BACKGROUND:Neurotrophins represent a novel therapeutic approach for spinal cord injury,showing promising clinical applicability.Autophagy modulation is one of the mechanisms by which neurotrophins exert their effects,yet the specific signaling pathways involved remain unclear. OBJECTIVE:To explore how neurotrophin-3(NT-3)modulates autophagy in oligodendrocytes via switching between P75NTR and TrkC receptors and promotes neurological function recovery after spinal cord injury,aiming to further clarify the specific molecular mechanisms involved. METHODS:Twenty-four Sprague-Dawley rats were randomly divided into three groups:sham operation,spinal cord injury,and NT-3 groups.The therapeutic effect of NT-3 on spinal cord injury in rats was evaluated using the Basso,Beattie,and Bresnahan locomotor rating scale.The expression levels of NT-3,Olig1,myelin basic protein,and the autophagy marker LC3B in rat spinal cord tissue were detected by western blot.In a cellular experiment,oligodendrocytes were cultured in vitro and divided into six groups:oxygen-glucose deprivation(OGD),OGD+NT-3,OGD+NT-3+P75NTR plasmid,OGD+NT-3+TrkC plasmid,OGD+3-methyladenine(an autophagy inhibitor),and OGD+rapamycin(an autophagy activator).Oligodendrocyte morphology was observed under a light microscope,cell apoptosis was assessed by TUNEL staining,and the expression of TrkC receptor,P75NTR,LC3B,and the phosphorylation status of the PI3K/AKT/mTOR and AMPK/mTOR signaling pathways were evaluated by western blot. RESULTS AND CONCLUSION:Animal experiments demonstrated that compared with the sham operation group,NT-3 expression significantly increased after spinal cord injury(P<0.05);exogenous NT-3 treatment accelerated neurological function recovery in rats post spinal cord injury(P<0.05)and increased the expression of Olig1 and myelin basic proteins(P<0.05).Cellular experiments revealed that 3 hours marked the early to middle/late phase transition.Compared with the OGD group,oligodendrocytes in the OGD+NT-3 group could maintain their morphology for a longer period of time,TrkC receptor expression was lower in the early phase and significantly upregulated in the middle/late phase(P<0.05),whereas P75NTR protein expression was upregulated in the early phase and downregulated in the middle/late phase(P<0.05),and autophagy levels showed an initial increase followed by a decrease(P<0.05).By comparing the morphology and TUNEL staining results of cells in the OGD+NT-3,OGD+rapamycin,and OGD+3-methyladenine groups,we found that either promoting or inhibiting autophagy alone had adverse effects on oligodendrocyte survival,whereas modulating autophagy in a manner similar to NT-3 could maximally maintain cell survival.NT-3 could promote autophagy in the early phase via the P75NTR/AMPK/mTOR signaling pathway and inhibit autophagy in the later phase through the TrkC/PI3K/AKT/mTOR signaling pathway.Based on these findings,it is concluded that NT-3 can bidirectionally regulate autophagy in oligodendrocytes through the switching of P75NTR/TrkC receptors,thereby maintaining cell survival and facilitating the recovery of neurological functions in rats after spinal cord injury.

As one of the chronic diseases with high incidence in contemporary society, cervical spondylosis has increasing patient groups who gradually present a low age, and it seriously affects social and public health. Although modern medicine has made great progress in the pathological research and clinical treatment of cervical spondylosis, patients still face gastrointestinal side effects of nonsteroidal anti-inflammatory drugs(NSAIDs), neck pain, limited mobility, upper limb numbness, and other symptoms after conservative or surgical treatment. In the theory of traditional Chinese medicine(TCM), cervical spondylosis belongs to the categories of "Bi syndrome" "stiff neck" "stiff Bi", etc. With the change of the times, the change of lifestyle, and the application of western medicine treatment, the etiology and pathogenesis of TCM in cervical spondylosis also show new characteristics. In terms of etiology and pathogenesis, it involves the invasion of wind, cold, and dampness, long-term strain, liver and kidney deficiency, Qi and blood stasis, which are associated with factors such as cervical degeneration, muscle tension and spasm, intervertebral disc herniation, and nerve root compression in modern medicine. In terms of the evolution of pathogenesis, in the early stage, wind, cold, and dampness, were more common in Xuanfu, resulting in unfavorable muscles and bones, poor flow of Qi and blood, and cervical spondylosis and radiculopathy. Medium-term phlegm stasis and internal knots, sluggish muscles and veins, and long-term weathering and fire are more likely to occur in the vertebral artery and sympathetic radiculopathy. In the later stage, the positive Qi is depleted; the true Yin is damaged, and the viscera Qi and blood are deficient, which is most common in cervical myelopathy. The strategy of treating cervical spondylosis with TCM classic formulas applies Gegen Decoction, Wutou Decoction, Qianghuo Shengshi Decoction, Mahuang Jiazhu Decoction to patients with wind, cold, and dampness. Patients with phlegm dampness and blood stasis are treated with Huoxue Xiaoling Dan, Jinlingzi Powder, Siwu Decoction, Banxia Baizhu Tianma Decoction, Shuanghe Decoction, etc. For those patients with liver, spleen, and kidney deficiency, Huangqi Guizhi Wuwu Decoction, Tianma Gouteng Decoction, Guishao Dihuang Pills, Shenling Baizhu Powder, and Lizhong Decoction are used to invigorate the spleen, nourish Qi and blood, and tonify liver and kidney. In clinical practice, the authors advocate a safe and effective treatment plan of classic formulas based on deficiency and excess, the integration of formulas and syndromes, and the combination of modern research results, so as to relieve symptoms, reduce recurrence, and reduce medical burden.
Humans ; Spondylosis/drug therapy* ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/therapeutic use* ; Cervical Vertebrae/pathology*

Evaluate the interventional effect of Lycium barbarum leaves extract on cataract rats and its effects on plasma and liver tissue metabolites. The ultimate goal is to explore the scientific connotation of Lycium barbarum leaves extract on vision improvement. All experiments were approved by the experimental animal ethics committee from Nanjing University of Chinese Medicine (202306A067). D-Galactose (D-gal) induced cataract model in rats was established. The lens opacity, lens and liver tissue pathology, level of oxidative stress and polyol metabolism regulation in the lens, level of oxidative stress in serum and liver tissue, and the content of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum and liver tissue were analysed to evaluate the effect of Lycium barbarum leaves extract on cataract. The metabolite profiles of plasma and liver tissue of rats were analyzed by UPLC-QTOF-MS/MS. Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were used to compare and analyze the metabolic data in control group and cataract group, and screen potential biomarkers. The related metabolic pathways were further constructed by KEGG database analysis. The results showed that lens and liver pathology of cataract rats were improved after being intervened by the leaves extract of Lycium barbarum. The contents of AR and Ca²⁺ were significantly decreased in lens, and the contents of SDH and GSH and the ability of CAT were significantly increased; the content of GSH and the ability of SOD were significantly improved in serum and liver tissue, the content of MDA, the abilities of ALT and AST and the level of inflammatory factors were significantly reduced. The metabolomics results showed that there were 15 different metabolites in plasma and liver tissue of cataract rats, and 9 different biomarkers including retinyl ester, stearic acid, and palmitic acid, were returned by Lycium barbarum leaves extract. As revealed by pathway enrichment in plasma and liver tissue, it was found that the retinol metabolic pathway was mainly regulated by Lycium barbarum leaves extract. In summary, Lycium barbarum leaves can effectively alleviate the pathological changes of cataract, inhibit inflammation and improve antioxidant capacity, which may relate to the retinol metabolic pathway. It provides scientific basis and support for revealing the scientific connotation of the effect of Lycium barbarum leaves on vision improvement.

The purpose of this study was to investigate the intervention effect and mechanism of Lycium barbarum leaves on letrozole-induced polycystic ovary syndrome (PCOS) mice. The PCOS model was prepared by letrozole combined with high-fat diet. After successful modeling, 40 mice were randomly divided into PCOS group, positive drug metformin group, low-dose Lycium barbarum leaves group, and high-dose Lycium barbarum leaves group. The corresponding drugs were given by gavage for 29 days. At the end of the experiment, the eyeballs were removed for blood collection and ovarian tissue was collected. The ovarian mass, fasting blood glucose (FBG), fasting insulin (FINS), testosterone (T), anti-Mullerian hormone (AMH), luteinizing hormone (LH), follicle stimulating hormone (FSH), and estradiol (E₂) levels were measured in each group. The morphology of ovarian tissue was observed by hematoxylin-eosin staining, and the oocytes, cystic follicles and corpus luteum were counted. Cecal contents of mice were collected for analysis of intestinal flora composition and differential flora. The animal experiment process was approved by the Animal Ethics Committee of Nanjing University of Traditional Chinese Medicine. The results showed that the estrous cycle of PCOS mice was disordered. Compared with the PCOS group, the Lycium barbarum leaves group can significantly reduce the ovarian damage of mice, reduce the number of cystic dilated follicles, and normalize the estrous cycle. After the intervention of Lycium barbarum leaves, the levels of FBG, FINS, T, AMH, LH, FSH and LH/FSH were significantly decreased (P < 0.05), while the level of E₂ was significantly increased (P < 0.001). In addition, Lycium barbarum leaves can regulate the disorder of intestinal flora diversity in PCOS mice, increase the abundance of Bacteroidetes, and reduce the abundance of Firmicutes, Ileibacterium, Romboutsia and Faecalibaculum. In summary, Lycium barbarum leaves can play a therapeutic role in PCOS mice by improving insulin resistance, regulating reproductive hormone disorders and gut microbiota imbalance. It provides scientific basis and useful reference for the rational utilization and development of Lycium barbarum leaves.

This study was aimed at understanding the trends in,and scope of,severe fever with thrombocytopenia syndrome(SFTS)in Nanjing,analyzing the spatial distribution pattern,detecting high incidence cluster areas and key popula-tions,and scientifically guiding prevention and control strategies and measures.We obtained data on SFTS cases from 2010 to 2023 in Nanjing from the China Disease Control and Prevention Information System,and described the time,popu-lation,and spatial distribution characteristics.We used joinpoint regression to calculate the annual percentage change(APC)in incidence,then used FleXScan spatial clustering scan analysis to explore spatial clustering areas at the street level.A total of 507 SFTS cases were reported from 2010 to 2023 in Nanjing.The APC was 31.8％(95％CI:22.5％-41.9％,P＜0.001),and the reported incidence in 2023 was 1.42/100 000(134 cases).The seasonal indices from May to August were 2.7,2.1,3.0,and 1.3,respectively,accounting for 76.1％of the total cases.The median age was 66(IQR:55,73)years,which gradually increased from 59 years in 2010-2011 to 68 in 2022-2023(P＜0.001);94.1％of cases were in individuals 45 years or older.Farmers,homemakers/unemployed individuals,and retirees accounted for 90.1％.The epidemic area increased from 11 streets in four districts in 2010-2011 to 58 streets in 11 dis-tricts in 2022-2023.Except for 2012-2013,global spatial autocorrelation analysis showed positive Moran's I values(0.224-0.526,P＜0.001),and FlexScan scan indicated that several streets in Lishui District and Jiangning District were the most likely clusters.Four streets in Pukou District were the secondary clusters from 2018 to 2023,and three streets in Luhe District in 2022-2023 were the secondary clusters(all P＜0.05).The reported incidence of SFTS in Nanjing showed a rapid upward trend,with spread of epidemic areas.The spatial distribution pattern was clustered.Strengthened training in diagnosis and treatment technology and detection ability of medical institutions,surveillance in high-incidence areas,tracing of case flow,and health education of tick and disease prevention knowledge are recommended.

Objective:To summarize the imaging characteristics of primary intestinal lymphoma (PIL).Methods:As a cross-sectional study, a total of 103 consecutive patients diagnosed as PIL by pathology were retrospectively enrolled at Affiliated Shandong Provincial Hospital of Shandong First Medical University between January 2013 to December 2023. Ninety-four patients underwent CT plain and enhanced scans, and the remaining 9 patients only underwent MRI examination. Imaging features were evaluated, including the location and shape of the tumor, the shape of the intestinal wall and lumen, abdominal lymph nodes, the density or signal intensity of the tumor, and the degree and mode of enhancement after the enhancement scan.Results:The most frequent location of PIL was the ileum (43.7%, 45/103), followed by the ascending colon (20.4%, 21/103). Ninety-one patients had a single lesion (88.3%), while the other 12 patients had multiple lesions (11.7%). Diffuse large B-cell lymphoma was the most common histopathological type of the PIL (65.0%, 67/103), followed by mucosa-associated lymphoid tissue lymphoma (9.7%, 10/103). Generally, PIL classically presented intestinal wall thickening (81.6%, 84/103) and exophytic mass (28.2%, 29/103). Aneurysmal dilatation of the lumen appeared in 19 patients. Nineteen tumors (18.4%) grew out of the lumen, and perforation was shown in 3 patients. Bulky mesenteric or retroperitoneal adenopathy occurred in 28 patients (27.2%). Seventy-two tumors (69.9%) showed homogeneous enhancement, and 75 (72.8%) showed mild-to-moderate enhancement. In DWI images, all 9 tumors showed significant diffusion limitation.Conclusions:The most frequent location of PIL was the ileum. The main imaging characteristics were segmental intestinal wall thickening, which showed mild-to-moderate homogeneous enhancement and restricted diffusion.

This paper explored the protective effect and potential mechanism of Shouhui Tongbian Capsules(SHTB) on cerebral ischemia-reperfusion rat models. Rats were randomly divided into sham surgery group, model group, low-dose SHTB group(0.2 g·kg~(-1)·d~(-1)), high-dose SHTB group(SHTB g·kg~(-1)·d~(-1)), and an edaravone positive drug group(5.4 mg·kg~(-1)·d~(-1)), with 12 rats in each group. Rats were given continuous intragastric administration seven days before surgery, and the suture method was used to establish the cerebral ischemia-reperfusion injury(CIRI) rat model. Zea-Longa rating scale for neurological functions was used to assess the degree of neurological function impairment in rats; hematoxylin-eosin(HE) staining was used to observe the pathological damage of rats' brain tissue; TTC staining was used to measure the area of cerebral infarction in rats; enzyme-linked immunosorbent assay(ELISA) was used to detect the serum levels of interleukin-6(IL-6), interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α) in each group. Western blot was used to detect the level of tight junction protein associated with the blood-brain barrier and intestinal barrier, as well as the protein expression of the TLR4/MyD88/NF-κB pathway in brain tissue. Changes in rats' brain tissue and metabolites in serum were detected by ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS), so as to explore the potential mechanism of SHTB treatment for CIRI in rats. Compared with the model group, SHTB could significantly alleviate the pathological damage to the brain of CIRI rats, reduce the volume of cerebral infarction, and lower the level of inflammation in the serum; Western blot results showed that SHTB could regulate the expression of tight junction proteins related to the blood-brain barrier and intestinal barrier in CIRI rats and downregulate the expression of TLR4, NF-κB, and MyD88 proteins in brain tissue. The UPLC-MS/MS results indicated that SHTB could significantly regulate the content of potential differential metabolites such as fatty acids, and serum and brain tissue are involved in pathways such as unsaturated fatty acid biosynthesis. SHTB could repair intestinal barrier function, reduce inflammation levels in the body, and improve the damaged blood-brain barrier, exerting a protective effect on brain nerves. Its mechanism may be achieved by balancing fatty acid metabolism and regulating the expression of TLR4/MyD88/NF-κB signaling pathway proteins.
Animals ; Rats ; Drugs, Chinese Herbal/administration & dosage* ; Reperfusion Injury/genetics* ; Male ; Rats, Sprague-Dawley ; Brain Ischemia/genetics* ; Metabolomics ; Disease Models, Animal ; Myeloid Differentiation Factor 88/metabolism* ; Toll-Like Receptor 4/metabolism* ; NF-kappa B/metabolism* ; Humans ; Brain/metabolism*

As one of the key components of clinical trials, blinding, if successfully implemented, can help to mitigate the risks of implementation bias and measurement bias, consequently improving the validity and reliability of the trial results. However, successful blinding in clinical trials of traditional Chinese medicine (TCM) is hard to achieve, and the evaluation of blinding success through blinding assessment lacks established guidelines. Taking into account the challenges associated with blinding in the TCM field, here we present a framework for assessing blinding. Further, this study proposes a blinding assessment protocol for TCM clinical trials, building upon the framework and the existing methods. An assessment report checklist and an approach for evaluating the assessment results are presented based on the proposed protocol. It is anticipated that these improvements to blinding assessment will generate greater awareness among researchers, facilitate the standardization of blinding, and augment the blinding effectiveness. The use of this blinding assessment may further advance the quality and precision of TCM clinical trials and improve the accuracy of the trial results. The blinding assessment protocol will undergo continued optimization and refinement, drawing upon expert consensus and experience derived from clinical trials. Please cite this article as: Wang XC, Liu XY, Shi KL, Meng QG, Yu YF, Wang SY, Wang J, Qu C, Lei C, Yu XP. Blinding assessment in clinical trials of traditional Chinese medicine: Exploratory principles and protocol. J Integr Med. 2023; 21(6): 528-536.
Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional/methods* ; Outcome Assessment, Health Care ; Reference Standards ; Reproducibility of Results ; Research Design ; Clinical Trials as Topic

OBJECTIVE: Aconite is a traditional Chinese herbal medicine that has been found to inhibit the development of liver cancer; however, its exact molecular mechanisms in this process remain unclear. This study explores how aconite aqueous extract (AAE) inhibits hepatocellular carcinoma (HCC). METHODS: An in vivo mouse model of subcutaneous liver cancer was established. After AAE treatment, immunohistochemistry (IHC) was used to determine the effect of AAE on natural killer (NK) cells. Subsequently, C57BL/6 mice were used to establish the subcutaneous tumor model, and a group of these mice were treated with anti-PK163 antibody to remove NK cells, which was verified by flow cytometry and IHC. The effect of AAE on the proliferation of HCC cells in vitro was determined using cell counting kit-8. The effect of AAE on chemokine production in HCC cells was measured using real-time quantitative polymerase chain reaction and an enzyme-linked immunosorbent assay. The effect of AAE on the migration of NK cells was determined using a transwell assay. Finally, the molecular mechanism was investigated using the Western blotting method. RESULTS: We demonstrated that the ability of AAE to induce overexpression of the cytokine C-C motif chemokine ligand 2 (CCL2) in HCC cells is fundamental to the infiltration of NK cells into the tumor bed. Mechanistically, we found that the upregulation of CCL2 was achieved by the activation of c-Jun N-terminal kinase but not extracellular regulated protein kinase or p38. CONCLUSION Our findings suggest that AAE can be used as an effective immune adjuvant to enhance antitumor immunity by increasing NK cell infiltration into tumors, which could help to improve the efficacy of HCC treatments. Please cite this article as: Yang KD, Zhang X, Shao MC, Wang LN. Aconite aqueous extract inhibits the growth of hepatocellular carcinoma through CCL2-dependent enhancement of natural killer cell infiltration. J Integr Med. 2023; 21(6): 575-583.
Animals ; Mice ; Carcinoma, Hepatocellular/drug therapy* ; Liver Neoplasms/drug therapy* ; Aconitum ; Ligands ; Mice, Inbred C57BL ; Killer Cells, Natural/metabolism* ; Chemokines/pharmacology* ; Cell Line, Tumor

Objective: This study aimed to identify the risk factors for genitourinary fistulas and delayed fistula recognition after radical hysterectomy for cervical cancer. Methods: This study was a retrospective analysis of data collected in the Major Surgical complications of Cervical Cancer in China (MSCCCC) database from 2004–2016. Data on sociodemographic characteristics, clinical characteristics, and hospital characteristics were extracted. Differences in the odds of genitourinary fistula development were investigated with multivariate logistic regression analyses, and differences in the time to recognition of genitourinary fistula were assessed by Kruskal–Wallis test. Results: In this study, 23,404 patients met the inclusion criteria. Surgery in a cancer center, a women’s and children’s hospital, a facility in a first-tier city, or southwest region, stage IIA, type C1 hysterectomy, laparoscopic surgery and ureteral injury were associated with a higher risk of ureterovaginal fistula (UVF) (p<0.050). Surgery in southwest region, bladder injury and laparoscopic surgery were associated with greater odds of vesicovaginal fistula (VVF) (p<0.050). Surgery at cancer centers and high-volume hospitals was associated with an increase in the median time to UVF recognition (p=0.016; p=0.005). International Federation of Gynecology and Obstetrics (FIGO) stage IIA1-IIB was associated with delayed recognition of VVF (p=0.040). Conclusion Intraoperative urinary tract injury and surgical approach were associated with differences in the development of UVFs and VVFs. Patients who underwent surgery in cancer centers and high-volume hospitals were more likely to experience delayed recognition of UVF. Patients with FIGO stage IIA1-IIB disease were more likely to experience delayed recognition of VVF.