OBJECTIVE: To explore the peripheral neural mechanism underlying representation along the distribution of stomach meridian induced by intestinal inflammatory reaction using diarrhea predominant-irritable bowel syndrome (IBS-D) mice. METHODS: Among 62 healthy male C57BL/6 mice of clean grade, 12 mice were randomly selected and divided into a control group and a model group, 6 mice in each group, additionally, 12 mice were randomly selected and divided into a Tianshu group, a Liangqiu group and a Zusanli group, 4 mice in each group. In the model group, citrobacter was administered orally to establish IBS-D model. In the control group and the model group, the visceral pain threshold was observed using fecal colorectal distension (fCRD) induced electromyography of external oblique muscle, the positive cell number of neutrophil in the colonic muscularis was detected by myeloperoxidase (MPO) staining, the number, location and distribution rule of Evans blue (EB) extravasation points were observed by injection of EB staining solution into the tail vein. In the Tianshu group, the Liangqiu group and the Zusanli group, fluorescent dye Dil was injected at bilateral "Tianshu" (ST25), "Liangqiu" (ST34) and "Zusanli" (ST36) respectively, to observe the dye-positive cell number in different dorsal root ganglion (DRG) segments. In the control group and the model group, the activation of satellite glial cells (SGCs) in different DRG segments was observed by immunofluorescence. RESULTS: Compared with the control group, in the model group, the area under curve of electromyography of external oblique muscle was increased at fCRD of 25, 50 and 75 μL distilled water (P<0.001, P<0.01); the MPO-positive cell number of neutrophil in the colonic muscularis was increased (P<0.01). Few EB extravasation points could be found in the control group, while there were much more EB extravasation points observed in the model group, which was specially distribution in the area of stomach meridian, from "Huaroumen" (ST24) to "Zusanli" (ST36), as well as the surface area dominated by L₂-L₅ segment of the spinal cord. The Dil-positive cells were mainly exhibited in the DRG of T₁₁, L₅ and L₄ segments in the Tianshu group, the Liangqiu group and the Zusanli group, respectively. Compared with the control group, the ratio of glial fibrillary acidic protein (GFAP)/glutamine synthetase (GS) co-expression was increased in the DRG of T₁₁, L₄ and L₅ segments in the model group (P<0.05, P<0.01). CONCLUSION The activation of SGCs within DRG of T₁₁, L₄ and L₅ segments may relate closely to the occurrence of the representation along the stomach meridian distribution in IBS-D mice.
Animals ; Male ; Mice ; Irritable Bowel Syndrome/therapy* ; Mice, Inbred C57BL ; Meridians ; Stomach/physiopathology* ; Humans ; Acupuncture Points ; Disease Models, Animal

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; Interleukin-33/metabolism* ; HMGB1 Protein/metabolism* ; Acetylation ; Mice, Knockout ; Mice, Inbred C57BL ; p300-CBP Transcription Factors/metabolism* ; Mice ; Spinal Cord/metabolism* ; Cells, Cultured ; Female ; Signal Transduction

OBJECTIVE To study the pharmacokinetics and tissue distribution of cannabidiol（CBD）-cholesterol succinate monoester-g-carboxymethyl chitosan （CCMC） nano-micelles in rats， and to evaluate its anti-inflammatory effect. METHODS CBD- CCMC nano-micelles were prepared by dialysis method and the properties were characterized. SD rats were divided into CBD group and CBD-CCMC nano-micelles group with 6 rats in each group. The rats were given 100 mg/kg CBD and CBD-CCMC nano- micelle by intragastric administration， respectively （based on the CBD load）. Blood was collected from the posterior ophthalmic venous plexus at 0.5， 1， 1.33， 1.5， 1.75， 2， 4， 8， 24， 48 h after administration. The heart， liver， spleen， lung， kidney and muscle tissues of rats were separated at 0.25， 1.5， 10 and 24 h after administration of CBD and CBD-CCMC nano-micelle with the same dose. The drug content in plasma and tissues was determined， the pharmacokinetic parameters were calculated， and the tissue distribution was analyzed. The inflammatory model of Caco-2 cells was induced by lipopolysaccharide， after 24 h of treatment with 5， 10， and 15 µg/mL CBD and CBD-CCMC nanomicelles （based on loaded CBD）， its anti-inflammatory activity was investigated by measuring cell viability， transepithelial electrical resistance （TEER） and inflammatory cytokines IL-1β， IL-8 and TNF-α. RESULTS The prepared CBD- CCMC nano-micelles had a particle size of （230.6±1.8） nm， a polydispersity index of 0.170±0.053， a Zeta potential of （－13.5± 1.2） mV， an encapsulation rate of （86.35±0.56）% and a drug loading of （9.18±0.32）%， respectively； the solubility was 68.240 μg/mL. The pharmacokinetic results showed that the AUC0-48 h， AUC0-∞， half-life time and peak concentration of CBD-CCMC nano- micelle group were significantly increased/extended compared with CBD group （P＜0.05 or P＜0.01）. The results of the tissue distribution study showed that at the same time point， the drug distribution concentration of CBD-CCMC nanomicelles in the rat tissue was higher than that in the CBD group. Research on anti-inflammatory effects shows that compared with CBD of the same mass concentration, CBD-CCMC nano-micelles can significantly increase cell viability （P＜0.05 or P＜0.01）， enhance TEER， and reduce the levels of IL-8， IL-1β and TNF-α in cells （P＜0.01）， and the secretion levels of inflammatory cytokines IL-8， IL-1β and TNF- α were significantly decreased （P＜0.01）. CONCLUSIONS CBD-CCMC nano-micelles can increase the plasma concentration and tissue distribution concentration of CBD， and improve anti-inflammatory activity of CBD.

Objective:To investigate the effect of high-frequency repetitive transcranial magnetic stimulation combined with sertraline on depressive symptoms and self-injurious behaviors in adolescents with depression and non-suicidal self-injury.Methods:This study was a prospective study. A total of 112 adolescent patients with depression and non-suicidal self-injury who received treatment at the Third Hospital of Quzhou from January 2021 to September 2023 were included in this study. These patients were divided into a control group and a study group, with 56 patients per group, using the random digital table method. The control group was treated with sertraline, while the study group was treated with high-frequency repetitive transcranial magnetic stimulation combined with sertraline. The depression scores [assessed using the 24-item Hamilton Depression Scale (HAMD-24) and the Self-Rating Depression Scale (SDS)], self-injury status, and inflammatory factor levels (tumor necrosis factor-α, interleukin-10, and interleukin-1β levels) were compared before and after the intervention.Results:Before intervention, there were no statistically significant differences in HAMD-24 scores and SDS scores between the two groups (both P > 0.05). After intervention, both HAMD-24 scores and SDS scores decreased significantly in both groups (both P < 0.05). Additionally, the HAMD-24 scores [(13.46 ± 3.98) points] and SDS scores [(50.28 ± 5.13) points] in the study group were significantly lower than those in the control group [(19.89 ± 4.23) points, (71.62 ± 6.88) points, t = -8.28, -18.61, both P < 0.05]. Before intervention, there were no statistically significant differences in the number of self-injury incidents and self-injurious behavior scores between the two groups (both P > 0.05). After intervention, the number of self-injury incidents and the score of self-injurious behaviors significantly decreased in the study group compared with before intervention (both P < 0.05). After intervention, the number of self-injury incidents in the control group was decreased compared with before intervention ( P < 0.05), while the score of self-injurious behaviors did not differ significantly compared with before intervention ( P > 0.05). After intervention, the number of self-injury incidents [(2.15 ± 1.06) times] and the score of self-injurious behaviors [(2.41 ± 0.65) points] in the study group were significantly lower than those in the control group [5.43 ± 3.61) times, (12.04 ± 3.01) points, t = -7.78, -23.40, both P < 0.05]. Before intervention, there were no statistically significant differences in interleukin-1β, tumor necrosis factor-α, and interleukin-10 levels between the two groups (all P > 0.05). After intervention, interleukin-1β and tumor necrosis factor-α levels in the study group were significantly lower than those before intervention (both P < 0.05), while interleukin-10 levels in the study group were significantly higher than those before intervention ( P < 0.05). There were no statistically significant differences in the levels of interleukin-1β, tumor necrosis factor-α, and interleukin-10 between the pre- and post-intervention measurements in the control group (all P > 0.05). After intervention, interleukin-1β levels [(57.15 ± 6.33) ng/L] and tumor necrosis factor-α levels [(13.87 ± 5.91) ng/L] in the study group were significantly lower than those in the control group [(73.61 ± 8.52) ng/L, (17.12 ± 5.28) ng/L], while interleukin-10 levels [(1.62 ± 0.66) ng/L] were significantly higher than those in the control group [(1.19 ± 0.63) ng/L, t = -11.60, 3.53, -3.07, all P < 0.05]. Conclusion:High-frequency repetitive transcranial magnetic stimulation combined with sertraline can significantly reduce depressive symptoms and self-injurious behaviors in adolescents with depression and non-suicidal self-injury. The reason may be due to the decrease in inflammatory factor levels in patients.

Objective:To investigate the effect of high-frequency repetitive transcranial magnetic stimulation combined with fluvoxamine treatment on improving depression, impulsivity, and self-injury levels in adolescent patients with depression.Methods:A total of 124 adolescent patients with depression who received treatment at the Department of Psychiatry, The Third Hospital of Quzhou, China from January 2022 to November 2023 were included in this study. The patients were randomly divided into a control group and an observation group, with 62 patients per group, using the random number table method. Patients in the control group received treatment with fluvoxamine, while patients in the observation group underwent high-frequency repetitive transcranial magnetic stimulation and treatment with fluvoxamine. Clinical efficacy and the scores of the Hamilton Depression Scale, Hamilton Anxiety Scale, the Barratt Impulsiveness Scale-ll revised version, and the Non-Suicidal Self-Injury Assessment Tool revised version were compared between the two groups.Results:The total response rate in the observation group was 90.32% (56/62), which was significantly higher than that in the control group [72.58% (45/62), χ2 = 6.46, P < 0.05]. After treatment, scores of the Hamilton Depression Scale and Hamilton Anxiety Scale in the observation group were (12.08 ± 1.97) points and (11.58 ± 1.59) points, respectively, which were significantly lower than those in the control group [(16.42 ± 2.33) points, (14.42 ± 1.94) points, t = -8.28, -18.61, both P < 0.05]. After treatment, the scores of the Barratt Impulsiveness Scale-ll revised version and Non-Suicidal Self-Injury Assessment Tool revised version in the observation group were significantly lower than those in the control group [(28.25 ± 3.91) points, (9.23 ± 2.12) points, t = 5.42, 9.44, both P < 0.05]. Conclusion:High-frequency repetitive transcranial magnetic stimulation combined with fluvoxamine treatment can significantly reduce depressive symptoms, impulsivity, and self-injury levels in adolescent patients with depression.

Objective:To investigate the repeatability of corneal topographic parameters with the Pentacam HR in patients with keratoconus of different severity.Methods:A diagnostic test study was performed.A total of 120 eyes from 98 patients with subclinical keratoconus or keratoconus were enrolled at Henan Eye Hospital from January 2019 to March 2022.The patients were divided into subclinical keratoconus group, mild keratoconus group, moderate keratoconus group and severe keratoconus group, with 30 eyes in each group.An additional 30 eyes of 30 subjects undergoing refractive surgery were selected as a control group.Three consecutive Pentacam HR measurements were performed by the same clinician.The recordings included a total of 53 parameters in anterior corneal surface, posterior corneal surface, thickness, composite index, and corneal densitometry.The within-subject standard deviation (Sw), repeatability limit ( r) and tolerance index (TI) were calculated to evaluate the repeatability of the parameters between different groups.This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2019[5]).All subjects were informed of the purpose and significance of the study and signed an informed consent form before enrollment. Results:Compared with the control group, the TI of the subclinical, mild, moderate and severe keratoconus groups were 54.71%(29/53), 66.04%(35/53), 90.57%(48/53) and 94.34%(50/53), respectively, higher than 0.31.The steep keratometry (Ks), the maximum keratometry (Kmax) of the anterior corneal surface, the anterior corneal radius of curvature, the flat keratometry (Kf) of the posterior corneal surface, the posterior corneal radius of curvature (PRC), the thinnest corneal thickness (TCT), the average densitometry for the anterior 120 μm in the 0-2 mm area (A.0-2 mm), average densitometry for the anterior 120 μm in the 2-6 mm area (A.2-6 mm), average densitometry for the central tissue in the 0-2 mm area (C.2-6 mm), average densitometry for the total cornea in the 0-2 mm area (T.0-2 mm) and average densitometry for the total cornea in the 2-6 mm area (T.2-6 mm) showed good repeatability in the subclinical and mild keratoconus groups (TI<0.31).Kmax Zonal Mean 3 mm, posterior corneal surface mean keratometry, central keratoconus index showed good repeatability in subclinical, mild and moderate keratoconus groups.Kmax Zonal Mean 4 mm and Kmax Zonal Mean 5 mm showed good repeatability in all groups (TI<0.31).Conclusions:For patients with subclinical and mild keratoconus, Kf of the posterior corneal surface, PRC and TCT are recommended to monitor disease progression.To monitor the condition of patients with moderate and severe keratoconus, we may focus on the detection of Kmax Zonal Mean 4 mm and Kmax Zonal Mean 5 mm.

Objective To analyze the causal relationship between statins and type 1 or type 2 diabetes mellitus by using Mendelian randomization(MR).Methods Based on the collected data of genome-wide association studies(GWAS),single nucleotide polymorphism(SNP),which were independent of each other and highly correlated with statins and diabetes mellitus,were selected as tool variables.MR-Egger regression,weighted median,inverse variance weighting(IVW),simple mode and weighted mode were used for two-sample MR analyses to evaluate the causal relationship between statins and type 1 or type 2 diabetes respectively,and heterogeneity tests,multiplicity analyses,and sensitivity analysis to evaluate the reliability of the study.Results A total of 78 SNPs independently associated with statins were included as tool variables in this study at the genome-wide significance level(P＜5×10-8).The results of IVW analysis showed that statins were causally associated with an increased risk of type 1 diabetes mellitus(OR=1.524,95％CI 1.077 to 2.157,P=0.017),and there was also a causal relationship between statins and the increased risk of type 2 diabetes(OR=1.261,95％CI 1.165 to 1.366,P＜0.001).The results were not affected by multiplicity and heterogeneity,and the reliability of the results was verified by sensitivity analysis.Conclusion Statins may be a risk factor for increasing the risk of type 1 or type 2 diabetes.However,further studies with larger sample sizes of GWAS data are still needed to verify the causal association.

Drug use monitoring and evaluation play a key role in promoting drugs to return to clinical value,optimizing the basic medicine system,and improving the drug supply guarantee system.In order to promote the implementation of drug use monitoring and evaluation in medical institutions,the Pharmaceutical Affairs Committee of the Chinese Hospital Association led the efforts of organizing relevant domestic experts to follow the group standard development process.It successfully formulated the group standard of Drug Use Monitoring and Evaluation through the steps of problem sorting,framework construction,evidence collection,draft writing,opinion consultation,and standard formation.This article introduces the standard formulation process in detail,and explains and analyzes the content of the standard,aiming to help readers better understand the connotation of drug use monitoring and evaluation,and provide practical guidance.