Azvudine and nirmatrelvir/ritonavir (Paxlovid) are recommended for COVID-19 treatment in China, but their safety and efficacy in the elderly population are not fully known. In this multicenter, retrospective, cohort study, we identified 5131 elderly hospitalized COVID-19 patients from 32,864 COVID-19 patients admitted to nine hospitals in Henan Province, China, from December 5, 2022, to January 31, 2023. The primary outcome was all-cause death, and the secondary outcome was composite disease progression. Propensity score matching (PSM) was performed to control for confounding factors, including demographics, vaccination status, comorbidities, and laboratory tests. After 2:1 PSM, 1786 elderly patients receiving azvudine and 893 elderly patients receiving Paxlovid were included. Kaplan-Meier and Cox regression analyses revealed that compared with Paxlovid group, azvudine could significantly reduce the risk of all-cause death (log-rank P = 0.002; HR: 0.71, 95% CI: 0.573-0.883, P = 0.002), but there was no difference in composite disease progression (log-rank P = 0.52; HR: 1.05, 95% CI: 0.877-1.260, P = 0.588). Four sensitivity analyses verified the robustness of above results. Subgroup analysis suggested that a greater benefit of azvudine over Paxlovid was observed in elderly patients with primary malignant tumors (P for interaction = 0.005, HR: 0.32, 95% CI: 0.18-0.57) compared to patients without primary malignant tumors. Safety analysis revealed that azvudine treatment had a lower incidence of adverse events and higher lymphocyte levels than Paxlovid treatment. In conclusion, azvudine treatment is not inferior to Paxlovid treatment in terms of all-cause death, composite disease progression and adverse events in elderly hospitalized COVID-19 patients.

Objective To analyze the magnetic resonance images (MRI) of patients with spinal epidural lipomatosis (SEL) in high-altitude areas and to determine the optimal cut-off value for diagnosis with epidural fat thickness. Methods This retrospective study included patients who underwent lumbosacral MRI examination for lumbosacral pain in Ping’an District Hospital of Traditional Chinese Medicine, Haidong City, China from January 1, 2021 to December 31, 2022. The epidural fat thickness in vertebral segments T12/L1 to L5/S1 was compared between the SEL group and the non-SEL group. The diagnostic efficacy with different cut-off values at each vertebral segment was evaluated. Between-group comparisons were performed using the t-test, Mann-Whitney U test, chi-square test, or modified chi-square test. The area under the receiver operating characteristic (AUC) was used to evaluate the diagnostic efficiency. The DeLong test was used to compare AUC between the two groups. Results A total of 370 patients were included (60 in the SEL group and 310 in the non-SEL group). There were no significant differences in age, sex, height, body weight, and body mass index between the two groups (all P > 0.05). At different vertebral segments, the epidural fat thickness was significantly higher in the SEL group than in the non-SEL group (all P < 0.05). The cut-off values for SEL diagnosis with epidural fat thickness in segments T12/L1 to L5/S1 were 2.23, 4.25, 4.85, 5.57, 7.21, and 8 mm, respectively. The AUC of MRI SEL diagnosis with epidural fat thickness in segment L5/S1 was the highest (0.945, 95% confidence interval [CI]: 0.916-0.966, P < 0.001). SEL diagnosis with epidural fat thickness > 8 mm in segment L5/S1 was the most accurate, with an AUC of 0.931 (95% CI: 0.901-0.955, P < 0.001), a sensitivity of 95.0%, and a specificity of 91.3%; this AUC was significantly higher than those of diagnosis with other cut-off values (all P < 0.05). Conclusion SEL patients have significantly increased epidural fat in the spinal canal. Epidural fat thickness > 8 mm in segment L5/S1 can be used for diagnosis of SEL with improved efficiency and accuracy.

Objective To explore the clinical efficacy of arthroscopy combined with cubital tunnel expansion and plasty in the treatment of patients with elbow osteoarthritis and cubital tunnel syndrome.Methods A total of 101 patients with elbow osteoarthritis and cubital tunnel syndrome who were admitted to the Department of Orthopedics,Cangzhou Hospital of Integrated TCM-WM Hebei from September 2020 to August 2023 were selected as the research subjects.According to different surgical methods,the patients were divided into an observation group(n=51)and a control group(n=50).The surgical method in the observation group was arthroscopy combined with cubital tunnel expansion and plasty,and the surgical method in the control group was conventional cubital tunnel expansion and plasty.The operation time,intraoperative blood loss,length of hospital stay,and complications were observed and recorded for both groups.The mayo elbow performance score(MEPS)was used to assess elbow function,the activities of daily living(ADL)scale was used to evaluate daily living ability,and the visual analogue scale(VAS)was used to assess pain levels preoperatively and at 6 months postoperatively.Elbow range of motion,including pronation,supination,and flexion-extension,was measured using a goniometer.Nerve recovery was evaluated by measuring compound muscle action potential(CMAP)of the abductor digiti minimi,ulnar nerve conduction velocity(NCV),and motor evoked potential latency(MEPLP)using a Keypoint electromyography device.Results The operation time and length of hospital stay in the observation group were significantly shorter than those in the control group,and the intraoperative blood loss and complications were significantly less than those in the control group(P＜0.05).Before operation,there were no statistically significant differences in MEPS scores,ADL scores and VAS scores between the observation group and the control group(P＞0.05);6 months after operation,the MEPS scores and ADL scores of patients in the observation group were signifi-cantly higher than those in the control group,and the VAS scores were significantly lower than those in the control group(P＜0.05).Before operation,there were no statistically significant differences in pronation,supination and flexion-extension between the observation group and the control group(P＞0.05);6 months after operation,the pronation,supination and flexion-extension of patients in the two groups were significantly higher than those before operation(P＜0.05),but there were no statistically significant differences in pronation,supination and flexion-extension between the observation group and the control group(P＞0.05).Before operation,there were no statistically significant differences in CMAP,NCV and MEPLP between the observation group and the control group(P＞0.05);6 months after operation,the CMAP and NCV of patients in the observation group were significantly higher than those in the control group,and the MEPLP ratio was significantly lower than that in the control group(P＜0.05).Conclusion Conventional cubital tunnel expansion and plasty and arthroscopy combined with cubital tunnel expansion and plasty can improve the range of motion of the elbow in patients with elbow osteoar-thritis and cubital tunnel syndrome,but the latter features less damage and faster recovery,is better in improving elbow function and daily living ability,reducing pain,and adjusting electromyographic examination indicators,and has fewer complications.

Objective To analyze the literature of leech in medicine using CiteSpace knowledge map,comprehensively understand the research status,hotspots and development trends of component analysis and pharmacological effects of leech,and provide reference for researchers in the field of leech.Methods CiteSpace 6.1 R3 software was used to analyze the relevant literature of leech in the field of medical research in CNKI and Web of Science databases from 1996 to 2022.The bibliometric and visual analysis of the number of articles,authors,research institutions,keyword co-occurrence,clustering and emergence were carried out.Results A total of 1 115 Chinese articles in CNKI database and 237 English articles in Web of Science database were included.The analysis of Chinese and English literature showed that the author Shi Hongzhuan had the largest number of Chinese articles,and the German author Hildebrandt had the largest number of English articles.Shandong University of Traditional Chinese Medicine and Chinese Academy of Sciences were the institutions with the largest number of articles in Chinese and English respectively.The country with the most published English literature is the United States.Chinese and English keyword co-occurrence and cluster analysis showed that Chinese literature focused on the study of its active ingredient hirudin,including molecular structure,pharmacological efficacy,mechanism of treating thrombosis,coronary heart disease,kidney disease and other diseases,and paid attention to the differences in the active ingredients of different types of leeches.In addition,English literature focused on the clinical external use of living leeches.The emergence of keywords suggested that the mechanism of action,the search and synthesis of hirudin analogues,and the pharmacodynamic mechanism of compatibility application were not only the current research hotspots,but also the future hot spots.Conclusion The analysis of leech components,the pharmacological mechanism of leech in the treatment of cardiovascular diseases,chronic kidney diseases and other diseases have always been the research hotspots.Hirudin analogues,the pharmacodynamic mechanism of compatibility application,network pharmacology,molecular docking and so on may be the future research hotspots and trends of leeches.

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) positively affect the initial control of non-small cell lung cancer (NSCLC). Rapidly acquired resistance to EGFR-TKIs is a major hurdle in successful treatment. However, the mechanisms that control the resistance of EGFR-TKIs remain largely unknown. RNA structures have widespread and crucial functions in many biological regulations; however, the functions of RNA structures in regulating cancer drug resistance remain unclear. Here, the psoralen analysis of RNA interactions and structures (PARIS) method is used to establish the higher-order RNA structure maps of EGFR-TKIs-resistant and -sensitive cells of NSCLC. Our results show that RNA structural regions are enriched in untranslated regions (UTRs) and correlate with translation efficiency (TE). Moreover, yrdC N⁶-threonylcarbamoyltransferase domain containing (YRDC) promotes resistance to EGFR-TKIs. RNA structure formation in YRDC 3' UTR suppresses embryonic lethal abnormal vision-like 1 (ELAVL1) binding, leading to EGFR-TKI sensitivity by impairing YRDC translation. A potential therapeutic strategy for cancer treatment is provided using antisense oligonucleotide (ASO) to perturb the interaction between RNA and protein. Our study reveals an unprecedented mechanism through which the RNA structure switch modulates EGFR-TKI resistance by controlling YRDC mRNA translation in an ELAVL1-dependent manner.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; ErbB Receptors/metabolism* ; GTP-Binding Proteins/therapeutic use* ; Lung Neoplasms/genetics* ; Mutation ; Protein Kinase Inhibitors/therapeutic use* ; RNA ; RNA-Binding Proteins/genetics* ; Tyrosine Kinase Inhibitors/therapeutic use*

Postmortem changes on corpses appear immediately after death, and can transform the original structure characteristics of the corpse to different degrees as well as show specific changes on computed tomography （CT） images, sometimes with false positives and false negatives, influencing the identification of injuries or diseases. This paper systematically summarizes the postmortem changes of computed tomography imaging characteristics on corpses, to further expand the application of virtopsy in the practices of forensic pathology identification, and provide reference for the identification of injuries, diseases and changes after normal death.
Autopsy ; Cadaver ; Forensic Pathology/instrumentation* ; Humans ; Postmortem Changes ; Research/trends* ; Tomography, X-Ray Computed

Objective? To evaluate the impacts of early enteral nutrition (EEN) support and delayed enteral nutrition(DEN) support in the nutritional status and infection complications in patients with severe traumatic brain injury. Methods? The articles of randomized controlled trials about EEN support and DEN support on the nutritional status and infection complications in patients with severe traumatic brain injury were searched in CBMdisc, CNKI, Wanfang Data, VIP, Cochrane Library, Web of Science, PubMed, EMbase from 1990 to 2017. The quality evaluation method in Cochrane-Handbook5.0 handbook was adopted to evaluate the quality of articles and test the heterogeneity of the included articles. Fixed-effect model or random-effect model were used to merge the effects. Results? A total of 10 randomized controlled trials were included. Meta-analysis results proved that, compared with DEN support, EEN support can increase the level of serum total protein, albumin and peripheral lymphocyte count (Z=10.20, 4.23, 5.24;P＜0.01) and reduce the incidence of pulmonary infection and craniocerebral infection in patients with craniocerebral injury (Z=4.12, 2.15; P＜0.05), but it has no effect on the incidence of upper gastrointestinal hemorrhage in patients with craniocerebral injury (Z=0.82, P=0.41). Conclusions? Compared with DEN support (within 48 hours of admission), EEN support (48 hours after admission) can effectively improve serum total protein and albumin, improve nutritional status, increase peripheral lymphocyte count, increase patient resistance and reduce the occurrence of cranial infection and pulmonary infection. Therefore, patients with severe craniocerebral injury should receive EEN support if there is no contraindication.

Objective: To investigate the clinical characteristics and treatment options for otogenic intracranial infections. Method: Clinical records of all the patients of otogenic intracranial infections admitted to the First Affiliated Hospital of Zhejiang University from 2008 to 2016 were retrospectively analyzed. Their clinical presentations, radiological findings, culture results, and medical and surgical therapy modalities, as well as treatment outcomes were studied. Results: Sixteen cases were identified. The majority of the otogenic patients had a history of cholesteatoma, other rare events included congenital cerebrospinal fluid otorhinorrhea, Gorham-Stout disease and after radiation therapy for nasopharyngeal carcinoma. Meningitis, cerebral venous thrombosis and brain abscess were the primary intracranial infection. Eight patients had received modified radical mastoidectomy at least one time. Results of routine culture for cerebrospinal and pus samples had high negative rate. All patients received initial empirical broadspectrum intravenous antibiotics therapy. Four cases of brain abscesses were drained or excised at the same time for otologic surgery. The mortality rate was 6.25% (1 case). Conclusions Cholesteatoma is still the most commonly primary disease of otogenic intracranial complications. Diagnosis and treatment of otogenic intracranial infections require multidisciplinary cooperation. Surgical intervention for primary ear lesions and intracranial abscess is still the main option in the treatment of otogenic intracranial infections.

Objective To investigate the clinical features of myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) associated hypertrophic pachymeningitis (HP).Methods Clinical data of 4 casesdiagnosed with MPO-ANCA vasculitis complicated with HP in our hospital were analyzed retrospectively and the related literaturewere reviewed.Results Four male patients with an age range from 44 to 66 years were diagnosed with ANCA-associated HP.The main clinical manifestations included headache and withvarious degree ofmultiple cranial paralysis.During active phase of the disease,all patients showed perinuclear(p)-ANCA positive,elevated levels of inflammatory biomarkers and titers of MPO-ANCA,whereas renal function,cytoplasmic (c)-ANCA and protease 3 (PR3)-ANCA were negative.Contrast-enhanced cranial magnetic resonance imaging (MRI) scan showed obviously thickened dura mater and sinusitis or mass in paranasal sinus.Four patients were sensitive to glucocorticoid.Three patients had a relapse during glucocorticoid tapering and were undercontrol when the dosage of glucocorticoid was increased and immunosuppressive agents were added.Levels of inflammatory biomarkers,titers of MPO-ANCA and p-ANCA recovered to normal,and the dural thickness on MRI was reduced in the remission stage.Conclusion MPO-ANCA associated HP is a type of central nervous system involvement in ANCA associated vasculitis (AAV).It involves the upper respiratory tract more frequently,and less frequently progresses to systemic AAV.This should be taken into consideration when middle-aged and elderly patients presented with headache and multiple cranial neuropathies.Enhanced MRI is the preferred examination for diagnosis,and dural biopsy should be done when necessary.

Objective To investigate the inhibitory effect of Glycyrrhizin in MHCC97-H cell line in vitro and explore the relevant mechanism.Methods MHCC97-H cells were cultured in vitro and treated with Glycyrrhizin in different concentrations and then cell viability was assayed at different time points.The concentration and time were selected with 50％ cell viability.MHCC97-H cell plate clone formation assay and invasion-migration experiment were also performed to study the tumor-suppressor efficacy of Glycyrrhizin.Acridine orange staining was used to evaluate the formation of autophagic vacuoles.Meanwhile,3-MA and Atg7-siRNA were both employed to avoid the autophagy activation in MHCC97-H cells and cell viability was reassessed.Western-blot was carried out to study the expression of autophagic proteins of LC3B,p-mTOR and p-ERK1/2.Results It showed Glycyrrhizin significantly inhibited MHCC97-H cell viability and the concentration and time at 50％ cell viability were 2 mmol/L and 48 h respectively.Clone number in Glycyrrhizin group was significantly smaller than that in the control group (176.7 ± 14.5 vs.410.0 ± 32.1).Invasion-migration rate was also lower in Glycyrrhizin group compared with the control group (41.0％ ±3.8％ vs.100％).Autophagic vacuoles was increased in MHCC97-H cells when treated with Glycyrrhizin and expression of LC3B-Ⅱ was enhanced and LC3B-Ⅱ/I Ratio was increased,at the same time degradation of P62 was accelerated.Reduced p-mTOR in concurrence with upregulated p-ERK1/2 could be observed in MHCC97-H cells administered with Glycyrrhi-zin.Cell groups additionally treated with 3-MA or Atg7-siRNA exerted higher cell viability (64.3％ vs.45.9％ and 67.7％ vs.47.1％,respectively).Conclusion Glycyrrhizin can induce excessive autophagy in hepatocellular carcinoma cells to cause autophagic cell death and exhibit great potential in clinical application.