This study explored how the human cortical folding pattern composed of convex gyri and concave sulci affected single-subject morphological brain networks, which are becoming an important method for studying the human brain connectome. We found that gyri-gyri networks exhibited higher morphological similarity, lower small-world parameters, and lower long-term test-retest reliability than sulci-sulci networks for cortical thickness- and gyrification index-based networks, while opposite patterns were observed for fractal dimension-based networks. Further behavioral association analysis revealed that gyri-gyri networks and connections between gyral and sulcal regions significantly explained inter-individual variance in Cognition and Motor domains for fractal dimension- and sulcal depth-based networks. Finally, the clinical application showed that only sulci-sulci networks exhibited morphological similarity reductions in major depressive disorder for cortical thickness-, fractal dimension-, and gyrification index-based networks. Taken together, these findings provide novel insights into the constraint of the cortical folding pattern to the network organization of the human brain.
Humans ; Cerebral Cortex/anatomy & histology* ; Male ; Female ; Magnetic Resonance Imaging ; Adult ; Connectome/methods* ; Young Adult ; Nerve Net/anatomy & histology* ; Neural Pathways ; Depressive Disorder, Major/diagnostic imaging*

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

To explore the prevalence and related risk factors of osteoporosis (OP) in the elderly ≥60 years old in Jiuting Town, Songjiang District, Shanghai City. A total of 2 175 local residents aged ≥60 years old who participated in the questionnaire survey at the physical examination center of Jiuting Community Health Service Center, Songjiang District, Shanghai City from July 2021 to December 2022 were selected by a cross-sectional study with multi-stage sampling method. Questionnaire survey, blood test and bone mineral density (BMD) test were conducted.The differences in all the parameters among the elderly with different bone mass level were analyzed using t-test, chi-square test, binary logistic regression was used to screen the potential risk factors of OP.The results showed that the prevalence of OP in the elderly aged≥60 years old in Jiuting Town was 45.89%.The prevalence of OP increased gradually with the advanced age. The prevalence rate of male was significantly lower than that of female( χ2=211.94, P<0.01).Single factor analysis showed that Dairy products( χ2=9.01, P<0.05), taking calcium( χ2=42.88, P<0.05), physical exercise( χ2=24.73, P<0.05), exercise time( χ2=76.40, P<0.05) and sun exposure( χ2=55.71, P<0.05) were the protective factors for osteoporosis. Multifactor analysis showed that female( wald χ 2=71.46, P<0.001) were the risk factors for osteoporosis. The age of the osteoporosis group was older than that of the non-osteoporosis group [osteoporosis group (72.47±6.89) years old, non-osteoporosis group (68.73±6.34) years old, and the difference was statistically significant, t=-11.67, P<0.05]. The waist circumference, alanine aminotransferase (ALT), creatinine (CR), blood urea nitrogen (BUN) and uric acid (UA) in the non-osteoporosis group were higher than those in the osteoporosis group, and the difference was statistically significant (all P<0.05). The levels of high-density lipoprotein (HDL)[osteoporosis group (1.34±0.35) mol/L, non-osteoporosis group (1.41±0.35) mol/L, t=-4.51, P<0.05] and alkaline phosphatase (ALP)[osteoporosis group (88.46±25.65) mol/L, osteoporosis group (94.56±32.32) mol/L, t=-4.79, P<0.05] in the osteoporosis group were lower than those in the non-osteoporosis group.Low awareness of the knowledge of osteoporosis risk factors(smoking, drinking coffee, high salt and drinking alcohol are 47.28%, 24.15%, 47.79% and 44.90%, respectively), diagnosis and treatment(The symptoms, prognosis, screening methods, medication time and follow-up screening time of osteoporosis were 26.87%, 17.88%, 21.77%, 6.65% and 15.99%, respectivel) and prevention(exercise mode, high calcium food, optimal age of calcium supplementation, the effect of vitamin D on OP, and the appropriate amount of milk to prevent osteoporosis were 33.16%, 42.01%, 13.27%, 12.07%, 9.01%, respectively) were in Jiuting Town. In conclusion, the prevalent rate of OP in the elderly ≥60 years old in Jiuting Town is 45.89%.The main risk factors are female and advanced age. Drinking tea, dairy products, combination of meat and vegetable, taking calcium, physical exercise and sun exposure were the protective factors for osteoporosis. The awareness rate of osteoporosis related knowledge is low, and health education should be strengthened in order to control and prevent the occurrence and development of osteoporosis.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

Objective:To investigate the surgical situations and perioperative outcome of pancreaticoduodenectomy in Jiangsu Province and the influencing factors for postoperative 90-day mortality.Methods:The retrospective case-control study was conducted. The clinicopathological data of 2 886 patients who underwent pancreaticoduodenectomy in 21 large tertiary hospitals of Jiangsu Quality Control Center for Pancreatic Diseases, including The First Affiliated Hospital of Nanjing Medical University, from March 2021 to December 2022 were collected. There were 1 732 males and 1 154 females, aged 65(57,71)years. Under the framework of the Jiangsu Provincial Pancreatic Disease Quality Control Project, the Jiangsu Quality Control Center for Pancreatic Diseases adopted a multi-center registration research method to establish a provincial electronic database for pancrea-ticoduodenectomy. Observation indicators: (1) clinical characteristics; (2) intraoperative and post-operative conditions; (3) influencing factors for 90-day mortality after pancreaticoduodenectomy. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(IQR), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers or constituent ratio, and comparison between groups was conducted using the chi-square test, continuity correction chi-square test and Fisher exact probability. Maximal Youden index method was used to determine the cutoff value of continuous variables. Univariate analysis was performed using the corresponding statistical methods based on data types. Multivariate analysis was performed using the Logistic multiple regression model. Results:(1) Clinical characteristics. Of the 2 886 patients who underwent pancreaticoduodenectomy, there were 1 175 and 1 711 cases in 2021 and 2022, respectively. Of the 21 hospitals, 8 hospitals had an average annual surgical volume of <36 cases for pancreaticoduodenectomy, 10 hospitals had an average annual surgical volume of 36-119 cases, and 3 hospitals had an average annual surgical volume of ≥120 cases. There were 2 584 cases performed pancreaticoduodenectomy in thirteen hospitals with an average annual surgical volume of ≥36 cases, accounting for 89.536%(2 584/2 886)of the total cases. There were 1 357 cases performed pancrea-ticoduodenectomy in three hospitals with an average annual surgical volume of ≥120 cases, accounting for 47.020%(1 357/2 886) of the total cases. (2) Intraoperative and postoperative conditions. Of the 2 886 patients, the surgical approach was open surgery in 2 397 cases, minimally invasive surgery in 488 cases, and it is unknown in 1 case. The pylorus was preserved in 871 cases, not preserved in 1 952 cases, and it is unknown in 63 cases. Combined organ resection was performed in 305 cases (including vascular resection in 209 cases), not combined organ resection in 2 579 cases, and it is unknown in 2 cases. The operation time of 2 885 patients was 290(115)minutes, the volume of intra-operative blood loss of 2 882 patients was 240(250)mL, and the intraoperative blood transfusion rate of 2 880 patients was 27.153%(782/2 880). Of the 2 886 patients, the invasive treatment rate was 11.342%(327/2 883), the unplanned Intensive Care Unit (ICU) treatment rate was 3.087%(89/2 883), the reoperation rate was 1.590%(45/2 830), the duration of postoperative hospital stay was 17(11)days, the hospitalization mortality rate was 0.798%(23/2 882), and the failure rate of rescue data in 2 083 cases with severe complications was 6.529%(19/291). There were 2 477 patients receiving postoperative 90-day follow-up, with the 90-day mortality of 2.705%(67/2477). The total incidence rate of complication in 2 886 patients was 58.997%(1 423/2 412). The incidence rate of severe complication was 13.970%(291/2 083). The comprehensive complication index was 8.7(22.6) in 2 078 patients. (3) Influencing factors for 90-day mortality after pancreaticoduodenectomy. Results of multivariate analysis showed that age ≥ 70 years, postoperative invasive treatment, and unplanned ICU treatment were independent risk factors for 90-day mortality after pancreaticoduodenectomy ( odds ratio=2.403, 2.609, 16.141, 95% confidence interval as 1.281-4.510, 1.298-5.244, 7.119-36.596, P<0.05). Average annual surgical volume ≥36 cases in the hospital was an independent protective factor for 90-day mortality after pancreaticoduodenectomy ( odds ratio=0.368, 95% confidence interval as 0.168-0.808, P<0.05). Conclusions:Pancreaticoduodenectomy in Jiangsu Province is highly con-centrated in some hospitals, with a high incidence of postoperative complications, and the risk of postoperative 90-day mortality is significant higher than that of hospitallization mortality. Age ≥ 70 years, postoperative invasive treatment, and unplanned ICU treatment are independent risk factors for 90-day motality after pancreaticoduodenectomy, and average annual surgical volume ≥36 cases in the hospital is an independent protective factor.

Objective:Exploring the efficacy and safety of bridging blinatumomab (BiTE) in combination with chimeric antigen receptor T (CAR-T) cell therapy for the treatment of adult patients with acute B-cell lymphoblastic leukemia (B-ALL) .Methods:Clinical data from 36 adult B-ALL patients treated at the First Affiliated Hospital of Suzhou University from August 2018 to May 2023 were retrospectively analyzed. A total of 36 cases were included: 18 men and 18 women. The median age was 43.5 years (21-72 years). Moreover, 21 cases of Philadelphia chromosome-positive acute lymphoblastic leukemia were reported, and 16 of these cases were relapsed or refractory. Eighteen patients underwent blinatumomab bridging followed by CAR-T cell therapy, and 18 patients received CAR-T cell therapy. This study analyzed the efficacy and safety of treatment in two groups of patients.Results:In the BiTE bridge-to-CAR-T group, 16 patients achieved complete remission (CR) after BiTE immunotherapy, with a CR rate of 88.9%. One month after bridging CAR-T therapy, bone marrow examination showed a CR rate of 100.0%, and the minimal residual disease (MRD) negativity rate was higher than the nonbridging therapy group (94.4% vs. 61.1%, Fisher, P=0.041). The incidence of cytokine release syndrome and other adverse reactions in the BiTE bridge-to-CAR-T group was lower than that in the nonbridging therapy group (11.1% vs. 50.0%, Fisher, P=0.027). The follow-up reveals that 13 patients continued to maintain MRD negativity, and five patients experienced relapse 8.40 months (2.57-10.20 months) after treatment. Two of five patients with relapse achieved CR after receiving the second CAR-T cell therapy. In the nonbridging therapy group, 10 patients maintained continuous MRD negativity, 7 experienced relapse, and 6 died. The 1 year overall survival rate in the BiTE bridge-to-CAR-T group was higher than that in the nonbridging therapy group, with a statistically significant difference at the 0.1 level (88.9%±10.5% vs. 66.7%±10.9%, P=0.091) . Conclusion:BiTE bridging CAR-T cell therapy demonstrates excellent efficacy in adult B-ALL treatment, with a low recent recurrence rate and ongoing assessment of long-term efficacy during follow-up.

To explore the prevalence and related risk factors of osteoporosis (OP) in the elderly ≥60 years old in Jiuting Town, Songjiang District, Shanghai City. A total of 2 175 local residents aged ≥60 years old who participated in the questionnaire survey at the physical examination center of Jiuting Community Health Service Center, Songjiang District, Shanghai City from July 2021 to December 2022 were selected by a cross-sectional study with multi-stage sampling method. Questionnaire survey, blood test and bone mineral density (BMD) test were conducted.The differences in all the parameters among the elderly with different bone mass level were analyzed using t-test, chi-square test, binary logistic regression was used to screen the potential risk factors of OP.The results showed that the prevalence of OP in the elderly aged≥60 years old in Jiuting Town was 45.89%.The prevalence of OP increased gradually with the advanced age. The prevalence rate of male was significantly lower than that of female( χ2=211.94, P<0.01).Single factor analysis showed that Dairy products( χ2=9.01, P<0.05), taking calcium( χ2=42.88, P<0.05), physical exercise( χ2=24.73, P<0.05), exercise time( χ2=76.40, P<0.05) and sun exposure( χ2=55.71, P<0.05) were the protective factors for osteoporosis. Multifactor analysis showed that female( wald χ 2=71.46, P<0.001) were the risk factors for osteoporosis. The age of the osteoporosis group was older than that of the non-osteoporosis group [osteoporosis group (72.47±6.89) years old, non-osteoporosis group (68.73±6.34) years old, and the difference was statistically significant, t=-11.67, P<0.05]. The waist circumference, alanine aminotransferase (ALT), creatinine (CR), blood urea nitrogen (BUN) and uric acid (UA) in the non-osteoporosis group were higher than those in the osteoporosis group, and the difference was statistically significant (all P<0.05). The levels of high-density lipoprotein (HDL)[osteoporosis group (1.34±0.35) mol/L, non-osteoporosis group (1.41±0.35) mol/L, t=-4.51, P<0.05] and alkaline phosphatase (ALP)[osteoporosis group (88.46±25.65) mol/L, osteoporosis group (94.56±32.32) mol/L, t=-4.79, P<0.05] in the osteoporosis group were lower than those in the non-osteoporosis group.Low awareness of the knowledge of osteoporosis risk factors(smoking, drinking coffee, high salt and drinking alcohol are 47.28%, 24.15%, 47.79% and 44.90%, respectively), diagnosis and treatment(The symptoms, prognosis, screening methods, medication time and follow-up screening time of osteoporosis were 26.87%, 17.88%, 21.77%, 6.65% and 15.99%, respectivel) and prevention(exercise mode, high calcium food, optimal age of calcium supplementation, the effect of vitamin D on OP, and the appropriate amount of milk to prevent osteoporosis were 33.16%, 42.01%, 13.27%, 12.07%, 9.01%, respectively) were in Jiuting Town. In conclusion, the prevalent rate of OP in the elderly ≥60 years old in Jiuting Town is 45.89%.The main risk factors are female and advanced age. Drinking tea, dairy products, combination of meat and vegetable, taking calcium, physical exercise and sun exposure were the protective factors for osteoporosis. The awareness rate of osteoporosis related knowledge is low, and health education should be strengthened in order to control and prevent the occurrence and development of osteoporosis.

OBJECTIVE: To evaluate the apoptosis and cycle arrest effects of Oldenlandia diffusa flavonoids on human gastric cancer cells, determine the action mechanisms in association with the mitochondrial dependent signal transduction pathway that controls production of reactive oxygen species (ROS), and evaluate the pharmacodynamics of a mouse xenotransplantation model to provide a reference for the use of flavonoids in prevention and treatment of gastric cancer. METHODS: Flavonoids were extracted by an enzymatic-ultrasonic assisted method and purified with D-101 resin. Bioactive components were characterized by high-performance liquid chromatography. Cell lines MKN-45, AGS, and GES-1 were treated with different concentrations of flavonoids (64, 96, 128, 160 µg/mL). The effect of flavonoids on cell viability was evaluated by MTT method, and cell nuclear morphology was observed by Hoechst staining. The apoptosis rate and cell cycle phases were measured by flow cytometry, the production of ROS was detected by laser confocal microscope, the mitochondrial membrane potential (MMP) were observed by fluorescence microscope, and the expression of apoptotic proteins related to activation of mitochondrial pathway were measured by immunoblotting. MKN-45 cells were transplanted into BALB/c nude mice to establish a xenograft tumor model. Hematoxylin and eosin staining was used to reveal the subcutaneous tumor tissue. The tumor volume and tumor weight were measured, the expression levels of proliferation markers proliferating cell nuclear antigen (PCNA) and Ki-67 were detected by immunohistochemistry, and the expression levels of CA72-4 were measured by enzyme linked immunosorbent assay. RESULTS: Oldenlandia diffusa flavonoids inhibited proliferation of MKN-45 and AGS human gastric cancer cells, arrested the cell cycle in G₁/S phase, induced accumulation of ROS in the process of apoptosis, and altered MMP. In addition, flavonoids increased Apaf-1, Cleaved-Caspase-3, and Bax, and decreased Cyclin A, Cdk2, Bcl-2, Pro-Caspase-9, and Mitochondrial Cytochrome C (P<0.05). The MKN-45 cell mouse xenotransplantation model further clarified the growth inhibitory effect of flavonoids towards tumors. The expression levels of PCNA and Ki-67 decreased in each flavonoid dose group, the expression level of CA72-4 decreased (P<0.05). CONCLUSION Flavonoids derived from Oldenlandia diffusa can inhibit proliferation and induce apoptosis of human gastric cancer cells by activating the mitochondrial controlled signal transduction pathway.
Humans ; Animals ; Mice ; Oldenlandia/metabolism* ; Proliferating Cell Nuclear Antigen ; Stomach Neoplasms ; Flavonoids/pharmacology* ; Reactive Oxygen Species/metabolism* ; Mice, Nude ; Ki-67 Antigen ; Cell Line, Tumor ; Apoptosis ; Plant Extracts/pharmacology* ; Caspases ; Cell Proliferation

Conventional tumor culture models include two-dimensional tumor cell cultures and xenograft models. The former has disadvantages including lack of tumor heterogeneity and poor clinical relevance, while the latter are limited by the slow growth, low engraftment successful rate, and high cost. In recent years, in vitro three-dimensional (3D) tumor models have emerged as the tool to better recapitulate the spatial structure and the in vivo environment of tumors. In addition, they preserve the pathological and genetic features of tumor cells and reflect the complex intracellular and extracellular interactions of tumors, which have become a powerful tool for investigating the tumor mechanism, drug screening, and personalized cancer treatment. 3D tumor model technologies such as spheroids, organoids, and microfluidic devices are maturing. Application of new technologies such as co-culture, 3D bioprinting, and air-liquid interface has further improved the clinical relevance of the models. Some models recapitulate the tumor microenvironment, and some can even reconstitute endogenous immune components and microvasculature. In recent years, some scholars have combined xenograft models with organoid technology to develop matched in vivo/in vitro model biobanks, giving full play to the advantages of the two technologies, and providing an ideal research platform for individualized precision therapy for specific molecular targets in certain subtypes of tumors. So far, the above technologies have been widely applied in the field of colorectal cancer research. Our research team is currently studying upon the application of patient-derived tumor cell-like clusters, a self-assembly 3D tumor model, in guiding the selection of postoperative chemotherapy regimens for colorectal cancer. A high modeling success rate and satisfactory results in the drug screening experiments have been achieved. There is no doubt that with the advancement of related technologies, 3D tumor models will play an increasingly important role in the research and clinical practice of colorectal cancer.
Humans ; Organoids/pathology* ; Cell Culture Techniques ; Colorectal Neoplasms/pathology* ; Tumor Microenvironment

Uric acid (UA) is the final product of purine metabolism in human body,and its metabolic disorder will induce hyperuricemia (HUA).The occurrence and development of HUA are associated with a variety of pathological mechanisms such as oxidative stress injury,activation of inflammatory cytokines,and activation of renin-angiotensin-aldosterone system.These mechanisms directly or indirectly affect the bioavailability of endogenous nitric oxide (NO).The decrease in NO bioavailability is common in the diseases with high concentration of UA as an independent risk factor.In this review,we summarize the mechanisms by which high concentrations of UA affect the endogenous NO bioavailability,with a focus on the mechanisms of high-concentration UA in decreasing the synthesis and/or increasing the consumption of NO.This review aims to provide references for alleviating the multisystem symptoms and improving the prognosis of HUA,and lay a theoretical foundation for in-depth study of the correlations between HUA and other metabolic diseases.
Humans ; Nitric Oxide ; Uric Acid ; Hyperuricemia ; Biological Availability ; Cytokines