BACKGROUND:Patients with degenerative cervical spondylosis often suffer from changed varicosity of the cervical spine,unbalanced neck-shoulder muscular strength,and descending power. OBJECTIVE:To probe into the correlation between sagittal curvature parameters and pain threshold for neck-shoulder muscles in degenerative cervical spondylosis. METHODS:Totally 50 patients with degenerative cervical spondylosis received treatment at the 3D Printed Outpatient Center of Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine from January 2022 to March 2023 were included in the study.After excluding the 10 patients of cervical lateral projection that failed to meet the measurement conditions,the cervical lateral projections were shot to measure the following iconography parameters:Borden value and C2-7 Cobb angle as well as pain thresholds on the midpoint of the superior trapezius muscle in bilateral bundles and at 1 cm beside the C5-6 interspike.The correlation between sagittal curvature parameters and pain threshold of neck-shoulder muscles in degenerative cervical spondylosis was analyzed. RESULTS AND CONCLUSION:(1)The Borden value of sagittal curvature showed a moderately positive correlation with the bundle pain threshold in the left upper trapezius muscle,the bundle pain threshold in the right upper trapezius muscle,and the pain threshold at the 1 cm of the left side beside the C5-6 interspike(r=0.498,P<0.01;r=0.448,P<0.05;r=0.405,P<0.05)and a weak positive correlation with the pain threshold at the 1 cm of the right side beside the C5-6 interspike(r=0.322,P<0.05).(2)The C2-7 Cobb angle showed a weak positive correlation with the left squared myalgia threshold(r=0.355,P<0.05),and there was no correlation with the pain threshold of the left trapezius muscle and the pain threshold at the 1 cm of both sides beside the C5-6 interspike.(3)There was a correlation between the pain threshold of the neck-shoulder muscles,and a high correlation between the pain threshold of the left and right muscles and the pain threshold within the left and right side muscles,indicating that the neck-shoulder muscles are consistent and may be related to the coordination of the neck-shoulder movements.

Objective To analyze the literature of leech in medicine using CiteSpace knowledge map,comprehensively understand the research status,hotspots and development trends of component analysis and pharmacological effects of leech,and provide reference for researchers in the field of leech.Methods CiteSpace 6.1 R3 software was used to analyze the relevant literature of leech in the field of medical research in CNKI and Web of Science databases from 1996 to 2022.The bibliometric and visual analysis of the number of articles,authors,research institutions,keyword co-occurrence,clustering and emergence were carried out.Results A total of 1 115 Chinese articles in CNKI database and 237 English articles in Web of Science database were included.The analysis of Chinese and English literature showed that the author Shi Hongzhuan had the largest number of Chinese articles,and the German author Hildebrandt had the largest number of English articles.Shandong University of Traditional Chinese Medicine and Chinese Academy of Sciences were the institutions with the largest number of articles in Chinese and English respectively.The country with the most published English literature is the United States.Chinese and English keyword co-occurrence and cluster analysis showed that Chinese literature focused on the study of its active ingredient hirudin,including molecular structure,pharmacological efficacy,mechanism of treating thrombosis,coronary heart disease,kidney disease and other diseases,and paid attention to the differences in the active ingredients of different types of leeches.In addition,English literature focused on the clinical external use of living leeches.The emergence of keywords suggested that the mechanism of action,the search and synthesis of hirudin analogues,and the pharmacodynamic mechanism of compatibility application were not only the current research hotspots,but also the future hot spots.Conclusion The analysis of leech components,the pharmacological mechanism of leech in the treatment of cardiovascular diseases,chronic kidney diseases and other diseases have always been the research hotspots.Hirudin analogues,the pharmacodynamic mechanism of compatibility application,network pharmacology,molecular docking and so on may be the future research hotspots and trends of leeches.

Objective:This study aimed to explore the clinical application value of the indication selection criteria for bi-pedicled deep inferior epigastric arterial perforator flap(DIEP) versus pedicled transverse rectus abdominis myocutaneous flap(TRAM) combined with DIEP for breast reconstruction.Methods:The clinical data of patients who underwent delayed bi-pedicled abdominal flap breast reconstruction after breast cancer surgery in the Department of Oncoplastic and Reconstructive Breast Surgery and Department of Mammoplasty, Plastic Surgery Hospital, Chinese Academy of Medical Sciences from January 2008 to April 2022 were retrospectively analyzed. According to the indications for each procedure, corresponding blood supply source was selected. Subsequently, patients were divided into two groups: bi-pedicled DIEP group and pedicled TRAM+ DIEP combined flap group according to the type of blood supply source. The indication selection criteria for pedicled TRAM+ DIEP combined flap was as follows: lack of two groups of recipient vessels; no dominant perforator in the abdominal donor site; previous abdominal liposuction or abdominal surgery with large dissection range and severe scar; patients were unable to tolerate prolonged surgery or had high risk factors for microsurgery. A comparison of breast reconstruction surgery characteristics was conducted between the two groups. Independent-samples t-test, rank sum test, Chi-square test and Fisher’s exact probability method were used to analyze various data including age, body mass index (BMI), time interval between breast cancer surgery and breast reconstruction surgery, history of radiotherapy, history of chemotherapy, history of smoking, history of lower abdominal surgery, history of hypertension, original surgical incision type, length and width of flap, hospitalization length, preoperative and postoperative conditions, as well as postoperative complications. Statistical significance was defined at P<0.05. Results:A total of 54 patients who underwent unilateral breast reconstruction were included in this study with a mean age of 42.2 years (range, 30-59 years). The pedicled TRAM+ DIEP combined flap group consisted of 21 patients with a mean age of 42.7 years (range, 33-56 years) while the bi-pedicled DIEP group comprised 33 patients with a mean age of 41.8 years (30-59 years). Out of the 54 patients, a total of 38 were eventually followed up, comprising 14 in the pedicled TRAM+ DIEP combined flap group and 24 in the bi-pedicled DIEP group. The average follow-up duration for the pedicled TRAM+ DIEP combined flap group was 42 months (range, 6-69 months). Abdominal bulge occurred in one patient, while another patient experienced abdominal hernia. The average follow-up duration for the bi-pedicled DIEP group was 47 months (6-179 months), with no reported cases of abdominal bulge or abdominal hernia. There were no statistically significant differences observed between the two groups regarding age, BMI, time interval between breast cancer surgery and breast reconstruction surgery, history of radiotherapy or chemotherapy, history of smoking, history of lower abdominal surgery, history of hypertension, original surgical incision type, length and width of flap, hospitalization length or time to ambulation (all P>0.05). However, there was a statistically significant difference noted in duration of surgery between the pedicled TRAM+ DIEP combined flap group and bi-pedicled DIEP group [6.0(5.5-6.5) hours vs. 8.5(8.0-8.8) hours] ( P<0.01). Comparison analysis revealed no statistically significant differences in terms of partial flap necrosis (0/21 vs. 1/33), abdominal incision dehiscence (2/21 vs. 2/33), abdominal bulge (1/14 vs. 0 /24) or abdominal hernia (1/1 vs. 0/24) between the two groups ( P>0.05). Conclusion:For patients who needed bilateral vascular pedicled lower abdominal wall for breast reconstruction, utilizing a pedicled TRAM+ DIEP combined flap did not increase surgical complication risks. The proposed indication selection criteria for using a pedicled TRAM + DIEP combined flap outlined in this study could serve as guidance when choosing methods for bi-pedicled abdominal flap breast reconstruction.

Objective:This study aimed to explore the clinical application value of the indication selection criteria for bi-pedicled deep inferior epigastric arterial perforator flap(DIEP) versus pedicled transverse rectus abdominis myocutaneous flap(TRAM) combined with DIEP for breast reconstruction.Methods:The clinical data of patients who underwent delayed bi-pedicled abdominal flap breast reconstruction after breast cancer surgery in the Department of Oncoplastic and Reconstructive Breast Surgery and Department of Mammoplasty, Plastic Surgery Hospital, Chinese Academy of Medical Sciences from January 2008 to April 2022 were retrospectively analyzed. According to the indications for each procedure, corresponding blood supply source was selected. Subsequently, patients were divided into two groups: bi-pedicled DIEP group and pedicled TRAM+ DIEP combined flap group according to the type of blood supply source. The indication selection criteria for pedicled TRAM+ DIEP combined flap was as follows: lack of two groups of recipient vessels; no dominant perforator in the abdominal donor site; previous abdominal liposuction or abdominal surgery with large dissection range and severe scar; patients were unable to tolerate prolonged surgery or had high risk factors for microsurgery. A comparison of breast reconstruction surgery characteristics was conducted between the two groups. Independent-samples t-test, rank sum test, Chi-square test and Fisher’s exact probability method were used to analyze various data including age, body mass index (BMI), time interval between breast cancer surgery and breast reconstruction surgery, history of radiotherapy, history of chemotherapy, history of smoking, history of lower abdominal surgery, history of hypertension, original surgical incision type, length and width of flap, hospitalization length, preoperative and postoperative conditions, as well as postoperative complications. Statistical significance was defined at P<0.05. Results:A total of 54 patients who underwent unilateral breast reconstruction were included in this study with a mean age of 42.2 years (range, 30-59 years). The pedicled TRAM+ DIEP combined flap group consisted of 21 patients with a mean age of 42.7 years (range, 33-56 years) while the bi-pedicled DIEP group comprised 33 patients with a mean age of 41.8 years (30-59 years). Out of the 54 patients, a total of 38 were eventually followed up, comprising 14 in the pedicled TRAM+ DIEP combined flap group and 24 in the bi-pedicled DIEP group. The average follow-up duration for the pedicled TRAM+ DIEP combined flap group was 42 months (range, 6-69 months). Abdominal bulge occurred in one patient, while another patient experienced abdominal hernia. The average follow-up duration for the bi-pedicled DIEP group was 47 months (6-179 months), with no reported cases of abdominal bulge or abdominal hernia. There were no statistically significant differences observed between the two groups regarding age, BMI, time interval between breast cancer surgery and breast reconstruction surgery, history of radiotherapy or chemotherapy, history of smoking, history of lower abdominal surgery, history of hypertension, original surgical incision type, length and width of flap, hospitalization length or time to ambulation (all P>0.05). However, there was a statistically significant difference noted in duration of surgery between the pedicled TRAM+ DIEP combined flap group and bi-pedicled DIEP group [6.0(5.5-6.5) hours vs. 8.5(8.0-8.8) hours] ( P<0.01). Comparison analysis revealed no statistically significant differences in terms of partial flap necrosis (0/21 vs. 1/33), abdominal incision dehiscence (2/21 vs. 2/33), abdominal bulge (1/14 vs. 0 /24) or abdominal hernia (1/1 vs. 0/24) between the two groups ( P>0.05). Conclusion:For patients who needed bilateral vascular pedicled lower abdominal wall for breast reconstruction, utilizing a pedicled TRAM+ DIEP combined flap did not increase surgical complication risks. The proposed indication selection criteria for using a pedicled TRAM + DIEP combined flap outlined in this study could serve as guidance when choosing methods for bi-pedicled abdominal flap breast reconstruction.

OBJECTIVE To study the immunomodulatory effect of Guipi pills on D-galactose（D-gal）-induced aging mice. METHODS The immune-related targets and related pathways for Guipi pills to exert immune effects were screened by network pharmacology and verified through pharmacodynamic experiments. Totally 105 male ICR mice were randomly divided into blank control （CON） group， model control （MOD） group， positive control （POS） group， Guipi pills low-dose （GD） group and Guipi pills high-dose （GG） group. Except for the CON group， other groups were subcutaneously injected with 400 mg/kg D-gal to induce the aging model； CON group and MOD group were given distilled water， POS group was given 300 mg/kg pidotimod oral solution intragastrically， GD group and GG group were given Guipi pills 300， 600 mg/kg intragastrically， once a day， for 8 weeks. After medication， the serum and spleen were collected， and the contents of interleukin 2 （IL-2）， IL-4， IL-6 and tumor necrosis factor α （TNF-α）， and the contents of immunoglobulin G （IgG）， IgM and IgA were detected. The spleen index was calculated and the histopathological changes in the spleen were observed. The activities of superoxide dismutase （SOD）， glutathione peroxidase （GSH- Px） and malondialdehyde （MDA）， and the content of 8-hydroxy-2 deoxyguanosine （8-OHdG） in spleen were detected； the expression of TNF/phosphoinositide-3-kinase-threonine protein kinase （PI3k-Akt）-related proteins in spleen was detected except for POS group. RESULTS The results of network pharmacology showed that TNF， IL-6 and Akt1 were core targets. The results of pharmacodynamic study showed that compared with MOD group， the contents of IL-2， IL-4， IgG， IgM and IgA were increased significantly in Guipi pills groups， while the contents of TNF-α and IL-6 were decreased significantly； the spleen index was increased significantly （P＜0.05 or P＜0.01）. The phenomenon of diffuse proliferation of lymphocytes was improved， the spleen cells were closely arranged， and the line between the white pulp and red pulp was clear. The activities of SOD and GSH-Px in spleen were increased significantly， while the activity of MDA， the content of 8-OHdG， and the protein expressions of TNF-α， PI3K and p-Akt were decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS Guipi pills can regulate the immune function of D-gal-induced aging mice， which is related to regulating the TNF/PI3k-Akt pathway， thereby reducing oxidative stress damage in spleen tissue of mice， and regulating protein expressions of TNF-α， PI3K and p-Akt.

Treating patients with esophageal squamous cell carcinoma (ESCC) is challenging due to the high chemoresistance. Growth differentiation factor 15 (GDF15) is crucial in the development of various types of tumors and negatively related to the prognosis of ESCC patients according to our previous research. In this study, the link between GDF15 and chemotherapy resistance in ESCC was further explored. The relationship between GDF15 and the chemotherapy response was investigated through in vitro and in vivo studies. ESCC patients with high levels of GDF15 expression showed an inferior chemotherapeutic response. GDF15 improved the tolerance of ESCC cell lines to low-dose cisplatin by regulating AKT phosphorylation via TGFBR2. Through an in vivo study, we further validated that the anti-GDF15 antibody improved the tumor inhibition effect of cisplatin. Metabolomics showed that GDF15 could alter cellular metabolism and enhance the expression of UGT1A. AKT and TGFBR2 inhibition resulted in the reversal of the GDF15-induced expression of UGT1A, indicating that TGFBR2-AKT pathway-dependent metabolic pathways were involved in the resistance of ESCC cells to cisplatin. The present investigation suggests that a high level of GDF15 expression leads to ESCC chemoresistance and that GDF15 can be targeted during chemotherapy, resulting in beneficial therapeutic outcomes.
Humans ; Esophageal Squamous Cell Carcinoma/drug therapy* ; Cisplatin/metabolism* ; Esophageal Neoplasms/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Carcinoma, Squamous Cell/genetics* ; Growth Differentiation Factor 15/therapeutic use* ; Receptor, Transforming Growth Factor-beta Type II/therapeutic use* ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic

The typical hallmark of tumor evolution is metabolic dysregulation. In addition to secreting immunoregulatory metabolites, tumor cells and various immune cells display different metabolic pathways and plasticity. Harnessing the metabolic differences to reduce the tumor and immunosuppressive cells while enhancing the activity of positive immunoregulatory cells is a promising strategy. We develop a nanoplatform (CLCeMOF) based on cerium metal-organic framework (CeMOF) by lactate oxidase (LOX) modification and glutaminase inhibitor (CB839) loading. The cascade catalytic reactions induced by CLCeMOF generate reactive oxygen species "storm" to elicit immune responses. Meanwhile, LOX-mediated metabolite lactate exhaustion relieves the immunosuppressive tumor microenvironment, preparing the ground for intracellular regulation. Most noticeably, the immunometabolic checkpoint blockade therapy, as a result of glutamine antagonism, is exploited for overall cell mobilization. It is found that CLCeMOF inhibited glutamine metabolism-dependent cells (tumor cells, immunosuppressive cells, etc.), increased infiltration of dendritic cells, and especially reprogrammed CD8⁺ T lymphocytes with considerable metabolic flexibility toward a highly activated, long-lived, and memory-like phenotype. Such an idea intervenes both metabolite (lactate) and cellular metabolic pathway, which essentially alters overall cell fates toward the desired situation. Collectively, the metabolic intervention strategy is bound to break the evolutionary adaptability of tumors for reinforced immunotherapy.

Objective:To investigate the effects of exposure to ambient fine particulate matter-bound polycyclic aromatic hydrocarbons on blood coagulation in adults.Methods:A total of 73 adult volunteers were recruited in a cohort study and had four clinical visits from November 2014 to January 2016. Blood samples were obtained and used to measure biomarkers of blood thrombogenicity, including soluble CD40 Ligand (sCD40L), soluble P-selection (sCD62P) and Fibrinogen (FIB). White blood cell (WBC), 8-Hydroxy-2′-Deoxyguanosine (8-OHdG), matrix metalloproteinase-2 (MMP-2) and HDL cholesterol efflux capacity (HDL-CEC) were also determined. Daily concentrations of ambient fine particulate matter-bound polycyclic aromatic hydrocarbons (PAHs) were measured throughout the study period, and positive matrix factorization (PMF) approach was used to identity PAHs sources. Linear mixed-effect models including single-pollutant model, two-pollutant model and stratification analysis were constructed to estimate the effects of exposure to ambient fine particulate matter-bound PAHs on blood thrombogenicity in adults after adjusting for potential confounders.Results:The mean age of participants was (23.3±5.4) years. During the study period, the median level of PM 2.5-bound PAHs was (55.29±74.99) ng/m 3. Six sources of PM 2.5-bound PAHs were identified by PMF, with traffic sources contributing more than 50%. The linear mixed-effect model showed that PAHs exposure had a significant effect on elevated blood thrombogenicity. Significant elevations in sCD40L, sCD62P and FIB associated with per IQR increase (60.33 ng/m 3) in exposure to PAHs were 14.36% (95% CI:6.94%-22.28%), 9.33% (95% CI: 1.71%-17.51%) and 2.07% (95% CI:0.44%-2.07%) at prior 5 days, respectively. Blood thrombogenicity levels were significantly and positively correlated with source-specific PAHs, especially gasoline vehicle emissions, diesel vehicle emission and coal burning at prior 1 or 5 days. Stronger associations between PAHs and increased blood thrombogenicity were found in participants with high plaque vulnerability, reduced HDL function, and high levels of inflammation and oxidative stress. Conclusion:Acute exposure to ambient fine particulate matter-bound PAHs, especially PAHs from traffic sources may promote blood thrombogenicity in adults, and PAHs have stronger effects on participants with reduced vascular function and high levels of inflammation and oxidative stress.

Objective:To investigate the effects of exposure to ambient fine particulate matter-bound polycyclic aromatic hydrocarbons on blood coagulation in adults.Methods:A total of 73 adult volunteers were recruited in a cohort study and had four clinical visits from November 2014 to January 2016. Blood samples were obtained and used to measure biomarkers of blood thrombogenicity, including soluble CD40 Ligand (sCD40L), soluble P-selection (sCD62P) and Fibrinogen (FIB). White blood cell (WBC), 8-Hydroxy-2′-Deoxyguanosine (8-OHdG), matrix metalloproteinase-2 (MMP-2) and HDL cholesterol efflux capacity (HDL-CEC) were also determined. Daily concentrations of ambient fine particulate matter-bound polycyclic aromatic hydrocarbons (PAHs) were measured throughout the study period, and positive matrix factorization (PMF) approach was used to identity PAHs sources. Linear mixed-effect models including single-pollutant model, two-pollutant model and stratification analysis were constructed to estimate the effects of exposure to ambient fine particulate matter-bound PAHs on blood thrombogenicity in adults after adjusting for potential confounders.Results:The mean age of participants was (23.3±5.4) years. During the study period, the median level of PM 2.5-bound PAHs was (55.29±74.99) ng/m 3. Six sources of PM 2.5-bound PAHs were identified by PMF, with traffic sources contributing more than 50%. The linear mixed-effect model showed that PAHs exposure had a significant effect on elevated blood thrombogenicity. Significant elevations in sCD40L, sCD62P and FIB associated with per IQR increase (60.33 ng/m 3) in exposure to PAHs were 14.36% (95% CI:6.94%-22.28%), 9.33% (95% CI: 1.71%-17.51%) and 2.07% (95% CI:0.44%-2.07%) at prior 5 days, respectively. Blood thrombogenicity levels were significantly and positively correlated with source-specific PAHs, especially gasoline vehicle emissions, diesel vehicle emission and coal burning at prior 1 or 5 days. Stronger associations between PAHs and increased blood thrombogenicity were found in participants with high plaque vulnerability, reduced HDL function, and high levels of inflammation and oxidative stress. Conclusion:Acute exposure to ambient fine particulate matter-bound PAHs, especially PAHs from traffic sources may promote blood thrombogenicity in adults, and PAHs have stronger effects on participants with reduced vascular function and high levels of inflammation and oxidative stress.

Objective: To explore the effects of red LEDs on the proliferation and osteogenic differentiation of human stem cells from apical papilla (hSCAPs). Methods: hSCAPs were obtained by isolation, culture and flow cytometry in vitro and irradiated with 1, 3, 5, and 7 J/cm2 red LEDs. The proliferation of hSCAPs was detected using a CCK-8 assay. The osteogenic differentiation of hSCAPs was evaluated using alkaline phosphatase (ALP) staining, ALP activity assay and Alizarin red quantitative detection. The effect of 5 J/cm2 red LEDs on the expression levels of the ALP, Runx2, OCN, OPN and BSP genes and proteins was detected by RT-PCR and western blot, respectively. Results: Red LEDs at 1, 3, 5, and 7 J/cm2 promoted the proliferation of hSCAPs (P < 0.05). The effects of red LEDs with different light energies on the proliferation of hSCAPs were different at different time points (P < 0.05). On the 7th and 14th days after irradiation, red LEDs promoted the osteogenic differentiation of hSCAPs, and the effect of 5 J/cm2 red LEDs was the most obvious under osteogenic induction culture conditions (P<0.05). Red LEDs (5 J/cm2) promoted the expression of the ALP, Runx2, OCN, OPN and BSP genes and proteins (P < 0.05). Conclusion Red LEDs promoted the proliferation and osteogenic differentiation of hSCAPs.