Anti-glial fibrillary acidic protein antibody and anti-aquaporin-4 antibody double-positive neuromyelitis optica spectrum disorder: A case report.

BACKGROUND: A case of neuromyelitis optica spectrum disorder (NMOSD) with positive cerebrospinal fluid (CSF) anti-aquaporin-4 antibody (AQP4-IgG) and anti-glial fibrillary acidic protein IgG (GFAP-IgG) at the time of relapse was reported. The exact roles of GFAP-IgG in NMOSD are not fully understood and are the subject of ongoing research. This study revealed the possible connection between GFAP-IgG and the occurrence or development of diseases. CASE SUMMARY: A 19-year-old woman was admitted to the hospital due to a constellation of symptoms, including dizziness, nausea, and vomiting that commenced 1 year prior, reoccurred 2 mo ago, and were accompanied by visual blurring that also began 2 mo ago. Additionally, she presented with slurred speech and ptosis, both of which emerged 1 mo ago. Notably, her symptoms deteriorated 10 d prior to admission, leading to the onset of arm and leg weakness. During hospitalization, magnetic resonance imaging showed high T2-fluid attenuated inversion recovery signals, and slightly high and equal diffusion-weighted imaging signals. The serum antibody of AQP4-IgG tested positive at a dilution of 1:100. CSF antibody testing showed positive results for GFAP-IgG at a dilution of 1:10 and AQP4-IgG at a dilution of 1:32. Based on these findings, the patient was diagnosed with NMOSD. She received intravenous methylprednisolone at a daily dose of 500 mg for 5 d, followed by a tapering-off period. Afterward, the rate of reduction was gradually slowed down and the timely use of immunosuppressants was implemented. CONCLUSION: The CFS was slightly GFAP-IgG-positive during the relapse period, which can aid in the diagnosis and treatment of the disease.

Preparation of pazopanib-fumarate disodium glycyrrhizinate nanocrystalline micelles by liquid-assisted ball milling.

Pazopanib (PZ) is a multikinase inhibitor, which is mainly used in the treatment of soft tissue sarcoma and advanced renal cancer. However, because of its water insolubility, oral bioavailability is poor. At the same time, photo lability and high dose oral administration lead to severe hepatotoxicity, which is limited in clinical application. In this paper, the novel pazopanib-fumarate disodium glycyrrhizinate nanocrystalline micelles are successfully prepared by liquid-assisted ball milling. The prepared cocrystals and nanocrystalline micelle structures are systematically characterized by X-ray diffraction (XRD), differential scanning calorimetry (DSC) and Fourier Transform Infrared Spectrometer (FTIR) analysis. In vitro solubility and dissolution experiments show that the solubility and dissolution of nanocrystalline micelles are significantly improved under different simulated physiological conditions. The accelerated stabilization experiments show that the nanocrystalline micelles have good physical and chemical stability and showed excellent stability in water (Zeta potential was 62.39 mV). In addition, the in vivo bioavailability of nanocrystalline micelles is 3 times higher than that of PZ, and the therapeutic threshold (> 20 µg/mL) is up to 30 h. This new strategy provides a feasible solution to the undesirable properties of PZ.

Nuclear localization of human MEIOB requires its NLS in the OB domain and interaction with SPATA22.

MEIOB is a vital protein in meiotic homologous recombination and plays an indispensable role in human gametogenesis. In mammals, MEIOB and its partner SPATA22 form a heterodimer, ensuring their effective localization on single-strand DNA (ssDNA) and proper synapsis processes. Mutations in human MEIOB (hMEIOB) cause human infertility attributed to the failure of its interaction with human SPATA22 (hSPATA22) and ssDNA binding. However, the detailed mechanism is still unclear. In our study, truncated or full-length hMEIOB and hSPATA22 are traced by fused expression with fluorescent proteins (i.e., copGFP or mCherry), and the live cell imaging system is used to observe the expression and localization of the proteins. When transfected alone, hMEIOB accumulates in the cytoplasm. Interestingly, a covered NLS in the OB domain of hMEIOB is identified, which can be exposed by hSPATA22 and is necessary for the nuclear localization of hMEIOB. When hSPATA22 loses its hMEIOB interacting domain or NLS, the nuclear localization of hMEIOB is aborted. Collectively, our results prove that the NLS in the OB domain of hMEIOB and interaction with hSPATA22 are required for hMEIOB nuclear localization.

Study of clinical correlation of motion sickness in patients with vestibular migraine.

Objective: In this study, clinical data from vestibular migraine (VM) patients and healthy control populations were collected to analyze the clinical data of VM patients, especially the history of motion sickness, and to understand their clinical characteristics. Methods: According to VM diagnostic criteria, 140 patients diagnosed with confirmed VM (cVM) and probable VM (pVM) who attended the outpatient and inpatient ward of Jiaxing First Hospital between August 2017 and June 2021, as well as 287 healthy check-ups in the health management center, were analyzed and compared in terms of age, gender, and previous history of motion sickness. Results: A comparison of clinical data related to VM patients and the control population showed that there were more women in the VM group (P < 0.01) and that patients in the VM group were older (P < 0.05) and had a higher prevalence of history of motion sickness history (P < 0.01). Analysis after matching gender and age revealed that patients in the cVM group were older than those in the pVM group (P < 0.05), but the proportion of motion sickness was lower than in the pVM group (P < 0.05). The age of the patients in the cVM group was mainly distributed around 50 years of age, following a normal distribution, whereas the age distribution of the patients in the pVM group did not have a significant trend of age concentration and was distributed at all ages. Conclusion: The history of motion sickness is significant in patients with VM and may be a potential suggestive factor for the diagnosis of VM.

Loss of Cep72 affects the morphology of spermatozoa in mice.

The centrosome regulates mammalian meiosis by affecting recombination, synapsis, chromosome segregation, and spermiogenesis. Cep72 is one of the critical components of the centrosome. However, the physiological role of Cep72 in spermatogenesis and fertility remains unclear. In this study, we identify Cep72 as a testis-specific expression protein. Although Cep72 knockout mice were viable and fertile, their sperms were morphologically abnormal with incomplete flagellum structures. Transcriptome analysis reveals significant differences in six genes (Gm49527, Hbb-bt, Hba-a2, Rps27a-ps2, Gm29647, and Gm8430), which were not previously associated with spermatogenesis. Overall, these results indicate that Cep72 participates in regulating sperm morphology and yet is dispensable for fertility in mice.

Azilsartan-nicotinamide cocrystal: Preparation, characterization and in vitro / vivo evaluation.

Azilsartan (AZL) is an angiotensin II receptor antagonist, which is mainly used for the treatment of hypertension. AZL has the advantages of high selectivity, hypotensive effect, protection of cardiovascular and cerebrovascular diseases. In order to improve the water solubility of AZL and its bioavailability, AZL -nicotinamide (NA) cocrystal was prepared by mechanical ball milling, and the effect of ball milling conditions on cocrystal preparation were studied. AZL-NA cocrystal was identified and characterized by powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, scanning electron microscopy and Fourier transform infrared spectrometry. The results showed that AZL-NA cocrystal with the molar ratio of 1:2 was successfully prepared. And the optimum ball milling condition was milling speed of 300 rpm, milling time of 50 min, the solvent was ethanol/acetonitrile (1:1, v/v), and the solvent dosage (η) was 0.8 µL/mg. The results of solubility tests showed that the solubility of AZL in the cocrystal was 3.39 times higher than the pure drug at 24 h. And the results of vitro dissolution tests showed that the cumulative dissolution of AZL in 2 h was about 10%. While distilled water, pH 1.2 and pH 4.5 acid or buffered solutions and pH 6.8 buffer phosphate salt solution was used as the dissolution medium, the cumulative dissolution of AZL in cocrystal reached 50%, 35%, 55% and 90%, respectively, showing obvious improvement of dissolution. In addition, the accelerated stability tests showed that the AZL-NA cocrystal had good chemical stability. And the pharmacokinetic results showed that AZL-NA cocrystal could significantly improve the bioavailability of AZL.

Fbxw17 is dispensable for viability and fertility in mice.

BACKGROUND: Skp1-Cullin-F-box (SCF) E3 ligase complex plays an important role in regulating spermatogenesis and fertility in mice. As a member of F-box proteins, the function of F-box and WD-40 domain protein 17 (Fbxw17) during spermatogenesis and fertility is unclear. In this study, we illustrate its function for spermatogenesis and fertility. METHODS AND RESULTS: Here, we generated the Fbxw17 knockout (KO) mouse model by using the CRISPR/Cas9 system and analyzed the meiotic process and the fertility. Then, our results demonstrated that testis and sperm in the Fbxw17 KO mice had normal morphology. The testis weight, sperm count and fertility of Fbxw17 KO mice showed no significant difference compared with the wild-type mice. Subsequently, histological analysis of Fbxw17 KO mice revealed apparently normal germ cells of all stages and mature spermatozoa. Meanwhile, nuclear spread analysis showed that the synaptonemal complex formation and DSB repair proceeded normally in Fbxw17-deficient spermatocytes. Furthermore, we didn't find defects in the meiotic prophase I spermatocytes and germ cells showed no apparent apoptosis in Fbxw17 KO mice. CONCLUSIONS: Our results show that Fbxw17 is dispensable for fertility in mice.

Chromatin-Associated Protein Sugp2 Involved in mRNA Alternative Splicing During Mouse Spermatogenesis.

Mammalian spermatogenesis is a highly ordered process that is determined by chromatin-associated moderators which still remain poorly understood. Through a multi-control group proteomics strategy, we confirmed that Sugp2 was a chromatin-associated candidate protein, and its signal arose along spermatogenesis. The expression results showed that Sugp2, which is mainly expressed in the testis, had two transcripts, encoding one protein. During spermatogenesis, Sugp2 was enriched in the nucleus of male germ cells. With the depletion of Sugp2 by CRISPER-Cas9 technology, we found that Sugp2 controlled a network of genes on metal ion and ATP binding, suggesting that alternative splicing regulation by Sugp2 is involved in cellular ion and energy metabolism during spermatogenesis, while it had a little effect on meiotic progression and male fertility. Collectively, these data demonstrated that, as a chromatin-associated protein, Sugp2 mediated the alternative splicing regulatory network during spermatogenesis.

Clinical and Preclinical Systematic Review of Panax ginseng C. A. Mey and Its Compounds for Fatigue.

BACKGROUND: Fatigue, as a complex, multidimensional symptom, is associated with many physical illnesses. Panax ginseng C. A. Mey (PG) is an important herbal drug which has been used for benefiting Qi for thousand years. Panax ginseng C. A. Mey and its compounds (PGC) possess various pharmacological activities, including anti-fatigue. Here, we conducted a systematic review of both randomized clinical trials (RCTs) and preclinical animal studies to investigate the efficacy and safety of PGC for fatigue. METHODS: Electronic searches were performed in 7 databases from the time of each database's inception to August 2019. The methodological quality of RCTs was assessed using 7-item checklist recommended by Cochrane Collaboration or by the CAMARADES 10-item quality checklist. All the data were analyzed using Rev-Man 5.3 and Stata SE software. RESULTS: Eight eligible RCTs and 30 animal studies were identified. The risk of bias scores in RCTs ranged from 4/7 to 7/7, and of animal studies varied from 4/10 to 7/10. Meta-analyses showed that PGC was superior to placebo according to their respective fatigue scales, heart rate recovery, and clinical effect (P < 0.05). There were a similar number of adverse effects between PGC and placebo group (P > 0.05). Meta-analyses showed that PGC can significantly decrease level of blood lactate, blood urea nitrogen, creatine kinase, malondialdehyde, and lactic dehydrogenase in serum, level of malondialdehyde in liver and level of gamma-aminobutyric acid, 5-hydroxytryptamine in brain tissue, and increase swimming time, level of glutathione peroxidase, glucose, superoxide dismutase in serum, level of glycogen and activity of superoxide dismutase, glutathione peroxidase, and catalase in skeletal muscle, level of hepatic glycogen in liver and level of dopamine, acetylcholine in brain tissue, compared with control (P < 0.05). Meta-analyses showed no significant difference in animal body weight between PGC and control (P > 0.05). CONCLUSION: The present findings supported, to a certain degree, that PGC can be recommended for routine use in fatigue. The possible mechanism of PGC resists fatigue, mainly through antioxidant stress, regulating carbohydrate metabolism, delaying the accumulation of metabolites, promoting mitochondrial function, neuroprotection, antiapoptosis, and regulating neurotransmitter disorder in central nervous system.

Efficacy and Safety of Chinese Herbal Medicine for Primary Intracerebral Hemorrhage: A Systematic Review of Randomized Controlled Trials.

Background: Primary intracerebral hemorrhage (ICH) is the most harmful subtype of stroke, but there have yet been no specific proven therapies. Chinese herbal medicine (CHM) has been used for ICH for more than a thousand years; however, currently it is still lacking of available evidence. The objective of this study is to assess the current available evidence of CHM for acute ICH according to randomized controlled trials. Methods: Eight databases were searched from the year of their respective inception to November 2017. Only the studies that assessed at least four domains with "yes" according to the Cochrane risk of bias tool were selected for analysis. All the data were analyzed by using Review Manager 5.3 software. P < 0.05 was considered to be statistically significant. Results: Forty-five studies with 4,517 individuals were identified. CHM paratherapy can improve dependency, neurological function deficit, volume of hematoma, clinical effective rate, and volume of perihematomal edema compared with CHM alone or placebo (all P < 0.05). By contrast, it was not significant for improving the mortality rate of ICH patients (P > 0.05). In addition, adverse events were reported in 16 studies, whereas 29 studies did not mention it. The frequency of adverse events was 70/972 in the trial group and 48/944 in the control group. Conclusion: The present study provided supportive evidence of CHM for improving dependency of ICH and showed generally safety; however, there is still lack of evidence for improving mortality rate, and it opens for further study.

Preclinical Evidence and Possible Mechanisms of Extracts or Compounds from Cistanches for Alzheimer's Disease.

Currently, disease-modified strategies to prevent, halt or reverse the progress of Alzheimer's disease (AD) are still lacking. Previous studies indicated extracts or compounds from Cistanches (ECC) exert a potential neuroprotective effect against AD. Thus, we conducted a preclinical systematic review to assess preclinical evidence and possible mechanisms of ECC in experimental AD. A systematical searching strategy was carried out across seven databases from their inceptions to July 2018. Twenty studies with 1696 rats or mice were involved. Neurobehavioral function indices as primary outcome measures were established by the Morris water maze test (n = 11), step-down test (n = 10), electrical Y-maze test (n = 4), step-through test (n = 3), open field test (n = 2) and passage water maze test (n = 1). Compared with controls, the results of the meta-analysis showed ECC exerted a significant effect in decreasing the escape latency, error times and wrong reaction latency in both the training test and the retention test, and in increasing the exact time and the percentage of time in the platform-quadrant and the number of platform crossings (all P<0.01). In conclusion, ECC exert potential neuroprotective effects in experimental AD, mainly through mechanisms involving antioxidant stress and antiapoptosic effects, inhibiting Aß deposition and tau protein hyperphosphorylation and promoting synapse protection. Thus, ECC could be a candidate for AD treatment and further clinical trials.

Chinese Herbal Medicine for Wilson's Disease: A Systematic Review and Meta-Analysis.

Wilson's disease (WD) is a rare autosomal recessive inherited disorder of chronic copper toxicosis. Currently, Chinese herbal medicines (CHM) is widely used for WD. Here, we conducted an updated systematic review to investigate the efficacy and safety of CHM for WD and its possible mechanisms. Randomized-controlled clinical trials (RCTs), which compared CHM with Western conventional medicine or placebo for WD, were searched in six databases from inception to July 2017. The methodological quality was assessed using 7-item criteria from the Cochrane's collaboration tool. All the data were analyzed using Rev-Man 5.3 software. Eighteen studies involving 1,220 patients were identified for the final analyses. A score of study quality ranged from 2/7 to 4/7 points. Meta-analyses showed that CHM could significantly increase 24-h urinary copper excretion and improve liver function and the total clinical efficacy rate for WD compared with control (p < 0.05). Additionally, CHM was well tolerated in patients with WD. The underlying mechanisms of CHM for WD are associated with reversing the ATP7B mutants, exerting anti-oxidation, anti-inflammation, and anti-hepatic fibrosis effects. In conclusion, despite the apparent positive results, the present evidence supports, to a limited extent because of the methodological flaws and CHM heterogeneity, that CHM paratherapy can be used for patients with WD but could not be recommended as monotherapy in WD. Further rigorous RCTs focusing on individual CHM formula for WD are warranted.

The reporting quality of acupuncture for neurogenesis in experimental ischemic stroke study.

BACKGROUND: There is increasing evidence demonstrating the highly inadequate reporting of preclinical research in multiple scientific publications. The purpose of this study is to systematically investigate the reporting quality of acupuncture for neurogenesis in animal models of acute ischemic stroke. METHODS: We searched eight databases, including PubMed, EMBASE, CINAHL, AMED, Chinese National Knowledge Infrastructure, VIP information database, Wanfang data Information Site, and Chinese Biomedical Literature Database. The methodological quality of included studies was assessed by using the CAMARADES 10-item checklist. The STRICTA statement was modified to gear to animal acupuncture research. The reporting quality was assessed according to the ARRIVE guidelines and the modified STRICTA statement. Data were analyzed with descriptive statistics. RESULTS: Ultimately, 44 studies containing 2,411 subjects were identified. The overall compliance with the CAMARADES 10-item checklist has a mean of 4.3. The reporting quality indicated that the overall compliance with ARRIVE guidelines has a mean of 59.9% and with the modified STRICTA statement a mean of 71.8%. The findings suggest that the reporting quality of acupuncture for preclinical stroke was generally poor. CONCLUSIONS: Full compliance with ARRIVE guidelines and/or modified STRICTA statement in designing, conducting and reporting preclinical acupuncture research is urgently needed in the future.

Chinese Herbal Medicine for Myasthenia Gravis: A Systematic Review and Meta-Analysis.

Myasthenia gravis (MG) is an acquired autoimmune disease with the disorder of the neuromuscular junction transmission caused by autoantibodies. Currently, various Chinese herbal medicines (CHMs) are widely used for MG. This meta-analysis was conducted to assess the effectiveness and safety of CHMs for MG and its possible mechanisms. Fourteen studies with 1039 individuals were identified by searching seven databases from inception to March 2017. The methodological quality was assessed by using 7-item criteria from the Cochrane's Collaboration tool, and which assessed ≥4 "yes" in the domains were selected for detailed assessment and meta-analysis. All the data were analyzed using Rev-Man 5.3 software. Meta-analysis showed a significant effect of CHM as adjuvant therapy for improving the effectiveness compared with WCM alone or placebo in treating MG (p < 0.01). Moreover, there were fewer adverse effects and relapse rate in total when compared with the control group. The possible mechanisms of CHM for MG are associated with immunoregulation by reconstituting the functional ability of Tregs. In conclusion, despite the apparent positive results, the present evidence supports, to an extent, that CHM can be used for MG patients because of the methodological flaws and CHM heterogeneity. Further rigorous RCT for MG is needed.

Suanzaoren Formulae for Insomnia: Updated Clinical Evidence and Possible Mechanisms.

Insomnia disorder is a widespread and refractory disease. Semen Ziziphi Spinosae, Suanzaoren, a well-known Chinese herbal medicine, has been used for treating insomnia for thousands of years. Here, we aimed to assess the available evidence of Chinese herbal formulae that contains Suanzaoren (FSZR) for insomnia according to high-quality randomized controlled trials (RCTs) and reviewed their possible mechanisms based on animal-based studies. Electronic searches were performed in eight databases from inception to November 2016. The primary outcome measures were polysomnography index and Pittsburgh sleep quality index. The secondary outcome measures were clinical effective rate and adverse events. The methodological quality of RCTs was assessed by Cochrane's collaboration tool, and only RCTs with positive for 4 out of 7 for the Cochrane risk of bias domains were included in analyses. Thirteen eligible studies with 1,454 patients were identified. Meta-analysis of high-quality RCTs showed that FSZR monotherapy was superior to placebo (P < 0.01); FSZR plus Diazepam was superior to Diazepam alone (P < 0.05); there were mixed results comparing FSZR with Diazepam (P > 0.05 or P < 0.05). Furthermore, FSZR caused fewer side effects than that of Diazepam. Suanzaoren contains complex mixtures of phytochemicals including sanjoinine A, Jujuboside A, spinosin and other flavonoids, which has sedative and hypnotic functions primarily mediated by the GABAergic and serotonergic system. In conclusion, the findings of present study supported that FSZR could be an alternative treatment for insomnia in clinic. FSZR exerted sedative and hypnotic actions mainly through the GABAergic and serotonergic system.