ObjectiveTo explore the dose-effect relationship and safety of high， medium， and low doses of raw Astragali Radix in the modified Huangqi Chifengtang （MHCD） for treating proteinuria in immunoglobulin A （IgA） nephropathy， and to provide scientific evidence for the clinical use of high-dose Astragali Radix in the treatment of proteinuria in IgA nephropathy. MethodsA total of 120 patients with IgA nephropathy， diagnosed with Qi deficiency and blood stasis combined with wind pathogen and heat toxicity， were randomly divided into a control group and three treatment groups. The control group received telmisartan combined with a Chinese medicine placebo， while the treatment groups were given telmisartan combined with MHCD containing different doses of raw Astragali Radix （60， 30， 15 g）. Each group contained 30 patients， and the treatment period was 12 weeks. Changes in 24-hour urinary protein （24 hUTP）， traditional Chinese medicine （TCM） syndrome scores， effective rate， and renal function were observed before and after treatment. Safety was assessed by monitoring liver function and blood routine. ResultsAfter 12 weeks of treatment， 24 hUTP significantly decreased in the high， medium， and low-dose groups， as well as the control group （P<0.05， P<0.01）. The TCM syndrome scores in the high， medium， and low-dose groups also significantly decreased （P<0.01）. Comparisons between groups showed that the 24 hUTP in the high-dose group was significantly lower than in the medium， low-dose， and control groups （P<0.05， P<0.01）， and the 24 hUTP in the medium-dose group was significantly lower than in the control group （P<0.05）. The TCM syndrome scores in the high and medium-dose groups were significantly lower than in the low-dose and control groups （P<0.05， P<0.01）. The total effective rates for proteinuria in the high， medium， low-dose， and control groups were 92.59% （25/27）， 85.19% （23/27）， 60.71% （17/28）， and 57.14% （16/28）， respectively. The effective rates in the high and medium-dose groups were significantly higher than in the low-dose and control groups （χ²=13.185， P<0.05， P<0.01）. The effective rates for TCM syndrome scores in the high， medium， low-dose， and control groups were 88.89% （24/27）， 81.48% （22/27）， 71.43% （20/28）， and 46.43% （13/28）， respectively. The efficacy of TCM syndrome scores in the high and medium-dose groups was significantly higher than in the control group （χ²=14.053， P<0.01）. Compared with pre-treatment values， there was no statistically significant difference in eGFR and serum creatinine in the high and medium-dose groups. However， eGFR significantly decreased in the low-dose and control groups after treatment （P<0.05）， and serum creatinine levels increased significantly in the control group （P<0.05）. No statistically significant differences were observed in urea nitrogen， uric acid， albumin， total cholesterol， triglycerides， liver function， and blood routine before and after treatment in any group. ConclusionThere is a dose-effect relationship in the treatment of IgA nephropathy with high， medium， and low doses of raw Astragali Radix in MHCD. The high-dose group exhibited the best therapeutic effect and good safety profile.

Objective To explore and analyze the implementation effect of the combined traditional Chinese medicine(TCM)and Western medicine DRG payment model in TCM hospitals,aiming to provide a reference for the reform of medical in-surance payment methods in such hospitals.Methods R language was utilized to statistically analyze the costs and other indica-tors of the sample hospitals before and after the implementation of the combined TCM and Western medicine DRG payment within 1-2 years.Results Following the implementation of the combined TCM and Western medicine DRG payment,there was a de-crease in average hospitalization costs and average length of stay,accompanied by an increase in CMI(average weight).The cost structure underwent changes:the proportions of western medicine fees and auxiliary examination fees decreased,whereas the pro-portion of TCM treatment fees increased.Significant statistical differences were observed in each group of data(p＜2.2e-16).Conclusion The combined TCM and Western medicine DRG payment reform model can facilitate TCM hospitals in reducing medical costs,controlling medical expenses,optimizing the cost structure,and promoting the development of TCM diagnosis and treatment characteristics.

Yi and Gui,its physiological characteristics and pathological manifestations are closely related to the lumbar spine.The intervertebral disc,chamber of arthrosis,requires nourishment from qi and blood circulation,as well as support from liver and kidney functions to maintain its health.Chinese medicine master Shi Qi has based on the pathological manifestations of discogenic low back pain patients at different stages and followed the guidelines of the Visceral manifestation theory.Combining more than 60 years of experience in traditional Chinese medicine diagnosis and treatment,he has used external observations to infer internal conditions and examined causes to find solutions.By entering the body from the outside and focusing on the"Homology of Yi and Gui"as a benchmark,he emphasizes the distinctive characteristic of traditional Chinese medicine in medical treatment.He states that"visceral pattern is fundamental"and"qi-blood is first,"emphasizing the importance of treating liver and kidney together.This article aims to draw on the wisdom of Taishan to provide a bridge for colleagues.

This study aims to investigate the anti-inflammatory and anti-apoptotic effects of total flavonoids of hawthorn leaves(TFHL)on lipopolysaccharide(LPS)-induced inflammatory injury in rat intestinal epithelial(IEC-6)cells,as well as the underlying mechanisms.An in vitro inflam-mation model was first established by treating IEC-6 cells with lipopolysaccharide(LPS).IEC-6 cells were then incubated with three concentrations of TFHL for 24 h prior to a further 24 h LPS treatment.RT-qPCR was used to quantify mRNA levels of the inflammatory genes COX-2 and iN-OS,while Western blotting was used to assess protein levels of the apoptotic markers Bax,cleaved Caspase-3,Bcl-2,and the JNK/p-JNK signaling pathway.Finally,cells were pretreated with TFHL and/or the JNK inhibitor SP600125 for 24 h before LPS exposure for 24 h,in order to evaluate the combined effects of TFHL and SP600125 on LPS-induced inflammatory cytokine expression and apoptotic protein levels in IEC-6 cells.The results showed that,compared with the LPS group,the mRNA level of COX-2 and iNOS in the 2.5,5.0,10.0 mg/L TFHL group and the Bax and Caspase-3 protein levels decreased significantly(P＜0.01),and the Bcl-2 protein level was significantly higher(P＜0.01),p-JNK protein level and p-JNK/JNK ratio decreased significantly(P＜0.01);compared with the LPS group,the COX-2 and iNOS mRNA levels of the TFHL+LPS group de-creased significantly(P＜0.01),Bax,and Caspase-3 protein levels decreased significantly(P＜0.01),and the level of Bcl-2 protein increased significantly(P＜0.05);compared with the LPS group,the COX-2 and iNOS mRNA levels of the TFHL+SP600125 group decreased significantly(P＜0.01),Bax and Caspase-3 protein levels decreased significantly(P＜0.01),and Bcl-2 protein level increased significantly(P＜0.01).These findings indicate that TFHL exerts anti-inflammato-ry and anti-apoptotic effects in LPS-challenged IEC-6 cells by inhibiting the JNK signaling path-way.

Objective:Mendelian randomization analysis (MR) was used to investigate the causal association between nine cathepsins and cholelithiasis.Methods:Single nucleotide polymorphism (SNP) sites closely associated and mutually independent with nine cathepsins and cholelithiasis were screened out from the Genome-Wide Association Study database and the FinnGen Biobank database, respectively. SNP corresponding to exposure factors were selected as instrumental variables. Two-sample bidirectional MR analysis was conducted with methods of inverse variance weighted (IVW), weighted median and MR-Egger regression. Additionally, multivariable Mendelian randomization (MVMR) was conducted to estimate the direct effect of cathepsins on cholelithiasis. Cochran's Q test, MR-PRESSO method and MR Egger regression were used to evaluate the levels of heterogeneity and pleiotropy. And the leave-one-out method was performed for the sensitivity analysis. Results:The univariable Mendelian randomization analysis results indicated that elevated cathepsin B levels increased the overall risk of cholelithiasis (IVW: OR=1.054, 95% CI: 1.025-1.083, P<0.001). The reverse MR analyses did not support a causal effect of cholelithiasis on cathepsin B (IVW: OR=0.998, 95% CI: 0.920-1.083, P=0.969). A multivariable analysis showed that elevated cathepsin B levels were still strongly associated with an increased risk of cholelithiasis (IVW: OR=1.038, 95% CI: 1.003-1.073, P=0.031). None evidence of significant pleiotropy and heterogeneity was observed, which was verified by sensitivity analysis. Conclusion:Cathepsin B may serve as a marker for cholelithiasis, and has important guiding significance in cholelithiasis treatment.

In recent years,the incidence of childhood cancer has shown a steady upward trend.Due to the unique nature of this disease,the issue of affiliate stigma among primary caregivers of children with cancer has gradually drawn attention.Affiliate stigma not only directly affects caregivers' mental health and quality of life,but also leads to reduced social support and lower self-efficacy,thereby impacting their engagement in the caregiving process and affecting the treatment adherence and prognosis of children with cancer indirectly.This article provides a review covering 5 main areas:the conceptual definition of affiliate stigma,measurement tools,influencing factors,intervention strategies,and insights and recommendations,to provide a theoretical basis and guidance for subsequent research and the development of interventions.

Acute respiratory distress syndrome(ARDS)is a common respiratory emergency,but current clinical treatment remains at the level of symptomatic support and there is a lack of effective targeted treatment measures.Our previous study confirmed that inhalation of hydrogen gas can reduce the acute lung injury of ARDS,but the application of hydrogen has flammable and explosive safety concerns.Drinking hydrogen-rich liquid or inhaling hydrogen gas has been shown to play an important role in scavenging reactive oxygen species and maintaining mitochondrial quality control balance,thus improving ARDS in patients and animal models.Coral calcium hydrogenation(CCH)is a new solid molecular hydrogen carrier prepared from coral calcium(CC).Whether and how CCH affects acute lung injury in ARDS re-mains unstudied.In this study,we observed the therapeutic effect of CCH on lipopolysaccharide(LPS)induced acute lung injury in ARDS mice.The survival rate of mice treated with CCH and hydrogen inhalation was found to be comparable,demonstrating a significant improvement compared to the untreated ARDS model group.CCH treatment significantly reduced pulmonary hemorrhage and edema,and improved pulmonary function and local microcirculation in ARDS mice.CCH promoted mitochon-drial peripheral division in the early course of ARDS by activating mitochondrial thioredoxin 2(Trx2),improved lung mitochondrial dysfunction induced by LPS,and reduced oxidative stress damage.The results indicate that CCH is a highly efficient hydrogen-rich agent that can attenuate acute lung injury of ARDS by improving the mitochondrial function through Trx2 activation.

This research study focuses on addressing the limitations of current neuropathic pain(NP)treatments by developing a novel dual-target modulator,E0199,targeting both Nav1.7,Nay1.8,and Nay1.9 and Kv7 channels,a crucial regulator in controlling NP symptoms.The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP.Through an experimental design involving both in vitro and in vivo methods,E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury(CCI)mouse model.The results demonstrated that E0199 significantly inhibited Nav1.7,Nav1.8,and Nav1.9 channels with a particularly low half maximal inhibitory concentration(ICs0)for Nay1.9 by promoting sodium channel inactivation,and also effectively increased Kv7.2/73,Kv7.2,and Kv7.5 channels,excluding Kv7.1 by promoting potassium channel acti-vation.This dual action significantly reduced the excitability of dorsal root ganglion neurons and alle-viated pain hypersensitivity in mice at low doses,indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically.The safety of E0199 was supported by neurobehavioral evaluations.Conclusively,E0199 represents a ground-breaking approach in NP treatment,showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe thera-peutic option for NP.This study introduces a promising direction for the future development of NP therapeutics.

Objective:Mendelian randomization analysis (MR) was used to investigate the causal association between nine cathepsins and cholelithiasis.Methods:Single nucleotide polymorphism (SNP) sites closely associated and mutually independent with nine cathepsins and cholelithiasis were screened out from the Genome-Wide Association Study database and the FinnGen Biobank database, respectively. SNP corresponding to exposure factors were selected as instrumental variables. Two-sample bidirectional MR analysis was conducted with methods of inverse variance weighted (IVW), weighted median and MR-Egger regression. Additionally, multivariable Mendelian randomization (MVMR) was conducted to estimate the direct effect of cathepsins on cholelithiasis. Cochran's Q test, MR-PRESSO method and MR Egger regression were used to evaluate the levels of heterogeneity and pleiotropy. And the leave-one-out method was performed for the sensitivity analysis. Results:The univariable Mendelian randomization analysis results indicated that elevated cathepsin B levels increased the overall risk of cholelithiasis (IVW: OR=1.054, 95% CI: 1.025-1.083, P<0.001). The reverse MR analyses did not support a causal effect of cholelithiasis on cathepsin B (IVW: OR=0.998, 95% CI: 0.920-1.083, P=0.969). A multivariable analysis showed that elevated cathepsin B levels were still strongly associated with an increased risk of cholelithiasis (IVW: OR=1.038, 95% CI: 1.003-1.073, P=0.031). None evidence of significant pleiotropy and heterogeneity was observed, which was verified by sensitivity analysis. Conclusion:Cathepsin B may serve as a marker for cholelithiasis, and has important guiding significance in cholelithiasis treatment.

In recent years,the incidence of childhood cancer has shown a steady upward trend.Due to the unique nature of this disease,the issue of affiliate stigma among primary caregivers of children with cancer has gradually drawn attention.Affiliate stigma not only directly affects caregivers' mental health and quality of life,but also leads to reduced social support and lower self-efficacy,thereby impacting their engagement in the caregiving process and affecting the treatment adherence and prognosis of children with cancer indirectly.This article provides a review covering 5 main areas:the conceptual definition of affiliate stigma,measurement tools,influencing factors,intervention strategies,and insights and recommendations,to provide a theoretical basis and guidance for subsequent research and the development of interventions.