Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg^-1) and a high dose (15 mg·kg^-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D₃03)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.

It has been demonstrated that long-term space flights have a significantly greater impact on the cardiovascular, skeletal, and nervous systems of astronauts. The structural and functional alterations in the skeletal and muscular systems resulting from exposure to weightlessness can lead to the development of low back pain, significantly impairing the ability of astronauts to perform tasks and respond to emergencies. Both space flight and simulated microgravity have been shown to result in low back pain among astronauts, with the following factors identified as primary contributors to this phenomenon. The occurrence of intervertebral disc (IVD) edema results in the stimulation of type IV mechanoreceptors, which subsequently activate nociceptive afferents. The protrusion of an IVD causes compression of the spinal nerve roots. Furthermore, the elongation of the vertebral column and/or the diminished lumbar curvature of the spine exert traction on the dorsal root nerves. Paravertebral muscle degeneration leads to the inhibition of decreased nociceptive activity of the wide-dynamic range neurons of the spinal dorsal horn. Moreover, endogenous pain descending facilitation triggered by conditioning stimulation can be enhanced via the thalamic mediodorsal nuclei, while endogenous pain descending inhibition triggered by conditioning stimulation can be weakened via the thalamic ventromedial nuclei. Psychological factors may contribute to the development of low back pain. The mechanisms governing the generation, maintenance, and alleviation of low back pain in weightlessness differ from those observed in normal gravitational environments. This presents a significant challenge for space medicine research. Therefore, the elucidation of the occurrence and development mechanism of low back pain in weightlessness is important for the prevention and treatment during space flight. To reduce the incidence of low back pain during long-term missions on the space station, astronauts may choose to wear specialized space clothing that can provide axial physiological loads, designed to stimulate both musculature and skeletal structures, mitigating potential increases in vertebral column length, diminished lumbar curvature, and intervertebral disc edema and/or muscular atrophy. Additionally, assuming a “fetal tuck position” described as the knees to chest position may increase lumbar IVD hydrostatic pressure, subsequently reducing disc volume, rectifying diminished lumbar curvature, and alleviating dorsal root nerve tensions. Moreover, this position may reduce type IV mechanoreceptor facilitation and nerve impulse propagation from the sinuvertebral nerves of the annulus fibrosus. Elongated posterior soft tissues (apophyseal joint capsules and ligaments) with spinal flexion may potentially stimulate type I and II mechanoreceptors. It is also recommended to exercise the paraspinal muscles to prevent and alleviate the decrease in their cross-sectional area and maintain their structure and function. Photobiomodulation has been proved to be an effective means of activating the pain descending inhibition pathway of the central nervous system. In addition, astronauts should be encouraged to participate in mission-related activities and strive to avoid psychological problems caused by the long-term confinement in a small space station. The article presents a concise review of potential causes and targeted treatment strategies for low back pain induced by space flight or simulated microgravity in recent years. Its objective is to further elucidate the mechanisms underlying the occurrence and development of low back pain in weightless environments while providing scientific evidence to inform the development of guidelines for preventing, treating, and rehabilitating low back pain during long-term space flights.

Lipid nanovehicles are currently the most advanced vehicles used for RNA delivery, as demonstrated by the approval of patisiran for amyloidosis therapy in 2018. To illuminate the unique superiority of lipid nanovehicles in RNA delivery, in this review, we first introduce various RNA therapeutics, describe systemic delivery barriers, and explain the lipid components and methods used for lipid nanovehicle preparation. Then, we emphasize crucial advances in lipid nanovehicle design for overcoming barriers to systemic RNA delivery. Finally, the current status and challenges of lipid nanovehicle-based RNA therapeutics in clinical applications are also discussed. Our objective is to provide a comprehensive overview showing how to utilize lipid nanovehicles to overcome multiple barriers to systemic RNA delivery, inspiring the development of more high-performance RNA lipid nanovesicles in the future.

Objective To investigate the factors that lead to diffuse chorioretinal atrophy(DCA)in patients with high myopia(HM)and to establish a prediction model.Methods In this retrospective case-control study,a total of 169 HM patients(338 eyes)admitted to the Department of Ophthalmology,Harbin 242 Hospital from October 2018 to October 2022 were selected.All patients underwent comprehensive ophthalmic examination at the time of inclusion.The incidence of DCA was evaluated according to the International Photographic Classification and Grading System for myopic maculopa-thy,and the risk factors of DCA in HM patients were analyzed by multivariate Logistic regression.The predictive model of DCA in HM patients was established by the receiver operating characteristic curve(ROC)based on risk factors,and the calibration degree of the predictive model was tested by Hosmer-Lemeshow(H-L).Results Among the 169 patients,34 patients were divided into the DCA group,and 135 patients were divided into the non-DCA group;there were statistically significant differences in age and gender distribution between the two groups(both P＜0.05).The axial length(AL),pat-tern standard deviation(PSD),positive rate of carbonic anhydrase 2(CAII)antibody in the DCA group were higher than those in the non-DCA group,while the best corrected visual acuity(BCVA),mean defect(MD)of the visual field,spheri-cal equivalent(SE),deep retinal microvessel density(MVD)and serum 25-hydroxyvitamin D[25(OH)D]were lower than those in the non-DCA group(all P＜0.05).Older age,longer AL and positive CAII antibody were the risk factors for DCA in HM patients(all P＜0.05),while greater deep retinal MVD and higher 25(OH)D were the protective factors(both P＜0.05).ROC analysis showed that the area under the curve of the prediction model for DCA in HM patients was 0.864(95％CI:0.802-0.911,P＜0.001),and the sensitivity and specificity were 85.29％and 88.15％,respectively.According to the H-L test,the prediction model for DCA in HM patients was relatively consistent with the actual results(P＞0.05).Con-clusion The occurrence of DCA in HM patients is affected by age,AL,CAII antibody,deep retinal MVD and 25(OH)D level,and a prediction model established based on the above factors can predict the risk of DCA well.

Objective:To explore the clinical efficacy of cenegermin in the treatment of neurotrophic keratitis (NK).Methods:An observational case series study was adopted.Twenty-two patients (26 eyes) with moderate and severe NK diagnosed in Xi'an No.1 Hospital from June to November 2021 were collected and locally treated with cenegermin eye drop.After the corneal epithelium of the affected eye healed, the treatment ended.Relevant index data of patients before and after treatment were obtained through eye examination.The main indicators were the fiber length of corneal sensation measured by Cochet-Bonnet aesthesiometer, the morphological and quantitative indexes of corneal nerves by in vivo confocal microscopy, including the density of corneal nerve fibers and the number of nerve bifurcation points, and tear meniscus height measured by Keratograph Ocular Surface Analyzer.The secondary indicators were best corrected visual acuity (BCVA) and adverse reactions.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Xi'an No.1 Hospital (No.2021-11). Written informed consent was obtained from each subject. Results:The average treatment duration of patients receiving cenegermin was (4.42±1.86) weeks.After treatment, the corneal epithelial defect of moderate and severe patients healed completely.After treatment, the fiber length of sensation of corneal epithelial defect area and superior defect area were improved, the differences were statistically significant ( Z=-2.45, -3.22; both at P<0.05). There was no significant difference in corneal sensation in inferior, nasal and temporal of corneal epithelial defect area between before and after treatment ( Z=-1.89, -0.31, -1.86; all at P>0.05). After treatment, the average corneal nerve fiber density and the number of corneal nerve fiber bifurcation points in the affected eyes were significantly increased ( Z=-3.95, -3.48; both at P<0.01). There was no significant difference in the tear meniscus height between before and after treatment ( Z=-1.58, P=0.11). After treatment, the BCVA (LogMAR) of patients was 0.22(0.10, 0.40), which was higher than 0.52(0.30, 0.70) at baseline, and the difference was statistically significant ( Z=-3.63, P<0.01). During the treatment of cenegermin eye drops, transient pain occurred in 3 eyes, and intraocular pressure increased in 1 eye, which all returned to normal after symptomatic treatment. Conclusions:Topical application of cenegermin can repair corneal nerve morphology and function in patients with NK.

Objective:To analyze the changes in the income structure of public hospitals at all levels in Hebei Province,evaluate the effectiveness of the compensation mechanism reform in public hospitals of Hebei Province,and provide policy recommendations for optimizing the compensation mechanism.Methods:Select some public hospitals at all levels in Hebei Province as samples,and use structural change analysis to analyze the income structure of the sample hospitals.Result:From 2016 to 2021,the proportion of medical income in tertiary and primary hospitals increased by 2.6 and 9.8 percentage points respectively,while the proportion of medical income in secondary hospitals decreased by 0.6 percentage points.The proportion of consumables revenue in hospitals at all levels has increased,and drug revenue remains the main driving factor for the growth of medical revenue in hospitals at all levels.The contribution rate of drug revenue to the growth of medical revenue in tertiary hospitals is 50％.Conclusion:The optimization of medical income structure in public hospitals in Hebei Province is significant,but the compensation mechanism still needs to be further improved,and the income structure still needs further adjustment.On the basis of consolidating and improving the policy of canceling consumable markup,it is needed to further standardize medical service behavior,improve precise and sustainable financial compensation mechanisms,adjust medical service prices,and broaden financing channels.

Quercetin can mediate the activation of mitogen-activated protein kinase(MAPK)signaling pathways to prevent osteoporosis(OP).This paper comprehensively discusses the interrelationship between MAPK and osteoporosis-related cells based on the latest domestic and international research.Additionally,it elucidates the research progress of quercetin in mediating the MAPK signaling pathway for OP prevention.The aim is to provide an effective foundation for the clinical prevention and treatment of OP and the in-depth development of quercetin.

Objective:To study positive rates and typing of oligoclonal bands (OCB) in patients with neurological disorders, and to reveal the clinical significance and applicational value of OCB test.Methods:A retrospective analysis was performed on the detection results of 3 217 patients with neurological disorders who undertook both serum and cerebrospinal fluid OCBs in the First Hospital of Peking University from January 2012 to August 2022. According to the final diagnosis, the patients were divided into 13 groups including multiple sclerosis (479 cases), neuromyelitis optica spectrum disorders (935 cases), autoimmune encephalitis (192 cases), viral encephalitis (94 cases), nervous system complication after HSCT (232 cases), Guillain-Barré syndrome (644 cases), chronic inflammatory demyelinating polyneuropathy (157 cases), etc. Cerebrospinal fluid and serum OCBs were detected using isoelectric focusing electrophoresis combining immunofixation, then classified into Ⅰ-Ⅴ types according to the morphology. Consequently, positive rates and types were analyzed for each group. χ2 test was used for comparison between groups. Results:The positive rates of cerebrospinal fluid OCB in multiple sclerosis, nervous system complication after hematopoietic stem cell transplantation (HSCT), autoimmune encephalitis, viral encephalitis, neuromyelitis optica spectrum disorders, Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy were respectively 66.8% (320/479), 48.7% (113/232), 46.4%(89/192), 19.1% (18/94), 17.6% (165/935), 9.9% (64/644), 5.1% (8/157). For patients with multiple sclerosis, neuromyelitis optica spectrum disorders, viral encephalitis, and autoimmune encephalitis, Type Ⅱ bands took the majority of cerebrospinal fluid OCB-positive cases with the rates of 94.1% (301/320), 78.7% (70/89), 77.8% (14/18), and 77.6% (128/165) respectively, indicating intrathecal IgG synthesis; for patients with nervous system complication after HSCT, Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy, type Ⅳ bands took the majority of cerebrospinal fluid OCB-positive cases with the rates of 94.7% (107/113), 82.8% (53/64) and 100% (8/8), indicating no obvious intrathecal IgG synthesis. The positive rates of cerebrospinal fluid oligoclonal bands were significantly different among all groups (χ 2=1 268.31, P<0.001). Conclusion:The positive rates of cerebrospinal fluid oligoclonal bands are different among different neurological disorders, in which the positive rate of cerebrospinal fluid OCB is higher with type Ⅱ bands as the majority type in multiple sclerosis, which indicates that the detection and typing of cerebrospinal fluid OCB are helpful for the diagnosis of various neurological diseases, especially for multiple sclerosis.

Objective:To construct a recombinant bioluminescent bacteriophage (HT7) targeting Escherichia coli, and evaluate its ability to identify Escherichia coli. Methods:Initially, pCRISPR-sg (1-10) and PFN-1000 plasmid strains were constructed by genetic engineering, and the most efficient small guild RNA (sgRNA) were screened by bilayer plate. By the gene editing technique, which comprised homologous recombination and clustered regularly interspaced short palin dromic repeats (CRISPR)-Cas system, the Nanoluc luciferase gene was integrated into the downstream non-coding region of 10A gene of T7 phage, to constructe the bioluminescent phage HT7 successfully. The difference of biological characteristics between HT7 phage and T7 phage was evaluated by plaque assay and liquid amplification assay. In addition, 51 strains of Escherichia coli, 20 strains of Klebsiella pneumoniae, 14 strains of Staphylococcus aureus, 6 strains of Enterococcus faecium, 5 strains of Enterococcus faecalis, 3 strains of Acinetobacter baumannii and 1 strain of Pseudomonas aeruginosa were collected and isolated to evaluate the limit of detection and specificity of HT7 phage. Results:Among the 10 CRISPR-targeted cleavage systems constructed, sgRNA8 exhibited the highest cleavage efficiency, with a cleavage rate of 0.18. After three rounds of recombination screening using the pCas9/pCRISPR/PFN-1000 triple-plasmid system, PCR validation yielded recombinant phage bands at 2 798 bp, indicating the successful construction of the HT7 phage. The recombinant phage showed significant differences in biological characteristics in terms of lysis efficiency ( P<0.001), one-step growth curve ( P=0.001), and infection multiplicity ( P=0.031). Both lysis burst time and log growth node were extended by 10 min, with the optimal infection multiplicity being 0.1. Clinical sample testing identified lysis of 6 strains of Escherichia coli within 4.5 h, while other strains remained unaffected, with detection of pathogenic bacteria below 10 CFU/ml. Conclusions:The developed pCas9/pCRISPR/PFN-1000 triple-plasmid editing system efficiently edits the bacteriophage genome. The constructed HT7 fluorescent bacteriophage enables the detection of Escherichia coli below 10 CFU/ml within 4.5 hours, demonstrating low detection limits and high detection specificity.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.