ObjectiveTo study the pharmacological substances and mechanisms through which sesquiterpene ZH-13 from Aquilariae Lignum Resinatum improves neuroinflammation. MethodsBV-2 microglial cells were stimulated with lipopolysaccharide （LPS） to induce neuroinflammation. The cells were divided into the normal group， the model group， and the ZH-13 low- and high-dose treatment groups （10， 20 μmol·L^-1）. The model group was treated with 1 μmol·L^-1 LPS. Cell viability was assessed using the cell proliferation and activity assay （CCK-8 kit）. Nitric oxide （NO） release in the cell supernatant was measured using a nitric oxide kit （Griess method）. The mRNA expression levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， inducible nitric oxide synthase （iNOS）， and interleukin-6 （IL-6） were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The phosphorylation of mitogen-activated protein kinase （MAPK） pathway proteins was assessed by Western blot. ResultsCompared with the model group， ZH-13 dose-dependently reduced NO release from BV-2 cells under LPS stimulation （P<0.05， P<0.01）. In the 20 μmol·L^-1 ZH-13 treatment group， the mRNA expression levels of IL-1β， TNF-α， iNOS， and IL-6 were significantly reduced compared to the model group （P<0.05， P<0.01）. In both the low- and high-dose ZH-13 groups， the expression of the inflammatory factor TNF-α and the phosphorylation of c-Jun N-terminal kinase （JNK） in the upstream MAPK pathway were significantly reduced （P<0.05）. After stimulation with the JNK agonist anisomycin （Ani）， both low- and high-dose ZH-13 treatment groups showed reduced phosphorylation of JNK proteins compared to the Ani-treated group （P<0.01）. ConclusionThe sesquiterpene compound ZH-13 from Aquilariae Lignum Resinatum significantly ameliorates LPS-induced neuroinflammatory responses in BV-2 cells by inhibiting excessive JNK phosphorylation and reducing TNF-α expression. These findings elucidate the pharmacological substances and mechanisms underlying the sedative and calming effects of Aquilariae Lignum Resinatum.

Background and Purpose:Previous studies have investigated the prognostic significance of skeletal muscle and adipose tissue composition and distribution in colorectal cancer patients,yet most have not differentiated between rectal and colon cancer patient cohorts.This study aimed to explore the relationship between body composition and long-term prognosis,and to develop a postoperative predictive model.Methods:Clinical data of rectal cancer patients who underwent surgical treatment at Qingdao University Affiliated Hospital from January 2018 to December 2021 were retrospectively collected.Inclusion criteria:①Age＞18 years;② Preoperative colonoscopy and pathological diagnosis of colorectal cancer;③ Complete surgical resection;④Abdominal computed tomography(CT)scan 1 month before surgery.Exclusion criteria:① Clinical data is missing;② Multiple metastases of tumors;③ Tumor T stage 0 or carcinoma in situ;④ Severe artifacts lead to poor quality CT imaging,making it difficult to distinguish between fat and muscle;⑤ Inability to obtain follow-up results.This study has been approved by the Medical Ethics Committee of the Affiliated Hospital of Qingdao University(approval number:QYFYWZLL30313),and informed consent has been waived in the ethical approval process.The skeletal muscle index(SMI)and subcutaneous adipose tissue index(SATI)were calculated by dividing the areas of skeletal muscle and subcutaneous fat observed on CT scans by the square of the patient's height.Univariate and multivariate COX regression analyses were conducted to identify risk factors influencing recurrence-free survival(RFS)and overall survival(OS)in rectal cancer patients.Based on the results of the multivariate analysis,a nomogram prediction model was developed,its predictive power and accuracy were assessed using the receiver operating characteristic(ROC)curve,calibration plots and decision curve analysis(DCA),and internal validation was conducted.Results:A total of 696 patients were included in this study,with 96(13.8%)patients experiencing postoperative recurrence and 89(12.8%)patients dying.Multivariate COX regression analysis showed that SMI,SATI,tumor T stage and N stage were independent factors affecting the postoperative RFS and OS of patients.Nomogram prediction models for RFS and OS in rectal cancer patients were constructed based on the above independent predictors.The area under ROC curve(AUC)for 3-,4-and 5-year RFS was 0.862,0.846 and 0.824,respectively;the AUC for 3-,4-and 5-year OS was 0.886,0.898 and 0.875,respectively.The models were evaluated using calibration curves and decision curves,and internal validation was performed,which showed that the prediction accuracy of the models was good.Conclusion:CT body composition is an independent predictor of RFS and OS in rectal cancer patients,and the nomogram model developed based on these factors demonstrates good predictive value for patient prognosis.

Objective To explore the brain damage of SD rats under different time points of hypobaric hypoxia exposure.Methods A rat high-altitube cerebral edema(HACE)model was constructed by simulating an altitude of 6 000 m in a hypobaric hypoxia animal experimental chamber.Thirty-six SD male rats were randomly divided into the control group and the hypobaric hypoxia exposure 3,7 and 14 d groups,with 9 rats in each group.Except for the control group,the rats in each group were continuously exposed to hypobaric hypoxia for 3,7,and 14 d.At the end of the modeling period,serum was collected by blood sampling via the abdominal aorta,and brain tissue samples were taken.The wet-to-dry ratio(W/D)of brain tissue was calculated,and the levels of relevant oxidative enzymes in serum and brain tissue were measured.The expression levels of hypoxia-inducible factor-1α(HIF-1α)and aquaporin 4(AQP4)mRNAs in brain tissue were detected by real-time fluorescence quantitative polymerase chain reaction.Results The W/D of brain tissues in the control group and the group exposed to hypobaric hypoxia for 3,7 and 14 d were 4.46±0.12,4.98±0.16,5.07±0.18 and 4.95±0.07;the superoxide dismutase contents were(111.86±2.45),(90.73±1.48),(79.64±2.56)and(55.33±1.45)U·g-1;the glutathione contents were(126.91±5.18),(125.26±1.53),(56.20±2.17)and(122.73±1.78)μg·mL-1;the malondialdehyde contents were(230.94±2.00),(362.65±3.28),(407.34±3.47)and(237.50±1.59)nmol·g-1;the relative expression levels of HIF-1 α mRNA were 1.00±0,2.99±0.49,4.72±0.49 and 1.91±0.28;the relative expression levels of AQP4 mRNA were 1.00±0,2.62±0.34,8.38±0.84 and 5.27±0.42,respectively.Statistically significant differences were found between the above indexes in the 3,7 and 14 d of hypobaric hypoxia exposure group compared with the control group(P＜0.05,P＜0.01).Conclusion Different time of hypobaric hypoxia exposure can up-regulate the expression of AQPs proteins in HACE rats and cause the disruption of the blood-brain barrier,and the HACE model constructed in the hypobaric hypoxia chamber with 6 000 m intervention for 7 d was more stable.

Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.

Objective:To investigate the efficacy and safety of bendamustine combined with anti-CD20 monoclonal antibody in the first-line treatment of older patients with indolent B-cell non-Hodgkin lymphoma (B-iNHL) .Methods:The clinical data of 159 patients with B-iNHL enrolled in 16 hospitals from Jiangsu Cooperative Lymphoma Group from December 1, 2019, to April 20, 2024, were analyzed for regimen efficacy and safety. Bendamustine plus rituximab (BR) and bendamustine plus obinutuzumab (BG) were administered to 139 (87.4% ) and 20 (12.6% ) patients, respectively.Results:Among the 159 patients, 101 (63.5% ) were male and 58 (36.5% ) were female, with a median age of 69 years (range: 60–84). Efficacy could be assessed in 138 (86.8% ) patients. The efficacy assessment demonstrated that the overall response rate was 92.0% with complete and partial remissions in 75 (54.3% ) and 52 (37.7% ) cases, respectively. With a median follow-up of 24 months (range: 4–64), the progression-free survival rate was (87.5 ± 3.0) % and the overall survival rate was (83.2 ± 3.3) %. Of the 27 patients who died, 6 (22.2% ) died due to disease progression. The mean applied dose of bendamustine per cycle was 73.0 (50.8–89.7) mg/m 2 per day, administered on days 1 and 2. Adverse events of grade 3 or higher were reported in 53 (33.3% ) patients, with infection (30 cases,18.9% ) and neutropenia (24 cases, 15.1% ) demonstrating the highest incidence. Conclusion:Bendamustine combined with anti-CD20 monoclonal antibody demonstrated good efficacy and is well-tolerated in the first-line treatment of elderly patients with B-iNHL.

Objective:To investigate whether neoadjuvant therapy can improve the prognosis of patients with pancreatic cancer.Methods:A retrospective case-control study analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database on 12, 103 patients who underwent surgical treatment between January 1, 2010, and December 31, 2021. Patients were divided into the neoadjuvant therapy group ( n=3 276) and the upfront surgery group ( n=8 827) based on whether they received neoadjuvant treatment. The neoadjuvant therapy group included 2 342 patients receiving neoadjuvant chemotherapy and 934 patients receiving neoadjuvant chemoradiotherapy. The upfront surgery group consisted of 4 335 patients receiving adjuvant chemotherapy, 1 987 patients receiving adjuvant chemoradiotherapy, 63 patients receiving adjuvant radiotherapy, and 2 442 patients undergoing surgery alone. Propensity score matching was used to eliminate group differences and create a cohort with no statistical differences in other clinicopathological features except for the grouping variable. Variables such as age, gender, tumor location, race, population of residence, tumor diameter, household income, TNM stage, and information on radiotherapy and chemotherapy were used for 1∶1 case matching. T stage, N stage, and the use of radiotherapy or chemotherapy were matched exactly. After matching, 1 182 patients were included in each group: the neoadjuvant therapy group contained 1 155 patients receiving neoadjuvant chemoradiotherapy and 27 receiving neoadjuvant chemotherapy, while the upfront surgery group comprised 848 patients receiving adjuvant chemotherapy and 334 receiving adjuvant chemoradiotherapy. TNM staging was reported according to the 7th edition of the AJCC guidelines. The primary outcome was overall survival. Measurement data with skewed distributions were expressed as M( Q1, Q3), and intergroup comparisons were conducted using the Wilcoxon rank-sum test. Categorical data were compared using the chi-square test or the Fisher′s exact test. The Log-rank test and subgroup analyses to assess interactions between neoadjuvant therapy and subgroup in COX regression models were used to compare survival benefits across variables. Landmark analysis was performed to create segmented survival curves, studying the impact of neoadjuvant therapy on prognosis during different follow-up periods. Results:The neoadjuvant therapy group had a higher proportion of T 4 tumor involving celiac axis, superior mesenteric artery, and/or common hepatic artery compared to the upfront surgery group (14.7% vs 2.8%, P<0.001). Additionally, significant differences were observed between groups in terms of race, location, population of residence, age, tumor diameter, tumor stage, and adjuvant therapy regimen ( P<0.05). The median overall survival time in the neoadjuvant therapy group was 30 months, compared to 22 months in the upfront surgery group ( P<0.001). In the neoadjuvant therapy group, the median survival was 30 months for both neoadjuvant chemotherapy and chemoradiotherapy patients; in the upfront surgery group, it was 26 months for both adjuvant chemotherapy and chemoradiotherapy patients, 17 months for adjuvant radiotherapy patients, and 12 months for surgery-only patients. After propensity score matching, there were no differences in the distribution of clinical characteristics between groups ( P>0.05), and all patients in the matched cohort had received chemotherapy. The matched neoadjuvant therapy group had a longer median overall survival compared to the upfront surgery group (30 months vs 27 months, P<0.001). Subgroup interaction analysis revealed that T stage had a significant interaction with neoadjuvant therapy, both before (T 4 stage: HR=0.382, 95% CI: 0.319-0.458; T 2-T 3 stages: HR=0.696, 95% CI: 0.656-0.738; T 1 stage: HR=1.199, 95% CI: 0.867-1.657; interaction P<0.001) and after matching (T 4 stage: HR=0.581, 95% CI: 0.414-0.814; T 2-T 3 stages: HR=0.827, 95% CI: 0.734-0.931; T 1 stage: HR=1.320, 95% CI: 0.716-2.433; interaction P=0.043). Subgroup interaction analysis indicated that T 1 patients did not benefit from neoadjuvant therapy; survival curves plotted for matched T 1 patients showed no difference in survival between the neoadjuvant therapy group and the upfront surgery group ( P=0.323). Conversely, non-T 1 (T 2-T 4) stage patients showed significant survival benefits in both unmatched and matched cohorts ( P<0.001). Landmark analysis showing that the survival benefits occurred mainly in the early postoperative period of up to 3 years ( P<0.001), but there was no difference in overall survival between the neoadjuvant therapy group and the upfront surgery group of >3 years ( P>0.05). Patients with Arterial invasion (T 4 stage compared to T 1-T 3 stages) showed a similarly significant interaction with the benefit of neoadjuvant therapy in both the pre-matching cohort (interaction P<0.001) and the post-matching cohort (interaction P=0.037). Patients with T 4 stage disease in the neoadjuvant therapy group had longer overall survival compared to the upfront surgery group (median overall survival in pre-matching cohort: 30 months vs 13 months, P<0.001; median overall survival in post-matching cohort: 28 months vs 18 months, P=0.001). Among T 4 stage patients in the post-matching cohort, neoadjuvant therapy provided significant survival benefits during the early postoperative period of up to 3 years ( P=0.001). However, there was no difference in overall survival between the neoadjuvant therapy group and the direct surgery group beyond 3 years( P=0.729). Conclusions:The prognosis in the neoadjuvant therapy group was better than in the upfront surgery group. Propensity score matching and subgroup interaction analysis showed that non-T 1 and T 4 stage patients benefited more from neoadjuvant therapy, with benefits mainly seen in the early postoperative period (≤3 years).

Objective To conduct a bibliometric analysis of domestic and international literature on the research of Sijunzi Decoction over the past 20 years,and to explore the research status,hotspots,and development trends of Sijunzi Decoction.Methods This article retrieved journal articles related to the research of Sijunzi Decoction from 2004 to 2024 in the CNKI,Wanfang,VIP,and Web of Science databases.Microsoft Excel was used for publication volume analysis,while CiteSpace software was employed for keyword co-occurrence,clustering,and burst analysis,and then the analysis results were visualized.Results After literature retrieval and screening,3 573 Chinese articles and 113 English articles were included.Over the past two decades,the publication volume showed a trend of steadily increasing.The most frequent keywords in Chinese and English literature on the research of Sijunzi Decoction were spleen deficiency syndrome and gene expression,while the keywords with strongest burst were experimental research and data mining.Conclusion The research of Sijunzi Decoction in the last 20 years was mainly through animal experiments and clinical applications,and the research hotspots focus on the treatment of diseases of spleen deficiency syndrome and on the improvement of immune function of cancer patients.The extraction and identification of active components in Sijunzi Decoction and the study on the therapeutic mechanism in diseases of spleen deficiency syndrome are probably the future research trends.

Objective To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application.Methods and Results Recommendations were formulated based on literature review and expert group discussion,and consensus was reached following expert consultation.The consensus recommendations are comprehensive,covering the entire treatment procedures from preoperative assessment and preparation,surgical operation process,postoperative management and traditional Chinese medicine treatment to individualized treatment planning.The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain,reduced the use of opioid drugs,and significantly improved the quality of life and enhanced immune function of the patients.Postoperative follow-up suggested good treatment tolerance among the patients without serious complications.Conclusion The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy.The combined treatment has a high clinical value with a good safety profile for management of cancer pain.

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction