OBJECTIVE To investigate the effect of pharmaceutical services guided by root cause analysis （RCA） in a problem-oriented manner combined with knowledge-attitude-practice （KAP） theory on reducing the incidence of protocol violations of investigational medicinal products in pediatric clinical trials. METHODS A total of 617 participants from 69 drug clinical trial projects conducted in our hospital from January 2016 to December 2020 were selected as the control group， and 868 participants from 72 drug clinical trial projects from January 2022 to December 2025 as the observation group. RCA was performed on the protocol violations of investigational medicinal product in the control group to identify the types and underlying causes. The control group received routine pharmaceutical services for drug clinical trials， while the observation group was provided with precision pharmaceutical services from the three dimensions of knowledge， attitude and practice on the basis of routine pharmaceutical services， according to the root causes identified by RCA. The occurrence of investigational medicinal products protocol violations was compared between the two groups. RESULTS The total incidence of protocol violations of investigational medicinal products， as well as the incidences of minor and major protocol violations， were all significantly lower in the observation group than in the control group （ P ＜0.001）. The main types of protocol violations in both groups included missed/under-/over-dosing of medications， non-adherence to administration time， failure to adjust dosage as required， and combined medication/vaccination in violation of the protocol. Regarding the responsible subjects of protocol violations， the incidences of protocol violations attributed to participants and their guardians as well as investigators and accidental factors were significantly lower in the observation group than in the control group （ P ＜0.001， P ＜0.001， P ＝0.025）. However， there were no statistically significant differences in the incidences of protocol violations caused by sponsor-related reasons between the two groups （ P ＞0.05）. CONCLUSIONS Pharmaceutical services led by pharmacists， based on problem-oriented RCA and combined with KAP theory， can effectively reduce the protocol violations of investigational medicinal products rate in pediatric clinical trials， thereby safeguarding the safety and rights of study participants.

OBJECTIVE To compare the effects of leuprorelin and mifepristone on sex hormone levels， ovarian function， adverse reactions， and recurrence in patients with endometriosis （EMs） after surgery. METHODS A total of 178 patients who underwent surgical treatment for EMs in Ji’an Central People’s Hospital from September 2021 to September 2023 were randomly divided into the leuprorelin group and the mifepristone group， with 92 cases in each group. Medication was initiated on days 1 to 5 of the first menstrual cycle following surgery. Patients in the leuprorelin group received subcutaneous injections of Leuprorelin acetate microspheres， 3.75 mg per time， once every four weeks， for a total of 6 injections. Patients in the mifepristone group took 12.5 mg of Mifepristone capsules orally once daily for six consecutive months. Visual analog scale （VAS）， serum sex hormone levels [follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and estradiol （E2）]， ovarian function indicators [anti- Müllerian hormone （AMH）， antral follicle count （AFC）]， and T helper 1 cell （Th1）/Th2 shift markers [interferon-γ （IFN-γ）， interleukin 2 （IL-2）， IL-4， and IL-10] were compared between the two groups before surgery and after treatment. Incidence and outcome of adverse reactions and recurrence within one year were also compared between the two groups. RESULTS There were no statistically significant differences in baseline indicators between the two groups before surgery （P＞0.05）. After treatment， both groups showed significantly lower VAS scores for chronic pelvic pain， dysmenorrhea and dyspareunia， and significantly reduced serum FSH， LH， E2， IL-4 and IL-10 levels compared to before surgery （P＜0.05）， while serum IFN-γ and IL-2 levels were significantly increased （P＜0.05）； the leuprorelin group showed significantly greater improvements than the mifepristone group in all these indicators （P＜0.05）. After treatment， serum AMH levels in both groups were significantly lower than before surgery levels， while AFC was significantly increased （P＜0.05）； the leuprorelin group had significantly higher serum AMH levels and more AFC compared to the mifepristone group （P＜0.05）. There were no significant differences in the incidence of adverse reactions and outcome rates between the two groups （P＞0.05）. During one year of follow-up after discontinuation， the recurrence rate in the leuprorelin group was significantly lower than in the mifepristone group （1.15% vs. 10.99%， P＜0.05）. CONCLUSIONS Both leuprorelin and mifepristone are effective therapeutic drugs for EMs， but the former has advantages in alleviating pain， regulating serum sex hormone levels， protecting ovarian function， regulating immune function and reducing recurrence rates.

OBJECTIVE To construct three-class （insufficient， normal， excessive） and two-class （insufficient， normal） models for predicting plasma concentration of valproic acid （VPA）， and compare the performance of these two models， with the aim of providing a reference for formulating clinical medication strategies. METHODS The clinical data of 480 patients who received VPA treatment and underwent blood concentration test at the Xi’an International Medical Center Hospital were collected from November 2022 to September 2024 （a total of 695 sets of data）. In this study， predictive models were constructed for target variables of three-class and two-class models. Feature ranking and selection were carried out using XGBoost scores. Twelve different machine learning algorithms were used for training and validation， and the performance of the models was evaluated using three indexes: accuracy， F1 score， and the area under the working characteristic curve of the subject （AUC）. RESULTS XGBoost feature importance scores revealed that in the three-class model， the importance ranking of kidney disease and electrolyte disorders was higher. However， in the two-class model， the importance ranking of these features significantly decreased， suggesting a close association with the excessive blood concentration of VPA. In the three-class model， Random Forest method performed best， with F1 score of 0.704 0 and AUC of 0.519 3 on the test set； while in the two-class model， CatBoost method performed optimally， with F1 score of 0.785 7 and AUC of 0.819 5 on the test set. CONCLUSIONS The constructed three-class model has the ability to predict excessive VPA blood concentration， but its prediction and model generalization abilities are poor； the constructed two-class model can only perform classification prediction for insufficient and normal blood concentration cases， but its model performance is stronger.

Homeostasis and energy and substance metabolism reprogramming shape various tumor microenvironment to sustain cancer stemness, self-plasticity and treatment resistance. Aiming at them, a lipid-based pharmaceutical loaded with CaO₂ and glucose oxidase (GOx) (LipoCaO₂/GOx, LCG) has been obtained to disrupt calcium homeostasis and interfere with glycometabolism. The loaded GOx can decompose glucose into H₂O₂ and gluconic acid, thus competing with anaerobic glycolysis to hamper lactic acid (LA) secretion. The obtained gluconic acid further deprives CaO₂ to produce H₂O₂ and release Ca²⁺, disrupting Ca²⁺ homeostasis, which synergizes with GOx-mediated glycometabolism interference to deplete glutathione (GSH) and yield reactive oxygen species (ROS). Systematical experiments reveal that these sequential multifaceted events unlocked by Ca²⁺ homeostasis disruption and glycometabolism interference, ROS production and LA inhibition, successfully enhance cancer immunogenic deaths of breast cancer cells, hamper regulatory T cells (Tregs) infiltration and promote CD8⁺ T recruitment, which receives a considerably-inhibited outcome against breast cancer progression. Collectively, this calcium homeostasis disruption glycometabolism interference strategy effectively combines ion interference therapy with starvation therapy to eventually evoke an effective anti-tumor immune environment, which represents in the field of biomedical research.

OBJECTIVES: The aim of this study is to determine the effect of cannabinoid receptor (CB) 2 inhibitor on desmoglein 3 (DSG3) expression in HaCaT cells co-cultured with pemphigus serum. METHODS: Immunohistochemical staining was used to compare CB expression in pemphigus patients and normal individuals. Enzyme-linked immunosorbent assay (ELISA) was employed to quantify the concentration of CB2 in the serum of pemphigus patients and normal individuals. A correlation analysis was performed to examine the relationship between the serum CB2 and DSG of pemphigus patients. The CCK-8 assay was used to evaluate the inhibitory effect of AM630 on HaCaT cells, and the half-maximal inhibitory concentration (IC₅₀) value was utilized to determine the experimental concentration. Serum from normal individuals (negative control group) and pemphigus patients (pemphigus group) was co-cultured with HaCaT cells at a 1∶1 ratio. HaCaT cells cultured in complete medium were used as the control group. HaCaT cells in the pemphigus group treated with AM630 were employed as the AM630 group. Real-time polymerase chain reaction (PCR) and Western blot were conducted to assess the expression levels of CB2, DSG3, and β-catenin. Cell dissociation experiments were conducted to evaluate the effect of AM630 on the adhesion of HaCaT cells. RESULTS: Immunohistochemistry revealed significant differences in CB2 expression between pemphigus and normal mucosa (P<0.000 1), but no difference was found in CB1 expression. ELISA analysis revealed a statistically significant difference in the expression levels of CB2 in the serum between normal individuals and pemphigus patients (P<0.001). The expression of CB2 in the serum of pemphigus patients exhibited a significant positive correlation with that of DSG3 (r=0.831, P=0.003). The CCK-8 assay indicated that the IC₅₀ of AM630 on HaCaT cells was 0.55 μmol/L. Real-time PCR and Western blot showed that the expression levels of CB2 and DSG3 increased in the pemphigus group, while the expression level of β-catenin decreased compared with that in the AM630 groups (P<0.05). CONCLUSIONS CB2 is highly expressed in oral mucosal pemphigus. AM630 inhibits overexpression of CB2 and DSG3 and underexpression of β-catenin levels, which can provide new therapeutic targets for pemphigus.
Humans ; Pemphigus/pathology* ; Receptor, Cannabinoid, CB2/metabolism* ; Desmoglein 3/metabolism* ; Acantholysis/metabolism* ; Mouth Mucosa/pathology* ; HaCaT Cells ; Coculture Techniques ; beta Catenin/metabolism*

OBJECTIVE To evaluate the efficacy and safety of immune checkpoint inhibitors combined with neoadjuvant chemotherapy and adjuvant chemotherapy in the treatment of early-stage triple-negative breast cancer （TNBC）. METHODS A systematic search was conducted in PubMed， Embase， Cochrane Library， CNKI， and Wanfang Data to collect randomized controlled trials （RCT） on the use of immune checkpoint inhibitors combined with neoadjuvant chemotherapy and adjuvant chemotherapy （experimental group） versus neoadjuvant chemotherapy and adjuvant chemotherapy （control group） in the treatment of TNBC. After literature screening， data extraction and literature quality evaluation， meta-analysis was performed using Stata 17.0. RESULTS A total of 5 RCT involving 1 498 patients were included. The meta-analysis results showed that the pathological complete response rate （pCR） [RR＝1.34， 95%CI （1.09， 1.63）， P＝0.03]， pCR in patients with positive programmed death-1 （PD-1） and its ligand （PD-L1） [RR＝1.33， 95%CI （1.16， 1.51）， P＝0.01]， pCR in patients with positive lymph nodes [RR＝ 1.56， 95%CI （1.27， 1.93）， P＝0.01]， the incidence of grade 3-4 adverse events （AEs） [RR＝1.07， 95%CI （1.01， 1.14）， P＝ 0.04]， the incidence of serious AEs [RR＝1.57， 95%CI （1.31， 1.87）， P＝0.03]， and the incidence of treatment discontinuation due to AEs [RR＝1.45， 95%CI （1.19， 1.76）， P＝0.01] were significantly higher in the experimental group than control group. There were no statistically significant difference in pCR in patients with negative PD-1/PD-L1[RR＝ E-mail：biejun23@126.com 1.26， 95%CI （0.98， 1.62）， P＝0.08] and pCR in patients with negative lymph nodes [RR＝1.14， 95%CI （0.97， 1.33）， P＝0.17] between the two groups. CONCLUSIONS Immune checkpoint inhibitors combined with neoadjuvant chemotherapy and adjuvant chemotherapy demonstrates significant efficacy in early-stage TNBC patients， with more pronounced benefits observed in those who are PD-1/PD-L1 positive and lymph node- positive. However， the incidence of AEs is relatively high.

ObjectiveTo investigate the therapeutic efficacy， influencing factors， and safety of a treatment regimen based on coblopasvir hydrochloride capsules/sofosbuvir tablets in patients with chronic hepatitis C virus （HCV） infection in a real-world setting. MethodsA total of 253 patients who attended The Third People’s Hospital of Kunming from September 1， 2021 to May 31， 2024 were enrolled， among whom there were 86 patients with compensated liver cirrhosis （CLC group） and 167 patients with chronic hepatitis C （CHC group）. The patients were treated with coblopasvir hydrochloride capsules （60 mg）/sofosbuvir tablets （400 mg） with or without ribavirin tablets for 12 weeks， and they were followed up for 12 weeks after drug withdrawal. The primary outcome measures were the rate of sustained virologic response at week 12 after treatment （SVR12） and safety， and the secondary outcome measures were the changes in liver function， renal function， blood routine， and liver stiffness measurements （LSM） after 4 weeks of treatment， after 12 weeks of treatment， and at 12 weeks after drug withdrawal. The independent-samples t test and the Mann-Whitney U test were used for comparison of continuous data between two groups， and the Friedman test was used for comparison between multiple groups， while the Bonferroni method was used for paired comparison within each group； the chi-square test was used for comparison of categorical data between two groups. The Logistic analysis was used to investigate related influencing factors. ResultsThe 253 patients with chronic HCV infection had a mean age of 49.38±8.65 years， and there were 151 male patients （59.7%）. Of all patients， 33.99% （86/253） had liver cirrhosis， 25.69% （65/253） had hypertension， 10.67% （27/253） had HIV infection， 8.70% （22/253） had diabetes， 3.95% （10/253） had liver cancer， 1.98% （5/253） had chronic hepatitis B， and 7.91% （20/253） were treatment-experienced patients. As for genotype distribution， 2.77% （7/253） had genotype 1， 12.65% （32/253） had genotype 2， 66.01% （167/253） had genotype 3， 16.60% （42/253） had genotype 6， and 1.98% （5/253） had unknown genotype. The patients had an overall SVR12 rate of 92.09%， with an SVR12 rate of 93.02% in the CLC group and 91.02% in the CHC group. The multivariate logistic regression analysis showed that age （odds ratio ［OR］=1.086， 95% confidence interval ［CI］： 1.007 — 1.170， P=0.032） and HCC （OR=9.178， 95%CI： 1.722 — 48.912， P=0.009） were independent influencing factors for sustained virologic response. Compared with baseline data， the CLC group had significant reductions in alanine aminotransferase （ALT） （χ²=107.103， P0.05）， aspartate aminotransferase （AST） （χ²=90.602， P0.05）， and LSM （χ²=42.235， P0.05） after 12 weeks of treatment， while the CHC group had significant reductions in total bilirubin （χ²=15.113， P0.05）， ALT （χ²=202.237， P0.05）， AST （χ²=161.193， P0.05）， and LSM （χ²=37.606， P0.05）. The incidence rate of serious adverse events was 1.58%， and none of the patients withdrew from drug therapy； the patients with such events were relieved after active symptomatic treatment. The incidence rate of all adverse events was 23.72%， among which fatigue （17.39%） and nausea （2.37%） were the most common adverse events， and these events often disappeared within 2 weeks or were gradually relieved after symptomatic treatment. ConclusionCoblopasvir hydrochloride capsules/sofosbuvir tablets with or without ribavirin tablets has good efficacy and safety in the treatment of chronic HCV infection.

Central serous chorioretinopathy(CSC)is a macular disease predominantly affecting young to middle-aged adults, characterized by serous retinal detachment in the posterior pole, leading to symptoms such as decreased central vision, visual distortion, and color changes. The disease has a certain degree of self-limitation but can recur. The pathogenesis is still uncertain and the treatment is controversial. Commonly used treatments include medication, retinal laser, photodynamic therapy(PDT)and vitreous anti-vascular endothelial growth factor(VEGF)therapy which have emerged in recent years, but the treatment of recurrent CSC is still tricky. The purpose of this article is to review the current therapeutic approaches regarding CSC, with a view to providing a reference for clinical treatment.

Objective:To observe the effects of moxibustion at Shenshu(BL23)and Zusanli(ST36)on Toll-like receptor 4(TLR4)-myeloid differentiation factor 88(Myd88)signaling pathway-mediated inflammatory factors in the synovial tissue of ankle joints of rats with rheumatoid arthritis(RA),and to explore the molecular and biological mechanisms underlying the anti-inflammatory and analgesic effects.Methods:A total of 24 male Sprague-Dawley(SD)rats were randomly divided into a normal group,a model group,and a moxibustion group,with 8 rats in each group.The RA model was established with exposure to wind,cold,and damp environmental factors,along with Freund's complete adjuvant.After three days of modeling,mild moxibustion was applied to bilateral Shenshu(BL23)and Zusanli(ST36)in the moxibustion group using moxa sticks of 0.9 cm in diameter for 30 min each time,once a day for 14 d.Structural changes in the synovial tissue and cells were then observed using hematoxylin-eosin staining and transmission electron microscopy,while immunohistochemistry analysis was used to detect tumor necrosis factor(TNF)-α,interleukin(IL)-17,IL-1β,and IL-6 levels.Moreover,the protein expression levels of Myd88,TLR4,and transient potential receptor vanilloid type 1(TRPV1)in the synovial tissue were detected using Western blotting,while their mRNA expression levels were detected using reverse transcription-polymerase chain reaction.Finally,the levels of IL-1β,IL-2,IL-6,IL-17A,and TNF-α in rat serum were detected using enzyme-linked immunosorbent assay.Results:Compared to the normal group,the model group exhibited notable pathological synovial tissue damage,along with significantly higher IL-1β,IL-6,and TNF-α levels(P<0.01)and a slightly higher IL-17 content(P>0.05).Furthermore,the Myd88,TLR4,and TRPV1 protein and mRNA expression levels and serum IL-1β,IL-2,IL-6,IL-17A,and TNF-α levels were all significantly higher in the model group than in the normal group(P<0.01).Compared to the model group,the moxibustion group exhibited a lower degree of synovial tissue pathological damage,along with significantly lower IL-1β,IL-6,and TNF-α levels(P<0.05 or P<0.01)and a lower IL-17 content without statistical significance(P>0.05).Moreover,the Myd88,TLR4,and TRPV1 protein and mRNA expression levels,and serum IL-1β,IL-2,IL-6,IL-17A,and TNF-α levels were all significantly lower in the moxibustion group than in the model group(P<0.01 or P<0.05).Conclusion:Mild moxibustion at Shenshu(BL23)and Zusanli(ST36)can effectively inhibit TLR4-MyD88 signaling pathway-mediated inflammatory factor expression in the synovial tissue of ankle joints of RA rats.Furthermore,the effect of moxibustion on synovial tissue inflammation in RA rats may be attributed to TRPV1 channel activation.

Objective:To develop a treatment-related quality of life scale for Chinese patients with multiple myeloma (MM) and to test its reliability and validity.Methods:The initial scale was constructed through a literature search, Delphi expert correspondence, and cognitive testing. This study conducted a preliminary survey of 379 patients with MM and a formal survey of 865 patients from the hematology departments of 155 hospitals nationwide from February 2024 to March 2024. The final scale was obtained after conducting item analysis and reliability and validity tests on the initial scale.Results:The constructed scale contains 36 items covering six domains: physiological, psychological, social, treatment side effects, general health, and others. In the preliminary survey, the Cronbach’s alpha coefficient of each item ranged from 0.597 to 0.939, and the test-retest reliability was 0.747 ( P<0.001). Exploratory factor analysis extracted eight common factors with a cumulative variance contribution of 60.058%. In the formal survey, the Cronbach’s alpha coefficient of each item ranged from 0.484 to 0.930, and the test-retest reliability was 0.835 ( P<0.001). Confirmatory factor analysis revealed a comparative fit index of 0.750, a root-mean-square error of approximation of 0.090, and a root-mean-square residual of 0.067. Conclusion:The treatment-related quality of life scale for Chinese patients with MM designed in this study exhibited good reliability and validity, reflecting the impact of treatment on the quality of life of patients. This scale can provide a reference to clinicians for assessing the disease status of patients.