OBJECTIVE: To investigate the effects of Huayu Tongluo (transforming stasis and unblocking collaterals) moxibustion on cognitive function and insulin resistance in patients with type 2 diabetes mellitus (T2DM) and cognitive decline. METHODS: Ninety patients with T2DM and cognitive decline were randomly divided into a moxibustion group (n=45, 3 cases dropped out, 2 cases were eliminated) and a waiting moxibustion group (n=45, 2 cases dropped out). Both groups received routine hypoglycemic treatment for 12 weeks. The moxibustion group additionally received Huayu Tongluo moxibustion at Baihui (GV20), Shenting (GV24), and Dazhui (GV14). Pressing moxibustion was applied to Baihui (GV20) for 20 min, while suspended moxibustion was applied to Shenting (GV24) and Dazhui (GV14) for 20 min each. Treatments of moxibustion were administered every other day (three times per week) for 12 weeks. All patients were followed up for 12 weeks, during which their original hypoglycemic medication regimen was maintained. Before treatment, after 12 weeks of treatment, and at the 12-week follow-up, the scores of Montreal cognitive assessment (MoCA), mini-mental state examination (MMSE), Addenbrooke's cognitive examination Ⅲ (ACE-Ⅲ), symbol digit modalities test (SDMT), and Athens insomnia scale (AIS) and the insulin resistance index (HOMA-IR) were observed in the two groups. RESULTS: Compared with before treatment, the MoCA scores, MMSE scores, ACE-Ⅲ subscale scores (attention, memory, language fluency, language, visuospatial ability) and total scores, and SDMT scores were increased (P<0.01), while the AIS scores were decreased (P<0.05) in the moxibustion group after treatment and at follow-up. Compared with before treatment, the MMSE score, ACE-Ⅲ subscale scores (memory, attention) and total score after treatment, as well as the ACE-Ⅲ subscale scores (language, memory, attention) and total score, and SDMT score at follow-up were increased (P<0.05, P<0.01) in the waiting moxibustion group. Compared with before treatment, HOMA-IR was decreased in both groups after treatment and at follow-up (P<0.01). At follow-up, ACE-Ⅲ subscale scores (attention, memory), and the total score in the moxibustion group were lower than those after treatment (P<0.05, P<0.01), and the ACE-Ⅲ language subscale score, total ACE-Ⅲ score, and SDMT score in the waiting moxibustion group were higher than those after treatment (P<0.01, P<0.05). After treatment and at follow-up, compared with the waiting moxibustion group, the moxibustion group had higher MoCA scores, MMSE scores, SDMT scores, ACE-Ⅲ subscale scores (attention, memory, language fluency) and total scores (P<0.05, P<0.01), and lower HOMA-IR (P<0.05). CONCLUSION Huayu Tongluo moxibustion can effectively improve cognitive function in patients with T2DM and cognitive decline. This improvement may be associated with the reduction in insulin resistance.
Humans ; Insulin Resistance ; Diabetes Mellitus, Type 2/complications* ; Male ; Female ; Moxibustion ; Middle Aged ; Aged ; Cognition ; Acupuncture Points ; Adult ; Cognitive Dysfunction/therapy*

Geniposidic acid(GA), a natural iridoid, exists in the roots, stems, leaves, flowers, bark, fruits, and seeds of medicinal plants of Rubiaceae, Eucommiaceae, and Plantaginaceae. Modern pharmacological studies have revealed that GA has multiple pharmacological activities, including organ-protective, anti-inflammatory, antioxidative, anti-osteoporosis, anti-neurodegenerative, and anti-cardiovascular effects. GA can enhance cell/organism defenses by upregulating key anti-inflammatory and antioxidant cytokines, while downregulating key node proteins in pro-inflammatory signaling pathways such as AhR and TLR4/MyD88, thereby exerting pharmacological effects such as organ protection. Pharmacokinetic investigations have suggested that after oral administration, GA can be distributed in multiple organs(kidney, liver, heart, spleen, lung, etc.). In addition, the pharmacokinetic behavior of GA could be significantly altered under disease conditions, as demonstrated by a marked increase in systematic exposure. This article comprehensively summarizes the reported pharmacological activities and mechanisms and systematically analyzes the pharmacokinetic characteristics and key parameters of GA, with the aim of providing a theoretical basis and scientific reference for the precise clinical application of GA-related Chinese patent medicines, as well as for the investigation and development of innovative drugs based on GA.
Humans ; Drugs, Chinese Herbal/chemistry* ; Animals ; Iridoid Glucosides/chemistry* ; Plants, Medicinal/chemistry* ; Anti-Inflammatory Agents/pharmacology*

OBJECTIVE: To explore prevalence, incidence and possible factors of immediate herniated discs after posterior cervical expansive open-door laminoplasty (EODL). METHODS: Totally 29 patients with cervical spinal stenosis and intervertebral disc herniation who underwent EODL from October 2020 to December 2021 were collected, including 24 males and 5 females, aged from 43 to 81 years old with an average of (61.3±9.0) years old;the courses of disease ranged from 1 to 120 months with an average of (36.4±37.0) months. Three or more intervertebral discs on C₃-C₇ were observed. The clinical efficacy was evaluated according to Japanese Orthopaedic Association (JOA) score before operation, 3 days and 1, 3, 6 and 12 months after operation, respectively. The changes of herniated disc before and after operation were measured by multipoint area method and two-dimensional distance method, and incidence and percentage of herniated disc regression were further calculated. Cervical imaging parameters such as Cobb angle (C₃-C₇), intervertebral angle, T₁ slope (T₁S), spinal canal sagittal diameter, K-line angle, dural sac sagittal diameter were measured and compared before and after operation. Pearson correlation was used to analyze correlation between cervical sagittal imaging parameters and disc herniation changes before and after operation. RESULTS: All patients obtained grade A wound healing, and 14 of them were followed up for 3(1.00, 5.25) months. There were no immediate or long-term postoperative complications. Totally 101 herniated intervertebral discs were measured, of which 79 regression numbers were obtained by area measurement. The number of intervertebral disc regressions by distance measurement was 77. There was no statistically significant difference in Cobb angle, intervertebral angle, T₁S and K-line angle of C₃-C₇ (P>0.05), however, there were statistically significant differences in sagittal diameter of spinal canal, sagittal diameter of dural sac, and JOA score before and after operation(P<0.05). The regression ratio of disc herniation ranged from 5% to 50%, and regression ratio of disc herniation was greater than 25% in 45.57%(36/79). Disc herniation in C_4,5 was positively correlated with sagittal plane diameter in C₅(r=0.423, P=0.028). There was a negative correlation between changes of C_3,4 and C_3,4 intervertebral angle (r=-0.450, P=0.041). The improvement rate of cervical JOA score immediately after operation was (59.54±15.07) %, and postoperative follow-up improved to (76.57±14.66) %. CONCLUSION Herniated disc regression immediately after EODL is a common occurrence, and EODL should be selected as far as possible under the premise of satisfying surgical indications. The regression of disc herniation is positively correlated with spinal canal sagittal diameter, and spinal canal should be enlarged as far as possible in the appropriate scope during EODL, so as to create more opportunities and conditions for disc regression and achieve better clinical results.
Humans ; Female ; Male ; Intervertebral Disc Displacement/diagnostic imaging* ; Spinal Stenosis/diagnostic imaging* ; Laminoplasty/methods* ; Middle Aged ; Aged ; Cervical Vertebrae/diagnostic imaging* ; Adult ; Aged, 80 and over ; Intervertebral Disc/surgery*

Objective To investigate the effects of Echinococcus multilocularis infection on levels of memory T (Tm) cells and their subsets in lymph nodes of mice at different stages of infection, so as to provide new insights into immunotherapy for alveolarechinococcosis. MethodsTwenty-four C57BL/6J mice aged 6 to 9 weeks were randomly divided into the infection group and the control group, of 12 mice in each group. Mice in the infection group were administered with 3 000 E. multilocularis protoscoleces via portal venous injection, while animals in the control group were administered with an equal volume of physiological saline. Three mice from each group were sacrificed 4, 12 weeks and 24 weeks post-infection, and lymph nodes were sampled and stained with hematoxylin and eosin (HE) to investigate the histopathological changes of mouse lymph nodes in the infection group. The expression and localization of T lymphocyte surface markers CD3, CD4, and CD8 were observed in mouse lymph nodes using immunohistochemical staining. In addition, lymphocyte suspensions were prepared from mouse lymph nodes in both groups at different time points post-infection, and the levels of Tm cell subsets and their secreted cytokines were detected using flow cytometry. Results HE staining showed diffuse structural alterations in the subcapsular cortical and paracortical regions of mouse lymph nodes in the infection group 4 weeks post-infection with E. multilocularis. Immunohistochemical staining detected CD3, CD4 and CD8 expression in mouse lymph nodes in both groups. Flow cytometry revealed higher proportions of CD4⁺ Tm cells [(55.3 ± 4.8)% vs. (38.8 ± 6.1)%; t = -4.259, P < 0.05] and CD4⁺ tissue-resident Tm (Trm) cells [(57.7 ± 3.7)% vs. (34.1 ± 11.2)%; t = -3.990, P < 0.05] in mouse lymph nodes in the infection group than in the control group 4 weeks post-infection, and higher proportions of CD4⁺ Tm cells [(34.6 ± 3.2)% vs. (23.3 ± 7.5)%; t = -2.764, P < 0.05] and CD4⁺ Trm cells [(44.0 ± 1.9)% vs. (31.2 ± 1.5)%; t = -4.039, P < 0.05] in mouse lymph nodes in the infection group than in the control group 24 weeks post-infection. The proportions of CD8⁺ Tm cells were higher in the infection group than in the control group 4 weeks [(56.8 ± 2.7)% vs. (43.9 ± 5.2)%; t = -4.416, P < 0.01] and 12 weeks post-infection [(25.4 ± 2.7)% vs. (12.0 ± 2.6)%; t = -2.552, P < 0.05], while the proportions of tumor necrosis factor (TNF)-α⁺ CD4⁺ T cells [(15.7 ± 5.0)% vs. (49.4 ± 6.4)%; t = 7.150, P < 0.01], TNF-α⁺CD8⁺ T cells [(20.7 ± 5.5)% vs. (57.5 ± 8.4)%; t = -6.694, P < 0.01], and TNF-α⁺ CD8⁺ Tm cells [7.0% (1.0%) vs. 31.0% (11.0%); Z = -2.236, P < 0.05] were lower in the infection group than in the control group 24 weeks post-infection. Conclusions Tm cells levels are consistently increased in lymph nodes of mice at different stages of E. multilocularis infection, with Trm cells as the predominantly elevated subset. The impaired capacity of CD8⁺ Tm cells to secrete the effector molecule TNF-α in mouse lymph nodes at the late-stage infection may facilitate chronic parasitism of E. multilocularis.

Despite therapy with potent antiviral agents, chronic hepatitis B (CHB) patients remain at high risk of hepatocellular carcinoma (HCC). While metabolites have been rediscovered as active drivers of biological processes including carcinogenesis, the specific metabolites modulating HCC risk in CHB patients are largely unknown. Here, we demonstrate that baseline plasma from CHB patients who later developed HCC during follow-up exhibits growth-promoting properties in a case-control design nested within a large-scale, prospective cohort. Metabolomics analysis reveals a reduction in long-chain acylcarnitines (LCACs) in the baseline plasma of patients with HCC development. LCACs preferentially inhibit the proliferation of HCC cells in vitro at a physiological concentration and prevent the occurrence of HCC in vivo without hepatorenal toxicity. Uptake and metabolism of circulating LCACs increase the intracellular level of acetyl coenzyme A, which upregulates histone H3 Lys14 acetylation at the promoter region of KLF6 gene and thereby activates KLF6/p21 pathway. Indeed, blocking LCAC metabolism attenuates the difference in KLF6/p21 expression induced by baseline plasma of HCC/non-HCC patients. The deficiency of circulating LCACs represents a driver of HCC in CHB patients with viral control. These insights provide a promising direction for developing therapeutic strategies to reduce HCC risk further in the antiviral era.

Objective:To detect the expression level and clinical significance of centromere protein I (CENPI) in hepatocellular carcinoma (HCC) and to preliminarily explore the effects of CENPI on the biological behavior of liver cancer cells and its possible molecular mechanisms. Methods:The TCGA database, real-time fluorescent quantitative polymerase chain reaction, Western blot, and immunohistochemical staining experiments were used to analyze and detect the expression differences of CENPI in liver cancer and adjacent tissues. The correlation between CENPI expression levels and clinical pathological features were analyzed in combination with clinical data from HCC patients. The value of CENPI in the diagnosis and prognosis assessment of HCC was explored by plotting receiver operating characteristic curves and Kaplan-Meier survival curves. Furthermore, we investigated the impact of CENPI overexpression on the migration and healing capabilities of liver cancer cells using Transwell and wound healing experiments. Finally, the effects of CENPI on the epithelial-mesenchymal transition process in liver cancer cells and the potential molecular mechanisms were explored using Western blot. Comparisons between two groups were analyzed using t-tests, and comparisons among multiple groups were analyzed using one-way ANOVA. The expression of CENPI and its correlation with clinical pathological features were analyzed using the χ2 test. Results:The TCGA database analysis showed that the expression level of CENPI was significantly higher in liver cancer tissues than adjacent tissues, which was further validated by real-time fluorescent quantitative polymerase chain reaction, Western blotting, and immunohistochemical staining experiments. Combined clinical data analysis from HCC patients demonstrated that high expression of CENPI was positively correlated with the degree of tumor malignancy, T stage, and disease prognosis. The Kaplan-Meier survival curve indicated that the 5-year survival rate was significantly lower in patients with high CENPI expression compared to those with low expression. The results of the receiver operating characteristic curve further indicated that the expression level of CENPI had accurately predicted the prognosis of liver cancer patients (area under the curve=0.962). Transwell and wound healing experiment results indicated that overexpressing CENPI in Hep3B and Huh7 cells significantly increased cell migration numbers and healing rates. Further research results showed that overexpressing CENPI significantly upregulated the expression of mesenchymal cell-related marker genes: N-cadherin, Vimentin, and Snail protein, while the expression of the epithelial cell-related marker gene E-cadherin was significantly reduced. The mechanistic study revealed that when CENPI was overexpressed, the MEK and ERK phosphorylation levels and the expression of RAS protein were significantly increased compared to the control group, and the difference was statistically significant. Conclusion:The high expression of CENPI in the tissues of HCC patients is associated with poor prognosis, potentially promoting the migration of liver cancer cells and the epithelial-mesenchymal transition process by activating the RAS/MEK/ERK signaling pathway axis, suggesting that the CENPI gene may be a promising target for HCC treatment.

BACKGROUND:A large number of studies have found that pyroptosis is closely related to the occurrence and development of motor system diseases,but there are few studies and reviews on pyroptosis in motor system diseases.OBJECTIVE:To review the current clinical and preclinical studies,summarize the role of pyroptosis in motor system diseases and related molecular mechanisms,and provide reference for the pyroptosis-targeted treatment for motor system diseases in the future.METHODS:The relevant literatures in PubMed and CNKI database were searched by computer from January 2000 to January 2024.The English search terms were"pyroptosis,tendons,ligaments,cartilage,muscles,bones"and the Chinese search terms were"pyroptosis,tendon,ligament,cartilage,skeletal muscle,bone"in Chinese.A combination of subject terms and free search terms was used.There were a total of 422 documents,including 334 in English and 88 in Chinese.After excluding duplicate literature and irrelevant literature,the literature without inclusion value was further excluded by reading the whole paper,and finally 78 documents were included for review and analysis.RESULTS AND CONCLUSION:Different pathways of pyroptosis and subsequent inflammatory responses can affect the progression of motor system diseases and the repair process of injuries.Excessive pyroptosis can not only cause a large number of tissue cells to die,but also aggravate tissue inflammation and degrade the extracellular matrix through substances such as inflammatory factors released after cell lysis,and damaging related molecular patterns can act as upstream signals to further aggravate pyroptosis.Current methods for preventing and treating motor system diseases mainly include NOD-like receptor thermal protein domain-associated protein 3 inhibitors,Chinese herbal extracts,exosome therapy,mesenchymal stem cell therapy,and exercise therapy.The review suggests that targeted intervention of some key factors in the process of pyroptosis may be a new direction for the treatment and prevention of motor system diseases.

Objective:To investigate the application value of self-pulling latter transection(SPLT)in esophagojeju-nal anastomosis during total laparoscopic total gastrectomy.Methods:From January 2021 to December 2023,80 pa-tients who underwent total laparoscopic total gastrectomy at the Department of General Surgery,Yancheng Third People's Hospital,were selected.Patients were grouped based on the intraoperative esophagojejunal anastomosis method:the SPLT group(35 cases,using SPLT esophagojejunostomy)and the Overlap group(45 cases,using esoph-agojejunal overlapping side-to-side anastomosis).Surgical related indicators,complication incidence,nutritional status,and quality of life assessment were compared between the two groups.Results:The time to first postoperative anal exhaust,the number of lymph nodes dissected,and the postoperative hospital stay were compared between the two groups(P＞0.05).The SPLT group had shorter operation time and esophagojejunal anastomosis time,and less intraopera-tive blood loss compared to the control group(P＜0.05).The incidence of postoperative complications in the SPLT group was 8.57%,and in the Overlap group was 11.11%,with no significant difference between the two groups(P＞0.05).The nutritional status at 6 months postoperatively in the SPLT group[Hb(116.97±10.94)g/L、ALB(39.74±1.29)g/L、PA(0.30±0.45)g/L]and Overlap group[Hb(119.78±12.84)g/L、ALB(39.64±1.42)g/L、PA(0.30±0.36)g/L]were compared(P＞0.05).The quality of life assessment(overall health status,functional domains,symptom domains)at 6 months postoperatively between the SPLT group and the Overlap group was compared(P＞0.05).Conclusion:The use of SPLT esophagojeju-nal anastomosis in total laparoscopic total gastrectomy can improve the surgical efficiency,achieve high anastomosis,and its medium and short-term safety is comparable to that of esophagojejunal overlap side-to-side anastomosis.

Objective:To investigate the effects of three surgical methods on anorectal dynamics indexes, pain symptoms and postoperative complications in patients with moderate to severe mixed hemorrhoids.Methods:Eighty patients with moderate to severe mixed hemorrhoids diagnosed and treated in Tongling People′s Hospital from March 2021 to December 2022 were retrospectively selected as the study objects, and they were divided into mucosal resection group (30 cases), sphincterotomy group (30 cases) and mixed hemorrhoidal resection group (20 cases) according to the treatment methods. The basic conditions of operation, anorectal dynamics indexes, pain symptoms and postoperative complications were compared among the three groups.Results:The operative time, intraoperative blood loss, first postoperative defecation time, postoperative bed time and hospital stay in the mucosa resection group were all shorter than those in the sphincterotomy group and the mixed hemorrhoidectomy group:(20.57 ± 5.85) min vs. (24.68 ± 4.66) and (33.86 ± 4.27) min, (4.19 ± 0.54) ml vs. (6.34 ± 0.82) and (9.25 ± 1.39) ml, (1.57 ± 0.12) d vs. (1.95 ± 0.32) and (2.48 ± 0.54) d, (1.43 ± 0.35) d vs. (1.64 ± 0.41) and (1.90 ± 0.44) d, (4.57 ± 0.39) d vs. (5.83 ± 0.47) and (7.64 ± 0.55) d, there were statistical differences ( P<0.05). The above indexes in the sphincterectomy group were shorter than those in the mixed hemorrhoidectomy group, there were statistical differences ( P<0.05). The maximum rectal volume threshold (RMTV), rectal perception threshold (RSTV) and maximum rectal systolic blood pressure (MASP) in the resection group were higher than those in the sphincterotomy group: (201.59 ± 40.13) ml vs. (178.45 ± 38.59) ml, (65.54 ± 18.29) ml vs. (54.62 ± 20.39) ml, (126.36 ± 12.29) mmHg (1 mmHg = 0.133 kPa) vs. (42.23 ± 14.46) mmHg, anal canal resting pressure (RASP) was lower than that in the sphincterotomy group: (32.59 ± 10.25) mmHg vs. (63.50 ± 13.69) mmHg, there were statistical differences ( P<0.05). The RMTV and RSTV in the sphincterotomy group were higher than those in the mixed hemorrhoidectomy group: (178.45 ± 38.59) ml vs. (135.85 ± 35.68) ml, (54.62 ± 20.39) ml vs. (41.34 ± 20.55) ml, the RASP and MASP were lower than those in the mixed hemorrhoidectomy group :(63.50 ± 13.69) mmHg vs. (73.33 ± 15.69) mmHg, (42.23 ± 14.46) mmHg vs. (128.66 ± 16.33) mmHg, there were statistical differences ( P<0.05). The postoperative visual analogue scale (VAS) score in the mucosa resection group were lower than those in the sphincterotomy group and the mixed hemorrhoidectomy group: (1.57 ± 0.25) score vs. (2.57 ± 0.36) and (3.42 ± 0.52) score, there were statistical differences ( P<0.05). The VAS scores in the sphincterectomy group was lower than that in the mixed hemorrhoidectomy group, there was statistical difference ( P<0.05). The incidence of postoperative complications in the mucosa resection group was lower than that in the sphincterectomy group: 3.33% (1/30) vs. 20.00% (6/30), and the incidence of postoperative complications in the sphincterectomy group was lower than that in the mixed hemorrhoidectomy group: 20.00% (6/30) vs. 50.00% (10/20), there were statistical differences ( χ2 = 4.04, 4.96, P<0.05). Conclusions:Compared with partial internal anal sphincterotomy and external stripping and internal ligation of mixed hemorrhoids, partial rectal mucosal resection is more effective in the treatment of Ⅲ~Ⅳ grade mixed hemorrhoids, which can effectively restore anorectal dynamic indexes, reduce postoperative pain and reduce the occurrence of complications.

BACKGROUND:Various clinical strategies for the treatment of tendinopathy have good short-term effects but poor long-term effects,and some studies have proven that mitochondria are closely related to the occurrence and development of tendinopathy.However,the relationship between mitochondria and tendinopathy and mitochondria-targeting therapeutic strategies for tendinopathy have not been summarized so far,which is not good for specialists and scholars in related fields to understand the recent research situation.OBJECTIVE:To review the existing clinical or preclinical original studies,in order to summarize the relationship between mitochondrial dysfunction and tendinopathy and the mitochondria-targeting methods for the treatment of tendinopathy,and to provide certain prospects for the evaluation and management of mitochondria in tendinopathy in the future.METHODS:The relevant literatures in PubMed,Web of Science,CNKI,WanFang and VIP databases were searched.The search time was from January 2009 to March 2024,and the search terms were"tendinopathy,tendon injuries,tendon,tendons,mitochondria,mitochondria dysfunction,mitochondria disease"both in English and Chinese.According to the exclusion and inclusion criteria,62 articles were finally included for review and analysis.RESULTS AND CONCLUSION:(1)In clinical tendinopathy patients or tendinopathy models,mitochondrial dysfunction is common,mainly represented by excessive production of reactive oxygen species,decreased activity of superoxide dismutase,ridge clutter and decreased number of mitochondria,which indicates that mitochondrial dysfunction will occur due to tendon injury,thus further worsening tendinopathy and forming a vicious cycle.(2)When the tendon has not been injured or tendinopathy has not yet occurred,the mitochondrial function will be affected by various internal and external factors,resulting in tendinopathy.This indicates that the normal tendon will be damaged,lesioned or even ruptured due to the abnormal function of the mitochondria.(3)Mechanical tensile stress,advanced glycosylation end products,aging and other internal and external factors are the main causes of mitochondrial dysfunction,and these factors will damage and weaken the biological activity and mechanical properties of normal tendons through molecular mechanisms such as apoptosis,inflammation and respiratory chain damage,and thereby induce tendinopathy.(4)According to molecular mechanisms,mitochondria-targeting therapies mainly include mitochondrial transfer/transplantation,transplantation,targeted antioxidants,etc.(5)This review mainly aims at clinical patients with tendinopathy or animal models with similar modeling methods,providing a reliable idea for clinical exploration of the pathogenesis of tendinopathy and targeted therapies for tendinopathy.However,the disadvantage is that the included studies are mainly animal experiments,and there is a lack of more clinical trials for verification.