Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

Objective To reveal the clinical characteristics of heterotopic pregnancy(HP)and enhance the understanding of its complexity.Methods A retrospective study was conducted among all 390 852 pregnant women who were treated in two tertiary hospitals of obstetrics and gynecology in Shanghai from Jan 2011 to May 2021.We screened and collected patients who were diagnosed as HP,and analyzed their clinical characteristics including menopause time,conception method,location of ectopic pregnancy(EP)and clinical manifestations.Results A total of 185 HP cases enrolled and 14 EP site rupture cases were recognized.Among the 185 cases,84.9%had their EP site in fallopian tube,12.4%were cornual HP.In vitro fertilization-embryo transfer(IVF-ET)ranked first in conception method with rate of 83.8%,followed by ovulation induction with rate of 10.3%and spontaneous conception ranked last with rate of 5.4%.Vaginal bleeding was appeared in 38.4%HP patients,21.1%patients experienced abdominal pain and 12.4%patients had vaginal bleeding complicated by abdominal pain.It is worth mentioning that,25.4%patients had no clinical manifestation.The incidence of EP site rupture was 7.6%.In 14 EP rupture cases,71.4%had abdominal pain as their first clinical manifestation.The post-operation live birth rate of EP site rupture patients was 78.6%,and abortion rate was 14.3%.Conclusion The clinical manifestations of HP are diverse.For patients with vaginal bleeding and abdominal pain,conception method is IVF-ET or ovulation induction,detailed and dynamic transvaginal ultrasound examination should be careful carried out in the uterus and adnexal areas.Patients with abdominal pain should be alert to EP site rupture and early intervention was needed.

Objective Studies on the relationship between iodine,vitamin A(VA),and vitamin D(VD)and thyroid function are limited.This study aimed to analyze iodine and thyroid-stimulating hormone(TSH)status and their possible relationships with VA,VD,and other factors in postpartum women. Methods A total of 1,311 mothers(896 lactating and 415 non-lactating)from Hebei,Zhejiang,and Guangxi provinces were included in this study.The urinary iodine concentration(UIC),TSH,VA,and VD were measured. Results The median UIC of total and lactating participants were 142.00 μg/L and 139.95 μg/L,respectively.The median TSH,VA,and VD levels in all the participants were 1.89 mIU/L,0.44 μg/mL,and 24.04 ng/mL,respectively.No differences in the UIC were found between lactating and non-lactating mothers.UIC and TSH levels were significantly different among the three provinces.The rural UIC was higher than the urban UIC.Obese mothers had a higher UIC and a higher prevalence of excessive TSH.Higher UICs and TSHs levels were observed in both the VD deficiency and insufficiency groups than in the VD-sufficient group.After adjustment,no linear correlation was observed between UIC and VA/VD.No interaction was found between vitamins A/D and UIC on TSH levels. Conclusion The mothers in the present study had no iodine deficiency.Region,area type,BMI,and VD may be related to the iodine status or TSH levels.

OBJECTIVE: To evaluate the efficacy and safety of Jianpi Jieyu Decoction (JJD) for treating patients with mild-to-moderate depression of Xin (Heart)-Pi (Spleen) deficiency (XPD) syndrome. METHODS: In this multi-center, randomized, controlled study, 140 patients with mild-to-moderate depression of XPD syndrome were included from Xiyuan Hospital of China Academy of Chinese Medical Sciences and Botou Hospital of Traditional Chinese Medicine from December 2017 to December 2019. They were randomly divided into JJD group and paroxetine group by using a random number table, with 70 cases in each group. The patients in the JJD group were given JJD one dose per day (twice daily at morning and evening, 100 mL each time), and the patients in the paroxetine group were given paroxetine (10 mg/d in week 1; 20 mg/d in weeks 2-6), both orally administration for a total of 6 weeks. The primary outcome was the change of 17-item Hamilton Depression Rating Scale (HAMD-17) score at week 6 from baseline. The secondary outcomes included the Hamilton Anxiety Scale (HAMA) score, Traditional Chinese Medicine Symptom Scale (TCMSS), and Clinlcal Global Impression (CGI) scores at the 2nd, 4th, and 6th weekends of treatment, HAMD-17 response (defined as a reduction in score of >50%) and HAMD-17 remission (defined as a score of ⩽7) at the end of the 6th week of treatment. Adverse events (AEs) were also recorded. RESULTS: From baseline to week 6, the HAMD-17 scores decreased 10.2 ± 4.0 and 9.1 ± 4.9 points in the JJD and paroxetine groups, respectively (P=0.689). The HAMD-17 response occurred in 60% of patients in the JJD group and in 50% of those in the paroxetine group (P=0.292); HAMD-17 remission occurred in 45.7% and 30% of patients, respectively (P=0.128). The differences of CGI scores at the 6th week were not statistically significant (P>0.05). There were significant differences in HAMD-17 scores between the two groups at 2nd and 4th week (P=0.001 and P=0.014). The HAMA scores declined 8.1 ± 3.0 and 6.9 ± 4.3 points from baseline to week 6 in the JJD and paroxetine groups, respectively (P=0.905 between groups). At 4th week of treatment, there was a significant difference in HAMA between the two groups (P=0.037). TCMSS decreased 11.4 ± 5.1, and 10.1 ± 6.8 points in the JJD and paroxetine groups, respectively (P=0.080 between groups). At the 6th week, the incidence of AEs in the JJD group was significantly lower than that in the paroxetine group (7.14% vs. 22.86%, P<0.05). CONCLUSION Compared with paroxetine, JJD was associated with a significantly lower incidence of AEs in patients with mild-to-moderate depression of XPD syndrome, with no difference in efficacy at 6 weeks. (Trial registration No. ChiCTR2000040922).
Humans ; Paroxetine/adverse effects* ; Spleen ; Anxiety ; Syndrome ; Medicine, Chinese Traditional ; Treatment Outcome ; Double-Blind Method

OBJECTIVE: To develop and validate a three-year risk prediction model for new-onset cardiovascular diseases (CVD) among female patients with breast cancer. METHODS: Based on the data from Inner Mongolia Regional Healthcare Information Platform, female breast cancer patients over 18 years old who had received anti-tumor treatments were included. The candidate predictors were selected by Lasso regression after being included according to the results of the multivariate Fine & Gray model. Cox proportional hazard model, Logistic regression model, Fine & Gray model, random forest model, and XGBoost model were trained on the training set, and the model performance was evaluated on the testing set. The discrimination was evaluated by the area under the curve (AUC) of the receiver operator characteristic curve (ROC), and the calibration was evaluated by the calibration curve. RESULTS: A total of 19 325 breast cancer patients were identified, with an average age of (52.76±10.44) years. The median follow-up was 1.18 [interquartile range (IQR): 2.71] years. In the study, 7 856 patients (40.65%) developed CVD within 3 years after the diagnosis of breast cancer. The final selected variables included age at diagnosis of breast cancer, gross domestic product (GDP) of residence, tumor stage, history of hypertension, ischemic heart disease, and cerebrovascular disease, type of surgery, type of chemotherapy and radiotherapy. In terms of model discrimination, when not considering survival time, the AUC of the XGBoost model was significantly higher than that of the random forest model [0.660 (95%CI: 0.644-0.675) vs. 0.608 (95%CI: 0.591-0.624), P < 0.001] and Logistic regression model [0.609 (95%CI: 0.593-0.625), P < 0.001]. The Logistic regression model and the XGBoost model showed better calibration. When considering survival time, Cox proportional hazard model and Fine & Gray model showed no significant difference for AUC [0.600 (95%CI: 0.584-0.616) vs. 0.615 (95%CI: 0.599-0.631), P=0.188], but Fine & Gray model showed better calibration. CONCLUSION It is feasible to develop a risk prediction model for new-onset CVD of breast cancer based on regional medical data in China. When not considering survival time, the XGBoost model and the Logistic regression model both showed better performance; Fine & Gray model showed better performance in consideration of survival time.
Humans ; Female ; Adult ; Middle Aged ; Adolescent ; Breast Neoplasms/epidemiology* ; Cardiovascular Diseases/etiology* ; Proportional Hazards Models ; Logistic Models ; China/epidemiology*

Objective To investigate whether physiological asymmetry of normal bilateral superficial veins located in dorsolateral aspects of hemispheres is existed on susceptibility-weighted imaging (SWI). Methods There were 45 healthy young volunteers in this study. After exclusion of intracranial lesions by using common brain magnetic resonance imaging examination, they underwent SWI examination. We observed the number, diameter and signal intensity of superficial veins located in dorsolateral aspects of hemispheres according to the images of SWI on transverse sections through the centrum semiovale, trunk of corpus callosum, splenium of corpus callosum, and superior colliculus. Results The frequencies of asymmetry of the bilateral superficial veins located in dorsolateral aspects of hemispheres on transverse sections through the centrum semiovale, trunk of corpus callosum, splenium of corpus callosum, and superior colliculus were 20.0%, 37.8%, 35.6% and 26.7%, respectively. The frequencies of mild asymmetry of the bilateral superficial veins located in dorsolateral aspects of hemispheres on above transverse sections were 17.8%, 31.1%, 31.1% and 24.4% respectively, and the frequencies of prominent asymmetry were 2.2%, 6.7%, 4.4% and 2.2%, respectively. According to chi square test, there was no gender difference in asymmetry of the bilateral superficial veins located in dorsolateral aspects of hemispheres. Conclusion SWI technique was used to show the physiological asymmetry of the bilateral superficial veins located in dorsolateral aspects of hemispheres on different transverse sections. Most of them are mild. Therefore, when cerebrovascular disease occurs, if transverse sections of images by SWI show asymmetry of the bilateral superficial veins located in dorsolateral aspects of hemispheres, the possibility of physiological phenomenon is needed to take into consideration.

Objective: To explore the effects of exposure of pregnant rats to radio frequency electromagnetic field on the ultrastructure of hippocampus and the levels of obesity related protein (FTO) and nerve growth factor (NGF) in offspring rats. Methods: In September 2019, 36 healthy 7-week-old Wistar rats were selected, including 24 female rats (150-200 g) and 12 male rats (200-250 g) . The male and female mice were mated in the cage at 2: 1 ratio at 18: 00 every night. The smear results showed that the sperm was positive and the mating was successful. The day was regarded as the 0 day of pregnancy. Pregnant rats were randomly divided into 3 experimental groups and 3 control groups, with 4 rats in each group. The experimental group was exposed to 1 800 MHz, Wi-Fi and 1 800 MHz+Wi-Fi respectively, and the three control groups were exposed to virtual exposure. 12 hours a day for 21 days in three batches. After the end of exposure, the offspring of each group were raised for 7 weeks. The ultrastructural changes of the hippocampus were observed by transmission electron microscopy, the FTO level in the hippocampus was determined by Western blot, and the NGF level in the brain tissue was determined by ELISA. Results: Transmission electron microscopy showed that the nuclei of hippocampal tissue of female and male rats in the 1800 MHz group were slightly contracted, the cytoplasm was slightly edema, and the nuclei of male rats were obviously irregular. In the offspring of male and female rats in the Wi-Fi group, the nucleus of hippocampal tissue contracted seriously, the cell membrane was irregular, and the cytoplasm appeared obvious edema. In the 1800 MHz+Wi-Fi group, the nuclei of hippocampal tissue of both male and female offspring rats were severely contracted, the nuclear membrane was irregular, and the cytoplasm was severely edema. there was no significant difference in FTO level among the groups (P>0.05) . Compared with other groups, NGF content in hippocampus of offspring rats in the 1800 MHz+Wi-Fi group was significantly higher (P<0.05) . Conclusion: Exposure to radio frequency electromagnetic fields will damage the morphological structure of hippocampal tissue of offspring and stimulate the increase of NGF expression in the hippocampus.
Animals ; Electromagnetic Fields ; Female ; Hippocampus ; Male ; Mice ; Nerve Growth Factor ; Pregnancy ; Rats ; Rats, Wistar ; Semen

OBJECTIVE: To evaluate the efficacy and safety of 585 nm Q-switched laser in the treatment of acne inflammatory lesions and postinflammatory erythema. METHODS: A total of 25 patients with moderate facial acne, symmetrical distribution of inflammatory lesions and postinflammatory erythema on both sides of the face, were enrolled. Among the 25 patients, 22 patients completed all the treatment and evaluation, and 3 patients were lost to follow-up. 585 nm Q-switched laser was used on a randomly selected side of the face for three times of treatment at a 2 week interval. The evaluations were made before each treatment, 2 and 4 weeks after the last treatment, therefore the evaluation time points were before the treatment, weeks 2, 4, 6, and 8, respectively, for a total of 5 times. Acne severity was assessed using the investigator' s global assessment (IGA) score, and erythema severity was assessed using the investigator' s subjective erythema score and narrow-spectrum reflectance spectrophotometer at each follow-up. RESULTS: After 3 times of treatment, there was statistically significant difference between the IGA score in week 8 and before treatment on both sides(Z=2.64, P < 0.01; Z=2.67, P < 0.01). There was no significant difference in IGA score between the treatment side and the control side before treatment and in week 8 (P=0.59, P=0.26). There was statistically significant difference between the investiga-tor' s subjective erythema score in week 8 and before treatment on the treatment side(Z=4.24, P < 0.01), while no significant difference was showed on the control side(Z=1.73, P=0.08). In week 8, the investigator's subjective erythema score of the treatment side was lower than that of the control side (Z=3.61, P < 0.01). The erythema index of the treatment side was significantly decreased at 5 time points (P < 0.01), and the index decreased significantly in week 8 compared with the index before treatment (P < 0.01), while the erythema index of the control side was not significantly different at 5 time points. The treatment related adverse events included erythema and edema after treatment and pain during treatment, the severity was mild to moderate, which resolved spontaneously within 1 to 3 days. Nine patients were very satisfied with the treatment, 7 patients were satisfied, and 6 patients considered average. CONCLUSION 585 nm Q-switched laser has some effect in the treatment of postinflammatory erythema, and it ensures good tolerance and safety. There was no statistically significant difference between the treatment side and the control side on the improvement of acne inflammatory lesions.
Acne Vulgaris/therapy* ; Erythema/etiology* ; Face ; Humans ; Immunoglobulin A ; Treatment Outcome

The present study explored the effective approaches to realize the leading role of traditional Chinese medicine （TCM） in preventing diseases， the synergistic role in treating serious diseases， the core role in the rehabilitation of diseases and summarized the experience to provide feasible plans for the evaluation of other dominant diseases of TCM. To evaluate the effectiveness， safety， and economy of TCM in the treatment of ischemic stroke， encephalopathy project team of the China Center for Evidence-based Traditional Chinese Medicine（CCEBTCM） established an evaluation group to determine the work plan and complete the evaluation work. The concepts of the evaluation involved high-quality evidence， expert opinion survey， expert interview， and drug catalog. Under the guidance of clinical experts and methodologists， the evaluation work was completed in accordance with four steps， i.e.， plan making， data collection and data extraction， evidence synthesis and evaluation， and report writing with the rapid review method. Through the review of TCM and western medicine experts， the advantage of TCM in the treatment of ischemic stroke was positioned in the convalescence period with the predominant effects of improving the neurological function defect and improving the daily living ability. In the convalescence period of stroke， TCM treatment could improve post-stroke motor dysfunction， post-stroke cognitive impairment， consciousness disorder， swallowing disorder， aphasia， constipation， urinary function， diplopia， etc.， and the advantages of acupuncture， Chinese medicine， and traditional exercise were more prominent. In terms of safety， TCM treatment of ischemic stroke showed lower incidence of adverse reactions， fewer adverse events， and a milder degree of related symptoms. In terms of economic performance， the combined treatment of TCM and western medicine played a synergistic role and made the treatment cost more reasonable. Compared with conventional intervention， the integrated TCM and western medicine rehabilitation program showed more economic and social benefits.

OBJECTIVES: To establish a carbofuran intragastric administration death model in rabbits, and to observe the postmortem distribution and postmortem redistribution of carbofuran-7-phenyl glucuronic acid (Glu-7PH) in rabbits. METHODS: The postmortem distribution: Rabbits were given an administration of 1/2LD50, LD50, 2LD50 carbofuran. Dead rabbits were dissected immediately. Rabbits that had remained alive 2 hours were sacrificed by carbon dioxide (CO₂) inhalation and dissected immediately. The myocardium, cardiac blood, liver, spleen, lung, kidney, brain and right hindlimb muscle were collected. The postmortem redistribution: After giving an administration of 4LD50 carbofuran, the myocardium, cardiac blood, liver, spleen, lung, kidney, brain, and right hindlimb muscle were collected at 0, 12, 24, 48, and 72 h postmortem in supine position at 15 ℃ room temperature. The quantity of Glu-7PH was determined by LC-MS/MS. RESULTS: The postmortem distribution: Among the three dose groups, there were significant differences in the quantities of Glu-7PH in different tissues. The postmortem redistribution: There was no significant difference in the Glu-7PH quantities in cardiac blood, mycardium, spleen, kidney, brain and right hindlimb muscle, but there was a significant difference in the Glu-7PH quantities in the liver and lung. CONCLUSIONS The mycardium, cardiac blood, liver, lung, kidney, brain and hindlimb muscle of rabbits can be used as appropriate samples for Glu-7PH detection. However, it should be noted that Glu-7PH was redistributed postmortem in rabbit liver and lung.
Animals ; Rabbits ; Carbofuran ; Chromatography, Liquid ; Postmortem Changes ; Tandem Mass Spectrometry ; Autopsy