Objective To observe the effect of electric stimulation on nuclear factor-κB(NF-κB)/NOD-like receptor protein 3(NLRP3)signaling pathway and microglial cell morphology in mice with lipopolysaccharide(LPS)induced chronic neuroinflammation,and to explore the protective mechanism of electric stimulation on brain of mice.Methods C57BL/6 mice were randomly divided into blank control group(n=8),model group(n=12),sham electroacupuncture group(n=6)and electroacupuncture group(n=6).Except blank control group,mice in other groups were injected intraperitoneally with LPS(0.25 mg/kg)for 7 consecutive days.On the 8th day,mice in the sham electroacupuncture group and electroacupuncture group were treated with acupuncture or Zusanli electroacupuncture for 7 consecutive days.The mice were weighed before the experiment,on the 7th and 14th days.On the 13th day,the elevated cross maze test was performed on the mice.The open field test was performed on the 14th day.After the experiment,immunofluorescence assay was used to determine the expression of microglial ionized calcium binding adaptor molecule-1(Iba-1)in prefrontal cortex region.The mRNA expression of NF-κB,inducible nitric oxide synthase(iNOS),tumor necrosis factor-α(TNF-α),Caspase-1 and interleukin(IL)-18 were detected by Real-time PCR.The protein expression levels of NF-κB,iNOS,NLRP3,apoptosis-associated speck-like protein containing a CARD(ASC),Caspase-1,IL-1βand IL-18 were detected by Western blotting.Results Weight change,On the 7th day,compared with the control group,the body weight of mice in model group,sham electroacupuncture group and electroacupuncture group decreased(P＜0.0001),respectively;On the 14th day,compared with the control group,the weight of mice in the model group decreased(P＜0.0001);Compared with the sham electroacupuncture group,the body weight of mice in the electroacupuncture group increased(P＜0.05).Elevated cross maze experiment,compared with the control group,the total distance and open arm retention time of mice in model group decreased,while the closed arm retention time increased(P＜0.05).The open field experiment showed that compared with the control group,the model group mice showed a decrease in total distance traveled,slower movement speed,and fewer entries into the central area(P＜0.001);Compared with the model group,the electroacupuncture group showed an increase in all three indicators(P＜0.01);Compared with the sham electroacupuncture group,the total distance and motion speed of mice in electroacupuncture group both increased(P＜0.05).Immunofluorescence assay,compared with the control group,the relative fluorescence of Iba-1 in prefrontal cortex area of mice in model group increased(P＜0.05).Compared with the model and sham electroacupuncture group,the relative fluorescence of Iba-1 in prefrontal cortex area of mice in electroacupuncture group decreased(P＜0.05).Real-time PCR showed that compared with the control group,mRNA expressions of NF-κB,iNOS,TNF-α,Caspase-1 and IL-18 in the model group increased(P＜0.05);Compared with the model group,mRNA expressions of NF-κB,iNOS,TNF-α,Caspase-1 and IL-18 in electroacupuncture group decreased(P＜0.05).Western blotting indicated that compared with the control group,the protein expressions of NF-κB,iNOS,Caspase-1,IL-1β and IL-18 in model group increased(P＜0.05);Compared with model group,the protein expressions of NF-κB,iNOS,NLRP3,ASC,Caspase-1,IL-1β and IL-18 in electroacupuncture group decreased(P＜0.05);Compared with the sham electroacupuncture group,IL-18 protein in electroacupuncture group decreased(P＜0.05).Conclusion Electroacupuncture can improve the behavioral performance of mice and inhibit the activation of microglia in the cortical region of mice,which may play an anti-inflammatory and protective role by regulating NF-κB/NLRP3 pathway.

Transcranial electrical stimulation (tES) is a non-invasive neural modulation technique known for its high safety, patient compliance, and portability. It holds promise as a potential non-pharmacological method for analgesia. However, challenges persist in utilizing tES for pain management, including inconsistent research findings and limited understanding of its analgesic mechanisms. Therefore, by summarizing the advances in the analgesic researches employing the 3 primary tES techniques, transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), and transcranial random noise stimulation (tRNS), we reviewed the analgesic effects on both acute and chronic pain, as well as the neural mechanisms underlying the analgesic effect of each technique. Accumulating evidence suggests that the analgesic effects of tDCS are significant, but studies on analgesic effects of tACS and tRNS remain limited. And the exact mechanisms of pain relief through tES turned out to be not yet well established. Furthermore, we systematically discussed the limitations of analgesia-related studies employing tES techniques across various aspects, involving research design, stimulation protocol formulation, neural response observation, analgesic effect assessment, and safety considerations. To address these limitations and advance clinical translation, we emphasized utilizing promising stimulation techniques and offered practical suggestions for future research endeavors. Specifically, employing numerical simulation of electric field guided by magnetic resonance imaging (MRI) would reduce variability of outcomes due to individual differences in head anatomy. For this purpose, it is advisable to establish standardized head models based on MRI data from the Chinese populations and validate simulated electric field results in tES research to diminish confounding factors concerning anatomy. Meanwhile, novel techniques like multi-site brain stimulation and interferential stimulation (IFS) could broaden the range of stimulation sites in both scope and depth. Multi-site brain stimulation facilitates modulation of entire neural networks, enabling more sophisticated investigations into the complexity of pain. IFS can reach deep brain tissues without invasive surgical procedures, achieving more comprehensive modulation. Regarding neural response observations, establishing a tES-neuroimaging synchronized platform would enable revealing its mechanisms and personalizing protocols based on inter-subject neural response variability detected through recordings. By integrating tES with various neuroimaging techniques, such as functional MRI, electroencephalography (EEG) and magnetoencephalography, into one unified platform, researchers could examine brain activities in baseline before stimulation, dynamic changes in brain activities during stimulation, and sustained brain responses after stimulation. Additionally, collecting finer-grained data on participant characteristics and pain intensity would enhance the sensitivity of future studies. In designing clinical trials to evaluate chronic pain treatments and reporting the results, adopting the six core outcome domain measures recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) could prove beneficial. Lastly, safety considerations can never be overemphasized in future tES studies especially when combining tES with MRI and EEG techniques. These efforts may help to broaden the research scope, reconcile inconsistencies in findings and elucidate the analgesic mechanisms of tES, thus facilitating the development of pragmatic pain management strategies such as combination therapies and home therapies. Ultimately, these suggestions will maximize the clinical application value of tES in pain treatment to achieve pain relief for patients.

Objective: To identify the maximum tolerated dose (MTD) of docetaxel combined with a fixed dose of cisplatin (75 mg/m 2 ) delivered as hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with ovarian cancer. Methods: In this phase I trial, a time-to-event Bayesian optimal interval design was used.Docetaxel was given at a starting dose of 60 mg/m2 and was increased in 5 mg/m2 increments until the MTD was determined or the maximum dose level of 75 mg/m2 was reached. The doselimiting toxicity (DLT) rate was set at 25%, with a total sample size of 30 patients. HIPEC was delivered immediately following debulking surgery at a target temperature of 43°C for 90 minutes. Results: From August 2022 to November 2022, 30 patients were enrolled. Among the patients who received a dose of docetaxel ≤65 mg/m2 , no DLT was reported. DLTs were observed in one patient who received 70 mg/m2 docetaxel (grade 3 anaemia) and in three patients who received 75 mg/m2 docetaxel (one case of grade 3 anaemia, one case of grade 3 hepatic impairment and one case of grade 4 thrombocytopenia). Patients treated with docetaxel 75 mg/m2 in combination with cisplatin 75 mg/m2 had an estimated DLT rate of 25%, which was the closest to the target DLT rate and was therefore chosen as the MTD. Conclusion Docetaxel, in combination with a fixed dose of cisplatin (75 mg/m2), can be used safely at intraperitoneal doses of 75 mg/m2 in ovarian cancer patients who received HIPEC (43°C, 90 minutes) following debulking surgery.

Objective: To identify the maximum tolerated dose (MTD) of docetaxel combined with a fixed dose of cisplatin (75 mg/m 2 ) delivered as hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with ovarian cancer. Methods: In this phase I trial, a time-to-event Bayesian optimal interval design was used.Docetaxel was given at a starting dose of 60 mg/m2 and was increased in 5 mg/m2 increments until the MTD was determined or the maximum dose level of 75 mg/m2 was reached. The doselimiting toxicity (DLT) rate was set at 25%, with a total sample size of 30 patients. HIPEC was delivered immediately following debulking surgery at a target temperature of 43°C for 90 minutes. Results: From August 2022 to November 2022, 30 patients were enrolled. Among the patients who received a dose of docetaxel ≤65 mg/m2 , no DLT was reported. DLTs were observed in one patient who received 70 mg/m2 docetaxel (grade 3 anaemia) and in three patients who received 75 mg/m2 docetaxel (one case of grade 3 anaemia, one case of grade 3 hepatic impairment and one case of grade 4 thrombocytopenia). Patients treated with docetaxel 75 mg/m2 in combination with cisplatin 75 mg/m2 had an estimated DLT rate of 25%, which was the closest to the target DLT rate and was therefore chosen as the MTD. Conclusion Docetaxel, in combination with a fixed dose of cisplatin (75 mg/m2), can be used safely at intraperitoneal doses of 75 mg/m2 in ovarian cancer patients who received HIPEC (43°C, 90 minutes) following debulking surgery.

Objective: To identify the maximum tolerated dose (MTD) of docetaxel combined with a fixed dose of cisplatin (75 mg/m 2 ) delivered as hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with ovarian cancer. Methods: In this phase I trial, a time-to-event Bayesian optimal interval design was used.Docetaxel was given at a starting dose of 60 mg/m2 and was increased in 5 mg/m2 increments until the MTD was determined or the maximum dose level of 75 mg/m2 was reached. The doselimiting toxicity (DLT) rate was set at 25%, with a total sample size of 30 patients. HIPEC was delivered immediately following debulking surgery at a target temperature of 43°C for 90 minutes. Results: From August 2022 to November 2022, 30 patients were enrolled. Among the patients who received a dose of docetaxel ≤65 mg/m2 , no DLT was reported. DLTs were observed in one patient who received 70 mg/m2 docetaxel (grade 3 anaemia) and in three patients who received 75 mg/m2 docetaxel (one case of grade 3 anaemia, one case of grade 3 hepatic impairment and one case of grade 4 thrombocytopenia). Patients treated with docetaxel 75 mg/m2 in combination with cisplatin 75 mg/m2 had an estimated DLT rate of 25%, which was the closest to the target DLT rate and was therefore chosen as the MTD. Conclusion Docetaxel, in combination with a fixed dose of cisplatin (75 mg/m2), can be used safely at intraperitoneal doses of 75 mg/m2 in ovarian cancer patients who received HIPEC (43°C, 90 minutes) following debulking surgery.

Objective:To investigate the clinical features and prognostic factors of patients with primary extranodal diffuse large B-cell lymphoma(DLBCL)in the rituximab era.Methods:The continuous data of newly diagnosed DLBCL patients with complete case data and first-line treated with rituximab,cyclophosphamide,epirubicin,vincristine,prednisone(R-CHOP)or R-CHOP treatment admitted to the Affiliated Hospital of Inner Mongolia Medical University from January 2013 to November 2023 were retrospectively analyzed.The clinical and molecular immunological features and prognosis of extranodal DLBCL were analyzed,Logistics regression model was used to analyzed the influencing factors of patients prognosis.Results:A total of 237 patients were enrolled,of which 54.4％(129 cases)were primary extranodal sources of DLBCL,and the most common extranodal sites were as follows:stomach(19.4％),colon(14.7％),tonsils(12.4％),skin/muscle(9.3％),central(7.7％),nasal/nasopharynx(6.2％),bone marrow(5.4％),testes(4.7％).The 3-year PFS and OS of DLBCL patients with extranodal involvement of bone marrow,central,liver,gastrointestinal or pulmonary origin were significantly lower than those of other patients with extranodal DLBCL of non-special site origin,and the difference was statistically significant(PFS:65.2％vs 76.7％,P=0.008;OS:82.6％vs 88.3％,P=0.04).Multivariate analysis showed that the prognostic factors affecting OS included NCCN-IPI score＞3(OR:0.142,95％CI:0.041-0.495,P=0.002),non-germinal center source(OR:2.675,95％CI:1.069-6.694,P=0.036),and DEL patients(OR:0.327,95％CI:0.129-0.830,P=0.019).An NCCN-IPI score＞3 was the only independent adverse prognostic factor for PFS(OR:0.235,95％CI:0.116-0.474,P＜0.001).Conclusion:Patients with primary extranodal source DLBCL are more common in gastrointestinal involvement,and the overall prognosis is worse than that of patients with lymph node origin.NCCN-IPI score is an important independent adverse prognostic factor for predicting overall survival and progression-free survival in patients with primary extranodal diffuse large B-cell lymphoma.

Objective:To investigate the early predictive value of halving time(HT)of BCR-ABLIS for deep molecular response(DMR)in patients with chronic myeloid leukemia(CML)treated with tyrosine kinase inhibitor(TKI).Methods:The continuous data of newly diagnosed CML patients with complete case data and first-line imatinib treatment admitted to the Affiliated Hospital of Inner Mongolia Medical University from January 2014 to June 2022 were retrospectively analyzed.Combined with the clinical characteristics of the patients and the efficacy analysis at each time point,a logistic regression model was used to explore the independent influencing factors of DMR,and combined HT of BCR-ABLIS with BCR-ABLIS level at 3 months to predict DMR of the patients.Results:Univariate and multivariate analyses showed that HT and 3-month BCR-ABLIS levels were independent influencing factors for MR4,MR4.5,and stable MR4.5(P＜0.05).ROC curve analysis determined that the best cut-off value of HT was 28 days.Compared with patients with HT＞28 d,patients with HT ≤28 d were more likely to obtain DMR at 2,3,and 5 years,respectively(74.2％vs 27.3％,71.2％vs 22.7％,and 63.6％vs 25.0％,all P＜0.001).The patients were divided into 4 groups according to BCR-ABLIS levels at 3 months and HT.Kaplan-Meier analysis showed that the patients in the BCR-ABLIS ≤10％and HT≤28 d group had a higher probability of obtaining cumulative MR4 and MR4.5 than those in the BCR-ABLIS≤10％and HT＞28 d group(P＜0.05);Patients in the BCR-ABLIS＞10％and HT≤28 d group had a higher probability of obtaining cumulative MR4 and MR4.5 than those in the BCR-ABLIS＞10％and HT＞28 d group(P＜0.05).Conclusion:In addition to BCR-ABLIS level,HT of BCR-ABLIS can be used as another important predictor of treatment efficacy in CML patients.The combination of BCR-ABLIS level and HT has a more accurate predictive value for long-term molecular response of CML patients after TKI treatment.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*

The plants of Rutaceae, with wide distribution in China, have a long history of medicinal use. They contain a wide variety of alkaloids, which include isoquinolines, quinolines, acridones, carbazoles, and indoles. Pharmacological studies have shown that most of these alkaloids have antitumor, anti-inflammatory, antiviral, antidiabetic and other activities. This article summarized 378 alkaloids isolated from plants of Rutaceae and their pharmacological effects, aiming to lay a basis for future drug development and sustainable utilization of plant resources.
Alkaloids/chemistry* ; Humans ; Rutaceae/chemistry* ; Animals ; Drugs, Chinese Herbal/chemistry* ; Anti-Inflammatory Agents/chemistry*

Objective: To examine the association of greenness exposure with waist circumference (WC) and central obesity in older adults in China. Methods: Based on the cross-sectional data from the Chinese Longitudinal Healthy Longevity Survey in 2017-2018, 14 056 participants aged 65 years and over were included. Demographic characteristics, lifestyle, WC, and other information were collected through a questionnaire and physical examination. Based on the satellite monitoring data of moderate-resolution imaging spectroradiometer (MODIS) provided by NASA, the annual mean of normalized difference vegetation index (NDVI) within a radius of 1 000 meters was obtained as the measurement value of greenness exposure. Multivariate linear regression model, multivariate logistic regression model, and restricted cubic splines (RCS) model were used to analyze the association and dose-response relationship between greenness exposure and WC and central obesity in older adults in China. Results: A total of 14 056 participants were enrolled with a median age of 84.0 years [IQR: 75.0-94.0 years]. About 45.0% (6 330) of them were male and 48.6% (5 853) were illiterate. There were 10 964 (78.0%) participants from rural. The mean of WC was (84.4±10.8) cm. Central obesity accounted for 60.2% (8 465), and the NDVI range was (-0.06, 0.78). After adjusting for confounding factors, the multivariate linear regression model showed that the change value of WC in the urban group [β (95%CI):-0.49 (-0.93, -0.06)] was smaller than that in the rural [-0.78 (-0.98, -0.58)] for every 0.1 unit increase in NDVI (P_interaction=0.022). Compared with the Q₁ group in NDVI, WC of Q₂ and Q₃ groups in rural decreased, and the β (95%CI) values were-1.74 (-2.5, -0.98) and-2.78 (-3.55, -2.00), respectively. The multivariate logistic regression model showed that after adjusting for confounding factors, the risk of central obesity decreased for urban and rural older adults with an increase of 0.1 unit in NDVI, and the OR (95%CI) values were 0.87 (0.80, 0.95) and 0.86 (0.82, 0.89), respectively (P_interaction=0.284). Compared with the Q₁ group in NDVI, the risk of central obesity in the Q₂ and Q₃ groups in rural was lower, and the OR (95%CI) values were 0.68 (0.58, 0.80) and 0.57 (0.49, 0.68), respectively. The results of the multivariate regression model with RCS showed that there was a non-linear association of NDVI with WC (P_nonlinear=0.006) and central obesity (P_nonlinear=0.025). Conclusion: Greenness exposure is negatively associated with WC and central obesity in older adults in China.