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 investigate the inhibitory effects of Wumeiwan on oxidative stress injury of ulcerative colitis mice induced by dextran sulfate sodium(DSS)by regulating Kelch-like ECH related protein 1(Keap-1)-nuclear factor E2 related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathwayand.Methods Forty C57BL/6 mice were randomly divided into five groups:normal group,model group,positive control group,experimental-L,-H groups.UC mice model were induced by free access to 2％DSS water.Mice in normal and model group were orally administered with 0.9％NaCl,mice in positive control group were orally treated with Mesalazine solution(0.005 g·10 g-1·d-1),while mice in experimental groups were orally administered with Wumeiwan decoction at the dose of 0.13 and 0.26 g·10 g-1·d-1,respectively.All the drugs were administered for consecutive 7 days,1 times a day.The levels of disease activity index(DAI)and the colon length were scored.The levels of superoxide dismutase(SOD),catalase(CAT),cyclooxygenase-2(COX-2)and inducible nitric oxide synthase(iNOS)in colon tissue of mice were determined by real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)method.The level of Keap-1,Nrf2,HO-1 proteins in colon tissue were determined by Western blot method.Results The levels of DAI of seventh day in normal group,positive control group,experimental-L,-H groups were 0、(2.62±0.33),(1.87±0.35),(1.87±0.35)and(1.58±0.35);the colon lengths were(8.16±0.47)、(5.98±0.24),(7.58±0.38),(7.33±0.24)and(7.48±0.51)cm;the SOD mRNA were 1.01±0.16、0.40±0.01,1.43±0.45,0.65±0.01 and 0.83±0.02;the CAT mRNA were 1.01±0.20、0.45±0.01,0.84±0.02,0.68±0.07 and 0.87±0.05;the COX-2 mRNA were 1.03±0.33、16.65±0.60,4.78±0.25,14.07±0.60 and 7.39±0.15;the iNOS mRNA were 1.04±0.40、20.71±0.66,8.09±0.93,15.44±0.68 and 11.66±0.06;the levels of Keap-1 were 1.22±0.16、1.10±0.05,1.18±0.05,1.94±0.08 and 1.17±0.08;the levels of Nrf2 were 1.12±0.16、0.76±0.15,0.65±0.13,0.70±0.16 and 0.82±0.18;the levels of HO-1 were 1.34±0.15、1.00±0.12,0.89±0.10,1.50±0.18 and 1.40±0.13,respectively.Significant difference was found between normal group and model group(P＜0.01,P＜0.05);significant difference was also found between the experimental-L,-H groups and model group(P＜0.01,P＜0.05).Conclusion Wumeiwan can inhibit oxidative stress in mice with UC,the mechanisms may be related to adjusted the expression of Keap-1-Nrf2/HO-1 signaling pathway protein in colon.

The paper presents professor WU Han-qing's experience in treatment of lumbar disc herniation (LDH) with "sinew-bone three needling technique" of Chinese medicine. Based on the theory of meridian sinew, the points are located by "three-pass method" in terms of the distribution of meridian sinew and syndrome/pattern differentiation. The cord-like muscles and adhesion are relieved by relaxing technique to work directly on the affected sites and alleviate the local compression to the nerve root. The needle technique is operated flexibly according to the affected regions involved, due to which, the needling sensation is increased while the safety ensured. As a result, the meridian qi is enhanced, the mind and qi circulation is regulated; and the clinical effect is improved.
Humans ; Medicine, Chinese Traditional ; Intervertebral Disc Displacement/therapy* ; Meridians ; Acupuncture Therapy/methods* ; Vascular Surgical Procedures ; Acupuncture Points

The cases of feeling comfort during acupuncture and moxibustion treatment in literature were summarized and its biological basis was explored. A simple classification of comfort was made, and the importance of obtaining comfort in acupuncture treatment was pointed out. Considering the pursuit of less pain and harmlessness in modern clinical treatment, sugar needle should be advocated and popularized in current clinical practice of acupuncture and moxibustion.
Sugars ; Moxibustion ; Acupuncture Therapy ; Emotions ; Needles

AIM: To evaluate the efficacy and safety of different Conbercept treatment on diabetic macular edema(DME)with 3+PRN and 5+PRN.METHODS: Retrospective case-control study. A total of 51 patients(92 eyes)with DME who were treated in our hospital during December 2019 and June 2020 were included, and they were divided into 3+PRN group with 26 cases(48 eyes)and 5+PRN group with 25 cases(44 eyes). All patients received monthly follow-up for 12mo and the changes of best-corrected visual acuity(BCVA)and central macular thickness(CMT), the number of intravitreal injections and the occurrence of complications were compared and observed in the two groups.RESULTS:After follow-up for 12mo, there was no difference in the average injection times between the 3+PRN group and the 5+PRN group(7.24±0.91 times vs. 7.56±1.04 times, P=0.117). The BCVA and CMT of the two groups improved at 3, 6, 9, and 12mo after treatment compared with those before treatment(all P<0.05), and the BCVA and CMT of the 5+PRN group were better than those of the 3+PRN group at 6, 9, and 12mo after treatment(all P<0.05). During the follow-up period, no serious adverse events occurred in the two groups of patients, and the total incidence of ocular adverse events in the two groups was 27%. All adverse events were improved after symptomatic treatment.CONCLUSION: Both the 3+PRN and 5+PRN treatment strategy of Conbercept can treat DME safely and effectively, the total times of injection were comparable. However, the BCVA and CMT improved more in the 5+PRN group than that in 3+PRN group.

OBJECTIVE: To evaluate the expression level of melatonin and its effects on immune function in aplastic anemia (AA) patients. METHODS: The enzyme-linked immunosorbent assay (ELISA) was used to detect the plasma levels of melatonin in AA patients, and the correlation between melatonin levels and laboratory indexs was analyzed. The activation, proliferation, and apoptosis of T cells from AA patients were analyzed by flow cytometry with or without melatonin in vitro. RESULTS: The plasma levels of melatonin in AA patients were significantly lower compared with healthy controls (HC) (12.23 pg/ml vs 20.04 pg/ml, P < 0.01), while the plasma melatonin levels of AA patients in remission group after immunosuppressive therapy (IST) were significantly higher than those in non-remission group (29.16 pg/ml vs 11.73 pg/ml, P =0.04). Moreover, the melatonin levels were positively correlated with platelets (r =0.49), the absolute reticulocyte count (r =0.45), and the percentage of neutrophils (r =0.43). Meanwhile, there was a negative correlation between melatonin levels and the percentages of lymphocytes (r =-0.45). The expressions of CD25 and CD69 in both CD4⁺ and CD8⁺ T cells from AA patients were remarkably inhibited by melatonin in vitro (all P < 0.05). When cultured with melatonin, the proliferation rates of both CD4⁺ and CD8⁺ T cells from AA patients were markedly suppressed (P =0.01 andP < 0.01). CONCLUSION The plasma levels of melatonin were decreased in AA patients, which might play an important role in the mechanism of immunological abnormalities. The hyperimmune status of AA patients could be partially ameliorated by melatonin in vitro.
Humans ; Anemia, Aplastic ; CD8-Positive T-Lymphocytes ; Melatonin ; Blood Cell Count

Objective:To evaluate the residual risk (RR) of transfusion transmitted HIV (TT-HIV) after the implementation of nucleic acid amplification test (NAT) in blood screening test among blood centers in China.Methods:The data of blood donors and HIV infection markers from 2017 to 2020 were collected from 28 blood centers via the Platform of Comparison of blood establishments Practice in Chinese Mainland. The new infection rate/window period mathematical model was used for two types of blood screening strategies, namely, two rounds ELISA plus individual NAT take turn with pooling NAT (2ELISA+ ID-NAT/MP-NAT) and two ELISA plus one round pooling NAT (2ELISA+ MP-NAT), and the RR of HIV infection was estimated also based on first donors (FDs) and repeated donors (RDs) in different blood donation years. T-test analyses were conducted for comparing TT HIV RR among FDs and RDs in different blood donation years with two blood screening strategies, and the variation trend of RR in HIV test was observed.Results:From 2017 to 2020, the RR of FDs in 2ELISA+ ID-NAT/MP-NAT blood screening strategy was 2.869/10 6 person-year, 3.795/10 6 persons-year, 3.879/10 6 person-year, and 2.890/10 6 person-year respectively. The RR of RDs was 1.797/10 6 person-year, 1.502/10 6 person-year, 1.857/10 6 person-year, and 1.483/10 6 person-year respectively. Significant difference exists between RR of FDs and RDs, with F=9.898 and p<0.05. In 2ELISA+ MP-NAT strategy, the RR of FDs was 3.508/10 6 person-year, 1.868/10 6 person-year, 2.204/10 6 person-year, and 1.765/10 6 person-year respectively. The RR of RDs was 0.948/10 6 person-year, 0.926/10 6 person-year, 0.748/10 6 person-year, and 0.682/10 6 person-year respectively. Statistical difference existed between RR of FDs and RDs, with F=17.126 and P<0.05. There was no significant difference between the RR of FDs in these two strategies with F=3.493 and P>0.05, while there was a difference between the RR of RDs in these two strategies with F=24.516 and P<0.05, and a difference between the RR of total donors (TDs) in these two strategies F=20.216 and P<0.05. Conclusions:The RR of TT HIV significantly decreased after the introduction of NAT into blood test among blood centers in China. There were some differences in the RR of HIV testing among different blood screening strategies. There could be significant differences in the RR of HIV testing among different groups of blood donors. Compared with FDs, RDs is the low risk group for HIV.

Objective:To explore the difference of lymphocyte subsets in peripheral blood(PB)between aplastic anemia(AA)and hypoplastic myelodysplastic syndrome(hypo-MDS)patients,meanwhile to compare the clinical parameters obtained from PB and bone marrow(BM).Methods:The lymphocyte subsets in hypo-MDS(n=25)and AA(n=33)patients were investigated by flow cytometry.Meanwhile,the differences in PB cell counts,biochemical indicators,BM cell counts and abnormal chromosomes between the two groups were analyzed.Results:The percentage of CD8+T cells in A A group was significantly higher than that in hypo-MDS group(P=0.001),while the percentage of CD4+T cells and the CD4+/CD8+ratio in AA group were obviously lower than those in hypo-MDS group(P=0.015 and0.001,respectively).Furthermore,the proportion of CD4+andCD8+activated T(TA)cells,and memory Tregs in AA group was distinctly lower than those in hypo-MDS group(P=0.043,0.015 and 0.024,respectively).Nevertheless,the percentage of CD8+naive T(TN)cells in AA patients was remarkably higher(P=0.044).And hypo-MDS patients had declined lymphocyte counts(P=0.025),increased levels of total bilirubin(TBil),lactate dehydrogenase(LDH),vitamin B12 and proportion of BM blasts than AA patients(P=0.019,0.023,0.027 and 0.045,respectively).Conclusion:In this study it was confirmed that the percentages of CD4+and CD8+TA cells,memory Tregs and CD8+TN cells were significantly different between AA and hypo-MDS patients,which provide an essential basis for the identification of these two diseases.

Objective: To investigate the predictive value of blood cell parameters in children with vasovagal syncope (VVS). Methods: In this case-control study, the VVS group included 111 patients with unexplained syncope or prodromata who were diagnosed with VVS by head-up tilt test in the Second Xiangya Hospital, Central South University from January 2018 to October 2020, and 111 healthy children were enrolled as control. The differences in blood cell parameters between the 2 groups were compared by t test and Mann-Whitney U test. Multivariate binary Logistic regression was used to analyze the independent correlation factors of VVS, and receiver operating characteristic (ROC) curve to explore the predictive value of blood cell parameters for diagnosing VVS. Results: Sex composition ratios were consistent in the 2 groups (51 males vs. 60 females), while the age of the VVS group was higher than that of the control group (11.0 (8.0, 12.5) vs. 8.0 (7.0, 11.0) years, Z=4.39, P<0.001). Compared with the control group, VVS group had lower level of white blood cell (WBC) (6.0 (5.3, 7.1)×10⁹ vs. 8.6 (6.7, 10.1)×10⁹/L, Z=-7.96, P<0.001), lymphocyte (LY) (2.3 (1.9, 2.7)×10⁹ vs. 4.0 (2.8, 6.3)×10⁹/L, Z=-8.49, P<0.001), lymphocyte ratio (0.39 (0.33, 0.44) vs. 0.52 (0.37, 0.69), Z=-5.59, P<0.001), monocyte (0.3 (0.3, 0.4)×10⁹ vs. 0.4 (0.3, 0.6)×10⁹/L, Z=-6.19, P<0.001), eosinophil (0.1 (0.1, 0.2)×10⁹ vs. 0.2 (0.2, 0.4)×10⁹/L, Z=-5.75, P<0.001), mean corpuscular-hemoglobin concentration (MCHC) ((328±12) vs. (333±11) g/L, t=-3.27, P<0.001) and blood platelet (263 (235, 313)×10⁹ vs. 341 (295, 409)×10⁹/L, Z=-2.69, P<0.001), but higher neutrophil ratio (0.53 (0.48, 0.58) vs. 0.37 (0.22, 0.54), Z=5.86, P<0.001), hematocrit (0.39±0.04 vs. 0.37±0.04, t=2.75, P=0.006), mean corpuscular volume (MCV) (85 (82, 88) vs. 81 (78, 84) fl, Z=5.56, P<0.001), mean corpuscular hemoglobin (28 (27, 29) vs. 27 (26, 28) pg, Z=3.39, P=0.001), red cell distribution width (39 (37, 41) vs. 37 (36, 40) fl, Z=4.02, P<0.001) and mean platelet volume (11 (10, 11) vs. 10 (9, 11) fl, Z=2.81, P=0.005) levels. After adjusting for confounding factors such as sex and age, LY (OR=0.42, 95%CI 0.29-0.62, P<0.001), WBC (OR=0.75, 95%CI 0.59-0.95, P=0.015), MCHC (OR=0.94, 95%CI 0.91-0.97, P<0.001) were independent negative correlation factors of VVS, while MCV (OR=1.08, 95%CI 1.01-1.15, P=0.021) was independent positive correlation factor. ROC curve showed that the combination of LY, WBC, MCV and MCHC had acceptable predictive value for the diagnosis of VVS, with area under curve of 0.88, sensitivity of 0.80, specificity of 0.83, and Youden index of 0.63. Conclusions: Compared with healthy children, the blood cell parameters usually change in those with VVS. Combination of LY, WBC, MCHC and MCV can facilitate the diagnosis of VVS in children with unexplained syncope or prodromata.
Case-Control Studies ; Child ; Female ; Humans ; Lymphocytes ; Male ; Syncope ; Syncope, Vasovagal/diagnosis* ; Tilt-Table Test

Abstract: Objective To analyze the occupational hazards of enterprises in Pingshan district of Shenzhen in 2017. Methods Occupational hazards were analyzed in 200 enterprises in Pingshan district of Shenzhen City selected using stratified Results random sampling method. A total of 24 industries were involved in the 200 enterprises. The declaration rate of ， occupational hazards was 91.5% and the exposure rate of occupational hazards among workers was 49.2%. The regular monitoring rate of occupational hazard factors in workplaces of the enterprises was 79.5%. There were 129 kinds of occupational ， ， hazard factors of which 19 factors exceeded the national occupational exposure limit accounting for 14.7%. The over standard ， ， ， ， ， ， ， ， rates of noise silica dust cotton dust methanol toluene and other dust were 28.7% 13.6% 11.8% 5.86% 0.5% and ， ， 0.4% respectively. There were 13 kinds of occupational hazard factors in the workplace of metal products industry all of which （ ） exceeded the occupational exposure limit. The exposure rate 56.7% of occupational hazard factors in workers was the highest. Conclusion ， ， The main occupational hazard factors were noise dust and chemical factor and the major occupational hazard industry was metal manufacturing in Pingshan district of Shenzhen City.