A circuit from lateral hypothalamic to dorsal hippocampal dentate gyrus modulates behavioral despair in mice.

Behavioral despair is one of the clinical manifestations of major depressive disorder and an important cause of disability and death. However, the neural circuit mechanisms underlying behavioral despair are poorly understood. In a well-established chronic behavioral despair (CBD) mouse model, using a combination of viral tracing, in vivo fiber photometry, chemogenetic and optogenetic manipulations, in vitro electrophysiology, pharmacological profiling techniques, and behavioral tests, we investigated the neural circuit mechanisms in regulating behavioral despair. Here, we found that CBD enhanced CaMKIIα neuronal excitability in the dorsal dentate gyrus (dDG) and dDGCaMKIIα neurons involved in regulating behavioral despair in CBD mice. Besides, dDGCaMKIIα neurons received 5-HT inputs from median raphe nucleus (MRN) and were mediated by 5-HT1A receptors, whereas MRN5-HT neurons received CaMKIIα inputs from lateral hypothalamic (LH) and were mediated by AMPA receptors to regulate behavioral despair. Furthermore, fluvoxamine exerted its role in resisting behavioral despair through the LH-MRN-dDG circuit. These findings suggest that a previously unidentified circuit of LHCaMKIIα-MRN5-HT-dDGCaMKIIα mediates behavioral despair induced by CBD. Furthermore, these support the important role of AMPA receptors in MRN and 5-HT1A receptors in dDG that might be the potential targets for treatment of behavioral despair, and explain the neural circuit mechanism of fluvoxamine-resistant behavioral despair.

Confidential multiple-input multiple-output optical camera communication aided by a two-dimensional pilot.

Optical camera communication (OCC) has attracted increased attention for its inherent security advantage. However, there still exists the risk of eavesdropping on the broadcasting channel of OCC. To achieve confidential communication, we propose the confidentiality-interference dual light-emitting diode (LED) communication (CIDLC) scheme at the transmitter (TX) and elimination of interference (EI) scheme at the receiver (RX). Meanwhile, interference signals refer to the bit shift of confidential signals. Further, we propose the two-dimensional pilot-aided channel estimation (2D-PACE) scheme to enhance the reliability of multiple-input multiple-output (MIMO) OCC. Experiment results validate the effectiveness of our schemes, which guarantee confidentiality while performing well at a 2 m non-line-of-sight (NLOS) distance. Finally, the communication-illumination integration OCC is constructed via the energy equalization coding (EEC) scheme.

Chronic nicotine exposure elicits pain hypersensitivity through activation of dopaminergic projections to anterior cingulate cortex.

BACKGROUND: Cigarette smoking is commonly reported among chronic pain patients in the clinic. Although chronic nicotine exposure is directly linked to nociceptive hypersensitivity in rodents, underlying neurobiological mechanisms remain unknown. METHODS: Multi-tetrode recordings in freely moving mice were used to test the activity of dopaminergic projections from the ventral tegmental area (VTA) to pyramidal neurones in the anterior cingulate cortex (ACC) in chronic nicotine-treated mice. The VTA→ACC dopaminergic pathway was inhibited by optogenetic manipulation to detect chronic nicotine-induced allodynia (pain attributable to a stimulus that does not normally provoke pain) assessed by von Frey monofilaments (force units in g). RESULTS: Allodynia developed concurrently with chronic (28-day) nicotine exposure in mice (0.36 g [0.0141] vs 0.05 g [0.0018], P<0.0001). Chronic nicotine activated dopaminergic projections from the VTA to pyramidal neurones in the ACC, and optogenetic inhibition of VTA dopaminergic terminals in the ACC alleviated chronic nicotine-induced allodynia in mice (0.06 g [0.0064] vs 0.28 g [0.0428], P<0.0001). Moreover, optogenetic inhibition of Drd2 dopamine receptor signalling in the ACC attenuated nicotine-induced allodynia (0.07 g [0.0082] vs 0.27 g [0.0211], P<0.0001). CONCLUSIONS: These findings implicate a role of Drd2-mediated dopaminergic VTA→ACC pathway signalling in chronic nicotine-elicited allodynia.

Biosynthesis of silver nanoparticles using Burkholderia contaminans ZCC and mechanistic analysis at the proteome level.

The biogenic synthesis of silver nanoparticles (AgNPs) by microorganisms has been a subject of increasing attention. Despite extensive studies on this biosynthetic pathway, the mechanisms underlying the involvement of proteins and enzymes in AgNPs production have not been fully explored. Herein, we reported that Burkholderia contaminans ZCC was able to reduce Ag+ to AgNPs with a diameter of (10±5) nm inside the cell. Exposure of B. contaminans ZCC to Ag+ ions led to significant changes in the functional groups of cellular proteins, with approximately 5.72% of the (C-OH) bonds being converted to (C-C/C-H) (3.61%) and CO (2.11%) bonds, and 4.52% of the CO (carbonyl) bonds being converted to (C-OH) bonds. Furthermore, the presence of Ag+ and AgNPs induced the ability of extracellular electron transfer for ZCC cells via specific membrane proteins, but this did not occur in the absence of Ag+ ions. Proteomic analysis of the proteins and enzymes involved in heavy metal efflux systems, protein secretion system, oxidative phosphorylation, intracellular electron transfer chain, and glutathione metabolism suggests that glutathione S-transferase and ubiquinol-cytochrome c reductase iron-sulfur subunit play importance roles in the biosynthesis of AgNPs. These findings contribute to a deeper understanding of the functions exerted by glutathione S-transferase and ferredoxin-thioredoxin reductase iron-sulfur subunits in the biogenesis of AgNPs, thereby hold immense potential for optimizing biotechnological techniques aimed at enhancing the yield and purity of biosynthetic AgNPs.

Microglia sustain anterior cingulate cortex neuronal hyperactivity in nicotine-induced pain.

BACKGROUND: Long-term smoking is a risk factor for chronic pain, and chronic nicotine exposure induces pain-like effects in rodents. The anterior cingulate cortex (ACC) has been demonstrated to be associated with pain and substance abuse. This study aims to investigate whether ACC microglia are altered in response to chronic nicotine exposure and their interaction with ACC neurons and subsequent nicotine-induced allodynia in mice. METHODS: We utilized a mouse model that was fed nicotine water for 28 days. Brain slices of the ACC were collected for morphological analysis to evaluate the impacts of chronic nicotine on microglia. In vivo calcium imaging and whole-cell patch clamp were used to record the excitability of ACC glutamatergic neurons. RESULTS: Compared to the vehicle control, the branch endpoints and the length of ACC microglial processes decreased in nicotine-treated mice, coinciding with the hyperactivity of glutamatergic neurons in the ACC. Inhibition of ACC glutamatergic neurons alleviated nicotine-induced allodynia and reduced microglial activation. On the other hand, reactive microglia sustain ACC neuronal excitability in response to chronic nicotine, and pharmacological inhibition of microglia by minocycline or liposome-clodronate reduces nicotine-induced allodynia. The neuron-microglia interaction in chronic nicotine-induced allodynia is mediated by increased expression of neuronal CX3CL1, which activates microglia by acting on CX3CR1 receptors on microglial cells. CONCLUSION: Together, these findings underlie a critical role of ACC microglia in the maintenance of ACC neuronal hyperactivity and resulting nociceptive hypersensitivity in chronic nicotine-treated mice.

RNase D Is Involved in 5S rRNA Degradation and Exopolysaccharide Production in Xanthomonas campestris pv. campestris.

Ribonucleases (RNases) play critical roles in RNA metabolism and are collectively essential for cell viability. However, most knowledge about bacterial RNases comes from the studies on Escherichia coli; very little is known about the RNases in plant pathogens. The crucifer black rot pathogen Xanthomonas campestris pv. campestris (Xcc) encodes 15 RNases, but none of them has been functionally characterized. Here, we report the physiological function of the exoribonuclease RNase D in Xcc and provide evidence demonstrating that the Xcc RNase D is involved in 5S rRNA degradation and exopolysaccharide (EPS) production. Our work shows that the growth and virulence of Xcc were not affected by deletion of RNase D but were severely attenuated by RNase D overexpression. However, deletion of RNase D in Xcc resulted in a significant reduction in EPS production. In addition, either deletion or overexpression of RNase D in Xcc did not influence the tRNAs tested, inconsistent with the finding in E. coli that the primary function of RNase D is to participate in tRNA maturation and its overexpression degrades tRNAs. More importantly, deletion, overexpression, and in vitro enzymatic analyses revealed that the Xcc RNase D degrades 5S rRNA but not 16S and 23S rRNAs that share an operon with 5S rRNA. Our results suggest that Xcc employs RNase D to realize specific modulation of the cellular 5S rRNA content after transcription and maturation whenever necessary. The finding expands our knowledge about the function of RNase D in bacteria.

Anti-CASPR2 encephalitis in a liver posttransplant patient receiving immune-suppression and lenvatinib: a case report and literature review.

It has been assumed that patients with strict immunosuppressive treatment after solid organ transplantation have only marginal risk in developing autoimmune encephalitis. We reported a woman in her late 40 s who presented with generalized convulsions and loss of consciousness. After detailed history review, neuropsychological tests, metagenomic next-generation sequencing of serum and cerebrospinal fluid (CSF), magnetic resonance imaging (MRI) brain, and electroencephalogram, she was diagnosed as anti-CASPR2 encephalitis based on the positive anti-CASPR2 auto-antibody in serum and CSF. The patient underwent liver transplantation and has taken lenvatinib for 2 months, in addition to tacrolimus, mycophenotale mofetil, and entecavir administered for half a year. This case was the first report of anti-CASPR2 encephalitis in post-organ transplantation patients. Together with the reports of other encephalitis cases in organ transplantation, it warns the possibility of developing immune-oriented encephalitis in patients undergoing immunosuppression, especially in combination with other treatments of immunomodulatory activity.

Saponins from Panax japonicus improve neuronal mitochondrial injury of aging rats.

CONTEXT: Panax japonicus is the dried rhizome of Panax japonicus C.A. Mey. (Araliaceae). Saponins from Panax japonicus (SPJ) exhibit anti-oxidative and anti-aging effects. OBJECTIVE: We evaluated the neuroprotective effects of SPJ on aging rats. MATERIALS AND METHODS: Sprague-Dawley rats (18-months-old) were randomly divided into aging and SPJ groups (n = 8). Five-month-old rats were taken as the adult control (n = 8). The rats were fed a normal chow diet or the SPJ-containing diet (10 or 30 mg/kg) for 4 months. An in vitro model was established by d-galactose (d-Gal) in the SH-SY5Y cell line and pretreated with SPJ (25 and 50 µg/mL). The neuroprotection of SPJ was evaluated via Nissl staining, flow cytometry, transmission electron microscopy and Western blotting in vivo and in vitro. RESULTS: SPJ improved the neuronal degeneration and mitochondrial morphology that are associated with aging. Meanwhile, SPJ up-regulated the protein levels of mitofusin 2 (Mfn2) and optic atrophy 1 (Opa1) and down-regulated the protein level of dynamin-like protein 1 (Drp1) in the hippocampus of aging rats (p < 0.05 or p < 0.01 vs. 22 M). The in vitro studies also demonstrated that SPJ attenuated d-Gal-induced cell senescence concomitant with the improvement in mitochondrial function; SPJ, also up-regulated the Mfn2 and Opa1 protein levels, whereas the Drp1 protein level (p < 0.05 or p < 0.01 vs. d-Gal group) was down-regulated. DISCUSSION AND CONCLUSIONS: Further research on the elderly population will contribute to the development and utilization of SPJ for the treatment of neurodegenerative disorders.

Involvement of Macrophages and Spinal Microglia in Osteoarthritis Pain.

PURPOSE OF REVIEW: Chronic pain in osteoarthritis (OA) is characterized by pain sensitization, which involves both peripheral and central mechanisms. Studies suggest synovial macrophage and spinal microglia are implicated in pain sensitization in OA. We, therefore, reviewed the evidence of whether synovial macrophage and spinal microglia facilitated pain sensitization at diverse levels and how this event occurred in OA. RECENT FINDINGS: Peripherally, joint inflammation is now believed to be a source of OA-related pain. Synovial macrophages accumulate in OA inflamed synovium and display a pro-inflammatory phenotype. Abundant macrophage-derived pro-inflammatory cytokines and other pain-causing substance facilitate hyperexcitation of primary sensory neuron in OA-related pain. Thus, activated synovial macrophage was considered a predictor for phenotyping of OA pain clinically. In response to affected joint-derived strong nociception, aberrant neuronal excitability is often associated with the hyperactivity of microglia in the spinal dorsal horn, thereby leading to central sensitization. Hyperactivity of synovial macrophage and spinal microglia underlies the mechanisms of pain sensitization at the peripheral and central level in OA. This concept provides not only a clinically relevant strategy for identifying the phenotype of OA-related pain but also has the potential to develop individualized interventions for OA, particularly in those patients with hyperactivity of macrophage and microglia.

Saponins from Panax japonicus attenuate cognitive impairment in ageing rats through regulating microglial polarisation and autophagy.

CONTEXT: Panax japonicus is the dried rhizome of Panax japonicus C.A. Mey. (Araliaceae). Saponins from Panax japonicus (SPJ) exhibit anti-inflammatory and antioxidative effects. OBJECTIVE: To explore the neuroprotective effect of SPJ on natural ageing of rat. MATERIALS AND METHODS: Sprague-Dawley (SD) rats 18-month-old were divided into ageing control, ageing treated with SPJ 10 or 30 mg/kg (n = 8). Five-month-old rats were taken as the adult control (n = 8). Rats were fed regular feed or feed containing SPJ for 4 months. Cognitive level was evaluated by Morris water maze (MWM) test. The mechanisms of SPJ's neuroprotection were evaluated by transmission electron microscope, western blot analysis, and immunofluorescence in vivo and in vitro. RESULTS: SPJ attenuated ageing-induced cognitive impairment as indicated by elevated number of times crossing the target platform (from 1.63 to 3.5) and longer time spent in the target platform quadrant (from 1.33 to 1.98). Meanwhile, SPJ improved the morphology of microglia and synapse, and activated M2 microglia polarisation including increased hippocampus levels of CD206 (from 0.98 to 1.47) and YM-1 (from 0.67 to 1.1), and enhanced autophagy-related proteins LC3B (from 0.48 to 0.82), Beclin1 (from 0.32 to 0.51), Atg5 (from 0.22 to 0.89) whereas decreased p62 level (from 0.71 to 0.45) of ageing rats. In vitro study also showed that SPJ regulated the microglial polarisation and autophagy. DISCUSSION AND CONCLUSIONS: SPJ improved cognitive deficits of ageing rats through attenuating microglial inflammation and enhancing microglial autophagy, which could be used to treat neurodegenerative disorders.

Clinical efficacy and safety of aidi injection combination with vinorelbine and cisplatin for advanced non-small-cell lung carcinoma: A systematic review and meta-analysis of 54 randomized controlled trials.

The Aidi injection contains multiple active ingredients, including astragaloside (Re, Rb1, and Rg1), ginsenoside, cantharidin, elentheroside E, and syringin, and it is administered with vinorelbine and cisplatin (NP) to treat non-small-cell lung carcinoma (NSCLC). In this study, we performed a systematic review and meta-analysis to determine the clinical efficacy and safety of the Aidi injection with NP, and the optimal threshold and treatment regimen to produce the desired responses. We collected all studies regarding the Aidi injection with NP for NSCLC from Chinese and English databases (up to April 2019). Risk of methodological bias was evaluated for each study. Data for analysis were extracted using a standard data extraction form. Evidence quality was assessed following the Grading of Recommendations Assessment, Development and Evaluation approach. We included 54 trials containing 4,053 patients for analysis. Combining the Aidi injection with NP significantly increased the objective response rate (odds ratio [OR], 1.32; confidence interval [CI], 1.23, 1.42), disease control rate (OR, 1.14; CI, 1.11, 1.18), and quality of life (OR, 1.80; CI, 1.61, 1.98), with decreased risks of myelosuppression, neutropenia, thrombocytopenia, anemia, gastrointestinal reaction, and liver dysfunction. For patients with a Karnofsky Performance Status score of ≥60, the Aidi injection (50 mL/day, two weeks/cycle, with two to three cycles) treatment with vinorelbine (25 mg/m2) and cisplatin (30-35 mg/m2 or 40-50 mg/m2) might be the optimal regimen for producing the desired tumor response and achieving a good safety level. Most results were robust, and their quality was moderate. The results suggest that administration of the Aidi injection and concomitant NP is beneficial to NSCLC, and provide evidence for the optimal threshold and treatment regimen that may improve tumor response with a good safety level.

Intraoperative Flurbiprofen Treatment Alters Immune Checkpoint Expression in Patients Undergoing Elective Thoracoscopic Resection of Lung Cancer.

OBJECTIVES: This study aimed to determine the effect of intraoperative administration of flurbiprofen on postoperative levels of programmed death 1 (PD-1) in patients undergoing thoracoscopic surgery. MATERIALS AND METHODS: In this prospective double-blind trial, patients were randomized to receive intralipid (control group, n = 34, 0.1 mL/kg, i.v.) or flurbiprofen axetil (flurbiprofen group, n = 34, 50 mg, i.v.) before induction of anesthesia. PD-1 levels on T cell subsets, inflammation, and immune markers in peripheral blood were examined before the induction of anesthesia (T0) and 24 h (T1), 72 h (T2), and 1 week (T3) after surgery. A linear mixed model was used to determine whether the changes from baseline values (T0) between groups were significantly different. RESULTS: The increases in the percentage of PD-1(+)CD8(+) T cells observed at T1 and T2 in the control group were higher than those in the flurbiprofen group (T1: 12.91 ± 1.65 vs. 7.86 ± 5.71%, p = 0.031; T2: 11.54 ± 1.54 vs. 8.75 ± 1.73%, p = 0.004), whereas no differences were observed in the changes in the percentage of PD-1(+)CD4(+) T cells at T1 and T2 between the groups. Moreover, extensive changes in the percentage of lymphocyte subsets and inflammatory marker concentrations were observed at T1 and T2 after surgery and flurbiprofen attenuated most of these changes. CONCLUSIONS: Perioperative administration of flurbiprofen attenuated the postoperative increase in PD-1 levels on CD8(+) T cells up to 72 h after surgery, but not after this duration. The clinical relevance of changes in PD-1 levels to long-term surgical outcome remains unknown.

[Study on rapid quality analysis method of Shengxuebao Mixture].

A rapid analysis method based on ultraviolet-visual(UV-Vis) spectroscopy, near infrared(NIR) spectroscopy and multivariable data analysis was established for quality evaluation of Shengxuebao Mixture. The contents of eight active ingredients of Shengxuebao Mixture including albiflorin, paeoniflorin, 2, 3, 5, 4'-tetra-hydroxy-stilbene-2-O-ß-D-glucopyranoside, specnuezhenide,ecliptasaponin D, emodin, calycosin-7-glucoside and astragaloside Ⅳ were simultaneously detected by using this method. HPLC-UV-MS was used as a reference method for determining the contents of these ingredients. Partial least squares(PLS) analysis was implemented as a linear method for multivariate models calibrated between UV spectrum/NIR spectrum and contents of 8 ingredients. Finally, the performance of the model was evaluated by 24 batches of test samples. The results showed that both UV-Vis and NIR models gave a good calibration ability with an R~2 value above 0.9, and the prediction ability was also satisfactory, with an R~2 value higher than 0.83 for UV-Vis model and higher than 0.79 for NIR model. The overall results demonstrate that the established method is accurate, robust and fast, therefore, it can be used for rapid quality evaluation of Shengxuebao Mixture.

Renin-angiotensin-system, a potential pharmacological candidate, in acute respiratory distress syndrome during mechanical ventilation.

While effective treatments for acute respiratory distress syndrome (ARDS) are lacking, mechanical lung ventilation can sustain adequate gas exchange in critically ill patients with respiratory failure due to ARDS. However, as a result of the phenomenon of ventilator-induced lung injury (VILI), there is an increasing need to seek beneficial pharmacological therapies for ARDS. Recent studies have suggested the renin-angiotensin system (RAS), which consists of the ACE/Ang-II/AT1R axis and ACE2/Ang-(1-7)/MasR axis, plays a dual role in the pathogenesis of ARDS and VILI. This review highlights the deleterious action of ACE/Ang-II/AT1R axis and the beneficial role of ACE2/Ang-(1-7)/MasR axis, as well as AT2R, in VILI and ARDS, and also discusses the possibility of targeting RAS components with pharmacological interventions to improve outcomes in ARDS.

Limited sampling strategy for the estimation of the area under the concentration-time curve for ganciclovir in Chinese adult renal allograft recipients.

OBJECTIVES: Valganciclovir (VGCV) treatment is recommended for the prevention of cytomegalovirus (CMV) infection in renal allograft recipients. The aim of the present study is to investigate the pharmacokinetic characteristics of ganciclovir (GCV) after administration of VGCV in Chinese adult renal allograft recipients and estimate the exposure to GCV using limited sampling strategy (LSS). METHODS: Forty Chinese renal allograft recipients were given 450 mg or 900 mg VGCV daily. Blood samples were drawn before treatment and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 h after 5 days of VGCV therapy, and the plasma concentrations of VGCV and GCV were determined using a liquid chromatography-mass spectrometry assay. The major pharmacokinetic parameters for GCV and VGCV were determined using a noncompartmental assay. Multiple stepwise linear regression analysis was conducted to establish a model equation for the estimation of the GCV AUC0-24 h in Chinese patients using LSS. RESULTS: In the 450 and 900 mg groups, the Cmax for VGCV was 0.2 ± 0.10 and 0.4 ± 0.16 mg/L, respectively; the Cmax for GCV was 4.2 ± 1.1 and 8.6 ± 1.6 mg/L, respectively; and the AUC0-24 h for GCV was 28.4 ± 8.4 and 60.7 ± 17.5 mg·h/L, respectively. For the establishment of LSS models, 40 patients were divided into the training group (n = 24) and validation group (n = 16). The model equations used for the calculation of AUC0-24 h for GCV were established in the training group by using multiple linear regression assay. Equations including AUC = 8.1 + 29.7 × C0 + 5.7 × C4 (r2 = 0.91) and AUC = - 0.4 + 11.0 × C0 + 2.1 × C2 + 13.7 × C8 (r2 = 0.98) were acceptable. The %MPE and %MAPE values obtained from the validation group for the two model equations were 5.89 ± 14.5% and 12.1 ± 9.53%, and - 1.30 ± 4.40% and 3.28 ± 3.11%, respectively. CONCLUSIONS: The LSS models that included C0 and C4 or C0, C2, and C8 in the estimation of AUC0-24 h for GCV had favorable performance and can be used for therapeutic drug monitoring in the prevention of CMV infection using VGCV in Chinese renal allograft recipients.

Protein binding hot spots prediction from sequence only by a new ensemble learning method.

Hot spots are interfacial core areas of binding proteins, which have been applied as targets in drug design. Experimental methods are costly in both time and expense to locate hot spot areas. Recently, in-silicon computational methods have been widely used for hot spot prediction through sequence or structure characterization. As the structural information of proteins is not always solved, and thus hot spot identification from amino acid sequences only is more useful for real-life applications. This work proposes a new sequence-based model that combines physicochemical features with the relative accessible surface area of amino acid sequences for hot spot prediction. The model consists of 83 classifiers involving the IBk (Instance-based k means) algorithm, where instances are encoded by important properties extracted from a total of 544 properties in the AAindex1 (Amino Acid Index) database. Then top-performance classifiers are selected to form an ensemble by a majority voting technique. The ensemble classifier outperforms the state-of-the-art computational methods, yielding an F1 score of 0.80 on the benchmark binding interface database (BID) test set. AVAILABILITY: http://www2.ahu.edu.cn/pchen/web/HotspotEC.htm .

[Treatments of stage-Is testicular mixed germ cell tumors: A report of 3 cases].

OBJECTIVE: To investigate different treatment methods for stage-Is testicular mixed germ cell tumors (TMGCTs). METHODS: We retrospectively analyzed the clinical data about 3'cases of stage-Is TMGCTs (aged 26-39 years) treated in the 175th Hospital of PLA, reviewed relevant literature, and explored the clinical characteristics of TMGCTs. RESULTS: Of the 3 patients, 1 was treated by radical orchiectomy, 1 by radical orchiectomy + retroperitoneal lymph node dissection + BEP chemotherapy scheme, and the other by radical orchiectomy + radiotherapy. The pathological components of TMGCTs were immature teratoma, seminoma, spermatocytoma, chorioepithelioma, embryonal carcinoma, and yolk sac tumor. No recurrence or distant metastasis was found during the 24-month follow-up after surgery. CONCLUSION: The diagnosis of TMGCTs primarily depends on physical examination, ultrasonography, MRI, and measurement of serum tumor markers, while its confirmation necessitates pathological examination, and its treatment is basically radical orchiectomy.

[Functions of T lymphocytes mediated by in vitro dendritic cells of chronic HBV infection patients in different immune states: a clinical research].

OBJECTIVE: To explore the improvement of dendritic cells' (DCs) functions in chronic hepatitis B (CHB) patients by two different drugs plasma, i.e., Shen supplementing and detoxification (SSD) and Pi invigorating and detoxification (PID), thus comparing which method was more effective to activate DCs to improve T lymphocyte functions. METHODS: Totally 30 CHB outpatients were recruited. They were assigned to the immune tolerant group and the immune clearance group, 15 in each group. Totally 60 mL peripheral blood was extracted to isolate and develop mature DCs. Chinese compound containing (Liuwei Ganlu Syrup for SSD) and (Sijun Ganlu Syrup for PID) plasma were added to promote the maturation of DCs on the 7th day. Besides, non-drug plasma was taken as the control. On the ninth day, HBV core 18-27 loaded core peptide and its own T lymphocyte were co-cultivated for 72 h. Then T lymphocytes were collected. The expression levels of CD3, CD28, CD4, and CD8, programmed death-1 (PD-1) were detected using flow cytometry. RESULTS: Compared with non-drug plasma, the expression levels of CD3, CD4, and CD28 could be improved, and the expression levels of CD8 and PD-1 could be reduced by the two methods, showing statistical difference (P < 0.05). Besides, SSD containing plasma showed better effect in improving the molecular CD28 expression rate, and reducing the molecular PD-1 expression rate on the T cell surface, showing statistical difference when compared with that of PID containing plasma (P < 0.05). CONCLUSIONS: In vitro intervention of DCs by SSD and PID containing plasmas combined co-cultivation of its own T lymphocytes could promote the activation of DCs to improve the function of T cells and the expression of T cell surface molecules. Besides, SSD showed more significant effect on infection immune of HBV patients in the tolerance stage.

Application of transgenic mice to the molecular pathogenesis of cataract.

One of the most prevalent disorders that cause blindness worldwide is cataract, and its essence is the visual disorder caused by the opacity of the lens. The significant degree of variation in cataracts and the fact that a variety of factors can impact a patient's lens transparency make it especially crucial to investigate the pathogenesis of cataracts at the molecular level. It has been found that more than 60 genes are linked to the formation of cataracts, and the construction of a transgenic mouse model of cataract similar to the selection of human lens clouding due to a variety of causes has become an important means of studying the pathogenesis of cataract. Therefore, the research on the application of transgenic mice to the molecular pathogenesis of cataracts will be the main topic of this review of the literature.