ObjectiveTo observe the clinical efficacy of Sanren Runchang formula in treating constipation-predominant irritable bowel syndrome （IBS-C） by regulating the brain-gut axis and the effects of the formula on serum levels of 5-hydroxytryptamine （5-HT）， vasoactive intestinal peptide （VIP）， and substance P （SP）. MethodsA randomized controlled design was adopted， and 72 IBS-C patients meeting Rome Ⅳ criteria were randomized into observation and control groups （36 cases）.The observation group received Sanren Runchang formula granules twice daily， and the control group received lactulose oral solution daily for 4 weeks. IBS Symptom Severity Scale （IBS-SSS）， IBS Quality of Life Scale （IBS-QOL）， and Bristol Stool Form Scale （BSFS） were used to assess clinical symptoms， and bowel movement frequency was recorded. The Self-Rating Anxiety Scale （SAS） and Self-Rating Depression Scale （SDS） were employed to evaluate psychological status. ELISA was employed to measure the serum levels of 5-HT， VIP， and SP. ResultsThe total response rate in the observation group was 91.67% （33/36）， which was higher than that （77.78%， 28/36） in the control group （χ²=4.50， P<0.05）. After treatment， both groups showed increased defecation frequency and BSFS scores， decreased IBS-SSS total score， abdominal pain and bloating scores， IBS-QOL health anxiety， anxiety， food avoidance， and behavioral disorders scores， SAS and SDS scores， serum 5-HT and VIP levels， and increased SP levels （P<0.05， P<0.01）. Moreover， the observation group showed more significant changes in the indicators above than the control group （P<0.05， P<0.01）. The SP level showed no significant difference between the two groups. During the 4-week follow-up， the recurrence rate was 5.88% in the observation group and 31.25% in the control group. No adverse events occurred in observation group， and 2 cases of mild diarrhea occurred in the control group. ConclusionSanren Runchang formula demonstrated definitive efficacy in alleviating gastrointestinal symptoms and improving the psychological status and quality of life in IBS-C patients， with a low recurrence rate. The formula can regulate serum levels of neurotransmitters such as 5-HT and VIP， suggesting its potential regulatory effect on the brain-gut axis through modulating neurotransmitters and neuropeptides. However， its complete mechanism of action requires further investigation through detection of additional brain-gut axis-related biomarkers.

ObjectiveTaking classical herbal pair compatibility research as the entry point， this study aimed to deeply investigate the material basis and compatibility rules underlying the antidepressant effects of the traditional Chinese medicine （TCM） formula Zhizi Houpotang， and to elucidate its antidepressant mechanism， with a particular focus on its regulation of neuroinflammatory responses mediated by the NOD-like receptor protein 3 （NLRP3）/gasdermin D （GSDMD） signaling pathway and the consequent improvement of neuronal synaptic plasticity. MethodsC57BL/6J mice were randomly divided into a blank control group， a chronic unpredictable mild stress （CUMS） depression model group， a Zhizi Houpotang full-formula group （6 g·kg^-1·d^-1）， a Magnoliae Officinalis Cortex （MOC）-Aurantii Fructus Immaturus （AFI） herbal pair group （4.2 g·kg^-1·d^-1）， a Gardeniae Fructus （GF）-MOC herbal pair group （4.2 g·kg^-1·d^-1）， a GF-AFI herbal pair group （3.6 g·kg^-1·d^-1）， and a positive drug group （fluoxetine， 12 mg·kg^-1·d^-1）. Depressive-like behaviors in mice were evaluated using behavioral tests. Immunofluorescence staining was used to label and quantify the expression of the microglial marker ionized calcium-binding adaptor molecule 1 （Ibal） and the purinergic receptor P2X ligand-gated ion channel 7 （P2RX7） in the prefrontal cortex （PFC）. Enzyme-linked immunosorbent assay （ELISA） was applied to detect the levels of inflammatory cytokines interleukin-1β （IL-1β） and interleukin-18 （IL-18） in serum and PFC tissues. Western blot was employed to determine the expression of pannexin 1 （Panx1）， P2RX7， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， Caspase-1， GSDMD， postsynaptic density protein 95 （PSD95）， and the presynaptic protein Synapsin 1 in PFC tissues. Golgi staining was used to assess dendritic spine density of neurons in the PFC. ResultsCompared with the blank control group， the depression model group exhibited significant depressive-like behaviors. In addition， the immunofluorescence areas of Ibal and P2RX7 in the PFC were significantly increased （P<0.01）， the levels of IL-1β and IL-18 in serum and the PFC were significantly elevated （P<0.01）， and the protein expression levels of Panx1， P2RX7， NLRP3， ASC， Caspase-1， and GSDMD in the PFC were significantly upregulated （P<0.01）. In contrast， the protein expression levels of PSD95 and Synapsin 1 were significantly downregulated （P<0.01）， and neuronal dendritic spine density was significantly reduced （P<0.01）. Compared with the model group， the Zhizi Houpotang full-formula group and the GF-MOC herbal pair group showed significant improvement in all the above indicators （P<0.01）. The GF-AFI herbal pair group improved all the above indicators except P2RX7， Caspase-1， GSDMD， and PSD95 （P<0.05， P<0.01）. In contrast， the MOC-AFI herbal pair group showed no statistically significant improvement in any of the above indicators compared with the model group. ConclusionZhizi Houpotang and its key herbal pair， GF-MOC， can effectively ameliorate CUMS-induced depressive-like behaviors in mice. Its core antidepressant mechanism may involve inhibition of P2RX7/Panx1 signaling， thereby blocking the NLRP3/GSDMD-mediated pyroptosis pathway and significantly reducing the release of inflammatory cytokines IL-1β and IL-18. Simultaneously， it upregulates the expression of synapse-related proteins PSD95 and Synapsin 1 and increases dendritic spine density， promoting the recovery of synaptic plasticity. These results suggest that GF plays a key role in the antidepressant effects of this formula， and that the compatibility of GF with MOC may represent the principal herbal pair combination responsible for its core therapeutic action.

OBJECTIVE To evaluate the cost-effectiveness of anlotinib combined with penpulimab versus sorafenib as first- line treatment for unresectable hepatocellular carcinoma （uHCC） from the perspective of China’s healthcare system. METHODS Based on data from the APOLLO study， a partitioned survival model was established with a 21-day model cycle to simulate patient survival status over 10 years under anlotinib combined with penpulimab regimen or sorafenib monotherapy. Quality-adjusted life year （QALY） was used as the core evaluation parameter to assess the incremental cost-effectiveness ratio （ICER） of different treatment regimens. Using 3 times China’s per capita gross domestic product （GDP） in 2024 （287 247 yuan/QALY） as the willingness-to-pay （WTP） threshold， cost-utility analysis was performed to evaluate the cost-effectiveness of the treatment regimens. Sensitivity analysis was conducted to validate the robustness of the baseline analysis conclusion. Scenario analysis was performed to consider the impact of anlotinib and penpulimab assistance programs on the results； the price reduction of penpulimab to ensure the cost-effectiveness of the combination regimen was examined under varying WTP thresholds （specifically， 1， 2， and 3 times China’s per capita GDP in 2024）. RESULTS The baseline analysis revealed that the ICER of anlotinib combined with penpulimab regimen relative to the sorafenib regimen was 338 611.20 yuan/QALY， which exceeded the WTP threshold set in this study. Univariate sensitivity analysis indicated that the utility value of progression free survival and penpulimab price significantly influenced the baseline analysis results. Probabilistic sensitivity analysis validated the robustness of the baseline results. The results of scenario analysis indicated that when considering the assistance programs for anlotinib and penpulimab， the obtained ICER values were all below the WTP threshold set at 3 times China’s per capita GDP in 2024. When the price of penpulimab was reduced by 58%， 35%， and 13%， the ICER values were below the WTP threshold， which was 1， 2 and 3 times the per capita GDP of China in 2024， respectively. CONCLUSIONS From the perspective of China’s healthcare system， anlotinib combined with penpulimab regimen for first-line treatment of uHCC lacks cost-effectiveness compared to sorafenib regimen. However， this conclusion would be reversed if the anlotinib and penpulimab assistance programs are taken into account or if the price of penpulimab is reduced by more than 13% and above.

ObjectiveAutism spectrum disorder (ASD) is a neurodevelopmental condition characterized by difficulties with communication and social interaction, restricted and repetitive behaviors. Previous studies have indicated that individuals with ASD exhibit early and lifelong attention deficits, which are closely related to the core symptoms of ASD. Basic visual attention processes may provide a critical foundation for their social communication and interaction abilities. Therefore, this study explores the behavior of children with ASD in capturing attention to changes in topological properties. MethodsOur study recruited twenty-seven ASD children diagnosed by professional clinicians according to DSM-5 and twenty-eight typically developing (TD) age-matched controls. In an attention capture task, we recorded the saccadic behaviors of children with ASD and TD in response to topological change (TC) and non-topological change (nTC) stimuli. Saccadic reaction time (SRT), visual search time (VS), and first fixation dwell time (FFDT) were used as indicators of attentional bias. Pearson correlation tests between the clinical assessment scales and attentional bias were conducted. ResultsThis study found that TD children had significantly faster SRT (P<0.05) and VS (P<0.05) for the TC stimuli compared to the nTC stimuli, while the children with ASD did not exhibit significant differences in either measure (P>0.05). Additionally, ASD children demonstrated significantly less attention towards the TC targets (measured by FFDT), in comparison to TD children (P<0.05). Furthermore, ASD children exhibited a significant negative linear correlation between their attentional bias (measured by VS) and their scores on the compulsive subscale (P<0.05). ConclusionThe results suggest that children with ASD have difficulty shifting their attention to objects with topological changes during change detection. This atypical attention may affect the child’s cognitive and behavioral development, thereby impacting their social communication and interaction. In sum, our findings indicate that difficulties in attentional capture by TC may be a key feature of ASD.

[Objective] To evaluate the efficacy and safety of sacral neuromodulation (SNM) in the treatment of patients with benign prostatic hyperplasia (BPH) complicated with underactive bladder (UAB) who respond poorly to transurethral resection of the prostate (TURP). [Methods] A retrospective analysis was performed on 10 patients with BPH and UAB treated with TURP by the same surgeon in Zhongda Hospital Southeast University during Jan.2018 and Jan.2023.The residual urine volume was not significantly relieved after operation, and the maximum urine flow rate and urine volume per discharge were not significantly improved.All patients underwent phase I SNM, and urinary diaries were recorded before and after surgery to observe the average daily frequency of urination, volume per urination, maximum urine flow rate, and residual urine volume. [Results] The operation time was (97.6±11.2) min.During the postoperative test of 2-4 weeks, if the residual urine volume reduction by more than 50% was deemed as effective, SNM was effective in 6 patients (60.0%). Compared with preoperative results, the daily frequency of urination [(20.2±3.8) times vs. (13.2±3.2) times], volume per urination [(119.2±56.7) mL vs. (246.5±59.2) mL], maximum urine flow rate [(8.7±1.5) mL/s vs. (16.5±2.6) mL/s], and residual urine volume [(222.5±55.0) mL vs. (80.8±16.0) mL] were significantly improved, with statistical significance (P<0.05). There were no complications such as bleeding, infection, fever or pain.The 6 patients who had effective outcomes successfully completed phase II surgery, and the fistula was removed.During the follow-up of 1 year, the curative effect was stable, and there were no complications such as electrode displacement, incision infection, or pain in the irritation sites.The residual urine volume of the other 4 unsuccessful patients did not improve significantly, and the electrodes were removed and the vesicostomy tube was retained. [Conclusion] SNM is safe and effective in the treatment of BPH with UAB patients with poor curative effects after TURP.

OBJECTIVE To evaluate the cost-effectiveness of toripalimab combined with paclitaxel （albumin binding type） in the treatment of metastatic or recurrent triple-negative breast cancer （TNBC）. METHODS Based on the data of TORCHLIGHT clinical trial， a three-state partitioned survival model including progression-free survival， disease progression， and death was established. The simulation cycle was 21 days， the study duration was 10 years， and the discount rate was 5%. Using quality- adjusted life year （QALY） and cost as output indicators， a cost-effectiveness analysis method was adopted to calculate the incremental cost-effectiveness ratio （ICER） of toripalimab combined with paclitaxel （albumin binding type） versus placebo combined with paclitaxel （albumin binding type）. Using three times the per capita gross domestic product （GDP） of China in 2023 as the willingness-to-pay（WTP） threshold（268 074 yuan/QALY）， the cost-effectiveness of the above two regimens was evaluated， and the sensitivity analysis was conducted. RESULTS ICER of toripalimab combined with paclitaxel （albumin binding type） versus placebo combined with paclitaxel （albumin binding type） in the treatment of Chinese metastatic or recurrent TNBC patients was 176 347.17 yuan/QALY， which was lower than the WTP threshold set in this study， demonstrating the cost-effectiveness of this regimen. The results of the single-factor sensitivity analysis showed that the parameters such as the cost of toripalimab， discount rate， and utility value of the progression-free survival state had a great impact on the ICER. The results of the probabilistic sensitivity analysis indicated that the results of the basic analysis were robust. CONCLUSIONS When three times the per capita GDP of China in 2023 is used as the WTP threshold， compared with the regimen of placebo combined with paclitaxel （albumin binding type）， toripalimab combined with paclitaxel （albumin binding type） is cost-effective in the treatment of metastatic or recurrent TNBC.

Objective To explore the diagnostic value of exhaled volatile organic compounds (VOCs) for cystic fibrosis (CF). Methods A systematic search was conducted in PubMed, EMbase, Web of Science, Cochrane Library, CNKI, Wanfang, VIP, and SinoMed databases up to August 7, 2024. Studies that met the inclusion criteria were selected for data extraction and quality assessment. The quality of included studies was assessed by the Newcastle-Ottawa Scale (NOS), and the risk of bias and applicability of included prediction model studies were assessed by the prediction model risk of bias assessment tool (PROBAST). Results A total of 10 studies were included, among which 5 studies only identified specific exhaled VOCs in CF patients, and another 5 developed 7 CF risk prediction models based on the identification of VOCs in CF. The included studies reported a total of 75 exhaled VOCs, most of which belonged to the categories of acylcarnitines, aldehydes, acids, and esters. Most models (n=6, 85.7%) only included exhaled VOCs as predictive factors, and only one model included factors other than VOCs, including forced expiratory flow at 75% of forced vital capacity (FEF75) and modified Medical Research Council scale for the assessment of dyspnea (mMRC). The accuracy of the models ranged from 77% to 100%, and the area under the receiver operating characteristic curve ranged from 0.771 to 0.988. None of the included studies provided information on the calibration of the models. The results of the Prediction Model Risk of Bias Assessment Tool (PROBAST) showed that the overall bias risk of all predictive model studies was high, and the overall applicability was unclear. Conclusion The exhaled VOCs reported in the included studies showed significant heterogeneity, and more research is needed to explore specific compounds for CF. In addition, risk prediction models based on exhaled VOCs have certain value in the diagnosis of CF, but the overall bias risk is relatively high and needs further optimization from aspects such as model construction and validation.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation, joint destruction, and functional impairment. Angiogenesis plays a key role in the pathological progression of RA with dysfunction of endothelial cells to promote synovial inflammation, sustain pannus formation, subsequently leading to joint damage. Colquhounia Root Tablets (CRT), a Chinese patent drug, has shown a satisfying clinical efficacy in treating RA, while the underlying mechanism by which CRT inhibits RA-associated angiogenesis remains unclear. In this study, we applied a research approach combining transcriptomic data analysis, bio-network mapping, and in vivo and in vitro experiments to explore the molecular mechanisms of CRT in suppressing angiogenesis in RA. Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences (ratification number: IBTCMCACMS21-2307-06). Network analysis identified that key genes such as nucleotide-binding oligomerization domain-containing protein 2 (NOD2), SMAD family member 3 (SMAD3), and vascular endothelial growth factor A (VEGFA) significantly enriched in pathways related to NOD-like receptor signaling and VEGF signaling, indicating that CRT may inhibit angiogenesis by regulating vascular endothelial cell function with modulating angiogenesis-related pathways. In vivo data showed that CRT significantly reduced the positive expression of CD31 and VEGF in the ankle joint of adjuvant-induced arthritis (AIA) rats. In vitro data further confirmed that CRT effectively inhibited VEGF-induced migration, invasion, and tube formation in HUVECs, while significantly reduced the expression of angiogenesis-related factors VEGF/CD31/Ang-1, as well as the positive expression of VEGF and CD31 in HUVECs. Furthermore, CRT markedly decreased the protein expression of NOD2, VEGFA, and SMAD3. In conclusion, these findings indicate that CRT may inhibit the RA-related angiogenesis by targeting the NOD2/SMAD3/VEGF signaling axis to improve endothelial cell function, enriching the scientific connotation of CRT in inhibiting pathological angiogenesis in RA and also offer new insights for clinical prevention and treatment of RA.

Two new coumarin glycosides were isolated and purified from the dichloromethane fraction of Angelica biserrata 75% ethanol extract using silica gel, Sephadex LH-20 column chromatography, and semi-preparative high-performance liquid chromatography. Through the comprehensive use of modern spectroscopic methods, their structures were identified as angelmanetin A (1) and angelmanetin B (2), respectively.

ObjectiveTo observe the clinical effectiveness and safety of Xiaozhong Zhitong Mixture （消肿止痛合剂） combined with antibiotic bone cement in the treatment of diabetic foot ulcer （DFU） with damp-heat obstructing syndrome. MethodsA total of 72 DFU patients with damp-heat obstructing syndrome were randomly assigned to treatment group （36 cases） and the control group （36 cases）. Both groups received standard treatment and topical antibiotic bone cement for ulcer wounds， while the treatment group received oral Xiaozhong Zhitong Mixture （50 ml per time， three times daily） in additionally. Both groups underwent daily wound dressing changes for 21 consecutive days. Ulcer healing rate， serum levels of tumor necrosis factor-alpha （TNF-α）， interleukin-1 beta （IL-1β）， malondialdehyde （MDA）， superoxide dismutase （SOD）， C-reactive protein （CRP）， and white blood cell （WBC） count were observed before and after treatment， and visual analog scale （VAS） scores for wound pain， traditional Chinese medicine （TCM） syndrome scores， and the DFU Healing Scale （DMIST scale） were also compared. Liver and kidney function were evaluated before and after treatment， and adverse events such as allergic reactions， worsening ulcer pain were recorded. ResultsTotally 35 patients in the treatment group and 33 in the control group were included in the final analysis. The ulcer healing rate in the treatment group was （87.93±9.34）%， significantly higher than （81.82±12.02）% in the control group （P = 0.035）. Compared to pre-treatment levels， both groups showed significant reductions in serum CRP， WBC， MDA， IL-1β， and TNF-α levels， with an increase in SOD level （P＜0.05）. TCM syndrome scores， VAS， and DMIST scores also significantly decreased in both groups （P＜0.05）， with greater improvements in the treatment group （P＜0.05）. No significant adverse reactions were observed in either group during treatment. ConclusionXiaozhong Zhitong Mixture combined with antibiotic bone cement has significant advantages in promoting DFU healing， reducing inflammatory response， and alleviating oxidative stress in DFU patients with damp-heat obstructing syndrome， with good safety for DFU patients with damp-heat obstructing syndrome.