-linked immunosorbent assay （ELISA）. Prussian blue staining was performed to detect myocardial iron deposition. The myocardial mitochondrial structure was observed by transmission electron microscopy. Levels of malondialdehyde （MDA） and glutathione （GSH） in the myocardial tissue were determined by lipid peroxidation assay kits. Immunofluorescence assay was conducted to observe the fluorescence intensity of nuclear factor E₂-related factor 2 （Nrf2） in the myocardial tissue. Western blot analysis was performed to evaluate the expression levels of proteins in the Nrf2/solute carrier family 7 member 11 （SLC7A11）/glutathione peroxidase 4 （GPX4） pathway. ResultsCompared with the sham group， the model group showed increased left ventricular end-diastolic diameter （LVEDD）， left ventricular end-systolic diameter （LVESD）， and serum levels of NT-proBNP， TGF-β， and MHC-β （P<0.01）， decreased left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） （P<0.01）， disarrangement of myocardial cells， inflammatory cell infiltration， severe myocardial fibrosis， increased myocardial iron deposition， and irregular mitochondrial morphology with vacuolation. Furthermore， the modeling led to increased MDA （P<0.01）， decreased GSH （P<0.01）， diminished Nrf2 fluorescence intensity in the myocardial tissue， and downregulated expression levels of Nrf2， SLC7A11， and GPX4 （P<0.01）. Compared with the model group， Gardeniae Fructus-Salviae Miltiorrhizae Radix et Rhizoma reduced the LVEDD， LVESD， and serum levels of NT-proBNP， TGF-β， and MHC-β （P<0.05， P<0.01）， increased the LVEF and LVFS （P<0.05， P<0.01）， alleviated pathological changes such as myocardial cell disarrangement， inflammatory cell infiltration， myocardial fibrosis， and iron deposition， lowered the level of MDA （P<0.05， P<0.01）， raised the level of GSH （P<0.05， P<0.01）， improved the mitochondrial morphology and reduced vacuolation in the myocardial tissue， enhanced Nrf2 fluorescence intensity， and upregulated the expression levels of Nrf2， SLC7A11， and GPX4 （P<0.05， P<0.01） in the rat model of myocardial infarction. ConclusionGardeniae Fructus-Salviae Miltiorrhizae Radix et Rhizoma alleviates pathological damage and myocardial remodeling in the rat model of myocardial infarction by inhibiting ferroptosis， the mechanism of which is related to the activation of Nrf2/SLC7A11/GPX4 signaling pathway.

ObjectiveTo investigate the effect of Gardeniae Fructus-Salviae Miltiorrhizae Radix et Rhizoma on ferroptosis in the rat model of myocardial infarction and further elucidate its role in myocardial remodeling. MethodsThe rat model of myocardial infarction was established by ligation of the left anterior descending coronary artery. The 50 successfully modeled rats were randomly divided into model group， ferroptosis inhibitor group （2 mg·kg^-1）， enalapril group （2.1 mg·kg^-1）， and low- and high-dose （4 g·kg^-1 and 8 g·kg^-1， respectively） Gardeniae Fructus-Salviae Miltiorrhizae Radix et Rhizoma， with 10 rats in each group. The rat model of myocardial infarction was established by ligation of the left anterior descending coronary artery. After 4 weeks of treatment， echocardiography was used to assess the cardiac structure and function. Hematoxylin-eosin （HE） staining and Masson staining were employed to observe pathological morphology and fibrosis of the myocardial tissue. Serum levels of N-terminal pro-B-type natriuretic peptide （NT-proBNP）， transforming growth factor-β （TGF-β）， and myosin heavy chain-β （MHC-β） were measured by enzyme-linked immunosorbent assay （ELISA）. Prussian blue staining was performed to detect myocardial iron deposition. The myocardial mitochondrial structure was observed by transmission electron microscopy. Levels of malondialdehyde （MDA） and glutathione （GSH） in the myocardial tissue were determined by lipid peroxidation assay kits. Immunofluorescence assay was conducted to observe the fluorescence intensity of nuclear factor E₂-related factor 2 （Nrf2） in the myocardial tissue. Western blot analysis was performed to evaluate the expression levels of proteins in the Nrf2/solute carrier family 7 member 11 （SLC7A11）/glutathione peroxidase 4 （GPX4） pathway. ResultsCompared with the sham group， the model group showed increased left ventricular end-diastolic diameter （LVEDD）， left ventricular end-systolic diameter （LVESD）， and serum levels of NT-proBNP， TGF-β， and MHC-β （P<0.01）， decreased left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） （P<0.01）， disarrangement of myocardial cells， inflammatory cell infiltration， severe myocardial fibrosis， increased myocardial iron deposition， and irregular mitochondrial morphology with vacuolation. Furthermore， the modeling led to increased MDA （P<0.01）， decreased GSH （P<0.01）， diminished Nrf2 fluorescence intensity in the myocardial tissue， and downregulated expression levels of Nrf2， SLC7A11， and GPX4 （P<0.01）. Compared with the model group， Gardeniae Fructus-Salviae Miltiorrhizae Radix et Rhizoma reduced the LVEDD， LVESD， and serum levels of NT-proBNP， TGF-β， and MHC-β （P<0.05， P<0.01）， increased the LVEF and LVFS （P<0.05， P<0.01）， alleviated pathological changes such as myocardial cell disarrangement， inflammatory cell infiltration， myocardial fibrosis， and iron deposition， lowered the level of MDA （P<0.05， P<0.01）， raised the level of GSH （P<0.05， P<0.01）， improved the mitochondrial morphology and reduced vacuolation in the myocardial tissue， enhanced Nrf2 fluorescence intensity， and upregulated the expression levels of Nrf2， SLC7A11， and GPX4 （P<0.05， P<0.01） in the rat model of myocardial infarction. ConclusionGardeniae Fructus-Salviae Miltiorrhizae Radix et Rhizoma alleviates pathological damage and myocardial remodeling in the rat model of myocardial infarction by inhibiting ferroptosis， the mechanism of which is related to the activation of Nrf2/SLC7A11/GPX4 signaling pathway.

ObjectiveTo observe the clinical efficacy and safety of Tianmeng Lingjiao Formula（天礞羚角方， TLF） as an adjunctive therapy for paroxysmal atrial fibrillation （PAF） with phlegm-heat harassing the interior syndrome. MethodsNinety patients with PAF and phlegm-heat harassing the interior syndrome were enrolled and randomly assigned in a 2∶1 ratio to test group （60 cases） and control group （30 cases）. The control group received conventional western medicine， while the test group received TLF in addition to the conventional treatment， with one dose administered daily. The treatment course for both groups was 4 weeks. The efficacy of traditional Chinese medicine （TCM） syndrome and the rate of atrial fibrillation （AF） conversion were compared between groups. Assessments included AF burden， frequency and duration of AF episodes， TCM syndrome scores， and European Heart Rhythm Association （EHRA） AF symptom classification before and after treatment. Safety indicators such as blood routine， urine routine， stool routine， liver function， kidney function， and electrolytes were also monitored. Adverse events were recorded. ResultsA total of 82 patients completed the study （54 in the test group and 28 in the control group）. After treatment， AF burden， the frequency and duration of AF episodes， and TCM syndrome scores were significantly reduced in both groups， and the test group showed lower indicators than the control group （P＜0.01 or P＜0.05）. The AF conversion rate was 25.93% （14/54） in the test group， significantly higher than 3.57% （1/28） in the control group （P＜0.05）. The total effective rate for TCM syndrome efficacy was 83.33% （45/54） in the test group， which was significantly higher than 67.86% （19/28） in the control group （P＜0.05）. After treatment， the EHRA atrial fibrillation symptom severity in the test group showed significant improvement， and the improvement in atrial fibrillation symptoms was superior to that in the control group （P＜0.01or P＜0.05）. No significant abnormalities were observed in safety indicators， and no adverse events occurred during the trial. ConclusionTLF as an adjunctive therapy can reduce AF burden， enhance the conversion rate of AF， decrease the frequency and duration of episodes， and improve clinical symptoms in patients with paroxysmal atrial fibrillation presenting with phlegm-heat harassing the interior syndrome， with a favorable safety profile.

BACKGROUND:Socket-shield technique can effectively maintain labial soft and hard tissues,but the incidence of postoperative complications such as exposure and displacement of root shield is relatively high.It is speculated that the root shield may be exposed and displaced due to excessive load after long-term function of dental implants. OBJECTIVE:Through three-dimensional finite element analysis,we aim to study the influence of varying root shield thicknesses on the stress distribution,equivalent stress peaks,and displacement in the root shield,periodontal ligaments,implant,and surrounding alveolar bone under normal occlusal loading.We also attempt to analyze the correlation between the thickness of the root shield and occurrence of mechanical events such as root shield exposure,displacement,and fracture. METHODS:Cone-beam CT data of a patient who met the indication standard of socket-shield technique for maxillary central incisor were retrieved from database.Reverse engineering techniques were used to build models of the maxillary bone and root shield,while forward engineering was used to create models for the implant components based on their parameters.Models depicting various root shield thicknesses(0.5,1.0,1.5,and 2.0 mm)were created using Solidworks 2022 software.ANSYS Workbench 2021 software was then used to simulate and analyze the effects of varying root shield thicknesses on stress distribution,equivalent stress peaks,and displacement of the root shields,periodontal ligaments,implants,and surrounding alveolar bone under normal occlusion. RESULTS AND CONCLUSION:(1)In all root shield models,the stress was concentrated on the palatal cervical side,both sides of the edges and the lower edge of the labial side.As the thickness of the root shield increased,the equivalent stress peak and displacement showed a decreasing trend.The 0.5 mm thickness model produced a stress concentration of 176.20 MPa,which exceeded the yield strength(150 MPa)of tooth tissue.(2)The periodontal ligament stress in each group was concentrated in the neck margin and upper region.With the increase of root shield thickness,the equivalent stress peak and displacement of periodontal ligament showed a decreasing trend.(3)Implant stress in all models was concentrated in the neck of the implant and the joint of the implant-repair abutment,and the labial side was more concentrated than the palatal side.With the increase of root shield thickness,the equivalent stress peak of the implant in the model showed an increasing trend.(4)In each group of models,stress of cortical bone concentrated around the neck of the implant and the periphery of the root shield,and the labial side was more concentrated than the palatal side.With the increase of the thickness of the root shield,the equivalent stress peak around the root shield decreased;the peak value of the equivalent stress of the bone around the neck of the implant showed an increasing trend.In the model,the stress of cancellous bone was mainly concentrated around the neck of the lip of the implant,the top of the thread,the root tip and the lower margin of the root shield,and the labial side was more concentrated than the palatal side.With the increase of the thickness of the root shield,the peak value of the equivalent stress of the bone around the root shield in the model showed a decreasing trend.The minimum principal stress of cortical bone in each group of models was concentrated around the neck of the implant,exhibiting a fan-shaped distribution.As the thickness of the root shield increased,the minimum principal stress of cortical bone showed an increasing trend.(5)These results indicate that different thicknesses of the root shield have different biomechanical effects.The root shield with a thickness of 0.5 mm is easy to fracture.For patients with sufficient bone width,the root shield with a thickness of 2.0 mm is an option to reduce the risk of complications such as root shield exposure,fracture,and displacement.Meanwhile,it should be taken into account to protect the periodontal ligament in the preparation process,and rounding treatments ought to be carried out on both sides and the lower edge of the root shield.

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Objective:To visualize and analyze the literature on the application of negative-pressure wound therapy (NPWT) in the field of wounds in the Web of Science core collection, and to explore the current status, frontiers, and trends of related research.Methods:The Web of Science core collection was used as the data source, and the search time period was from June 30, 2019 to June 30, 2024. Visual bibliometric analysis of the included literature was performed using VOSviewer 1.6.20 and CiteSpace 6.2.R4 for the number of publications, country and institution of publication, and keywords.Results:A total of 941 papers were included, with an increasing and then decreasing trend in the number of publications. The country with the largest number of publications was the United States (245), and although China ranked 2nd in the number of publications (208), the average number of citations in the literature was low. There was no strong cooperation network among publishing institutions. The proportion of articles published by core authors was 47.61% (448/941), with no significant core group of authors. In the past 5 years, research on NPWT in the field of wounds focused on chronic wound nursing and treatment, acute surgical incision complications and their prevention, wound closure and skin reconstruction, and risk factors for NPWT.Conclusions:The clinical application scope of NPWT has been expanded from simple wounds to complex wounds, tissue regeneration, and other fields. Researchers can carry out multi-center, large-sample, high-quality randomized controlled studies, enhance inter-institutional cooperation, and focus on interdisciplinary intersections and the formulation of NPWT care plans.

Objective:To discuss the expression of Rh family C glycoprotein(RHCG)in the esophageal squamous cell carcinoma(ESCC)tissue and its effect on the malignant biological behavior of ESCC cells,and to clarify the value of RHCG as a diagnostic and prognostic marker for the ESCC patients.Methods:A total of 143 ESCC tissue samples and 105 adjacent normal tissue samples were collected.Using immunohistochemical staining method,141 ESCC samples were divided into two groups:RHCG low expression group(immunohistochemistry score≤6)and RHCG high expression group(immunohistochemistry score>6).Immunohistochemical method was used to detect the RHCG protein expression in 143 ESCC tissues and 105 normal tissues,and the relationship between the clinicopathological characteristics of the ESCC patients was analyzed.Receiver operating characteristic(ROC)curve and Kaplan-Meier survival analysis were used to evaluate the value of RHCG in diagnosis and prognosis of the ESCC patients;univariate and multivariate COX regression analysis were used to determine the independent risk factors affecting the prognosis of the ESCC patients.Gene Expression Profiling Interactive Analysis(GEPIA2)database was used to analyze the expression of RHCG mRNA in various tumor tissues.The ESCC TE-1 cells were cultured and transfected in to 6-well cell culture plates with different Lipofectamine2000∶RHCG ratios;the cells in RHCG transfection group were transfected with weights of 2.0,2.5,and 3.0 μg for 24 and 48 h,respectively,and the cells in NC group transfected with empty vector as control.Western blotting method was used to detect the RHCG protein expression level in the TE-1 cells in various groups after transfection at different concentrations and verify the optimal transfection conditions;cell counting kit-8(CCK-8)assay was used to detect the proliferation activities of the TE-1 cells;plate clone formation assay was used to detect the colony formation numbers of the TE-1 cells;Transwell chamber assay was used to detect the numbers of migrating TE-1 cells.Results:Compared with adjacent normal tissue,the RHCG gene expression level in various cancer tissues including ESCC,glioblastoma multiforme,and head and neck squamous cell carcinoma was significantly decreased(P<0.05).RHCG protein was mainly located on the cell membrane of normal esophageal squamous epithelial cells;the RHCG protein expression intensity in ESCC tissues was lower than that in adjacent normal esophageal tissue(χ2=109.373,P<0.001),and the patients in RHCG low expression group had poorer differentiation than those in RHCG high expression group(P=0.041).The area under the curve(AUC)value of RHCG for diagnosing ESCC was 0.86,with sensitivity and specificity of 95.1%and 75.0%,respectively;the Kaplan-Meier survival analysis results showed that compared with high RHCG expression group,the patients in low RHCG expression group had shorter survival time and poorer prognosis[harard ratio(HR)=0.269,95%confidence interval(CI):0.113-0.639,P=0.020];the COX regression analysis results showed that low RHCG expression could serve as an independent risk factor affecting the prognosis of ESCC[HR=4.569,95%CI=1.315-15.877,P=0.017)].The Western blotting results verified that the optimal transfection condition was 3.0 μg RHCG plasmid for 48 h,at which time RHCG overexpression was optimal and RHCG protein expression level was highest.The CCK-8 assay results showed that compared with control group,the proliferation activity in RHCG overexpression group was decreased on the 4th day after cell seeding(P<0.001).In the TE-1 cells,the colony formation number of the TE-1 cells in RHCG over-expression group was lower than that in control group(t=17.70,P<0.001).The Transwell chamber assay results showed that compared with control group,the number of migrating cells in RHCG over-expression group was decreased(t=23.74,P<0.001).Conclusion:RHCG expression is decreased in ESCC tissues and associated with poor prognosis in ESCC patients;overexpression of RHCG can inhibit the proliferation and migration of the TE-1 cells,providing a theoretical basis for RHCG as a novel diagnostic and prognostic marker and therapeutic target for ESCC.