Human herpesvirus 7 meningitis in an adolescent with normal immune function: A case report.

BACKGROUND: Human herpesvirus type 7 (HHV-7) is a less common herpes virus that usually causes mild, self-limiting illnesses. However, in recent years, there have been increasing reports of HHV-7 causing serious central nervous system infections, especially meningitis. The pathogenesis and clinical features of HHV-7 meningitis, particularly in adolescents with normal immune function, remain incompletely studied. Therefore, the purpose of this report is to share a case of HHV-7 meningitis in an immunocompetent adolescent with a view to deepening our understanding of the disease. CASE SUMMARY: A 12-year-old female was admitted with fever, headache, and vomiting. 4 d before admission, the patient developed a fever without obvious induction, with a temperature up to 39.5 °C, no convulsions, accompanied by chills, headaches, fatigue, and no muscle aches. The patient was treated with fever reduction, which could be reduced to 38 °C; repeated high fever, accompanied by vomiting 7-8 times; and no abdominal pain or diarrhea. The patient was diagnosed with "acute suppurative tonsillitis" in a local hospital, and the blood routine was generally normal. The patient was given symptomatic support treatment such as "ceftriaxone sodium" and antiemetic rehydration for 2 d, and his condition did not improve. The patient's physical examination showed pharyngeal congestion, bilateral tonsil grade I hypertrophy, regression of purulent secretions, and cervical resistance. Ocular B-ultrasound: Opacity of the vitreous body and edema of the optic disc in both eyes. Optical coherence tomography examination showed that the macular fovea was generally normal in both eyes, with edema of the optic disc. DNA virus monitoring results: HHV-7. We gave ganciclovir antiviral therapy, dexamethasone anti-inflammatory treatment, mannitol to reduce cranial pressure, omeprazole to protect gastrointestinal mucosa, and calcium and potassium supplementation. CONCLUSION: This study reports a case of HHV-7 meningitis in an adolescent with normal immune function. Through comprehensive analysis of the clinical manifestations, laboratory tests, and treatment methods of the patient, it is found that early identification and antiviral treatment are essential for the outcome of the disease. This case suggests that despite normal immune function, adolescents may still suffer from herpes virus type 7 meningitis, so clinicians should be vigilant and take effective treatment measures in time.

γ-aminobutyric acid alleviates LPS-induced acute lung injury in mice through upregulating type B receptors.

Introduction: In recent years, studies have shown that GABA has a certain therapeutic effect on acute lung injury (ALI), but its specific mechanism has not been fully elucidated. The study was designed to investigate the protective effect and mechanism of γ-aminobutyric acid (GABA) on ALI induced by lipopolysaccharide (LPS) in mice. Material and methods: C57BL/6 mice were randomly divided into a control group, LPS group, LPS + GABA (10 mg/kg) group and LPS + dexamethasone (Dex, 5 mg/kg) group. The survival rate of each group was observed at different time points after modeling. The levels of tumor necrosis factor α (TNF-α), interleukin (IL) 1ß, 10, myeloperoxidase (MPO) and the cell count and protein concentration in bronchoalveolar lavage fluid (BALF) were measured. Lung histopathology and the expression of GABA receptors were observed by HE staining and immunohistochemistry respectively. Lung water content was assessed by wet-dry weight ratio. Results: GABA could significantly improve the survival rate and prolong the survival time of animals, alleviate the degree of inflammatory injury and pulmonary edema, reduce the content of MPO, down-regulate the levels of pro-inflammatory cytokines IL-1ß and TNF-α, and up-regulate the expression of anti-inflammatory cytokine IL-10. Moreover, GABA could significantly decrease the expression of type A receptors and enhance type B receptors. Conclusions: GABA can effectively alleviate ALI induced by LPS in mice, and its effect may be related to the upregulation of type B receptors.

The Effect of Behavior Couples Therapy on Alcohol and Drug Use Disorder: a Systematic Review and Meta-Analysis.

AIMS: Behavior couples therapy (BCT) is widely considered to be effective in the treatment of substance use disorders. However, the effect size of BCT in different outcome measures, and at different time points requires further study to prove it. METHODS: Systematic searches were performed in various databases. Ultimately, we identified 12 studies, involving 19 randomized controlled trials. We used Hedges' g as the effect size, and all pooled analyses were performed using random-effects models. RESULTS: After treatment, BCT was superior to control conditions (either an active or inactive control group) in frequency of substance use (g = 0.17), substance use consequences (g = -0.28) and relationship satisfaction (g = 0.45). After a 12-month follow-up, BCT remained superior to control conditions in frequency of substance use (g = 0.32), substance use consequences (g = -0.34) and relationship satisfaction (g = 0.31). In addition, BCT was more effective in reducing the frequency of substance use than individual-based treatment (IBT) (g = 0.23). There was no significant relationship between the effect size of BCT and publication year (t = 0.92, P = 0.372), percentage of females (t = -0.02, P = 0.987) or the number of treatment sessions (t = -0.52, P = 0.609). CONCLUSIONS: BCT was superior to the control conditions in all three outcome measures after treatment and at follow-up, and showed a relatively large effect size for relationship satisfaction. Moreover, BCT was superior to IBT in reducing the frequency of substance use.

The effect of exposure and response prevention therapy on obsessive-compulsive disorder: A systematic review and meta-analysis.

This meta-analysis mainly examined the effect size of exposure and response prevention (ERP) for obsessive-compulsive disorder (OCD) when compared with different control conditions, and the difference in the efficacy of different variants of ERP in the treatment of OCD. Thirty studies were included, involving 39 randomized controlled trials with 1793 participants, from 30 studies up to January 18, 2022. Hedge's g was calculated using random-effects models. The results showed that ERP had a definite effect on OCD (g = 0.37), and its effect was significant when the control condition was placebo (g = 0.97) or drug (g = 0.59). However, ERP did not show statistical differences with other therapies in improving OCD (g = -0.07). In addition, we found that both therapist and self-controlled exposure (at the same time as the therapist controls, self-control is exercised after the therapy session) and total response prevention can better improve OCD symptoms. In addition, compared with the control group, ERP reduced depression (g = 0.15) and anxiety symptoms (g = 0.23) in patients with OCD. Meta-regression results showed that the longer the length of sessions, the better the treatment effect (t = 2.41, p = 0.022).

Case Report: Clinical Features of a Chinese Boy With Epileptic Seizures and Intellectual Disabilities Who Carries a Truncated NUS1 Variant.

The mental retardation-55 with seizures (MRD55) is a rare genetic disease characterized by developmental delay, intellectual disability, language delay and multiple types of epileptic seizures. It is caused by pathogenic variants of the NUS1 gene, which encodes Nogo-B receptor (NgBR), a necessary subunit for the glycosylation reactions in mammals. To date, 25 disease-causing mutations of NUS1 have been reported, which are responsible for various diseases, including dystonia, Parkinson's disease, developmental and epileptic encephalopathy as well as congenital disorder of glycosylation. In addition, only 9 of these mutations were reported with detailed clinical features. There are no reports about Chinese cases with MRD55. In this study, a novel, de novo pathogenic variant of NUS1 (c.51_54delTCTG, p.L18Tfs*31) was identified in a Chinese patient with intellectual disability and epileptic seizures. This pathogenic variant resulted in truncated NgBR proteins, which might be the cause of the clinical features of the patient. Oxcarbazepine was an effective treatment for improving speech and movement of the patient, who consequently presented with no seizure. With this novel pathogenic variant found in NUS1, we expand the genotype spectrum of MRD55 and provide valuable insights into the potential genotype-phenotype correlation.

miRNA-23a has effects to improve lung injury induced by sepsis in vitro and vivo study.

AIM: The aim of this study is to explain the effects and mechanism of miRNA-23a in lung injury which were induced by sepsis in vitro and vivo. METHODS: In the vitro study, The BEAS-2B cells were divided into 4 groups: NC, MC, miRNA and miRNA + PTEN agonist groups. The cell proliferation and apoptosis of difference groups were measured by MTT and flow cytometry, the relative proteins expression of difference groups were measured by WB assay. In the vivo study, the rats were also divided into 4 groups: NC, MC, miRNA and miRNA + PTEN agonist groups. The miRNA-23a expression of difference groups were evaluated by ISH in lung tissues of rats. The cell apoptosis of difference groups were evaluated by TUNEL assay in lung tissues; the relative proteins expression of difference groups were evaluated by IHC assay. RESULTS: Compared with NC group, the cell apoptosis rate of MC groups were significantly increased in vitro and vivo studies (P ＜ 0.05, respectively). The relative proteins (PTEN, PI3K, AKT and P53) expressions of MC group were significantly differences (P ＜ 0.05, respectively) compared with those of NC groups in vitro and vivo studies. However, with miRNA-23a infection, the cell apoptosis of miRNA group were significantly suppressed compared with MC groups, and the relative proteins (PTEN, PI3K, AKT and P53) of miRNA group were also significantly differences compared with MC groups in vitro and vivo studies (P ＜ 0.05, respectively). CONCLUSION: The miRNA-23a has improved lung injury induced by sepsis via PTEN/PI3K/AKT/P53 pathway in vitro and vivo studies.

Exploring lipid markers of the quality of coix seeds with different geographical origins using supercritical fluid chromatography mass spectrometry and chemometrics.

BACKGROUND: Lipids, a group of primary metabolites, could be used as quality markers of Traditional Chinese medicine. PURPOSE: The present study was designed to develop a research method to explore lipid markers of the quality of coix seeds with different geographical origins. STUDY DESIGN: The geographical origins of coix seeds were divided into three regions based on the latitude. A central composite design (CCD test) was used to optimize the chromatographic parameters of supercritical fluid chromatography to obtain optimal lipid profile of coix seed. METHODS: An untargeted method based on ultra-performance convergence chromatography - quadrupole/time-of-flight hybrid mass spectrometry (UPC2-QTOF) was developed. Four chromatographic parameters were optimized using CCD test, and a fusion index established by Derringer function was used to evaluate. The lipid profile of 27 batches of coix seeds were acquired and processed by Progenesis QI software, and the MS/MS spectrums were obtained to identify, simultaneously. The difference lipids were explored by orthogonal partial least squares discriminant analysis (OPLS-DA). The lipids that showed differences depending on their seeds' geographical origin were selected as markers of the quality of coix seeds from the three regions. RESULTS: A Torus 2-PIC (1.7 µm, 100 mm × 3.0 mm) was selected as the optimal column of the untargeted method which the run time was only 8 minutes. From the CCD test, the interaction of chromatographic parameters between column temperature and backpressure was founded which the optimal parameters were 55 °C and 2600 psi, respectively. Thirty-two peaks in the lipid profile of coix seed were tentatively identified, of which 20 were triglyceride, and 12 were diglyceride. Nine features that could potentially be used to distinguish the coix seeds by their geographical origin were identified, most of which were diglycerides, such as OP. CONCLUSIONS: Our findings confirm that UPC2-QTOF combined with chemometrics could be used as an efficient method for exploring potential lipid markers of the quality of herbal medicine.

Combining different types of multifunctional liposomes loaded with ammonium bicarbonate to fabricate microneedle arrays as a vaginal mucosal vaccine adjuvant-dual delivery system (VADDS).

To develop effective mucosal vaccines, two types of multifunctional liposomes, the mannosylated lipid A-liposomes (MLLs) with a size of 200nm and the stealth lipid A-liposomes (SLLs) of 50nm, both loaded with a model antigen and NH4HCO3, were fabricated together into microneedles, forming the proSLL/MLL-constituted microneedle array (proSMMA), which upon rehydration dissolved rapidly recovering the initial MLLs and SLLs. Mice vaccinated with proSMMAs by vaginal mucosa patching other than conventional intradermal administration established robust antigen-specific humoral and cellular immunity at both systemic and mucosal levels, especially, in the reproductive and intestinal ducts. Further exploration demonstrated that the MLLs reconstituted from the administered proSMMAs were mostly taken up by vaginal mucosal dendritic cells, whereas the recovered SLLs trafficked directly to draining lymph nodes wherein to be picked up by macrophages. Moreover, the antigens delivered by either liposomes were also cross-presented for MHC-I displaying by APCs thanks to lysosome escape and ROS (reactive oxygen species) stimulation, both of which occurred when lysosomal acidifying the liposome-released NH4HCO3 into CO2 and NH4+/NH3 to rupture lysosomes by gas expansion and to cause ROS production by excessive ammonia induction, resulting in a mixed Th1/Th2 type response which was also promoted by liposomal lipid A via activation of TLR4. In addition, vaginal vaccination of the engineered HSV2 antigen gD-loaded proSMMAs successfully protected mice from the virus challenge. Thus, the proSMMAs are in fact a vaccine adjuvant-dual delivery system capable of eliciting robust humoral and cellular immunity against the invading pathogens, especially, the sexually transmitted ones.

Multifunctional particle-constituted microneedle arrays as cutaneous or mucosal vaccine adjuvant-delivery systems.

To overcome drawbacks of current injection vaccines, such as causing needle phobia, needing health professionals for inoculation, and generating dangerous sharps wastes, researchers have designed novel vaccines that are combined with various microneedle arrays (MAs), in particular, with the multifunctional particle-constructed MAs (MPMAs). MPMAs prove able to enhance vaccine stability through incorporating vaccine ingredients in the carrier, and can be painlessly inoculated by minimally trained workers or by self-administration, leaving behind no metal needle pollution while eliciting robust systemic and mucosal immunity to antigens, thanks to delivering vaccines to cutaneous or mucosal compartments enriched in professional antigen-presenting cells (APCs). Especially, MPMAs can be easily integrated with functional molecules fulfilling targeting vaccine delivery or controlling immune response toward a Th1 or Th2 pathway to generate desired immunity against pathogens. Herein, we introduce the latest research and development of various MPMAs which are a novel but promising vaccine adjuvant delivery system (VADS).

Microneedle arrays delivery of the conventional vaccines based on nonvirulent viruses.

Recently, microneedle arrays (MAs) have been developed for painless inoculation of vaccines and possess many prominent advantages, including convenience for inoculation, and exact delivery of vaccine to the exact epidermal and dermal or mucosal compartments which teem with antigen-presenting cells (APCs). Among different types of MAs, while the micro-environmental stimulus-responsive MAs represent one of the developmental trends in the field, the MAs combined with the conventional vaccines that are based on nonvirulent viruses, such as live attenuated or whole inactivated viruses, and antigen-encoding DNA viral vectors, have developed rapidly into the advanced stages, with certain products already on clinical trials. The pre- and clinical research outcomes showed that the painless MA delivery of the conventional vaccines through mammalian skin or mucosa can not only elicit robust systemic and even mucosal immunity to pathogens but also, in certain circumstances, redirect the immune response toward a specific Th1 pathway, resulting in cytotoxic T lymphocytes (CTL) to erase the cell-hidden pathogens, thanks to the robust adjuvant function of MAs exerted through damaging the contacted cells to release dangerous signals. This paper focuses on reviewing the latest research and advancements in MA delivery of the conventional vaccines that are based on nonvirulent viruses, underlining MA enhancement of the overall vaccine performance and the most advanced MA vaccine products that are relatively close to markets.

Multifunctional liposomes constituting microneedles induced robust systemic and mucosal immunoresponses against the loaded antigens via oral mucosal vaccination.

To develop effective, convenient and stable mucosal vaccines, mannose-PEG-cholesterol (MPC)/lipid A-liposomes (MLLs) entrapping model antigen bovine serum albumin (BSA) were prepared by the procedure of emulsification-lyophilization and used to constitute microneedles, forming the proMLL-filled microneedle arrays (proMMAs). The proMMAs were rather stable and hard enough to pierce porcine skin and, upon rehydration, dissolved rapidly recovering the MLLs without size and entrapment change. The proMMAs given to mice via oral mucosal (o.m.) route, rather than routine intradermal administration, elicited robust systemic and mucosal immunoresponses against the loaded antigens as evidenced by high levels of BSA-specific IgG in the sera and IgA in the salivary, intestinal and vaginal secretions of mice. Enhanced levels of IgG2a and IFN-γ in treated mice revealed that proMMAs induced a mixed Th1/Th2 immunoresponse. Moreover, a significant increase in CD8(+) T cells confirmed that strong cellular immunity had also been established by the immunization of the proMMAs. Thus, the proMMAs can be immunized via o.m. route to set up an effective multiple defense against pathogen invasion and may be an effective vaccine adjuvant-delivery system (VADS) applicable in the controlled temperature chain.

Phospholipid bilayer-coated aluminum nanoparticles as an effective vaccine adjuvant-delivery system.

The phospholipid bilayer-coated aluminum nanoparticles (PLANs), formed via chemisorption, were prepared by reverse ethanol injection-lyophilization (REIL) utilizing the phosphophilicity of aluminum. The anhydrous antigen-loaded PLANs obtained by REIL proved stable, satisfying using the controlled-temperature-chain instead of the integrated cold-chain for distribution, and could be rehydrated to reconstitute instantly an aqueous suspension of the antigen-PLANs, which were more readily taken up by antigen-presenting cells and, when given subcutaneously to mice, induced more robust antigen-specific humoral and cellular immunoresponses but less local inflammation than the antigen-alum. Thus, the PLANs are a useful vaccine adjuvant-delivery system with advantages over the widely used naked alum.

Mannosylated and lipid A-incorporating cationic liposomes constituting microneedle arrays as an effective oral mucosal HBV vaccine applicable in the controlled temperature chain.

To develop an effective, convenient and stable mucosal vaccine against hepatitis B virus (HBV), the mannose-PEG-cholesterol/lipid A-liposomes (MLLs) loaded with HBsAg were prepared by the procedure of emulsification-lyophilization and, subsequently, filled into the microholes of microneedle array reverse molds and dried to form the proHBsAg-MLLs microneedle arrays (proHMAs). The proHMAs were stable even at 40 °C for up to 3 days and hard enough to pierce porcine skin but, upon rehydration, rapidly dissolved recovering the HBsAg-MLLs without obvious changes in size and antigen association efficiency. Notably, immunization of mice only once with the proHMAs at oral mucosa induced robust systemic and widespread mucosal immunoresponses, as evidenced by the high levels of HBsAg-specific IgG in the sera and IgA in the salivary, intestinal and vaginal secretions. In addition, a strong cellular immunity against HBV had been established through a mixed Th1/Th2 response, as confirmed by a significant increase in CD8(+) T cells as well as the enhanced levels of IgG2a and IFN-γ in the treated mice. Thus, the proHMAs can be conveniently vaccinated via oral mucosal route to set up a multiple immune defense against HBV invasion and, in addition, may be a stable HBV vaccine applicable in the controlled temperature chain for wide distribution.