An evidence-based guideline on treating lumbar disc herniation with traditional Chinese medicine.

BACKGROUND: Lumbar disc herniation (LDH), as one of the most common causes of lower back pain, imposes a heavy economic burden on patients and society. Conservative management is the first-line choice for the majority of LDH patients. Traditional Chinese medicine (TCM) is an important part of conservative treatment and has attracted more and more international attention. STUDY DESIGN: Evidence-based guideline. METHODS: We formed a guideline panel of multidisciplinary experts. The clinical questions were identified on the basis of a systematic literature search and a consensus meeting. We searched the literature for direct evidence on the management of LDH and assessed its certainty-generated recommendations using the grading of recommendations, assessment, development, and evaluation (GRADE) approach. RESULTS: The guideline panel made 20 recommendations, which covered the use of Shentong Zhuyu decoction, Shenzhuo decoction, Simiao San decoction, Duhuo Jisheng decoction, Yaobitong capsule, Yaotongning capsule, Osteoking, manual therapy, needle knife, manual acupuncture, electroacupuncture, Chinese exercise techniques (Tai Chi, Baduanjin, or Yijinjing), and integrative medicine, such as combined non-steroidal anti-inflammatory drugs, neural nutrition, and traction. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. CONCLUSION: This is the first LDH treatment guideline for TCM and integrative medicine with a systematic search, synthesis of evidence, and using the GRADE method to rate the quality of evidence. We hope these recommendations can help support healthcare workers caring for LDH patients.

Superconductivity in a Layered Cobalt Oxychalcogenide Na2CoSe2O with a Triangular Lattice.

Unconventional superconductivity in bulk materials under ambient pressure is extremely rare among the 3d transition metal compounds outside the layered cuprates and iron-based family. It is predominantly linked to highly anisotropic electronic properties and quasi-two-dimensional (2D) Fermi surfaces. To date, the only known example of a Co-based exotic superconductor is the hydrated layered cobaltate, NaxCoO2·yH2O, and its superconductivity is realized in the vicinity of a spin-1/2 Mott state. However, the nature of the superconductivity in these materials is still a subject of intense debate, and therefore, finding a new class of superconductors will help unravel the mysteries of their unconventional superconductivity. Here, we report the discovery of superconductivity at ∼6.3 K in our newly synthesized layered compound Na2CoSe2O, in which the edge-shared CoSe6 octahedra form [CoSe2] layers with a perfect triangular lattice of Co ions. It is the first 3d transition metal oxychalcogenide superconductor with distinct structural and chemical characteristics. Despite its relatively low TC, this material exhibits very high superconducting upper critical fields, µ0HC2(0), which far exceeds the Pauli paramagnetic limit by a factor of 3-4. First-principles calculations show that Na2CoSe2O is a rare example of a negative charge transfer superconductor. This cobalt oxychalcogenide with a geometrical frustration among Co spins shows great potential as a highly appealing candidate for the realization of unconventional and/or high-TC superconductivity beyond the well-established Cu- and Fe-based superconductor families and opens a new field in the physics and chemistry of low-dimensional superconductors.

Clinical efficacy of ceftazidime/avibactam combination therapy for severe hospital-acquired pulmonary infections caused by carbapenem-resistant and difficult-to-treat Pseudomonas aeruginosa.

OBJECTIVES: This retrospective study aimed to identify the effectiveness of ceftazidime/avibactam (CAZ/AVI) and its optimisation programs for severe hospital-acquired pulmonary infections (sHAPi) caused by carbapenem-resistant and difficult-to-treat Pseudomonas aeruginosa (CRPA and DTR-P. aeruginosa). METHODS: We retrospectively analysed observational data on treatment and outcomes of CAZ/AVI for sHAPi caused by CRPA or DTR-P. aeruginosa. The primary study outcomes were to evaluate the clinical and microbiology efficacy of CAZ/AVI. RESULTS: The cohort consisted of 84 in-patients with sHAPi caused by CRPA (n = 39) and DTR-P. aeruginosa (n = 45) who received at least 72 h of CAZ/AVI therapy. The clinical cure rate was 63.1% in total. There was no significant difference in study outcomes between patients treated with CAZ/AVI monotherapy and those managed with combination regimens. CAZ/AVI as first-line therapy possessed prominent clinical benefits regarding infections caused by DTR-P. aeruginosa. The clinical cure rate was positively relevant with loading dose for CAZ/AVI (odds ratio [OR] 0.03; 95% confidence interval [CI] 0.004-0.19; P < 0.001) and with CAZ/AVI administration by prolonged infusion (odds ratio 0.15; 95% confidence interval 0.03-0.77; P = 0.002). APACHE II score>15 (P = 0.013), septic shock at infection onset (P = 0.001), and CAZ/AVI dose adjustment for renal dysfunction (P = 0.003) were negative predictors of clinical cure. CONCLUSION: CAZ/AVI is a valid alternative for sHAPi caused by CPRA and DTR-P. aeruginosa, even when used alone. Optimisations of the treatment with CAZ/AVI in critically ill patients, including loading dose, adequate maintenance dose and prolonged infusion, were positively associated with potential clinical benefits.

Protective Effect of Salvianolic Acid A against N-Methyl-N-Nitrosourea-Induced Retinal Degeneration.

Objective: Retinal degeneration (RD) is a serious, irreversible, and blinding eye disease, which seriously affects the visual function and quality of life of patients. At present, there is no effective method to treat RD. The final outcome of its development is photoreceptor cell oxidation and apoptosis. Therefore, looking for safe, convenient, and effective antioxidant therapy is still the key research field of Rd. In this study, the mice model of RD was induced by N-methyl-N-nitrosourea (MNU) in vivo to explore the therapeutic effect and mechanism of salvianolic acids (Sal A) on RD. In vitro, the protective effect of Sal A on MNU injured 661 W cell line of mouse retina photoreceptor cone cells was investigated preliminarily. Methods: Male C57BL/6 mice (7-8 weeks old) received a single intraperitoneal injection (ip) of 60 mg/kg MNU or vehicle control. Treatment groups then received Sal-A 0.5 mg/kg and 1.0 mg/kg via daily intravenous injections. On day 7, functional and morphological examinations were performed, including photopic and scotopic electroretinography (ERG) and hematological analyses to observe functional changes and damage to the outer nuclear layer (ONL). On the 3rd and 7th days, the levels of superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were determined. The expression of retinal Bax, Bcl-2, and caspase-3 was quantified by Western blot and RT-PCR assays. 661 W strain of mice retinal photoreceptor cone cells were cultured in vitro and treated with 1 µm MNU. The cells in the treatment group were given 50 µM Sal A as an intervention. The growth of 661 W cells was observed and recorded under an inverted light microscope, and the activity of cells was detected by the MTT method. Results: Sal A treatment was effective against MNU-induced RD in mice at both 0.5 mg/kg/d and 1.0 mg/kg/d doses, and the protective effect was dose-dependent. Sal A can alleviate MNU-mediated alterations to retinal ERG activity and can support maintenance of the thickness of the ONL layer. Sal A treatment increases the expression of retinal SOD and reduces the lipid peroxidation product MDA, suggesting that its protective effect is related to the oxidation resistance. It can offset changes to the expression of apoptotic factors in the retina caused by MNU treatment. Sal A mitigates MNU-mediated damage to cultured mice photoreceptor cone cells 661 W in vitro. Conclusion: Sal A alleviates the damage caused by MNU to retinal photoreceptor cells in vivo and in vivo, and its protective effect is related to its antioxidant and antiapoptotic activities.

Topical retinoic acid induces corneal strengthening by upregulating transglutaminase 2 in murine cornea.

Transglutaminase 2 (TG2) is the most abundant crosslinking enzyme in murine and human cornea, while retinoids are well-known inducers of TG2 expression. This study aims to determine if the retinoic acid supplementation can increase corneal stiffness by crosslinking through upregulating the corneal TG2 expression. The right eyes of C57BL/6 mice were treated with 2 × 10-2M retinol palmitate (VApal) eyedrops or control eyedrops and hold for 30 min, once a day for 28 consecutive days. The WB and qPCR results showed increased expression of TG2 in murine cornea with the prolongation of VApal eyedrop application. After 28 days of VApal eyedrop treatment, the increased TG2 were found catalytically active and distributed in corneal epithelium and stroma as detected by 5-(biotinamido) pentylamine (5-BP) incorporation method and immunofluorescence staining. The transmission electron microscope image revealed that VApal treated cornea manifested with increased collagen density in anterior and middle layer of stroma. The higher elastic module was found among VApal treated cornea by nano-indentation test. In cultured corneal epithelial cells and keratocytes, all-trans retinoid acid (ATRA) treatment increased the content of TG2 in cell lysis and in culture medium. These results indicate that retinoic acid induce the reinforcement of the cornea by TG2 mediated crosslinking via increasing the TG2 expression in corneal epithelium and keratocyte. As TG2 was found to be less in the cornea of keratoconus patients in several RNA-sequencing studies, retinoic acid could serve as a non-invasive prevention method for keratoconus progression.

Berberine hydrochloride inhibits inflammation and fibrosis after canalicular laceration repair in rabbits.

AIMS: This study was designed to investigate the molecular mechanisms underlying the anti-inflammatory and anti-fibrosis effects of Berberine hydrochloride (BBR) following canalicular laceration (CL) surgical repair. MAIN METHODS: We used a rabbit CL model in this study. BBR and the control medicine were administered during and after the surgical operation. The degree of fibrosis in the canaliculi was evaluated using hematoxylin and eosin and Masson's trichrome staining 7 days after the operation. Inflammation inside the canaliculi was observed using a transcanalicular endoscope. Expression levels of inflammatory cell cytokines [tumor growth factor-ß1 (TGF-ß1), connective tissue growth factor (CTGF), intracellular adhesion molecule-I (ICAM-1), and interleukin-ß1 (IL-1ß)] were detected using immunohistochemistry. P38 and ERK1 phosphorylation and activation were determined using western blot analysis. KEY FINDINGS: The degree of inflammation and fibrosis were less in the BBR groups compared to Surgery group. The anti-inflammatory and anti-fibrosis effects of BBR were concentration-dependent. The levels of TGF-ß1, CTGF, ICAM-1, and IL-1ß were significantly lower in the BBR groups compared to Surgery group. BBR reduced the phosphorylation of P38 compared to Surgery group. SIGNIFICANCE: In conclusion, this study shows that BBR can reduce local fibrosis after CL surgical repair via its anti-inflammatory and anti-fibrosis effects.

Nascent RNA sequencing reveals a dynamic global transcriptional response at genes and enhancers to the natural medicinal compound celastrol.

Most studies of responses to transcriptional stimuli measure changes in cellular mRNA concentrations. By sequencing nascent RNA instead, it is possible to detect changes in transcription in minutes rather than hours and thereby distinguish primary from secondary responses to regulatory signals. Here, we describe the use of PRO-seq to characterize the immediate transcriptional response in human cells to celastrol, a compound derived from traditional Chinese medicine that has potent anti-inflammatory, tumor-inhibitory, and obesity-controlling effects. Celastrol is known to elicit a cellular stress response resembling the response to heat shock, but the transcriptional basis of this response remains unclear. Our analysis of PRO-seq data for K562 cells reveals dramatic transcriptional effects soon after celastrol treatment at a broad collection of both coding and noncoding transcription units. This transcriptional response occurred in two major waves, one within 10 min, and a second 40-60 min after treatment. Transcriptional activity was generally repressed by celastrol, but one distinct group of genes, enriched for roles in the heat shock response, displayed strong activation. Using a regression approach, we identified key transcription factors that appear to drive these transcriptional responses, including members of the E2F and RFX families. We also found sequence-based evidence that particular transcription factors drive the activation of enhancers. We observed increased polymerase pausing at both genes and enhancers, suggesting that pause release may be widely inhibited during the celastrol response. Our study demonstrates that a careful analysis of PRO-seq time-course data can disentangle key aspects of a complex transcriptional response, and it provides new insights into the activity of a powerful pharmacological agent.