Effects of adjunctive Chinese patent medicine on outcome of viral encephalitis in children: A multicenter retrospective study in China.

BACKGROUND: Some patients with viral encephalitis in China seek treatment with Chinese patent medicine (CPM) to improve their symptoms, but few studies have focused on the impact of CPM on the prognosis of viral encephalitis (VE). The aim of this multicenter retrospective study was to assess the benefit of adjunctive CPM therapy on the outcome of children with VE in China. METHODS: This study retrospectively included 834 children with viral encephalitis who were hospitalized at five medical institutions from 2018 to 2021. Univariate and multivariate logistic regression was used to assess the effect of CPM on sequelae in patients with VE. 1:1 propensity score matching was used to exclude the effect of confounding factors. Forest plots were used to observe the effect of CPM on the prognosis of VE in different subgroups. RESULTS: There were fewer patients with sequelae in the group of patients using CPM regardless of whether they were matched or not. The results of multivariate logistic regression analysis showed that the use of CPM was an independent protective factor for the development of sequelae in VE patients (OR = 0.063, 95 % CI: 0.011-0.350, p = 0.002). Subgroup analyses showed that CPM was a protective factor for the development of sequelae regardless of the presence or absence of coma and comorbidities. In addition, we evaluated other outcome indicators and found shorter duration of illness, fever and headache in children with EV in the CPM group. CONCLUSION: Adjunctive CPM therapy may significantly reduce sequelae in children with VE, as well as effectively alleviate patients' clinical symptoms. However, more prospective studies and clinical trials are needed to further evaluate its efficacy and safety.

Acyclovir Combined with Naloxone in the Treatment of Viral Encephalitis: A Meta-Analysis.

Background: The aim of this study was to systematically evaluate the efficacy and prognosis of acyclovir combined with naloxone in the treatment of patients with viral encephalitis (VE). Methods: PubMed, Web of Science, Embase, CNKI, and WanFang Data were searched for relevant literature published between 2000 and 2021. Meta-analysis was performed using Stata16.0 software. The treatment group was treated with acyclovir combined with naloxone, and the control group was treated with acyclovir alone. Results: A total of 12 studies with 986 participants were included. Compared with the control group, the treatment group could not only significantly improve the treatment response rate (OR = 5.53, 95% CI: 3.50, 8.74; P ≤ 0.001), but also reduce the incidence of adverse reactions (OR = 0.25, 95% CI: 0.17, 0.38; P ≤ 0.001). In addition, the combined treatment significantly inhibited the levels of inflammatory factors and neuron-specific enolase (NSE) in VE patients. The time for cerebrospinal fluid to return to normal (SMD = -2.73, 95% CI: -2.96, -2.51; P ≤ 0.001), as well as the disappearance time of meningeal irritation (SMD = -3.58, 95% CI: -4.96, -2.20; P ≤ 0.001), headache (SMD = -3.87, 95% CI: -5.84, -1.91; P ≤ 0.001), convulsion (SMD = -3.65, 95% CI: -4.56, -2.75; P < 0.001), tic (SMD = -4.083, 95% CI: -5.18, -2.98; P ≤ 0.001) and disturbance of consciousness (SMD = -4.96, 95% CI: -6.28, -3.63; P ≤ 0.001) in the treatment group were significantly shorter than those in the control group. Conclusion: A combination of acyclovir and naloxone can reduce the inflammatory response and shorter the time to symptom relief and disappearance, which is worthy of clinical promotion.

Drug-Screening Strategies for Inhibition of Virus-Induced Neuronal Cell Death.

A number of viruses, including Herpes Simplex Virus (HSV), West Nile Virus (WNV), La Crosse Virus (LACV), Zika virus (ZIKV) and Tick-borne encephalitis virus (TBEV), have the ability to gain access to the central nervous system (CNS) and cause severe neurological disease or death. Although encephalitis cases caused by these viruses are generally rare, there are relatively few treatment options available for patients with viral encephalitis other than palliative care. Many of these viruses directly infect neurons and can cause neuronal death. Thus, there is the need for the identification of useful therapeutic compounds that can inhibit virus replication in neurons or inhibit virus-induced neuronal cell death. In this paper, we describe the methodology to test compounds for their ability to inhibit virus-induced neuronal cell death. These protocols include the isolation and culturing of primary neurons; the culturing of neuroblastoma and neuronal stem cell lines; infection of these cells with viruses; treatment of these cells with selected drugs; measuring virus-induced cell death using MTT or XTT reagents; analysis of virus production from these cells; as well as the basic understanding in mode of action. We further show direct evidence of the effectiveness of these protocols by utilizing them to test the effectiveness of the polyphenol drug, Rottlerin, at inhibiting Zika virus infection and death of neuronal cell lines.

Evaluation of the adjunctive effect of Xing Nao Jing Injection for viral encephalitis: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: To systematically evaluate the effect and safety of Xing Nao Jing (XNJ) injection as an add-on treatment on the treatment for viral encephalitis (VE). METHODS: Trials assessing the adjunctive effectiveness of XNJ injection for VE were searched from 4 electronic databases from inception to October 31, 2018. Two authors independently extracted data and assessed risk of bias. Statistical analyses were performed using RevMan 5.3 software. Meta-analysis and additional analysis were conducted if data permitted. Trial Sequential Analysis and Grading of Recommendations Assessment, Development and Evaluation (GRADE) were also performed. RESULTS: This review involved 23 trials and 1757 participants, all trials were assessed as having unclear risk of bias. Results from 5 meta-analyses, 13 subgroup meta-analyses, and the single studies showed that based on conventional therapy XNJ injection (0.4-0.6 mL/kg daily for children, 20 mL/day for adults) may have better effect on increasing the numbers of cured patients and decreasing the time of recovery of main symptoms for patients with viral encephalitis. Patients used combination of XNJ injection and conventional therapy had higher cured rate (risk ratio 1.61, 95% confidence interval 1.45-1.80, 19 trials, 1456 participants) and less mortality rate (risk ratio 0.26, 95% confidence interval 0.10-0.71, 9 trials, 595 participants). The average difference of time for fever, conscious, or convulsive recovery was average 2 hours shorter in combination group than in control. No difference was found between children and adults according to the subgroup analysis. Safety of the XNJ injection was failed to evaluate due to the insufficient evidence in this review. CONCLUSIONS: This review found "very low" quality evidence which showed the potential effectiveness of combination of XNJ injection and conventional therapies for VE. Considering the TSA results, conclusion could only be draw on effectiveness of the XNJ injection as add-on treatment for VE patients on increasing the cured rate. Firm conclusion on other outcome measures for effectiveness assessment or safety of XNJ injection could not be draw according to this review due to the insufficient evidence.

Efficacy of Scutellaria baicalensis for the Treatment of Hand, Foot, and Mouth Disease Associated with Encephalitis in Patients Infected with EV71: A Multicenter, Retrospective Analysis.

This study aimed to evaluate the clinical efficacy and safety of using the traditional Chinese herbal medicine Scutellaria baicalensis for the treatment of severe HFMD in 725 patients aged >1 year in a multicenter, retrospective analysis. The patients were divided into the S. baicalensis and ribavirin groups, and the temperatures, presence or absence of skin rashes and oral lesions, nervous system (NS) involvement, and viral loads of the patients, as well as the safety of the treatments, were evaluated. The median duration of fever, median time to NS involvement, and the number of patients with oral ulcers and/or vesicles, as well as skin rashes, were decreased in the S. baicalensis group compared with the ribavirin group. In addition, the EV71 viral loads were decreased in the S. baicalensis group, suggesting that S. baicalensis exerted more potent antiviral effects compared with ribavirin. The present study demonstrated that S. baicalensis was suitable for the treatment of severe HFMD in patients aged >1 year, since it was shown to rapidly relieve fever, attenuate oral lesions and rashes, and improve NS involvement. Furthermore, it was demonstrated to be relatively safe for topical application.

[Effect of Shuanghuanglian injection on cerebral nuclear factor-kappaB expression in mice with viral encephalitis].

OBJECTIVE: To observe the effect of Shuanghuanglian injection on cerebral expression of nuclear factor-kappaB (NF-kappaB) in mice with viral encephalitis. METHODS: The mice with experimental viral encephalitis received treatment with Shuanghuanglian injection at the dose of 0.2, 1.5, and 5 for 5, 10 or 20 consecutive days. The total RNA of the brain tissue was extracted to analyze the protein and mRNA expression of NF-kappaB using Western blotting and RT-PCR, respectively. RESULTS: Compared with the control group, the mice with experimental viral encephalitis showed significantly increased protein and mRNA expressions of NF-kappaB (P<0.01). Treatment with Shuanghuanglian injection at the doses of 0.2 and 1.5 mg/kg significantly lowered NF-kappaB protein and mRNA expressions in the brain of mice with viral encephalitis (P<0.05), and the effect was even more obvious at the dose of 5 mg/kg (P<0.01). CONCLUSION: Shuanghuanglian injection can reduce the expression of NF-kappaB in the brain of mice with viral encephalitis in a dose- and time-dependent manner.

[Salt-wasting nephropathy induced by foscarnet treatment for HHV-6 encephalitis in a hematopoietic stem cell transplant].

A 51-year-old woman with myelodysplastic syndrome developed HHV-6 encephalitis on day 34 after unrelated bone marrow transplantation. Although prompt treatment with foscarnet stabilized encephalitis and there were no serious neurological sequelae, the patient developed both hyponatremia and natriuresis 11 days after intravenous administration of foscarnet. Subsequent investigation demonstrated hyponatremia due to salt-wasting nephropathy induced by foscarnet. Discontinuation of foscarnet and fluid replacement therapy with adequate sodium chloride (NaCl) resulted in a gradual resolution of hyponatremia and natriuresis. Currently, 8 months after these clinical events, the patient is under outpatient treatment for persistent nephropathy that requires small amounts of oral NaCl supplement, but she is otherwise in good clinical condition.

[Protective effects of trichosanthin in Herpes simplex virus-1 encephalitis in mice].

OBJECTIVE: Trichosanthin (TCS), a ribosome-inactivating protein extracted from the root tuber of Chinese medicinal herb Trichosanthes kirilowii maximowicz, has various pharmacological properties including abortifacient, anti-tumor and anti-virus. This study aimed to evaluate the effects of TCS on infectious brain injury induced by Herpes simplex virus-1 (HSV-1) in mice. METHODS: Ninety mice were randomly assigned into three groups: Normal control group (n=30), Model group (n=30) and TCS-treated group (n=30). Viral encephalitis was induced by intracranial inoculation of HSV-1 in the latter two groups. The TCS-treated group was injected with TCS 30 minutes before HSV-1 inoculation. The water content of brain tissue was measured at 1, 12, 24 and 48 hrs, and at 4 and 7 days after HSV-1 inoculation. The viral titer of brain tissue and brain histopathological changes were detected at 7 days after HSV-1 inoculation. The neurological deficient scores were determined daily. RESULTS: The water content of brain tissue in the TCS-treated group between 48 hrs and 7 days after HSV-1 inoculation was significantly lower than that in the Model group (P < 0.05), although it was significantly higher than that in the Normal control group (P < 0.05). The viral titer of brain tissue in the TCS-treated group was markedly lower than that in the Model group (1.16 +/- 0.45 vs 2.89 +/- 0.44; P < 0.05) 7 days after HSV-1 inoculation. The neurological deficient scores of the TCS-treated group after 24 hrs of HSV-1 inoculation were significantly lower than that in the Model group but were higher than those of the Normal control group. TCS treatment resulted in alleviated pathological changes of brain tissue compared with the Model group 7 days after HSV-1 inoculation. CONCLUSIONS: TCS has protective effects against infectious brain injury induced by HSV-1 in mice.

A novel model for the study of the therapy of flavivirus infections using the Modoc virus.

The murine Flavivirus Modoc replicates well in Vero cells and appears to be as equally sensitive as both yellow fever and dengue fever virus to a selection of antiviral agents. Infection of SCID mice, by either the intracerebral, intraperitoneal, or intranasal route, results in 100% mortality. Immunocompetent mice and hamsters proved to be susceptible to the virus only when inoculated via the intranasal or intracerebral route. Animals ultimately die of (histologically proven) encephalitis with features similar to Flavivirus encephalitis in man. Viral RNA was detected in the brain, spleen, and salivary glands of infected SCID mice and the brain, lung, kidney, and salivary glands of infected hamsters. In SCID mice, the interferon inducer poly IC protected against Modoc virus-induced morbidity and mortality and this protection was associated with a reduction in infectious virus content and viral RNA load. Infected hamsters shed the virus in the urine. This allows daily monitoring of (inhibition of) viral replication, by means of a noninvasive method and in the same animal. The Modoc virus model appears attractive for the study of chemoprophylactic or chemotherapeutic strategies against Flavivirus infections.

Protective effect of Astragali Radix by intraperitoneal injection against Japanese encephalitis virus infection in mice.

We examined the protective effect of Astragali Radix extracts (AE) by intraperitoneal injection against Japanese encephalitis virus (JEV) infection in mice. A protective effect was observed by all four samples of AE used. However, the degree of effectiveness for each AE was different. The observed survival rates of the groups injected with sample A (from Shanhsi, Japanese name Sansei-syo) and sample D (from Hokkaido) extracts were higher than 80% at 21 d after JEV inoculation. The groups injected with sample B (from Hopei, Japanese name Kahoku-syo) and sample C (from Hsiahsi, Japanese name Sensei-syo) extracts had a 60% survival rate. The increase in hemagglutination inhibition antibody titer was negligible in mice that survived 21 d after JEV inoculation. The antiviral effect of AE was examined by plaque assay in vitro, but no antiviral effect was shown. In mice injected with AE, the peritoneal exudate cell (PEC) numbers increased significantly, compared to the control. In these PEC, active oxygen production was also high. Also the group as a whole displayed a high survival rate against JEV infection, these were so strong. From these results, we propose that the protective effect of AE is dependent on a non-specific mechanism during the early stage of infection, before it shifts to antibody production, and that PEC plays an important role.

[The immunomodulating and metabolic actions of thymalin in an experimental herpetic infection]. / Immunomoduliruiushchee i metabolicheskoe deistvie timalina pri éksperimental'noi gerpeticheskoi infektsii.

In experiments on the intracerebral inoculation of herpes virus, type I, into 38 CBA mice the phagocytic activity of peritoneal exudate, cells, spontaneous migration of leukocytes and their response to phytohemagglutinin (PHA), the activity of key enzymes of gluconeogenesis, lipid peroxidation in liver tissue, as well as the level of glucose and glycosylated hemoglobin in the blood, were determined simultaneously with the histological study of the brain and the main internal organs of the animals, receiving thymalin treatment and not receiving it. As demonstrated in these experiments, the development of experimental infection was accompanied by the inhibition of the phagocytic activity of peritoneal macrophages and response of leukocytes to PHA, as well as metabolic shifts in liver tissue. Treatment with thymalin produced a combined immunomodulating and metabolic effect.