Percutaneous Endoscopic Unilateral-Approach Bilateral Decompression for Lumbar Spinal Stenosis.

Lumbar spinal stenosis (LSS) involves the narrowing of the spinal canal due to degenerative changes in the vertebral joints, intervertebral discs, and ligaments. LSS encompasses central canal stenosis (CCS), lateral recess stenosis (LRS), and intervertebral foramen stenosis (IFS). The utilization of lumbar endoscopic unilateral laminotomy for bilateral decompression (LE-ULBD) has gained popularity in the treatment of CCS and LRS. This popularity is attributed to the rapid development of endoscopic instruments and the progress of endoscopic philosophy. In this technical report, a detailed introduction to the steps and key points of LE-ULBD is provided. Simultaneously, a retrospective review of 132 consecutive patients who underwent LE-ULBD for central canal and/or lateral recess stenosis was conducted. The outcomes after more than two years of follow-up were assessed using the visual analogue score (VAS), Oswestry Disability Index (ODI), Japanese Orthopaedic Association (JOA) scores, and the modified MacNab criteria to evaluate surgical efficacy. All 132 patients underwent LE-ULBD successfully. Among them, 119 patients were rated as "excellent," while 13 patients were rated as "good" based on the modified MacNab criteria during the last follow-up. Incidental dural tears occurred in four cases, but there were no post-operative epidural hematomas or infections. The experience demonstrates that LE-ULBD is a less invasive, effective, and safe approach. It can be considered as an alternative option for treating patients with lumbar central canal stenosis and/or lateral recess stenosis.

Anxiety, depression, insomnia, and PTSD among college students after optimizing the COVID-19 response in China.

BACKGROUND: The number of COVID-19 infections has increased sharply and quickly after optimizing the COVID-19 response in China. In the context of this population-size infection, college students' psychological response is yet to be understood. METHODS: A cross-sectional study was designed to investigate anxiety, depression, insomnia, and post-traumatic stress disorder (PTSD) symptoms among college students from December 31, 2022, to January 7, 2023. The questionnaire included the Generalized Anxiety Disorder 7 (GAD-7), Patient Health Questionnaire 9 (PHQ-9), Insomnia Severity Index (ISI), Impact of Event Scale (IES-R), and self-designed questionnaire. RESULTS: Of the 22,624 respondents, the self-reported prevalence of anxiety, depression, insomnia, PTSD, and any of the four psychological symptoms appeared as 12.7 %, 25.8 %, 11.6 %, 7.9 %, and 29.7 %, respectively. The self-reported COVID-19 infection rate was 80.2 %. Changes in the place for learning, longer time online, not recovering after infection, a higher proportion of family member infection, insufficient drug reserve, worry about sequela after infection, future studies, or employment contributed to a higher risk of anxiety/depression/insomnia symptoms or PTSD symptoms. Multinomial logistic regression showed that those who spent more extended time on the Internet, recovered after infection, and had insufficient drug reserves were less likely to have PTSD than anxiety/depression/insomnia symptoms. LIMITATIONS: The study was a non-probability sampling survey. CONCLUSIONS: Anxiety, depression, insomnia, and PTSD were common psychological symptoms among college students when infection went through a large-scale population. This study highlights the importance of continuing to care for the psychological symptoms of college students, especially timely responses to their concerns related to the epidemic situation and COVID-19 infection.

Upregulation of miR-520c-3p via hepatitis B virus drives hepatocellular migration and invasion by the PTEN/AKT/NF-κB axis.

Hepatitis B virus (HBV) is a major risk factor for the development and progression of hepatocellular carcinoma (HCC). It has been reported that viral infection can interfere with the expression of cellular microRNA (miRNA) to affect oncogenesis. In this study, we showed that miR-520c-3p was upregulated in liver tumor specimens, and we revealed that HBV infection enhanced the expression of miR-520c-3p through the interaction of viral protein HBV X protein (HBx) with transcription factor CREB1. We further showed that miR-520c-3p induced by HBV transfection/infection caused epithelial-mesenchymal transition (EMT). Using the miRNA target prediction database miRBase and luciferase reporter assays, we identified PTEN as a novel target gene of miR-520c-3p and miR-520c-3p directly targeted PTEN's 3'-untranslated region. Moreover, we discovered that HBV promoted EMT via the miR-520c-3p-PTEN to activate AKT-NFκB signaling pathway, leading to increased HCC migration and invasion. Importantly, miR-520c-3p antagomir significantly represses invasiveness in HBx-induced hepatocellular xenograft models. Our findings indicate that miR-520c-3p is a novel regulator of HBV and plays an important role in HCC progression. It may serve as a new biomarker and molecular therapeutic target for HBV patients.

Advances in CRISPR/Cas-based Gene Therapy in Human Genetic Diseases.

CRISPR/Cas genome editing is a simple, cost effective, and highly specific technique for introducing genetic variations. In mammalian cells, CRISPR/Cas can facilitate non-homologous end joining, homology- directed repair, and single-base exchanges. Cas9/Cas12a nuclease, dCas9 transcriptional regulators, base editors, PRIME editors and RNA editing tools are widely used in basic research. Currently, a variety of CRISPR/Cas-based therapeutics are being investigated in clinical trials. Among many new findings that have advanced the field, we highlight a few recent advances that are relevant to CRISPR/Cas-based gene therapies for monogenic human genetic diseases.

Effects of compound probiotics on the weight, immunity performance and fecal microbiota of forest musk deer.

Probiotics are intended to provide health benefits when consumed, generally by improving or restoring the gut flora. The health problems of forest musk deer (FMD, Moschus berezovskii), a threatened species currently under conservation, restrict the development of captive musk deer. This study was conducted with the aim of analyzing the effects of forest musk deer compound probiotics (FMDPs) on weight, immunity performance and fecal microbiota in FMD by measuring average daily weight gain (ADG) and immune-related factors and by using high-throughput 16S rRNA sequencing to investigate differences in the fecal microbiota among the control group (4 samples), treatment group A (4 samples) and treatment group B (4 samples). The results showed that the ADG of treatment groups A and B was significantly higher than that of the control group (p = 0.032, p = 0.018). The increase in IgA and IgG levels in treatment group B was significantly higher than that in the control group (p = 0.02, p = 0.011). At the phylum and genus levels, the difference in bacterial community structure was significant between treatment group B and the control group. Both the alpha diversity and beta diversity results showed significant differences in the microbiota of FMD before and after FMDP feeding. In summary, the results indicated that FMDPs could promote the growth of growing FMD, improve immunity and balance the role of intestinal microbes.

Hepatitis B Virus Induces Autophagy to Promote its Replication by the Axis of miR-192-3p-XIAP Through NF kappa B Signaling.

Hepatitis B virus (HBV) is a major risk factor for the development and progression of hepatocellular carcinoma. It has been reported that viral infection can interfere with cellular microRNA (miRNA) expression and participate in the pathogenesis of oncogenicity. Here, we report that decreasing levels of the expression of the miRNA miR-192-3p is associated with rising levels of HBV DNA in the serum of HBV patients. We revealed that HBV infection repressed the expression of miR-192-3p through hepatitis B x protein interaction with c-myc. We further showed that miR-192-3p was repressed by HBV transfection in vitro and in a mouse model, leading to cellular autophagy. Using an miRNA target prediction database miRBase, we identified X-linked inhibitor of apoptosis protein (XIAP) as a target gene of miR-192-3p and demonstrated that miR-192-3p directly targeted the XIAP 3'-untranslated region of XIAP messenger RNA. Importantly, we discovered that HBV promoted autophagy through miR-192-3p-XIAP axis and that this process was important for HBV replication in vitro and in vivo. We demonstrated that miR-192-3p functioned through the nuclear factor kappa B signaling pathway to inhibit autophagy, thereby reducing HBV replication. Conclusions: Our findings indicate that miR-192-3p is a regulator of HBV infection and may play a potential role in hepatocellular carcinoma. It may also serve as a biomarker or therapeutic target for HBV patients.

Genome editing of the HIV co-receptors CCR5 and CXCR4 by CRISPR-Cas9 protects CD4+ T cells from HIV-1 infection.

BACKGROUND: The main approach to treat HIV-1 infection is combination antiretroviral therapy (cART). Although cART is effective in reducing HIV-1 viral load and controlling disease progression, it has many side effects, and is expensive for HIV-1 infected patients who must remain on lifetime treatment. HIV-1 gene therapy has drawn much attention as studies of genome editing tools have progressed. For example, zinc finger nucleases (ZFN), transcription activator like effector nucleases (TALEN) and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 have been utilized to successfully disrupt the HIV-1 co-receptors CCR5 or CXCR4, thereby restricting HIV-1 infection. However, the effects of simultaneous genome editing of CXCR4 and CCR5 by CRISPR-Cas9 in blocking HIV-1 infection in primary CD4+ T cells has been rarely reported. Furthermore, combination of different target sites of CXCR4 and CCR5 for disruption also need investigation. RESULTS: In this report, we designed two different gRNA combinations targeting both CXCR4 and CCR5, in a single vector. The CRISPR-sgRNAs-Cas9 could successfully induce editing of CXCR4 and CCR5 genes in various cell lines and primary CD4+ T cells. Using HIV-1 challenge assays, we demonstrated that CXCR4-tropic or CCR5-tropic HIV-1 infections were significantly reduced in CXCR4- and CCR5-modified cells, and the modified cells exhibited a selective advantage over unmodified cells during HIV-1 infection. The off-target analysis showed that no non-specific editing was identified in all predicted sites. In addition, apoptosis assays indicated that simultaneous disruption of CXCR4 and CCR5 in primary CD4+ T cells by CRISPR-Cas9 had no obvious cytotoxic effects on cell viability. CONCLUSIONS: Our results suggest that simultaneous genome editing of CXCR4 and CCR5 by CRISPR-Cas9 can potentially provide an effective and safe strategy towards a functional cure for HIV-1 infection.

Hepatitis B virus promotes cancer cell migration by downregulating miR-340-5p expression to induce STAT3 overexpression.

BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide, and infection with hepatitis B virus (HBV) is a leading cause of HCC. Previous studies have demonstrated that expression of the tumor inhibitor miR-340 is significantly downregulated in HCC tissues compared with normal liver tissues. However, the precise biological role of miR-340-5p in HBV-HCC and its molecular mechanism of action remain unknown. RESULTS: Expression of miR-340-5p was downregulated in HBV-associated HCC liver tissue and HBV-infected cells, facilitating migration of liver cancer cells. Signal transducer and activator of transcription (STAT)3 was found to be a direct functional target of miR-340-5p. The regulation of STAT3 expression by miR-340-5p was assessed using qRT-PCR and western blotting, and the effects of exogenous miR-340-5p and STAT3 on the migration of HBV-infected cells were evaluated in vitro using Transwell® and wound-healing assays. The expression of E-cadherin and vimentin, associated with epithelial-mesenchymal transition, was also assessed using Western blotting after transfection of miR-340-5p mimics and/or STAT3 expression vectors. Overexpression of STAT3 resulted in rescue of HBV effects, decreased E-cadherin expression, increased vimentin expression, and ultimately, enhanced cell migration. Re-introduction of the STAT3 CDS led to marked reversal of the inhibition of cell migration in HBV-infected cells mediated by miR-340-5p. CONCLUSIONS: Hepatitis B virus promotes the migration of liver cancer cells by downregulating miR-340-5p expression to induce STAT3 overexpression. Our results show that STAT3 plays a key role in regulating cell migration in HBV-HCC involving miR-340-5p.

Inhibition of hepatitis B virus replication by activation of the cGAS-STING pathway.

Cyclic GMP-AMP (cGAMP) synthase (cGAS) senses cytosolic DNA and catalyses synthesis of the second messenger cGAMP, which activates the downstream signalling adaptor protein STING, leading to the expression of type I interferons. Hepatitis B virus (HBV) is a small DNA virus, and the cGAS-STING pathway may inhibit HBV RNA synthesis and viral assembly in cell culture, but the exact roles of the cGAS pathway in the restriction of HBV replication in infection systems remain to be elucidated. In this study, replication of HBV was significantly inhibited both in cell culture and in vivo in a mouse model when the cGAS-STING pathway was activated by dsDNA or cGAMP. In contrast, the presence of enzymatically inactive cGAS mutant did not influence HBV replication. Moreover, knockdown of cGAS in human peripheral blood monocytes led to a higher level of intracellular HBV DNA. Collectively, our data indicate that the cGAS-STING pathway plays a role in the surveillance of HBV infection and may be exploited for development of novel anti-HBV strategies.

Phthalate degradation by glow discharge plasma enhanced with pyrite in aqueous solution.

In order to prevent health risk from potential exposures to phthalates, a glow discharge plasma (GDP) process was applied for phthalate degradation in aqueous solution. The results revealed that the phthalate derivatives 4-hydroxyphthalic acid, 4-methylphthalic acid and 4-tert-butylphthalic anhydride could be degraded efficiently in GDP process (498 V, 0.2 A) with high removal efficiencies of over 99% in 60 minutes. Additionally, pyrite as a promising heterogeneous iron source in the Fenton reaction was found to be favorable for GDP process. The phthalate degradation reaction could be significantly enhanced by the continuous formation of •OH and the inhibition of the quenching reaction in the pyrite Fenton system due to the constant dissolution of Fe(II) from pyrite surface. Meanwhile, the initial pH value showed little impact on the degradation of phthalates and the energy efficiency of GDP system for phthalate degradation ranged between 0.280 × 10-9 and 1.210 × 10-9 mol/J, which is similar to the GDP system with phenol, bisphenol A and methyl tert-butyl ether as the substrates. Further, the X-ray diffraction and scanning electron microscopy with energy dispersive X-ray spectroscopy analyses indicated that the pyrite was relatively stable in GDP system and there was no obvious polymeric compound formed on the catalyst surface. Overall, this GDP process offers high removal efficiency, simple technology, considerable energy efficiency and the applicability to salt-containing phthalate wastewater.

The pathophysiology of venous hypertensive myelopathy--study of an animal model: laboratory investigation.

OBJECT: The authors undertook this study to establish an animal model to investigate the pathophysiological changes of venous hypertensive myelopathy (VHM). METHODS: This study was a randomized control animal study with blinded evaluation. The VHM model was developed in 24 adult New Zealand white rabbits by means of renal artery and vein anastomosis and trapping of the posterior vena cava; 12 rabbits were subjected to sham surgery. The rabbits were investigated by spinal function evaluation, abdominal aortic angiography, spinal MRI, and pathological examination of the spinal cord at different follow-up stages. RESULTS: Twenty-two (91.67%) of 24 model rabbits survived the surgery and postoperative period. The patency rate of the arteriovenous fistula was 95.45% in these 22 animals. The model rabbits had significantly decreased motor and sensory hindlimb function as well as abnormalities at the corresponding segments of the spinal cord. Pathological examination showed dilation and hyalinization of the small blood vessels, perivascular and intraparenchymal lymphocyte infiltration, proliferation of glial cells, and neuronal degeneration. Electron microscopic examination showed loose lamellar structure of the myelin sheath, increased numbers of mitochondria in the thin myelinated fibers, and pyknotic neurons. CONCLUSIONS: This model of VHM is stable and repeatable. Exploration of the sequential changes in spinal cord and blood vessels has provided improved understanding of this pathology, and the model may have potential for improving therapeutic results.

Highly efficient detoxification of Cr(VI) by chitosan-Fe(III) complex: process and mechanism studies.

Metal-biopolymer complexes has recently gained significant attention as an effective adsorbent used for the removal of Cr(VI) from water. Unfortunately, despite increasing research efforts in the field of removal efficiency, whether this kind of complex can reduce Cr(VI) to less-toxic Cr(III) and what are the mechanisms of detoxification processes are still unknown. In this study, despite the highly adsorption efficiency (maximum adsorption capacity of 173.1 mg/g in 10 min), the significant improvement of Cr(VI) reduction by chitosan-Fe(III) complex compared with normal crosslinked chitoan has been demonstrated. In addition, the structure of chitosan-Fe(III) complex and its functional groups concerned with Cr(VI) detoxification have been characterized by the powerful spectroscopic techniques X-ray absorption fine structure (XAFS) and X-ray photoelectron spectroscopy (XPS). The XPS spectra indicated that the primary alcoholic function on C-6 served as an electron donor during Cr(VI) reduction and was oxidized to a carbonyl group. The X-ray adsorption near edge spectra (XANES) of the Cr(VI)-treated chitosan-Fe(III) complex revealed the similar geometrical arrangement of Cr species as that in Cr(III)-bound chitosan-Fe(III). Overall, a possible process and mechanism for highly efficient detoxification of Cr(VI) by chitosan-Fe(III) complex has been elucidate.