Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNpc), primarily manifesting as motor dysfunctions such as resting tremor, muscle rigidity, and bradykinesia. According to the classical model of basal ganglia motor control, approximately half of the medium spiny neurons (MSNs) in the striatum are D1-MSNs, which constitute the direct pathway. These neurons express D₁-dopamine receptor (D₁R) and substance P, and they mainly participate in the selection, initiation, and execution of movements. The other half are D2-MSNs, which constitute the indirect pathway. These neurons express D₂-dopamine receptor (D₂R) and adenosine 2A receptors and are involved in inhibiting unnecessary movements or terminating ongoing movements, thereby adjusting movement sequences to perform more precise motor behaviors. The direct pathway in the striatum modulates the activity of motor cortex neurons by exciting D1-MSNs through neurotransmitters such as glutamate (Glu), allowing the motor cortex to send signals more freely to the motor system, thus facilitating the generation and execution of specific motor behaviors. Studies using D1-Cre and D2-Cre mice with neurons labeled for D₁R and D₂R have shown that both types of neurons are involved in the execution of movements, with D1-MSNs participating in movement initiation and D2-MSNs in inhibiting actions unrelated to the target movement. These findings suggest that the structural and functional plasticity of D1-MSNs and D2-MSNs in the basal ganglia circuitry enables motor learning and behavioral regulation. Additionally, when SNpc DA neurons begin to degenerate, D1-MSNs are initially affected but do not immediately cause motor impairments. In contrast, when D2-MSNs undergo pathological changes, they are first activated by upstream projecting neurons, leading to the inhibition of most motor behaviors and resulting in motor dysfunction. Therefore, it is hypothesized that motor impairments such as bradykinesia and initiation difficulties are more closely related to the functional activity of D2-MSNs. The extracellular signal-regulated kinase (Erk)/mitogen-activated protein kinase (MAPK) signaling pathway has been identified as a critical modulator in the pathophysiology of PD. Recent findings indicate that Erk/MAPK signaling pathway can mediate DA and Glu signaling in the central nervous system, maintaining normal functional activity of striatal MSNs and influencing the transmission of motor control signals. Within this complex regulatory network, the Erk/MAPK signaling pathway plays a key role in transmitting motor information to downstream neurons, regulating normal movements, avoiding unnecessary movements, and finely tuning motor behaviors. Our laboratory’s previous research found that 4 weeks of aerobic exercise intervention improved motor dysfunction in PD mice by inhibiting the Erk1/2 signaling upstream of striatal MSNs, primarily involving the Erk1/2 signaling in D2-MSNs rather than D1-MSNs. This review summarizes the neurobiological mechanisms of Erk/MAPK signaling pathway in D2-MSNs for the prevention and treatment of motor dysfunction in PD. By exploring the role of this signaling pathway in regulating motor abnormalities and preventing motor dysfunction in the central nervous system of PD, this review provides new theoretical perspectives for related mechanistic research and therapeutic strategies.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Lung cancer is one of the top 10 causes of death in the world today,and it is a great concern worldwide for its high mortality rate.Currently,the researchers are digging into various factors influencing the occurrence and develop-ment of lung cancer in order to increase the odds for curing lung cancer,improve the prognosis of lung cancer patients as well as reduce its morbidity.The Mediterranean diet(MD)is a special dietary structure that is based on eating vegetables,fruits,coarse grains,legumes and low-fat fish,which have anti-inflammatory,antioxidant and lipid-lowering effects.Recent studies have revealed that the MD may prevent lung cancer occurrence to some extent and inhibit its development.The purpose of this paper is to summarize and analytically discuss the effects of the MD on the oncogenesis and development of lung cancer through a review of the relevant literatures,thus to provide references for MD to prevent and treat lung cancer.

Purpose: Triple-negative breast cancer (TNBC) is a subtype of breast cancer known for its poor prognosis and the absence of viable targets for standard receptor-based therapies.Several studies have suggested that targeting programmed death-ligand 1 (PD-L1) in tumors that express this biomarker, either on tumor cells and/or in the tumor inflammatory infiltrate, may be beneficial in some patients. This study aimed to assess the overall prevalence of PD-L1 positivity using the SP142 antibody clone in patients with advanced TNBC in Malaysia. Methods: This was a multicenter, cross-sectional prevalence study on PD-L1 positivity among patients with advanced-stage TNBC in Malaysia. Patients were identified using medical records and were enrolled in the study if they met the inclusion criteria. PD-L1 evaluation was performed using archived formalin-fixed paraffin-embedded tissue specimens. Demographic and clinical data were also obtained and summarized using descriptive statistics. The association of these parameters with PD-L1 positivity was assessed using chi-square and logistic regression analysis. Results: Three medical centers provided 138 complete cases for analysis. Of these 138 cases, 52 (37.7%; 95% confidence interval, 29.6%–46.3%) showed positive PD-L1 expression, defined as immune cell PD-L1 expression ≥ 1%. In a univariate analysis, stage III of the disease and tumor samples from resected specimens were significantly associated with a positive PD-L1 status. However, further assessment using a multivariate model revealed that only resected tumor samples remained significantly associated with PD-L1 positivity after controlling for disease staging. Conclusion The prevalence of PD-L1 positivity among patients with stage III or IV TNBC was 37.7%. A significant association was noted between PD-L1 positivity and the tumor tissue obtained from resected specimens. Although the mechanism and clinical significance of this association remain unclear, this finding indicates a possible disparity in the PD-L1 status of samples obtained using surgical resection or biopsy.

Purpose: Triple-negative breast cancer (TNBC) is a subtype of breast cancer known for its poor prognosis and the absence of viable targets for standard receptor-based therapies.Several studies have suggested that targeting programmed death-ligand 1 (PD-L1) in tumors that express this biomarker, either on tumor cells and/or in the tumor inflammatory infiltrate, may be beneficial in some patients. This study aimed to assess the overall prevalence of PD-L1 positivity using the SP142 antibody clone in patients with advanced TNBC in Malaysia. Methods: This was a multicenter, cross-sectional prevalence study on PD-L1 positivity among patients with advanced-stage TNBC in Malaysia. Patients were identified using medical records and were enrolled in the study if they met the inclusion criteria. PD-L1 evaluation was performed using archived formalin-fixed paraffin-embedded tissue specimens. Demographic and clinical data were also obtained and summarized using descriptive statistics. The association of these parameters with PD-L1 positivity was assessed using chi-square and logistic regression analysis. Results: Three medical centers provided 138 complete cases for analysis. Of these 138 cases, 52 (37.7%; 95% confidence interval, 29.6%–46.3%) showed positive PD-L1 expression, defined as immune cell PD-L1 expression ≥ 1%. In a univariate analysis, stage III of the disease and tumor samples from resected specimens were significantly associated with a positive PD-L1 status. However, further assessment using a multivariate model revealed that only resected tumor samples remained significantly associated with PD-L1 positivity after controlling for disease staging. Conclusion The prevalence of PD-L1 positivity among patients with stage III or IV TNBC was 37.7%. A significant association was noted between PD-L1 positivity and the tumor tissue obtained from resected specimens. Although the mechanism and clinical significance of this association remain unclear, this finding indicates a possible disparity in the PD-L1 status of samples obtained using surgical resection or biopsy.

Purpose: Triple-negative breast cancer (TNBC) is a subtype of breast cancer known for its poor prognosis and the absence of viable targets for standard receptor-based therapies.Several studies have suggested that targeting programmed death-ligand 1 (PD-L1) in tumors that express this biomarker, either on tumor cells and/or in the tumor inflammatory infiltrate, may be beneficial in some patients. This study aimed to assess the overall prevalence of PD-L1 positivity using the SP142 antibody clone in patients with advanced TNBC in Malaysia. Methods: This was a multicenter, cross-sectional prevalence study on PD-L1 positivity among patients with advanced-stage TNBC in Malaysia. Patients were identified using medical records and were enrolled in the study if they met the inclusion criteria. PD-L1 evaluation was performed using archived formalin-fixed paraffin-embedded tissue specimens. Demographic and clinical data were also obtained and summarized using descriptive statistics. The association of these parameters with PD-L1 positivity was assessed using chi-square and logistic regression analysis. Results: Three medical centers provided 138 complete cases for analysis. Of these 138 cases, 52 (37.7%; 95% confidence interval, 29.6%–46.3%) showed positive PD-L1 expression, defined as immune cell PD-L1 expression ≥ 1%. In a univariate analysis, stage III of the disease and tumor samples from resected specimens were significantly associated with a positive PD-L1 status. However, further assessment using a multivariate model revealed that only resected tumor samples remained significantly associated with PD-L1 positivity after controlling for disease staging. Conclusion The prevalence of PD-L1 positivity among patients with stage III or IV TNBC was 37.7%. A significant association was noted between PD-L1 positivity and the tumor tissue obtained from resected specimens. Although the mechanism and clinical significance of this association remain unclear, this finding indicates a possible disparity in the PD-L1 status of samples obtained using surgical resection or biopsy.

ObjectiveTo investigate the effect and mechanism of total flavones of Spatholobi Caulis （TFSC） against depression in rats. MethodThe fifty KM mice were randomly divided into the normal group and high-， medium-， and low-dose （1， 0.5， 0.25 g·kg^-1） TFSC groups and gavaged with the corresponding drugs for 12 successive days. One hour after the last administration， the immobility time in forced swimming test and tail suspension test was recorded. The SD rats were randomly divided into the normal group， model group， fluoxetine （5 mg·kg^-1） group， and high- and low-dose （1， 0.25 g·kg^-1） TFSC groups. Following the exposure of rats to two different kinds of stimuli daily for inducing chronic unpredictable stress， they were administered with the corresponding drugs for 21 d. After the experiment， the levels of serum neurotransmitters and inflammatory factors in rats were detected by enzyme-linked immunosorbent assay （ELISA）. The changes in hippocampal neurons of rats were observed by hematoxylin-eosin （HE） and Nissl staining. The mRNA expression levels of nuclear factor-κB （NF-κB） and tumor necrosis factor-α （TNF-α） in the hippocampus of rats were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and the protein expression levels of cAMP-response element binding protein （CREB）， phosphorylated CREB （p-CREB）， and brain-derived neurotrophic factor （BDNF） in hippocampal tissues by Western blot. ResultCompared with the normal group， TFSC significantly shortened the immobility time of mice in tail suspension and swimming tests （P<0.05）. Compared with the normal group， the model group exhibited reduced sucrose intake and wilderness activity （P<0.01）， decreased 5-HT， DA， NE （P<0.05， P<0.01）， MAO， IL-6， TNF-α （P<0.05， P<0.01）， damaged neurons， increased mRNA levels of TNF-α and NF-κB （P<0.01）， and down-regulated BDNF and CREB protein expression （P<0.05）. Compared with the model group， TFSC significantly enhanced sucrose intake and wilderness activity of rats （P<0.05）， increased the serum 5-HT， DA and NE （P<0.05， P<0.01）， and decreased the serum MAO， IL-6， and TNF-α （P<0.05， P<0.01） as well as NF-κB and TNF-α mRNA expression （P<0.01）， up-regulated the protein expression levels of BDNF and CREB （P<0.01）， and improved the pathological symptoms of hippocampus. ConclusionTFSC improved the hippocampal neurons of rats via CREB/BDNF signaling pathway and reduced depressive pathological damage， thus relieving depression.

Objective: To describe gastric cancer incidence in Suzhou cohort, explore the environmental risk factors of gastric cancer in Suzhou, and provide appropriate suggestions for gastric cancer prevention and control. Methods: The participants were from the Suzhou cohort of China Kadoorie Biobank. Baseline survey was conducted from 2004 to 2008, followed by long-term follow-up until December 31, 2013. After the exclusion of those who had been previously diagnosed with peptic ulcer and malignant tumor reported at baseline survey and gastric cancer within six months after enrollment, a total of 50,136 participants were included. Cox proportional risk models were used to identify risk factors of gastric cancer and their hazard ratios in Suzhou. The effect modifications of gender on the association between risk factors and gastric cancer were analyzed. Results: In the follow-up of 7.19 years (median), 374 gastric cancers cases occurred. The standardized incidence was 94.57 per 100 000 person-years. Multivariate Cox proportional risk model analysis found that age (10 years old as a age group, HR=2.20, 95%CI: 1.92-2.53, P<0.001), current smoking (HR=1.84, 95%CI: 1.10-3.07 P=0.020), consumption of preserved vegetables weekly (HR=2.28, 95%CI: 1.28-4.07, P=0.005) and daily (HR=2.05, 95%CI: 1.16-3.61, P=0.013) were risk factors for gastric cancer. Female (HR=0.44, 95%CI: 0.25-0.76, P=0.003) and refrigerator use (10 years as a limit, HR=0.85, 95%CI: 0.74-0.97, P=0.016) were protective factors for gastric cancer. Further analysis showed that there was heterogeneity between males and females in the association between refrigerator use years and the incidence of gastric cancer (P=0.009), and there was an interaction effect between gender and refrigerator use on the incidence of gastric cancer (P=0.010). Conclusions: The incidence of gastric cancer in Suzhou cohort was high. The risk factors of gastric cancer varied. There was a synergistic interaction effect between gender and refrigerator use years on the incidence of gastric cancer.
Child ; Cohort Studies ; Female ; Humans ; Incidence ; Male ; Proportional Hazards Models ; Prospective Studies ; Risk Factors ; Stomach Neoplasms/epidemiology*

Objective: To compare the differences between CAS risk model and CHA₂DS₂-VASc risk score in predicting all cause death, thromboembolic events, major bleeding events and composite endpoint in patients with nonvalvular atrial fibrillation. Methods: This is a retrospective cohort study. From the China Atrial Fibrillation Registry cohort study, the patients with atrial fibrillation who were>18 years old were randomly divided into CAS risk score group and CHA₂DS₂-VASc risk score group respectively. According to the anticoagulant status at baseline and follow-up, patients in the 2 groups who complied with the scoring specifications for anticoagulation were selected for inclusion in this study. Baseline information such as age and gender in the two groups were collected and compared. Follow-up was performed periodically to collect information on anticoagulant therapy and endpoints. The endpoints were all-cause death, thromboembolism events and major bleeding, the composite endpoint events were all-cause death and thromboembolism events. The incidence of endpoints in CAS group and CHA₂DS₂-VASc group was analyzed, and multivariate Cox proportional risk model was used to analyze whether the incidence of the endpoints was statistically different between the two groups. Results: A total of 5 206 patients with AF were enrolled, average aged (63.6±12.2) years, and 2092 (40.2%) women. There were 2 447 cases (47.0%) in CAS risk score group and 2 759 cases (53.0%) in CHA₂DS₂-VASc risk score group. In the clinical baseline data of the two groups, the proportion of left ventricular ejection fraction<55%, non-paroxysmal atrial fibrillation, oral warfarin and HAS BLED score in the CAS group were lower than those in the CHA₂DS₂-VASc group, while the proportion of previous diabetes history and history of antiplatelet drugs in the CAS group was higher than that in the CHA₂DS₂-VASc group, and there was no statistical difference in other baseline data. Patients were followed up for (82.8±40.8) months. In CAS risk score group, 225(9.2%) had all-cause death, 186 (7.6%) had thromboembolic events, 81(3.3%) had major bleeding, and 368 (15.0%) had composite endpoint. In CHA₂DS₂-VASc risk score group, 261(9.5%) had all-cause death 209(7.6%) had thromboembolic events, 112(4.1%) had major bleeding, and 424 (15.4%) had composite endpoint. There were no significant differences in the occurrence of all-cause death, thromboembolic events, major bleeding and composite endpoint between anticoagulation in CAS risk score group and anticoagulation in CHA₂DS₂-VASc risk score group (log-rank P =0.643, 0.904, 0.126, 0.599, respectively). Compared with CAS risk score, multivariable Cox proportional hazards regression models showed no significant differences for all-cause death, thromboembolic events, major bleeding and composite endpoint between the two groups with HR(95%CI) 0.95(0.80-1.14), 1.00(0.82-1.22), 0.83(0.62-1.10), 0.96(0.84-1.11), respectively. All P>0.05. Conclusions: There were no significant differences between CAS risk model and CHA₂DS₂-VASc risk score in predicting all-cause death, thromboembolic events, and major bleeding events in Chinese patients with non-valvular atrial fibrillation.
Adolescent ; Anticoagulants ; Atrial Fibrillation/drug therapy* ; Cohort Studies ; Female ; Hemorrhage/complications* ; Humans ; Male ; Retrospective Studies ; Risk Assessment ; Stroke/epidemiology* ; Stroke Volume ; Thromboembolism/etiology* ; Ventricular Function, Left

OBJECTIVE: To explore the influencing factors of low back pain and the relationship of the influence of bad working posture, weight load and frequency of load and the dose-response relationship among the occupational workers of key industries in China. METHODS: A total of 57 501 employees from 15 key industries in China were selected as research subjects using stratified cluster sampling method. The occurrence of low back pain in the past one year, as well as occupational factors such as job type, labor organization and work posture were investigated by using the Chinese version Musculoskeletal Disorders Questionnaire. RESULTS: The prevalence of low back pain in the occupational population of key industries in China was 16.4%(9 448/57 501). Multivariate Logistic regression analysis showed that the risk of low back pain in females was higher than that in males(P<0.01). Married, obese, occasional and frequent smokers, and a history of lower back disease were associated with increased risk of low back pain(all P<0.05). The risk of low back pain was associated with older age, higher education level, and lower frequency of physical exercise(all P<0.01). The risk of low back pain was higher with longer working time, greater back curvature, and the high frequency of long standing and sitting position work, uncomfortable working posture, repeated operation per minute, and lifting>5 kg weight(all P<0.01). CONCLUSION: The influencing factors of low back pain in the occupational population of key industries in China include bad working posture, high frequency load, weight load and other individual factors. There is a dose-response relationship with low back posture load and frequency of load.