The ventral anterior (VA) nucleus of the thalamus is a major target of the basal ganglia and is closely associated with the pathogenesis of Parkinson's disease (PD). Notably, the VA receives direct innervation from the hypothalamic histaminergic system. However, its role in PD remains unknown. Here, we assessed the contribution of histamine to VA neuronal activity and PD motor deficits. Functional magnetic resonance imaging showed reduced VA activity in PD patients. Optogenetic activation of VA neurons or histaminergic afferents significantly alleviated motor deficits in 6-OHDA-induced PD rats. Furthermore, histamine excited VA neurons via H1 and H2 receptors and their coupled hyperpolarization-activated cyclic nucleotide-gated channels, inward-rectifier K⁺ channels, or Ca²⁺-activated K⁺ channels. These results demonstrate that histaminergic afferents actively compensate for Parkinsonian motor deficits by biasing VA activity. These findings suggest that targeting VA histamine receptors and downstream ion channels may be a potential therapeutic strategy for PD motor dysfunction.
Animals ; Histamine/metabolism* ; Male ; Oxidopamine/toxicity* ; Rats ; Ventral Thalamic Nuclei/physiopathology* ; Rats, Sprague-Dawley ; Disease Models, Animal ; Parkinson Disease/metabolism* ; Neurons/physiology* ; Humans ; Optogenetics

Objective: The coronavirus disease 2019 (COVID-19) pandemic continues to present a major challenge to public health. Vaccine development requires an understanding of the kinetics of neutralizing antibody (NAb) responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: In total, 605 serum samples from 125 COVID-19 patients (from January 1 to March 14, 2020) varying in age, sex, severity of symptoms, and presence of underlying diseases were collected, and antibody titers were measured using a micro-neutralization assay with wild-type SARS-CoV-2. Results: NAbs were detectable approximately 10 days post-onset (dpo) of symptoms and peaked at approximately 20 dpo. The NAb levels were slightly higher in young males and severe cases, while no significant difference was observed for the other classifications. In follow-up cases, the NAb titer had increased or stabilized in 18 cases, whereas it had decreased in 26 cases, and in one case NAbs were undetectable at the end of our observation. Although a decreasing trend in NAb titer was observed in many cases, the NAb level was generally still protective. Conclusion We demonstrated that NAb levels vary among all categories of COVID-19 patients. Long-term studies are needed to determine the longevity and protective efficiency of NAbs induced by SARS-CoV-2.
Adult ; Aged ; Aged, 80 and over ; Antibodies, Neutralizing/immunology* ; Antibodies, Viral/immunology* ; COVID-19/immunology* ; Female ; Humans ; Kinetics ; Male ; Middle Aged ; Neutralization Tests ; SARS-CoV-2

The mammalian epididymis not only plays a fundamental role in the maturation of spermatozoa, but also provides protection against various stressors. The foremost among these is the threat posed by oxidative stress, which arises from an imbalance in reactive oxygen species and can elicit damage to cellular lipids, proteins, and nucleic acids. In mice, the risk of oxidative damage to spermatozoa is mitigated through the expression and secretion of glutathione peroxidase 5 (GPX5) as a major luminal scavenger in the proximal caput epididymidal segment. Accordingly, the loss of GPX5-mediated protection leads to impaired DNA integrity in the spermatozoa of aged Gpx5

AIM:To evaluate the feasibility and advantages of two-port 27-gauge pars plana vitrectomy for treatment of recurrent retinal detachment in silicone oil dwelling eyes.METHODS:A retrospective study.Two-port 27-gauge pars plana vitrectomy was performed in 7 eyes with recurrent retinal detachment without remove of silicone oil.Proliferative membrane peeling, endolaser treatment, and drainage of subretinal fluid were performed.Scleral bulking was performed if necessary.RESULTS:Sucessful retina re-attachment was accomplishied in all eyes.No visually significant intraoperative complication occurred.All eyes expericend quick recoveray of visual acuity and mild postoperative irritation.One eye developed a recurrent inferior retinal detchment in 20d after the surgery using non-remove technique, and recovered after conventional silicone oil removal and retinal reattachment surgery.CONCLUSION:Two-port 27-gauge pars plana vitrectomy is an efficacious (and potentially cost-efficient) method to treat early stage recurrent retinal detachment in silicone oil dwelling eyes.

OBJECTIVETo investigate the role and molecular mechanism of membrane-associated guanylate kinase inverted 3 (MAGI3) in glioma cell proliferation.

METHODSThe expression levels of MAGI3 and PTEN were assessed in glioma samples by Western blotting. MAGI3 was stably transfected into C6 glioma cells to obtain C6-MAGI3 cells. Then, the proliferation, the expression levels of MAGI3 and PTEN, and Akt phosphorylation were evaluated in C6 and C6-MAGI3 cells. Xenograft tumor models were established by subcutaneous injection of C6 and C6-MAGI3 cells into nude mice, and the growth rates of xenografts in the mice were compared. The potential role of MAGI3 expression in PI3K/Akt signaling activation was further investigated by examining the correlation between MAGI3 expression and the expression of PI3K/Akt signaling downstream target genes in a glioma dataset using gene set enrichment analysis (GSEA).

RESULTSExpression levels of MAGI3 and PTEN were significantly downregulated in gliomas. Overexpression of MAGI3 in the glioma C6 cell line upregulated PTEN protein expression, inhibited the phosphorylation of Akt, and suppressed cell proliferation. MAGI3 overexpression also inhibited the growth of C6 glioma tumor xenografts in nude mice. Analysis based on the GEO database confirmed the negative correlation between activation of PI3K/Akt pathway and MAGI3 mRNA levels in human glioma samples.

CONCLUSIONThe loss of MAGI3 expression in glioma may enhance the proliferation of glioma cells via downregulation of PTEN expression, leading to the activation of the PI3K/Akt pathway. MAGI3 is a potential glioma suppressor.

Animals ; Brain Neoplasms ; genetics ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; genetics ; Down-Regulation ; Glioma ; genetics ; metabolism ; pathology ; Humans ; Membrane Proteins ; genetics ; metabolism ; Mice, Nude ; PTEN Phosphohydrolase ; genetics ; metabolism ; Phosphatidylinositol 3-Kinases ; metabolism ; Phosphorylation ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats ; Signal Transduction ; Transfection ; Up-Regulation ; Xenograft Model Antitumor Assays

OBJECTIVETo investigate the clinicopathologic features, diagnosis and treatment of biliary intraductal papillary neoplasm (IPN-B).

METHODSThe clinical, histopathological, treatment and prognosis data of 23 patients with IPN-B treated from January 1998 to December 2007 were retrospectively analyzed.

RESULTSThere were 13 male and 10 female, aged from 30 to 80 years [mean age was (61 +/- 12) years]. The clinical manifestation included 10 cases with asymptomatic, 7 cases with abdominal pain, 4 cases with jaundice, 1 case with emaciation, and 1 case with acute cholangitis, respectively. Nine patients were also associated with hepatolithiasis. The average diameter of the tumors was (6 +/- 4) cm, 4 lesions were located in the right lobe, 15 in the left lobe, and 4 in the extrahepatic bile duct. Histopathologically, there were 4 adenomas, 1 borderline neoplasm, 6 carcinomas in situ, and 12 carcinomas. All patients received operation;the mean duration of follow-up was (33 +/- 28) months. Overall 3-year and 5-year survival rates of IPN-B were 85.3% and 68.2% respectively.

CONCLUSIONSIPN-B represents a distinct clinicopathologic entity. Favorable prognosis for IPN-B is offered by curative resection.

Adult ; Aged ; Aged, 80 and over ; Bile Duct Neoplasms ; pathology ; surgery ; Carcinoma, Papillary ; pathology ; surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Prognosis ; Retrospective Studies

OBJECTIVETo compare the efficiency of response evaluation by clinical examination, ultrasonograghy and mammography in neoadjuvant chemotherapy (NAC) for breast cancer.

METHODSA retrospective cohort study was conducted to analyze the data of 141 patients treated with neoadjuvant chemotherapy. Response evaluation was performed by clinical palpation, ultrasound and mammography.

RESULTSOnly 12 (8.5%) among the 141 patients presented with a stage I tumor. The tumor size determined by palpation was often larger than that by ultrasound before therapy (P < 0.01). Among patients with suspicions axillary nodes checked by ultrasound, 88.3% (53/60) of them had positive nodes by pathology before NAC, and 34.5% (10/29) of patients with negative nodes determined by ultrasound had positive nodes by pathology. In all the 141 patients, 21(14.9%) showed pathological complete remission in both the primary tumor and lymph node. For response evaluation, the false complete remission rate judged by clinical examination was 46.8% (22/47), and the false tumor residual rate by ultrasound was 84.0% (21/25). In 53.5% (23/43) of patients the response could not be assessed by mammography due to that the tumors were undistinguishable in size. The range of microcalcification was not reduced in 5 patients with a partial response of the tumor. 25 patients experienced needle puncture during therapy. Among them, in the 9 pathologically negative patients, only 3 achieved pCR, and the other 16 positive patients didn't achieve pCR.

CONCLUSIONUsing the puncture or sentinel lymph node biopsy, clinicians should pay enough emphasis on the pathological determination of the node status before chemotherapy. Clinicians will make a quite of false judgment of the tumor by clinical examination, ultrasound or mammography. They may use needle puncture during therapy to evaluate the response of neoadjuvant chemotherapy, and the result should be analyzed synthetically.

Adult ; Aged ; Aged, 80 and over ; Axilla ; Breast Neoplasms ; diagnostic imaging ; drug therapy ; pathology ; Carcinoma, Ductal, Breast ; diagnostic imaging ; drug therapy ; pathology ; Chemotherapy, Adjuvant ; Cohort Studies ; Female ; Humans ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Mammography ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Staging ; Remission Induction ; methods ; Retrospective Studies ; Sentinel Lymph Node Biopsy ; Ultrasonography

Objective To explore the possible role of voltage-gated potassium channel-interacting protein 1 (KChIP1) in the pathogenesis of epilepsy. Methods Sprague Dawley female adult rats were treated with pentylenettrazole (PTZ) to develop acute and chronic epilepsy models. The approximate coronal sections of normal and epilepsy rat brain were processed for immunohistochemistry. Double-labeling confocal microscopy was used to determine the coexistence of KChIP1 and gamma-aminobutyric acid (GABA). Results KChIP1 was expressed abundantly throughout adult rat brain. KChIP1 is highly co-localize with GABA transmitter in hippocampus and cerebral cortex. In the acute PTZ-induced convulsive rats, the number of KChIP1-postive cells was significantly increased especially in the regions of CA1 and CA3 (P < 0.05); whereas the chronic PTZ-induced convulsive rats were found no changes. The number of GABA-labeled and co-labeled neurons in the hippocampus appeared to have no significant alteration responding to the epilepsy-genesis treatments. Conclusion KChIP1 might be involved in the PTZ-induced epileptogenesis process as a regulator to neuronal excitability through influencing the properties of potassium channels. KChIP1 is preferentially expressed in GABAergic neurons, but its changes did not couple with GABA in the epileptic models.

OBJECTIVESTo evaluate if the humoral immune response of hepatitis B DNA vaccine pVAX1-S2S could be enhanced by Talpha1 and/or IFNa expression plasmid co-inoculated.

METHODSThe following mammalian expression recombinant plasmids were constructed: the plasmid pVAX1-S2S expressing hepatitis B surface antigen S2S, the plasmid pVAX1-T/I co-expressing thymosin a and IFNalpha, the plasmid pVAX1-I/S2S co-expressing IFNalpha and S2S. These plasmids were inoculated intramuscularly into several BALB/c mice groups in different combinations. In the co-immunization group 1 (pVAX1-I/S2S), each mouse was inoculated with 100 microg of pVAX1-I/S2S; in the co-immunization group 2 (pVAX1-S2S) each mouse was co-inoculated with pVAX1-S2S and 50 microg of pVAX1-TI; in the control group each mouse was inoculated with 100 microg of pVAX1-S2S. All the immunizations were boosted at 2 and 4 week intervals; then the serum samples were collected to detect the anti-HBs and anti-preS2 strengths.

RESULTS3, 5 and 8 weeks after the first inoculation, the positive rates of anti-HBs were 12.5%, 12.5%, 62.5% respectively in the co-immunization group 1 and 25%, 50%, 50% in the co-immunization group 2, while those in the control group were 0, 25%, 37.5%. The titers of anti-preS2 in co-immunization group 2 was 5 times higher than those in the other two groups.

CONCLUSIONThe data shows that Talpha1 and/or IFNalpha expression plasmid co-inoculated with pVAX1-S2S might act as an adjuvant to enhance the humoral immune response induced by pVAX1-S2S.

Adjuvants, Immunologic ; genetics ; therapeutic use ; Animals ; Female ; Hepatitis B ; immunology ; therapy ; Hepatitis B Vaccines ; immunology ; therapeutic use ; Interferon-alpha ; genetics ; immunology ; Mice ; Mice, Inbred BALB C ; Recombinant Fusion Proteins ; immunology ; Thymosin ; genetics ; immunology ; Vaccines, DNA ; immunology

Adult ; Female ; Hepatitis B, Chronic ; complications ; surgery ; Humans ; Liver Cirrhosis ; etiology ; surgery ; Liver Neoplasms ; surgery ; virology ; Liver Transplantation ; Male ; Middle Aged ; Postoperative Complications ; etiology ; Recurrence