Objective To investigate the correlation between cognitive development and levels of dopamine(DA) and 3,4-dihydroxyphenylacetic acid(DOPAC)in the hippocampus of 80-day-old neonatal rats born of fear-impaired pregnant rats. Methods The pregnant rat model of fear-impaired kidney was established by watching other rats shocked with electricity. The cognitive development of the neonatal rats was assessed by Morris water maze test at 80 days after birth. The brain microdialysis samples of the right hippocampus were collected using a stereotaxic instrument, and the levels of DA and DOPAC were determined by HPLC-ECD. Results Compared with the control group, the mean escape latency of the 80-day-old neonatal rats in the model group was increased. Their swimming speed was slower. The 20% time spent in the peripheral zone became longer, and the frequency of platform crossing was decreased, showing significant differences(P< 0.05). The levels of DA and DOPAC in the extracellular fluid of the hippocampus of the 80-day-old neonatal rats in the model group were decreased at each time points of perfusion, showing a significant difference(P <0.05). The level of DA, a kind of monoamine neurotransmitter in the hippocampus, was positively correlated with the mean escape latency,the frequency of passing the platform of the 80-day-old rats,while was negatively correlated with the 20% time spent in the peripheral zone, with a significant correlation(P < 0.05). In addition, there was a positive correlation between the DOPAC level and the mean escape latency, the frequency of passing the platform(P< 0.05). Conclusions Fear-impaired pregnant rats can affect the spatial learning and memory ability of their 80-day-old neonatal rats,with reduction in the levels of DA and DOPAC in the hippocampus, which is closely correlated with the cognitive development of the neonatal rats.

Objective:To study influencing factors of prognosis of patients with atrial fibrillation(AF)and heart fail-ure(HF)after rhythm control therapy.Methods:According to rhythm control methods,a total of 379 AF+HF patients treated in our hospital were divided into medication group(n=133)and surgery group(n=246,received catheter ablation of AF);according to AF type,patients were divided into paroxysmal AF group(n=208)and per-sistent AF group(n=171),and general clinical data and rhythm control effect were compared among all groups.According to NYHA cardiac function classification,patients were divided into NYHA classⅡ group(n=160),classⅢ group(n=188)and class Ⅳ group(n=31),and rhythm control effect was compared among above groups.Re-sults:Compared with medication,there were significant reductions in percentage of AF recurrence and LAD after treatment,and significant rise in percentage of heart function improvement in paroxysmal AF group,persistent AF group,NYHA class Ⅱ and Ⅲ group in those underwent surgery(P＜0.05 or＜0.01).Multivariate Logistic re-gression analysis indicated that medication,persistent AF were independent risk factors for AF recurrence and no cardiac function improvement after rhythm control therapy(OR=2.426～7.908,P=0.001 all),and NYHA classⅡ was an independent protective factor for AF recurrence after rhythm control therapy(OR=0.393,P=0.049).Conclusion:Atrial fibrillation catheter ablation can significantly improve prognosis of AF+HF patients.Persistent AF and antiarrhythmic medication are independent risk factors for poor prognosis after rhythm control therapy.

OBJECTIVETo improve Luo-Ye pump-based stress-forming system and optimize the stimulating effect on smooth muscle cells during cultivation of tissue-engineered blood vessels (TEBV).

METHODSA new Luo-Ye pump-based TEBV 3D culture system was developed by adding an air pump to the output of the bioreactor. A pressure guide wire was used to measure the stress at different points of the silicone tube inside the TEBV bio-reactor, and fitting curves of the stress changes over time was created using Origin 8.0 software. The TEBVs were constructed by seeding vascular smooth muscle cells (VSMCs) isolated from human umbilical artery on polyglycolic acid (PGA) and cultured under dynamic conditions with 40 mmHg resistance (improved group), dynamic conditions without resistance (control group) or static condition (static group) for 4 weeks. The harvested TEBVs were then examined with HE staining, masson staining, α-SMA immunohistochemical staining, and scanning and transmission electron microscopy with semi-quantitative analysis of collagen content and α-SMA expression.

RESULTSThe measured stress values and the fitting curves showed that the stress stimuli from the Luo-Ye pump were enhanced by adding an air pump to the output of the bioreactor. Histological analysis revealed improved VSMC density, collagen content and α-SMA expression in the TEBVs constructed with the improved method as compared with those in the control and static groups.

CONCLUSIONAdding an air pump to the Luo-Ye pump significantly enhances the stress stimulation in the TEBV 3-D culture system to promote the secretion function of VSMCs.

Bioreactors ; Blood Vessel Prosthesis ; Cells, Cultured ; Collagen ; metabolism ; Humans ; Myocytes, Smooth Muscle ; cytology ; Polyglycolic Acid ; Tissue Engineering ; methods

OBJECTIVEGua Sha and Blood-letting at the acupoints were Chinese traditional therapies for heatstroke. The purpose of present study was to assess the therapeutic effect of Gua Sha on the DU Meridian and Bladder Meridian combined with Blood-letting acupoints at Shixuan (EX-UE 11) and Weizhong (BL 40) on heatstroke.

METHODSAnesthetized rats, immediately after the onset of heatstroke, were divided into four major groups: Gua Sha group, Blood-letting group, Gua Sha combined with Blood-letting group and model group. They were exposed to ambient temperature of 43 °C to induce heatstroke. Another group of rats were exposed to room temperature (26 °C) and used as normal control group. Their survival times were measured. In addition, their physiological and biochemical parameters were continuously monitored.

RESULTSWhen rats underwent heatstroke, their survival time values were found to be 21-25 min. Treatment of Gua Sha combined with Bloodletting greatly improved the survival time (230±22 min) during heatstroke. All heatstoke animals displayed and activated coagulation evidenced by increased prothrombin time (PT), activated partial thromboplastin time (aPTT), D-dimer, and decreased platelet count, protein C. Furthermore, the animals displayed systemic inflammation evidenced by increased the serum levels of cytokines interleukin-1ß (IL-1ß), tumor necrosis factor α (TNF-α) and malondialdehyde (MDA). Biochemical markers evidenced by cellular ischemia and injury/dysfunction included increased plasma levels of blood urea nitrogen (BUN), creatinine, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), and alkaline phosphatase (ALP) were all elevated during heatstroke. Core temperatures (Tco) were also increased during heatstroke. In contrast, the values of mean arterial pressure were signifificantly lower during heatstroke. These heatstroke reactions were all signifificantly suppressed by treatment of Gua Sha and Blood-letting, especially the combination therapy.

CONCLUSIONGua Sha combined with Blood-letting after heatstroke may improve survival by ameliorating systemic inflflammation, hypercoagulable state, and tissue ischemia and injury in multiple organs.

Animals ; Blood Coagulation Disorders ; drug therapy ; therapy ; Bloodletting ; Combined Modality Therapy ; Complementary Therapies ; methods ; Cytokines ; blood ; Heat Stroke ; physiopathology ; Inflammation ; drug therapy ; therapy ; Ischemia ; drug therapy ; therapy ; Male ; Malondialdehyde ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Survival Rate

OBJECTIVELyme disease and Human granulocytic anaplasmosis are tick-borne diseases caused by Borrelia burgdorferi and Anaplasma phagocytophilum respectively. We have investigated infection and co-infection of the two diseases in the population of forest areas of eight provinces in China by measuring seroprevalence of antibodies against B. burgdorferi and A. phagocytophilum.

METHODSForest areas in 8 provinces were chosen for investigation using whole sampling and questionnaire survey methods. 3 669 serum samples from people in the forest areas were tested for the presence of antibodies by indirect immunofluorescent assay (IFA).

RESULTSSeroprevalence against B. burgdorferi was 3% to 15% and against A. phagocytophilum was 2% to 18% in the study sites in the 8 provinces in China. We also found co-infection of B. burgdorferi and A. phagocytophilum in 7 of the 8 provinces (the exception being the Miyun area in Beijing). The seroprevalence for both B. burgdorferi and A. phagocytophilum was significantly higher among people exposed to ticks than among people who were not exposed to ticks.

CONCLUSIONWe conclude that both pathogens are endemic in the forest areas in the eight provinces, but the prevalence of B. burgdorferi and A. phagocytophilum differs between the provinces.

Adolescent ; Adult ; Anaplasma phagocytophilum ; pathogenicity ; Anaplasmosis ; blood ; epidemiology ; Animals ; Borrelia burgdorferi ; pathogenicity ; Child ; China ; Coinfection ; Female ; Humans ; Lyme Disease ; blood ; epidemiology ; Male ; Middle Aged ; Seroepidemiologic Studies ; Tick-Borne Diseases ; blood ; epidemiology ; Trees ; Young Adult

BACKGROUNDThe continual and rapid development of techniques which are used for diagnosis and treatment makes management of colorectal cancer more difficult depending on single discipline. Colorectal cancer multidisciplinary team (MDT) working model is recommended by UK and other countries, but there is little information on the impact of MDT working on management of colorectal cancer in China. The aim of this study was to assess the effect on management of colorectal cancer after the inception of an MDT.

METHODSA total of 595 consecutive colorectal cancer patients were referred to the Department of Gastroenterological Surgery, the pre-MDT cohort include 297 patients, recruited from January 1999 to November 2002, and the MDT cohort had 298 patients enrolled from December 2002 to September 2006. Information recorded included: TNM stage from histological reports, degree of differentiation, the number of examined lymph nodes and CT TNM staging performed or not, and its accuracy, including local and distant recurrence.

RESULTSThe number of examined lymph nodes and the accuracy of TNM staging by CT in the MDT group were significantly more than those in pre-MDT group. CT TNM staging was more accurate in the MDT group compared to the pre-MDT group (P = 0.044). The rate of tumor recurrence in the MDT group was lower than pre-MDT group (log-rank test, P < 0.001). Multivariate analysis revealed that age (P = 0.001), management after inception of the MDT (P = 0.002), degree of differentiation (P = 0.003), number of examined lymph nodes (P = 0.002), and TNM stage (P = 0.000) were important factors that independently influence overall survival.

CONCLUSIONSThe inception of MDT working improved the diagnostic accuracy and overall survival of colorectal cancer patients. MDT working promoted communication and cooperation between disciplines and ensured high-quality diagnosis, evidence-based decision making, and optimal treatment planning.

Aged ; Colorectal Neoplasms ; diagnostic imaging ; pathology ; surgery ; Disease Management ; Female ; Humans ; Interdisciplinary Communication ; Male ; Middle Aged ; Neoplasm Staging ; Radiography ; Treatment Outcome

BACKGROUNDGambogic acid is a pure active compound isolated from the traditional Chinese medicinal plant gamboge (Garcinia morella Desv.). Based on the preliminary results of a phase I study, this phase IIa study compared the efficacy and safety of different dosage schedules of gambogic acid in patients with advanced malignant tumors.

METHODSPatients with advanced or metastases cancer who had not received any effective routine conventional treatment or who had failed to respond to the existing conventional treatment were randomly assigned to receive either 45 mg/m(2) gambogic acid intravenously from Days 1 to 5 of a 2-week cycle (Group A), or 45 mg/m(2) every other day for a total of five times during a 2-week cycle (Group B). The primary endpoint was objective response rate (ORR).

RESULTSTwenty-one patients assigned to Group A and 26 to Group B were included in the final analysis. The ORRs were 14.3% in Group A and 0% in Group B. It was not possible to analyze the significant difference because one of the values was zero. The disease control rates (DCRs) were 76.2% in Group A and 61.5% in Group B (P = 0.0456). The observed adverse reactions were mostly Grades I and II, and occurred in most patients after administration of the trial drug. There was no significant difference in the incidence of adverse reactions between the two arms.

CONCLUSIONSThe preliminary results of this phase IIa exploratory study suggest that gambogic acid has a favorable safety profile when administered at 45 mg/m(2). The DCR was greater in patients receiving gambogic acid on Days 1 - 5 of a 2-week cycle, but the incidence of adverse reactions was similar irrespective of the administration schedule.

Adult ; Aged ; Antineoplastic Agents, Phytogenic ; administration & dosage ; Female ; Humans ; Injections ; Male ; Middle Aged ; Neoplasms ; drug therapy ; Xanthones ; administration & dosage ; adverse effects

Objective: To explore the efficacy of adjuvant programmed cell death 1 (PD-1) monoclonal antibody immunotherapy in Chinese patients with resected stage Ⅱ-Ⅲ melanoma. Methods: A total of 296 patients who underwent radical surgery for stage Ⅱ-Ⅲ cutaneous orlimb melanoma at Fudan University Shanghai Cancer Center and Shanghai Electric Power Hospital between 2017 and 2021 and received adjuvant PD-1 monoclonal antibody immunotherapy, low-dose interferon (IFN), or observational follow-up were enrolled in this study. Patients were divided into the PD-1 monoclonal antibody group (164 cases) and the IFN or observation group (IFN/OBS group, 132 cases) based on postoperative adjuvant treatment methods. Patients' disease recurrence and survival were observed. Results: Among the 296 patients, 77 had cutaneous melanoma and 219 had limb melanoma; 110 were stage Ⅱ and 186 were stage Ⅲ. Among stage Ⅱ patients, the median recurrence-free survival (RFS) in the PD-1 monoclonal antibody group (46 cases) did not reach, while the median RFS in the IFN/OBS group (64 cases) was 36 months. The 1-year RFS rates were 85.3% and 92.1% and the 2-year RFS rates were 71.9% and 63.7% in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with no statistically significant difference (P=0.394). Among stage Ⅲ patients, the median RFS rates in the PD-1 monoclonal antibody group (118 cases) and the IFN/OBS group (68 cases) were 23 and 13 months, respectively. The 1-year RFS rates were 70.0% and 51.8% and the 2-year RFS rates were 51.8% and 35.1%in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with a statistically significant difference (P=0.010). Stratified analysis showed that the advantage of PD-1 monoclonal antibody adjuvant therapy in improving RFS persisted in the subgroups of primary ulceration (HR=0.558, 95% CI: 0.348-0.893), lymph node macroscopic metastasis (HR=0.486, 95% CI: 0.285-0.828), stage ⅢC (HR=0.389, 95% CI: 0.24-0.63), and the subgroup without BRAF/c-Kit/NRAS gene mutations (HR=0.347, 95% CI: 0.171-0.706). In terms of recurrence patterns, in stage Ⅱ patients, the recurrence and metastasis rate was 15.2% (7/46) in the PD-1 monoclonal antibody group, significantly lower than the IFN/OBS group [43.8% (28/64), P=0.002]. In stage Ⅲ melanoma patients, the recurrence and metastasis rate was 42.4% (50/118) in the PD-1 monoclonal antibody group, also lower than the IFN/OBS group [63.2% (43/68), P=0.006]. Conclusions: In real-world settings, compared with patients receiving low-dose IFN adjuvant therapy or observational follow-up, PD-1 monoclonal antibody immunotherapy can reduce the recurrence and metastasis rate of cutaneous and limb melanoma, and prolong the postoperative RFS of stage Ⅲ cutaneous and limb melanoma patients. Patients with a heavier tumor burden benefit more from immunotherapy.
Humans ; Antibodies, Monoclonal/therapeutic use* ; Apoptosis ; China ; Disease-Free Survival ; East Asian People ; Immunotherapy ; Interferon-alpha/therapeutic use* ; Lymphatic Metastasis ; Melanoma/pathology* ; Programmed Cell Death 1 Receptor/therapeutic use* ; Skin Neoplasms/pathology* ; Melanoma, Cutaneous Malignant

Objective: To explore the efficacy of adjuvant programmed cell death 1 (PD-1) monoclonal antibody immunotherapy in Chinese patients with resected stage Ⅱ-Ⅲ melanoma. Methods: A total of 296 patients who underwent radical surgery for stage Ⅱ-Ⅲ cutaneous orlimb melanoma at Fudan University Shanghai Cancer Center and Shanghai Electric Power Hospital between 2017 and 2021 and received adjuvant PD-1 monoclonal antibody immunotherapy, low-dose interferon (IFN), or observational follow-up were enrolled in this study. Patients were divided into the PD-1 monoclonal antibody group (164 cases) and the IFN or observation group (IFN/OBS group, 132 cases) based on postoperative adjuvant treatment methods. Patients' disease recurrence and survival were observed. Results: Among the 296 patients, 77 had cutaneous melanoma and 219 had limb melanoma; 110 were stage Ⅱ and 186 were stage Ⅲ. Among stage Ⅱ patients, the median recurrence-free survival (RFS) in the PD-1 monoclonal antibody group (46 cases) did not reach, while the median RFS in the IFN/OBS group (64 cases) was 36 months. The 1-year RFS rates were 85.3% and 92.1% and the 2-year RFS rates were 71.9% and 63.7% in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with no statistically significant difference (P=0.394). Among stage Ⅲ patients, the median RFS rates in the PD-1 monoclonal antibody group (118 cases) and the IFN/OBS group (68 cases) were 23 and 13 months, respectively. The 1-year RFS rates were 70.0% and 51.8% and the 2-year RFS rates were 51.8% and 35.1%in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with a statistically significant difference (P=0.010). Stratified analysis showed that the advantage of PD-1 monoclonal antibody adjuvant therapy in improving RFS persisted in the subgroups of primary ulceration (HR=0.558, 95% CI: 0.348-0.893), lymph node macroscopic metastasis (HR=0.486, 95% CI: 0.285-0.828), stage ⅢC (HR=0.389, 95% CI: 0.24-0.63), and the subgroup without BRAF/c-Kit/NRAS gene mutations (HR=0.347, 95% CI: 0.171-0.706). In terms of recurrence patterns, in stage Ⅱ patients, the recurrence and metastasis rate was 15.2% (7/46) in the PD-1 monoclonal antibody group, significantly lower than the IFN/OBS group [43.8% (28/64), P=0.002]. In stage Ⅲ melanoma patients, the recurrence and metastasis rate was 42.4% (50/118) in the PD-1 monoclonal antibody group, also lower than the IFN/OBS group [63.2% (43/68), P=0.006]. Conclusions: In real-world settings, compared with patients receiving low-dose IFN adjuvant therapy or observational follow-up, PD-1 monoclonal antibody immunotherapy can reduce the recurrence and metastasis rate of cutaneous and limb melanoma, and prolong the postoperative RFS of stage Ⅲ cutaneous and limb melanoma patients. Patients with a heavier tumor burden benefit more from immunotherapy.
Humans ; Antibodies, Monoclonal/therapeutic use* ; Apoptosis ; China ; Disease-Free Survival ; East Asian People ; Immunotherapy ; Interferon-alpha/therapeutic use* ; Lymphatic Metastasis ; Melanoma/pathology* ; Programmed Cell Death 1 Receptor/therapeutic use* ; Skin Neoplasms/pathology* ; Melanoma, Cutaneous Malignant

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.