ObjectiveThis study focused on the marketed Chinese patent medicines for the treatment of Functional Diarrhea （FDr） in China and their prescription characteristics， in order to provide support for the clinical application and research and development of anti-FDr Chinese patent medicines. MethodsCollect the information of Chinese patent medicines that have been marketed to treat FDr， use Microsoft Excel 2021 software to conduct preliminary data collation and statistical analysis， and use the ancient and modern medical record cloud platform （V2.3.9） to analyze the standardized Chinese patent medicine prescriptions from the aspects of drug nature and taste， medication characteristics and prescription rules. Results147 kinds of FDr Chinese patent medicines were included in this study. There are a total of 40 varieties of FDr Chinese patent medicines suitable for children； The distribution of dosage forms is mainly pills， tablets， and capsules. 110 prescriptions were screened， among which the proportion of Chinese patent medicines for the treatment of spleen deficiency syndrome was the highest； The top three drug use frequency were licorice， Atractylodes macrocephala， and Poria cocos； The medicinal properties are mainly warm and flat， and the medicinal taste is mostly pungent， sweet and bitter， and most of them belong to the two meridians of the spleen and stomach； The association rules analysis obtains 20 strong association pairing sets； Three drug combinations were obtained by cluster analysis. ConclusionFDr Chinese patent medicine shows unique value in clinical application， especially in the field of children. However， there are still problems such as strong professionalism in the indication expression of drug instructions， limited coverage of the medical insurance catalog， and lack of high-level evidence-based medicine and pharmacoeconomic evidence. To this end， in the future， efforts should be made to build a multi-level evidence-based evidence system， improve medication compliance， and deepen research on syndrome-based medication laws， so as to enhance the clinical application value and scientific connotation of FDr Chinese patent medicines.

Health economics evidence plays an important role in linking clinical value evidence with health resource allocation decisions in the development of clinical practice guidelines. It can not only effectively balance clinical effectiveness and economic feasibility but also avoid forming "idealized" recommendations that are detached from the affordability of the healthcare system or the burden-bearing capacity of patients. To promote guideline developers to use health economics evidence more standardizedly and fully, this paper conducts an in-depth analysis of the current application status, existing challenges, access channels, and application processes of health economics evidence in current guidelines, and on this basis, puts forward considerations and suggestions for strengthening and standardizing the application of health economics evidence in China's clinical practice guidelines.

ObjectiveThis paper aims to investigate the effect of Huangqi Guizhi Wuwu Tang combined with low-molecular-weight heparin sodium on preventing deep vein thrombosis of the lower extremities in parturients undergoing cesarean section. MethodsA total of 781 parturients who underwent cesarean section （from June 2022 to October 2025） were included in the study and randomly divided into a control group and an observation group using a random number table method. Two cases were lost to follow-up in this study. The parturients undergoing cesarean section in the control group （389 cases） received low-molecular-weight heparin sodium and a traditional Chinese medicine placebo （similar in color to the traditional Chinese medicine in the observation group）. The parturients in the observation group （390 cases） were treated with Huangqi Guizhi Wuwu Tang in addition to the intervention of the control group. The incidence of deep vein thrombosis of the lower extremities in parturients from both groups undergoing cesarean section， the numerical rating scale （NRS） pain scores on the first day， third day， and seventh day after cesarean section， the venous blood flow velocity in the lower extremities of parturients before and after treatment （popliteal vein， femoral vein）， the venous clinical severity score （VCSS） of parturients in the two groups after treatment， the coagulation function indicators before and after treatment ［prothrombin time（PT），activated partial thromboplastin time （APTT），fibrinogen（FIB），D-Dimer］， hemorheological indicators ［high shear viscosity（HSV），low shear viscosity（LSV），erythrocyte sedimentation rate（ESR）］， and the incidence of adverse reactions were compared. ResultsThe incidence of deep venous thrombosis in the lower extremities of parturients after cesarean section in the observation group （0.77%） was lower than that in the control group （2.83%） （χ²=4.862， P=0.031）. On the first， third， and seventh days after cesarean section， the NRS scores of the parturients in the observation group were lower than those of the control group （t=69.509， 23.266， 90.979； P<0.05 for all）. Before treatment， the venous blood flow velocities （popliteal vein， femoral vein） of the lower extremities in the parturients from the two groups were compared， and no statistical difference was found. After treatment， the venous blood flow velocities （popliteal vein， femoral vein） of the lower extremities in the parturients from these two groups increased， with higher indicator levels among the parturients in the observation group than those in the control group （t=40.492， 21.587； P<0.05 for all）. After treatment， the scores of each item in the VCSS of parturients were lower in the observation group than those in the control group （t=46.234， 37.786， 69.016， 39.464； P<0.05 for all）. Before treatment， coagulation function indicators （PT， APTT， FIB， and D-Dimer） of the parturients from the two groups were compared， and there was no statistical significance in the differences . After treatment， PT and APTT increased（P<0.05）， while FIB and D-Dimer decreased in the parturients from both groups（P<0.05）. The degrees of increase and decrease of all indicators were greater among parturients in the observation group than those in the control group （t=18.916， 12.522， 24.787， 27.635； P<0.05 for all）. Before treatment， the hemorheology indicators （HSV， LSV， ESR） in the parturients from both groups were compared， and there was no statistical significance in the differences. After treatment， these indicators in the parturients from both groups decreased， with lower indicator levels in the observation group than those in the control group （t=85.734， 26.280， 56.792； P<0.05 for all）. The incidence of adverse reactions of parturients after cesarean section in the observation group （3.85%） compared with that in the control group （3.34%）， and there was no statistically significant difference （χ²=0.143， P=0.705）. ConclusionHuangqi Guizhi Wuwu Tang combined with low-molecular-weight heparin sodium demonstrates a favorable preventive effect on deep vein thrombosis of the lower extremities in parturients undergoing cesarean section. This combined regimen improves lower extremity function， alleviates postoperative pain after cesarean section， and enhances lower-extremity blood perfusion in parturients， with safety and reliability.

ObjectiveTo systematically characterize the in vitro chemical constituents of Entada phaseoloides and its absorbed prototype compounds and metabolites in a neuropathic pain （NP） model， thereby elucidating the potential pharmacological material basis underlying its analgesic activity. MethodsUltra-high-performance liquid chromatography coupled with quadrupole-Orbitrap high-resolution mass spectrometry （UHPLC-Q-Orbitrap HRMS） was used to analyze the constituents of the 80% methanol extract of E. phaseoloides. Thirty-six mice were divided into a blank group， low-， medium-， and high-dose E. phaseoloides extract groups （25， 50， and 100 mg·kg^-1， respectively）， an aspirin group （400 mg·kg^-1）， and a morphine group （10 mg·kg^-1）， with six mice in each group. The tail-flick threshold was measured. Twenty-four mice were randomly divided into a blank group and low-， medium-， and high-dose E. phaseoloides extract groups （25， 50， and 100 mg·kg^-1， respectively）， with six mice in each group， and motor coordination was evaluated. A spinal nerve ligation （SNL） model was established in mice. Twenty-four mice were randomly divided into a sham-operated （Sham） group， an SNL group， an SNL + E. phaseoloides extract group （750 mg·kg^-1）， and an SNL + pregabalin group （20 mg·kg^-1）， with 6 mice in each group. Mechanical allodynia and thermal hyperalgesia were evaluated. Behavioral assessments were combined to determine the optimal onset time of the analgesic effect， and plasma samples were collected at this time point. Absorbed components and metabolites were systematically identified based on accurate mass， MS/MS fragmentation patterns， retention time， and comparisons with literature data and reference standards. Meanwhile， network pharmacology， target similarity analysis， and molecular docking validation were integrated to evaluate the potential effects of absorbed components on disease intervention. ResultsCompared with the blank group， the high-dose E. phaseoloides extract group and morphine group showed significantly increased pain response thresholds （P<0.01）， without affecting motor coordination in normal mice. Compared with the Sham group， the SNL group exhibited significantly decreased thresholds for mechanical allodynia and thermal hyperalgesia （P<0.01）. Compared with the SNL group， the SNL + E. phaseoloides extract group and SNL + pregabalin group showed significantly increased thresholds for mechanical allodynia and thermal hyperalgesia （P<0.01）. The analgesic effect of E. phaseoloides was most significant at 2 h after administration. A total of 70 constituents were identified in vitro， and 22 prototype compounds and 29 metabolites were detected in plasma. The targets of the absorbed components were mainly enriched in biological processes associated with pain signal perception and transmission and showed a high degree of overlap with disease genes related to neuropathic pain. In addition， multiple components exhibited strong binding energies with core pain-related targets. Based on integrated analysis of in vitro content， plasma exposure levels， and target associations， ketanthamide A-β-D-pyranoside and ketengzide were identified as the most representative pharmacologically active substances responsible for the analgesic effect. ConclusionThis study systematically elucidates the material basis of E. phaseoloides intervention in neuropathic pain from three aspects， including chemical constituent characteristics， in vivo behavioral characteristics， and potential targets， providing important theoretical foundations and experimental support for further studies on its pharmacological mechanism and analgesic drug development.

Objective To investigate the value of serum ribosomal biogenesis factor nucleolar protein53(NOP53)mRNA and fibronectin type Ⅲ domain containing 1(FNDC1)mRNA in evaluating the efficacy of neoadjuvant chemoradiotherapy(NACRT)in patients with locally advanced rectal cancer.Methods A total of 140 patients with locally advanced rectal cancer who received NACRT treatment in Yulin Hospital the First Affiliated Hospital of Xi'an Jiaotong University from January 2020 to January 2023 were selected as the study group.According to the efficacy of NACRT treatment,they were divided into good response group(99 cases)and poor response group(41 cases).At the same time,70 healthy people were selected as control group.Real-time fluorescence quantitative PCR was used to detect serum NOP53 mRNA and FNDC1 mRNA levels in the two groups.Logistic regression analysis was used to analyze the factors affecting the efficacy of NACRT.The value of serum NOP53 mRNA and FNDC1 mRNA in evaluating the efficacy of NACRT for rectal cancer was analyzed by receiver operating characteristic analysis.Results The expression of serum NOP53 mRNA(3.21±0.36)and FNDC1 mRNA(2.73±0.34)in the study group was higher than that in the control group(0.61±0.17,0.72±0.18),and the differences were statistically significant(t=57.267,46.287,all P<0.001).The expression of serum NOP53 mRNA(4.08±0.43,4.10±0.40)and FNDC1 mRNA(3.62±0.39,3.40±0.39)in patients with T stage T4 and N stage N1+N2 rectal cancer was higher than that in patients with T stage T3(2.52±0.30,2.02±0.29)and N stage N0(2.21±0.31,1.02±0.30),and the differences were statistically significant(t=25.241～40.106,all P<0.001).The proportion of T stage T4(73.17%),N stage N1+N2(75.61%),serum NOP53 mRNA(5.56±0.39)and FNDC1 mRNA(4.42±0.38)in the poor response group were higher than those in the good response group(32.32%,43.43%,2.24±0.31,2.03±0.29),and the differences were statistically significant(t=12.045～53.337,all P<0.001).T stage T4,N stage N1+N2,high serum NOP53 mRNA,high serum FNDC1 mRNA were risk factors affecting the efficacy of NACRT for rectal cancer(Wald χ2=9.463～15.589,all P<0.001).The AUC of serum NOP53 mRNA combined with FNDC1 mRNA in evaluating the efficacy of NACRT for rectal cancer higher than predicted by serum NOP53 mRNA and FNDC1 mRNA alone,and the differences were statistically significant(Z=4.645,4.321,all P<0.001).Conclusion The levels of serum NOP53 mRNA and FNDC1 mRNA in patients with locally advanced rectal cancer are increased,which are related to the poor clinicopathological features of patients.Combined with serum NOP53 mRNA,FNDC1 mRNA can effectively predict the clinical efficacy of NACRT in patients with rectal cancer.

Objective To evaluate the efficacy and safety of enteric-coated metformin hydrochloride capsules(Junlida?)in patients with T2DM and poor glycemic control under lifestyle interventions.Methods In this study,419 patients with T2DM were recruited from 15 research centers from July 2020 to March 2022,and randomly divided into observation(Obs)group(n=209)and control group(Con,n=210)using a multicenter,randomized,double-blind,non-inferiority trial design.Patients in the Obs group were treated with enteric-coated Metformin hydrochloride capsules(Junlida?),and patients in the Con group were treated with Metformin hydrochloride tablets(Glucophage?).The optimal effective dose of 2 g/d was achieved within 4 weeks,and the reasonable dose was maintained until the end of treatment.The treatment period was 24 weeks.HbA1c and its compliance rate,FPG,and body weight were compared between the two groups in full analysis set(FAS)and protocol set(PPS).Safety and adverse events(AE)were evaluated in safety set(SS).Results A total of 414 participants were randomized(207 cases in Obs group and 207 cases in Con group).414 cases in FAS population(207 cases in Obs group and 207 cases in Con group),and 328 cases in PPS population(164 cases in Obs group and 164 cases in Con group),and 414 cases in SS population(207 cases in Obs group and 207 cases in Con group).After treatment,HbA1c,FPG and body weight were lower in both groups(P<0.05)in FAS and PPS.HbA1c compliance rate was not significantly different between the two groups in FAS and PPS(P>0.05).The results of non-inferiority test showed that the lower limit was>-0.4%in both FAS(-0.154,95%CI-0.384～0.069)and PPS(-0.139,95%CI-0.390～0.112),and the Obs group reached non-inferiority end point.The achievement rate,compliance rate,safety index and incidence of AE were not significantly different between the two groups(P>0.05).Conclusions Junlida? demonstrated non-inferiority to Glucophage? in glycemic control and can be safely and effectively used in patients with diabetes.

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

ObjectiveWith the development of society and the increasing demand for pregnancy at an advanced age， diminished ovarian reserve （DOR） has attracted wider attention. This disease affects the normal menstruation of women and poses a threat to their mental health. Current research on DOR is still in the initial stage， and advancing research progress in DOR necessitates the construction of effective and clinically relevant animal models. Building on existing literature and integrating the diagnosis criteria of DOR in traditional Chinese medicine （TCM） and Western medicine， this study summarized， analyzed， and evaluated existing models， providing a reference for optimizing DOR animal models. MethodsA retrospective analysis of literature on DOR-related animal models was conducted， and the diagnostic criteria of DOR in TCM and Western medicine were sorted out. By means of evaluation methods of animal models， the clinical relevance of each model to TCM and Western medicine was assessed. ResultsDOR animal models included those based on natural factors， iatrogenic factors， immune factors， metabolic factors， and environmental factors. Among them， the model based on iatrogenic factors， especially models induced by Tripterygium wilfordii preparations， cyclophosphamide， and cisplatin， had a high degree of relevance to both Western medical diseases and TCM syndromes and was confirmed as the optimal modeling method for studying DOR at present. ConclusionThe existing DOR modeling methods mostly have a high degree of clinical relevance to Western medical diseases， while the number of DOR animal models with clear TCM syndromes is very limited. TCM plays an indispensable role in exploring DOR treatment methods. Therefore， the development of DOR animal models related to TCM syndromes should be strengthened， further exploring the potential of TCM and providing strong theoretical support for the application of TCM in DOR treatment.

Background Arsenic is an environmentally harmful substance that causes hepatic insulin resistance and liver damage, increasing the risk of type 2 diabetes mellitus. Objective To explore whether the insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) is involved in insulin resistance in HepG2 cells after arsenic exposure through the peroxisome-proliferator-activated receptor γ (PPAR-γ) / glucose transporter 4 (GLUT4) pathway. Methods Cell viability was determined using cell counting kit 8 (CCK8) and an appropriate NaAsO₂ infection dose was determined. A cellular arsenic exposure model of HepG2 cells was established by four concentrations of NaAsO₂ solution for 24 h (the experiment was divided into four groups: 0, 2, 4, and 8 μmol·L⁻¹); HepG2 cells were firstly treated with pcDNA3.1-IGF2BP2 and pcDNA3.1-NC respectively for 6 h, then with 8 μmol·L⁻¹ NaAsO₂ for 24 h to establish a IGF2BP2 overexpression cell model (the experiment was divided into 4 groups: control, NaAsO₂, NaAsO₂+pcDNA3.1-IGF2BP2, and NaAsO₂+pcDNA3.1-NC); finally the cells were subject to 100 nmol·L⁻¹ insulin stimulation for 30 min. Glycogen and glucose in HepG2 cells were determined by glycogen and glucose assay kits; mRNA expression levels of IGF2BP2 were measured by quantitative real-time PCR; protein expression levels of IGF2BP2, PPAR-γ, and GLUT4 in HepG2 were detected by Western blot (WB); and the binding of IGF2BP2 to PPAR-γ and PPAR-γ to GLUT4 was verified by co-immunoprecipitation (CO-IP) experiment. Results The results of CCK8 experiment showed a dose-effect relationship between NaAsO₂ concentration and cell viability. When the concentration of NaAsO₂ was ≥4 μmol·L⁻¹ , the cell viabilities were lower than that of the control group (P <0.05). With the increasing dose of NaAsO₂ infection, reduced glucose consumption and glycogen levels in HepG2 cells were found in the 2, 4, and 8 μmol·L⁻¹ NaAsO₂ treatment groups compared to the control group (P <0.05). The difference between the mRNA expression level of IGF2BP2 in the HepG2 cells treated with 4 or 8 μmol L⁻¹ NaAsO₂ and the control group was significant (P <0.05). In the IGF2BP2 overexpression cell model, compared with the control group, glucose consumption and glycogen levels were lowered in the NaAsO₂ group (P <0.05), the mRNA expression level of IGF2BP2 and the protein expression levels of IGF2BP2, PPAR-γ, and GLUT4 in the cell membrane were all decreased (P <0.05). Compared with the NaAsO₂ group, the glucose consumption and glycogen levels were increased in the NaAsO₂+pcDNA3.1-IGF2BP2 group (P <0.05), and the mRNA expression level of IGF2BP2 and the protein expression levels of IGF2BP2, PPAR-γ, and GLUT4 in the cell membrane were all increased (P <0.05). The results of CO-IP experiments showed that IGF2BP2 interacted with PPAR-γ as well as PPAR-γ with GLUT4 protein. Conclusion IGF2BP2 is involved in arsenic exposure-induced insulin resistance in HepG2 cells by acting on the PPAR-γ/GLUT4 pathway.