1.Epidemiological characteristics of category C intestinal infectious diseases among children and adolescents in Shenzhen from 2012 to 2024 and the association with meteorological factors
Chinese Journal of School Health 2026;47(4):553-557
Objective:
To analyze the epidemiological characteristics of category C intestinal infectious diseases among children and adolescents in Shenzhen from 2012 to 2024 and the association with meteorological factors, so as to provide a scientific basis for the targeted prevention and control of infectious diseases for children and adolescents.
Methods:
Using data from the "Infectious Disease Reporting Information Management System" of the "China Disease Prevention and Control Information System" covering the period from January 1, 2012 to December 31, 2024, the study analyzed clinical and confirmed cases of hand, foot, and mouth disease, other infectious diarrhea, and acute hemorrhagic conjunctivitis among individuals aged 6-19 years old to describe demographic and temporal characteristics. It used Joinpoint regression to calculate the average annual percent change (AAPC) and annual percent change (APC) to analyze incidence trends, and Spearman s correlation was combined to generalize linear models so as to assess the association between category C intestinal infectious diseases and meteorological factors.
Results:
From 2012 to 2024, a cumulative total of 61 019 cases of hand, foot, and mouth disease among children and adolescents, 58 498 cases of other infectious diarrhea, and 6 377 cases of acute hemorrhagic conjunctivitis were reported. The AAPC in the incidence rates of these three diseases was 19.19%, 31.03% and 31.48 %, respectively(all P <0.05). Notably, the incidence of hand, foot, and mouth disease increased significantly after 2022 (APC= 133.66 %, P <0.01). The temporal distribution showed that hand,foot,and mouth disease was most prevalent in May,June and July (seasonal index of 2.39,3.64,1.97), other infectious diarrhea was most prevalent in February,March and December (seasonal index of 1.22,1.25,1.47), and acute hemorrhagic conjunctivitis peaked in September and October (seasonal index of 4.22,2.16). Monthly average temperature could increase the risk of hand,foot,and mouth disease( β = 0.18 ,95% CI =0.11-0.25); as monthly average wind speed increased, the incidence of other infectious diarrhea ( β =-0.86, 95% CI = -1.50 to -0.22) and acute hemorrhagic conjunctivitis ( β =-1.32, 95% CI =-2.60 to -0.05) both decreased (all P < 0.05 ).
Conclusions
Among children and adolescents in Shenzhen, category C intestinal infectious diseases remain prevalent throughout the year;the number of reported hand, foot, and mouth disease cases has shown an upward trend in recent years.Temperature and wind speed significantly affect the number of reported cases of three types with category C intestinal infectious diseases.
2.Impact of optimized varicella vaccination strategy on varicella incidence among nursery children in Shenzhen
Chinese Journal of School Health 2026;47(5):728-731
Objective:
To analyze the epidemiological characteristics of varicella among nursery children in Shenzhen from 2015 to 2024, and to evaluate the impact of optimizing varicella vaccine (VarV) immunization strategies on varicella incidence.
Methods:
Varicella incidence data for nursery children in Shenzhen from 2015 to 2024 were obtained from the China Disease Prevention and Control Information System. The study period was divided into three phases:one dose self pay VarV (January 2015 to October 2017), two dose self pay VarV (November 2017 to October 2019), and two dose free VarV (November 2019 to December 2024). Interrupted time series (ITS) analysis was conducted to assess changes in the level and trend of varicella incidence associated with each phase of policy implementation.
Results:
A total of 27 517 varicella cases was reported among nursery children from 2015 to 2024, with an average annual incidence of 514.01/100 000. During the same period, 136 clustered outbreaks were reported in nursery institutions, involving a cumulative total of 1 091 cases. ITS analysis showed that during the self pay 1 dose stage, the varicella incidence among nursery children showed an upward trend, with an average monthly increase of 2.58/100 000 (95% CI =2.21/ 100 000 -2.95/100 000, P <0.01). After the implementation of the self pay 2 dose strategy, the incidence decreased, with a change in incidence of -26.12/100 000 (95% CI =-37.30/100 000 to -14.94/100 000) and a change in slope of -2.65/100 000 (95% CI = -3.38/100 000 to -1.93/100 000)(all P <0.01). After the implementation of the free 2 dose strategy, the incidence decreased further, with a change in incidence of -40.03/100 000 (95% CI =-50.39/100 000 to -29.66/100 000, P <0.01) and a change in slope of -0.56/100 000 (95% CI =-1.20/100 000-0.08/100 000, P =0.09).
Conclusion
The gradual optimization of the VarV vaccination strategy in Shenzhen from self pay 1 dose to free 2 dose has significantly reduced the varicella incidence among nursery children, demonstrating good short term control and long term intervention effectiveness.
3.Textual Research on Key Information of Famous Classical Formula Jiegengtang
Yang LEI ; Yuli LI ; Xiaoming XIE ; Zhen LIU ; Shanghua ZHANG ; Tieru CAI ; Ying TAN ; Weiqiang ZHOU ; Zhaoxu YI ; Yun TANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):182-190
Jiegengtang is a basic formula for treating sore throat and cough. By means of bibliometrics, this study conducted a textual research and analysis on the key information such as formula origin, decocting methods, and clinical application of Jiegengtang. After the research, it can be seen that Jiegengtang is firstly contained in Treatise on Febrile and Miscellaneous Disease, which is also known as Ganjietang, and it has been inherited and innovated by medical practitioners of various dynasties in later times. The origins of Chinese medicines in this formula is basically clear, Jiegeng is the dried roots of Platycodon grandiflorum, Gancao is the dried roots and rhizomes of Glycyrrhiza uralensis, the two medicines are selected raw products. The dosage is 27.60 g of Glycyrrhizae Radix et Rhizoma and 13.80 g of Platycodonis Radix, decocted with 600 mL of water to 200 mL, taken warmly after meals, twice a day, 100 mL for each time. In ancient times, Jiegengtang was mainly used for treating Shaoyin-heat invasion syndrome, with cough and sore throat as its core symptoms. In modern clinical practice, Jiegengtang is mainly used for respiratory diseases such as pharyngitis, esophagitis, tonsillitis and lung abscess, especially for pharyngitis and lung abscess with remarkable efficacy. This paper can provide literature reference basis for the modern clinical application and new drug development of Jiegengtang.
4.Textual Research on Key Information of Famous Classical Formula Jiegengtang
Yang LEI ; Yuli LI ; Xiaoming XIE ; Zhen LIU ; Shanghua ZHANG ; Tieru CAI ; Ying TAN ; Weiqiang ZHOU ; Zhaoxu YI ; Yun TANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):182-190
Jiegengtang is a basic formula for treating sore throat and cough. By means of bibliometrics, this study conducted a textual research and analysis on the key information such as formula origin, decocting methods, and clinical application of Jiegengtang. After the research, it can be seen that Jiegengtang is firstly contained in Treatise on Febrile and Miscellaneous Disease, which is also known as Ganjietang, and it has been inherited and innovated by medical practitioners of various dynasties in later times. The origins of Chinese medicines in this formula is basically clear, Jiegeng is the dried roots of Platycodon grandiflorum, Gancao is the dried roots and rhizomes of Glycyrrhiza uralensis, the two medicines are selected raw products. The dosage is 27.60 g of Glycyrrhizae Radix et Rhizoma and 13.80 g of Platycodonis Radix, decocted with 600 mL of water to 200 mL, taken warmly after meals, twice a day, 100 mL for each time. In ancient times, Jiegengtang was mainly used for treating Shaoyin-heat invasion syndrome, with cough and sore throat as its core symptoms. In modern clinical practice, Jiegengtang is mainly used for respiratory diseases such as pharyngitis, esophagitis, tonsillitis and lung abscess, especially for pharyngitis and lung abscess with remarkable efficacy. This paper can provide literature reference basis for the modern clinical application and new drug development of Jiegengtang.
5.Study on the efficacy of automatic-controlled pressure cupping for lumbar disc herniation.
Bo-Chen PENG ; Min-Shan FENG ; Li LI ; Gui-Ju REN ; Yi-Zhen YUAN ; Li-Jie CHANG ; Shu-Ying REN ; Liu ZENG ; Guang-Wei LIU ; Li-Guo ZHU ; Na YUAN
China Journal of Orthopaedics and Traumatology 2025;38(11):1133-1138
OBJECTIVE:
To observe the clinical efficacy and safety of automatic pressure-controlled pressure cupping in patients with lumbar disc herniation, and compare it with traditional cupping.
METHODS:
A total of 100 patients diagnosed with lumbar disc herniation from January 2022 to August 2024 were selected and divided into two groups:the automatic pressure-controlled pressure cupping group (controlled pressure cupping group) and the traditional cupping group (control group), 50 cases in each group. In the controlled pressure cupping group, there were 18 males and 32 females, with an age of (51.98±12.69) years;in the control group, there were 16 males and 34 females, with an age of (51.32±12.05) years. The visual analogue scale(VAS), comfort score, and lumbar range of motion were observed before treatment and after the 1st, 3rd, and 7th treatments to evaluate the efficacy and safety.
RESULTS:
All patients completed the treatment intervention, with complete follow-up data collected. No adverse reactions or complications occurred during treatment and follow-up. After the 3rd treatment, the VAS score of the controlled pressure cupping group was (2.38±0.49), which was lower than that of the control group (2.94±0.68), with a statistically significant difference (P<0.001). In the controlled pressure cupping group, the VAS scores after the 1st, 3rd, and 7th treatments were significantly better than those before treatment (P=0.026);in the control group, the VAS scores after the 3rd and 7th treatments were better than those before treatment, but the difference was not statistically significant(P=0.182). Repeated-measures analysis of variance (ANOVA) on VAS scores at different time points in both groups showed that there were statistically significant differences in inter-group, time, and interaction effects (P<0.05). After the 1st treatment, in the controlled pressure cupping group, 0 patients felt comfortable, 42 patients (84%) felt mild discomfort, and 8 patients (16%) felt moderate discomfort;in the control group, 0 patients felt comfortable, 28 patients (56%) felt mild discomfort, and 22 patients(44%) felt moderate discomfort;the difference between the two groups was statistically significant(P=0.005). After the 3rd treatment, in the controlled pressure cupping group, 30 patients(60%) felt comfortable, 20 patients (40%) felt mild discomfort, and 0 patients felt moderate discomfort; in the control group, 9 patients (18%) felt comfortable, 41 patients (82%) felt mild discomfort, and 0 patients felt moderate discomfort;the difference between the two groups was statistically significant(P<0.001). There was no statistically significant difference in comfort between the two groups after the 7th treatment(P>0.001). There was no statistically significant difference in lumbar range of motion between the two groups before and after treatment(P>0.05);compared with before treatment, the lumbar range of motion of both groups after treatment was significantly improved, with statistically significant differences (P<0.001).
CONCLUSION
Automatic pressure-controlled pressure cupping can effectively relieve symptoms in patients with lumbar disc herniation, with excellent safety.
Humans
;
Female
;
Male
;
Intervertebral Disc Displacement/physiopathology*
;
Middle Aged
;
Adult
;
Lumbar Vertebrae/physiopathology*
;
Cupping Therapy/methods*
;
Pressure
;
Aged
;
Treatment Outcome
6.Effect of Hesperidin on Chronic Unpredictable Mild Stress-Related Depression in Rats through Gut-Brain Axis Pathway.
Hui-Qing LIANG ; Shao-Dong CHEN ; Yu-Jie WANG ; Xiao-Ting ZHENG ; Yao-Yu LIU ; Zhen-Ying GUO ; Chun-Fang ZHANG ; Hong-Li ZHUANG ; Si-Jie CHENG ; Xiao-Hong GU
Chinese journal of integrative medicine 2025;31(10):908-917
OBJECTIVES:
To determine the pharmacological impact of hesperidin, the main component of Citri Reticulatae Pericarpium, on depressive behavior and elucidate the mechanism by which hesperidin treats depression, focusing on the gut-brain axis.
METHODS:
Fifty-four Sprague Dawley male rats were randomly allocated to 6 groups using a random number table, including control, model, hesperidin, probiotics, fluoxetine, and Citri Reticulatae Pericarpium groups. Except for the control group, rats in the remaining 5 groups were challenged with chronic unpredictable mild stress (CUMS) for 21 days and housed in single cages. The sucrose preference test (SPT), immobility time in the forced swim test (FST), and number in the open field test (OFT) were performed to measure the behavioral changes in the rats. Enzyme-linked immunosorbent assay was used to determine the levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) in brain tissue, and the histopathology was performed to evaluate the changes of colon tissue, together with sequencing of the V3-V4 regions of 16S rRNA gene on feces to explore the changes of intestinal flora in the rats.
RESULTS:
Compared to the control group, the rats in the model group showed notable reductions in body weight, SPF, and number in OFT (P<0.01). Hesperidin was found to ameliorate depression induced by CUMS, as seen by improvements in body weight, SPT, immobility time in FST, and number in OFT (P<0.05 or P<0.01). Regarding neurotransmitters, it was found that at a dose of 50 mg/kg hesperidin treatment upregulated the levels of 5-HT and BDNF in depressed rats (P<0.05). Compared to the control group, the colon tissue of the model group exhibited greater inflammatory cell infiltration, with markedly reduced numbers of goblet cells and crypts and were significantly improved following treatment with hesperidin. Simultaneously, the administration of hesperidin demonstrated a positive impact on the gut microbiome of rats treated with CUMS, such as Shannon index increased and Simpson index decreased (P<0.01), while the abundance of Pseudomonadota and Bacteroidota increased in the hesperidin-treated group (P<0.05).
CONCLUSION
The mechanism responsible for the beneficial effects of hesperidin on depressive behavior in rats may be related to inhibition of the expressions of BDNF and 5-HT and preservation of the gut microbiota.
Animals
;
Hesperidin/therapeutic use*
;
Rats, Sprague-Dawley
;
Depression/drug therapy*
;
Male
;
Stress, Psychological/drug therapy*
;
Brain/metabolism*
;
Brain-Derived Neurotrophic Factor/metabolism*
;
Serotonin/metabolism*
;
Gastrointestinal Microbiome/drug effects*
;
Behavior, Animal/drug effects*
;
Rats
;
Brain-Gut Axis/drug effects*
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Chronic Disease
;
Colon/drug effects*
7.Establishment and evaluation of a predictive model for spontaneous peritonitis in HBV-related primary liver cancer
Hong-Yan WEI ; Yong-Zhen CHEN ; Ren-Hai TIAN ; Li-Xian CHANG ; Ying-Yuan ZHANG ; Dan-Qing XU ; Chun-Yun LIU ; Li LIU
Medical Journal of Chinese People's Liberation Army 2025;50(8):949-957
Objective To establish and evaluate a nomogram prediction model for spontaneous peritonitis in HBV-related primary liver cancer.Methods A retrospective study was conducted on 1298 patients with HBV-related primary liver cancer hospitalized in the Kunming Third People's Hospital from January 2012 to December 2022.General data and serological indicators were collected,and patients were divided into infection group(n=262)and control group(n=1036)based on the occurrence of spontaneous peritonitis.Univariate and LASSO regression analyses were used to screen variables,followed by binary logistic regression to analyze the influencing factors of spontaneous peritonitis in HBV-related primary liver cancer patients,leading to the establishment of a nomogram prediction model.Finally,the Hosmer-lemeshow(H-L)goodness of fit test,receiver operating characteristic(ROC)curve,calibration curve,decision curve analysis(DCA)and clinical impact curve(CIC)were utilized to evaluate the fit degree,accuracy,calibration,and clinical practicability of the nomogram prediction model.Results Single factor analysis revealed significant differences between infection group and control group in portal vein cancer thrombus(PVTT),Child-Pugh grade,China Liver Cancer Staging(CNLC)stage,alcohol consumption history,smoking history,white blood cell count(WBC),neutrophil count(NE),hemoglobin(Hb),fibrinogen(FIB),abnormal prothrombin(PIVKA-Ⅱ),aspartate aminotransferase(AST),alanine aminotransferase(ALT),total protein(TP),prealbumin(PA),γ-glutamyltransferase(GGT),alkaline phosphatase(ALP),cholinesterase(CHE),total bile acid(TBA),total cholesterol(TC),low density lipoprotein(LDL),creatinine(Cr),HBV DNA,CD3+T cells count,CD4+T cells count,CD8+T cells count,CD4+T cells/CD8+T cells ratio,procalcitonin(PCT),serum amyloid A(SAA),interleukin-6(IL-6),high-sensitivity C-reactive protein(hs-CRP),alpha-fetoprotein(AFP),and IL-4(P<0.05).LASSO regression analysis identified 5 variables:Child-Pugh grade,PVTT,WBC,CHE and hs-CRP.Binary logistic regression analysis indicated that Child-Pugh grade(Grade B:OR=5.780,95%CI 3.271-10.213,P<0.001;Grade C:OR=14.818,95%CI 7.697-28.526,P<0.001),PVTT(OR=2.893,95%CI 2.037-4.108,P<0.001),WBC(OR=1.088,95%CI 1.031-1.148,P=0.002),and hs-CRP(OR=1.005,95%CI 1.001-1.010,P=0.026)were the independent risk factors of spontaneous peritonitis in HBV-related primary liver cancer patients.Using these 4 variables,a nomogram prediction model was constructed and evaluated.The P-value of the H-L goodness of fit test was 0.760.Moreover,the area under ROC curve(AUC)was 0.866,with a sensitivity of 0.870 and a specificity of 0.716.The average absolute error of the calibration curve is 0.022.DCA and CIC analyses demonstrated that the nomogram prediction model possessed some clinical utility.Conclusion The nomogram prediction model for spontaneous peritonitis in HBV-related primary liver cancer patients,constructed using Child-Pugh grade,PVTT,WBC and hs-CRP,exhibits a high fitting degree and accuracy,with the prediction probability highly consistent with the actual occurrence probability,and possesses certain clinical practicability.
8.Analysis of factors influencing global longitudinal strain based on cardiac magnetic resonance after acute myocardial infarction
Ke LIU ; Yi-Qing ZHAO ; Zhen-Yan MA ; Xin A ; Li LI ; Wei-Ran KONG ; Lei ZHAO ; Hong-Bo ZHANG ; Ying ZHANG ; Geng QIAN
Medical Journal of Chinese People's Liberation Army 2025;50(11):1382-1389
Objective To investigate the factors influencing global longitudinal strain(GLS)measured by cardiac magnetic resonance(CMR)in patients with acute ST-segment elevation myocardial infarction(STEMI).Methods Clinical data of 315 hospitalized patients diagnosed with acute STEMI who underwent percutaneous coronary intervention(PCI)at the First Medical Center of Chinese PLA General Hospital from June 2016 to September 2021 were retrospectively collected.After analyzing CMR images of all patients,GLS and other strain parameters were obtained,and then the patients were divided into two groups according to the median GLS.In order to balance gender and age differences,1:1 propensity score matching was performed,and 206 patients were eventually included:GLS>-11.3%group(indicating severe GLS impairment,n=103)and GLS≤-11.3%group(n=103).Baseline characteristics,laboratory indicators,coronary angiographic parameters,electrocardiogram(ECG)features,and CMR parameters were compared between the two groups.Variables showing significant differences were analyzed for their correlation with GLS.Multivariate logistic regression and multiple stepwise linear regression analyses were performed to identify factors associated with GLS impairment.Results Compared with GLS≤-11.3%group,GLS>-11.3%group had significantly higher peak levels of creatine kinase-MB(CK-MB)and troponin T(TnT)(P<0.001).A higher proportion of patients in GLS>-11.3%group had the left anterior descending artery(LAD)as the culprit vessel,while a lower proportion had the right coronary artery(RCA)as the culprit vessel(P<0.001).Additionally,GLS>-11.3%group had longer QRS duration(P<0.001)and a higher incidence of pathological Q waves(P=0.001).Regarding CMR parameters,GLS>-11.3%group exhibited larger global circumferential strain(GCS),infarct size(IS),and left ventricular end-systolic volume(LVESV),as well as lower global radial strain(GRS)and left ventricular ejection fraction(LVEF)(P<0.001).Multivariate logistic regression indicated that peak TnT(OR=1.092,P=0.001),LAD culprit vessel(OR=3.744,P<0.001),and QRS duration(OR=1.026,P<0.001)were significantly associated with severely impaired GLS.Multiple stepwise linear regression analysis showed that the logarithmic value of peak TnT,LAD as the culprit vessel,and the square root of QRS duration were linearly correlated with GLS values(adjusted R2=0.301,P<0.001),and these independent variables explained 30.1%of the variation in GLS.Conclusion Elevated peak TnT,prolonged QRS duration,and LAD as the culprit vessel are significantly associated with severe GLS impairment in STEMI patients,indicating more severe myocardial infarction and worse left ventricular function.
9.Stimulation mechanism of osteoblast proliferation and differentiation by Duzhong Decoction-containing serum through L-VGCCs.
Ze-Bin CHEN ; Lan-Lan LUO ; Xin-Yi SHI ; Rui-Tong ZHAO ; Cai-Xian HU ; Yun-Ying FU ; Su-Zhen CHAO ; Bo LIU
China Journal of Chinese Materia Medica 2025;50(12):3335-3345
This paper aimed to explore the effects of Duzhong Decoction(DZD)-containing serum on the proliferation and osteoblast differentiation of MC3T3-E1 cells through L-type voltage-gated calcium channels(L-VGCCs). L-VGCCs inhibitors, nifedipine and verapamil, were used to block L-VGCCs in osteoblasts. MC3T3-E1 cells were divided into a control group, a low-dose DZD-containing serum(L-DZD) group, a medium-dose DZD-containing serum(M-DZD) group, a high-dose DZD-containing serum(H-DZD) group, a nifedipine group, a H-DZD + nifedipine group, verapamil group, and a H-DZD + verapamil group. The CCK-8 method was used for cell proliferation analysis, alkaline phosphatase(ALP) assay kits for intracellular ALP activity measurement, Western blot for protein expression level in cells, real-time fluorescence quantitative PCR technology for intracellular mRNA expression level determination, fluorescence spectrophotometer for free Ca~(2+) concentration determination in osteoblasts, and alizarin red staining(ARS) for mineralized nodule formation in osteoblasts. The experimental results show that compared to the control group, DZD groups can promote MC3T3-E1 cell proliferation, ALP activity, and mineralized nodule formation, increase intracellular Ca~(2+) concentrations, and upregulate the protein expression of bone morphogenetic protein 2(BMP2), collagen Ⅰ(COL1), α2 subunit protein of L-VGCCs(L-VGCCα2), and the mRNA expression of Runt-related transcription factor 2(RUNX2), and BMP2. After blocking L-VGCCs with nifedipine and verapamil, the intervention effects of DZD-containing serum were inhibited to varying degrees. Both nifedipine and verapamil could inhibit ALP activity, reduce mineralized nodule areas, and downregulate the expression of bone formation-related proteins. Moreover, the effects of DZD-containing serum on increasing MC3T3-E1 cell proliferation, osteoblast differentiation, and Ca~(2+) concentrations, upregulating the mRNA expression of osteoprotegerin(OPG) and protein expression of phosphorylated protein kinase B(p-Akt) and phosphorylated forkhead box protein O1(p-FOXO1), and upregulating phosphatase and tensin homolog(PTEN) expression were reversed by nifedipine. The results indicate that DZD-containing serum can increase the Ca~(2+) concentration in MC3T3-E1 cells to promote bone formation, which may be mediated by L-VGCCs and the PTEN/Akt/FoxO1 signaling pathway, providing a new perspective on the mechanism of DZD in treating osteoporosis.
Animals
;
Osteoblasts/metabolism*
;
Cell Proliferation/drug effects*
;
Cell Differentiation/drug effects*
;
Mice
;
Drugs, Chinese Herbal/pharmacology*
;
Calcium Channels, L-Type/genetics*
;
Alkaline Phosphatase/genetics*
;
Serum/chemistry*
;
Cell Line
;
Osteogenesis/drug effects*
;
Bone Morphogenetic Protein 2/genetics*
10.Hippocampal Extracellular Matrix Protein Laminin β1 Regulates Neuropathic Pain and Pain-Related Cognitive Impairment.
Ying-Chun LI ; Pei-Yang LIU ; Hai-Tao LI ; Shuai WANG ; Yun-Xin SHI ; Zhen-Zhen LI ; Wen-Guang CHU ; Xia LI ; Wan-Neng LIU ; Xing-Xing ZHENG ; Fei WANG ; Wen-Juan HAN ; Jie ZHANG ; Sheng-Xi WU ; Rou-Gang XIE ; Ceng LUO
Neuroscience Bulletin 2025;41(12):2127-2147
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
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Laminin/genetics*
;
Hippocampus/metabolism*
;
Neuralgia/metabolism*
;
Cognitive Dysfunction/etiology*
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Male
;
Peripheral Nerve Injuries/metabolism*
;
Extracellular Matrix/metabolism*
;
Integrin beta1/metabolism*
;
Pyramidal Cells/metabolism*
;
Signal Transduction


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