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 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 observe the impacts of Xingnao Kaiqiao acupuncture(AC)method on synaptic plasticity and intestinal flora in stroke rats.Methods The middle cerebral artery occlusion method was applied to establish a rat model of ischemic stroke,and the rats with Zea Longa score of 1-3 were randomly grouped into model(M)group and AC group,and rats without middle cerebral artery occlusion were regarded as the sham(S)group,with 15 animals per group.After modeling,groups S and M were not intervened,and group AC was intervened with AC,once a day,for 7 consecutive days.The Zea Longa method was applied to assess neurological function;transmission electron microscopy(TEM)and Golgi staining were applied to visualize synaptic structures in the ischemic penumbra(IP);Western blot was applied to detect the protein expression of BDNF,SYN and GAP-43 in the IP cortex tissue;ELISA was applied to detect the content of IL-1β,TNF-α,IL-17 in the IP cortex tissue;16S rDNA amplification and sequencing method was applied to analyze the structure of rat intestinal flora.Results Compared with the S group,the M group had irregular synaptic morphology,blurred boundaries,thinned postsynaptic zona densities,higher neurological function scores,protein levels of BDNF,SYN,GAP-43 and content of IL-1β,TNF-α,IL-17(P<0.05),and lower density of spines(P<0.05).Compared with the M group,AC intervention could improve the synaptic morphology,reduce the neurological function score and content of IL-1β,TNF-α,IL-17(P<0.05),and increase the density of dendritic spines,BDNF,SYN,and GAP-43 protein levels(P<0.05).The intestinal flora analysis showed that compared with the S group,the M group had a reduced diversity and number of bacterial flora,at the phylum level,the M group had a lower relative abundance of Bacteroidetes,and higher F/B ratio(P<0.05);at the genus level,the group M had a higher relative abundances of Bacteroides and Rikenbacteria(P<0.05),and lower relative abundances of Lactobacillus and Lachnospiraceae_UCG-006(P<0.05).Compared with the M group,AC intervention could increase the diversity and quantity of the flora,increase the relative abundance of Bacteroidetes and reduce the F/B ratio at the phylum level(P<0.05),increase the relative abundances of Faecalibacterium and Lactobacillus and reduce the relative abundances of Riken,Escherichia-Shigella,etc.at the genus level(P<0.05).Conclusion Xingnao Kaiqiao acupuncture can restore the relative abundance of beneficial bacteria,reduce the relative abundance of harmful bacteria,attenuate brain inflammation,improve synaptic plasticity,and reduce neurological damage in stroke rats.

Objective:To explore clinical features, diagnosis, localization, and therapeutic strategy of migratory pharyngeal and cervical esophageal foreign bodies.Methods:A total 23 cases of pharyngeal and cervical esophageal migratory foreign bodies were admitted between January 2015 and December 2021. There were 14 females and 9 males with the age ranged from 35 to 82 (55.0±12.7)years. In all the cases, esophageal CT was taken to confirm the esophageal foreign body. Multiplanar reconstruction (MPR) was performed to locate the foreign body from the horizontal, coronal and sagittal dimensions as well as the corrected reconstructed MPR. According to the location of the foreign body, appropriate surgical method was selected.The symptoms, complications, types of foreign body, positioning, surgical methods, and relevant information were recorded.Data were analyzed using the descriptive method and SPSS 25.0 software.Results:The clinical symptoms of 23 migrating esophageal foreign bodies included pharyngodynia (20/23), foreign body sensation (6/23), hoarsenss (1/23), difficulty in turning neck(1/23), difficulty in opening mouth (1/23), fever (7/23), poor appetite (1/23), and abdominal pain (1/23). The foreign bodies included 19 fish bones, 2 wires, 1 embroidery needle and 1 chicken bone. There were 9 cases (39.1%) of foreign bodies located in extraluminal cervical esophagus, 2 cases (8.7%) of foreign bodies located in the muscular layer of the cervical esophagus and 12 cases (52.2%) of foreign bodies located in pharynx. Twenty-one cases of foreign bodies were removed by cervical lateral incision, in which 11 were removed by cervical lateral incision directly, 10 by the second lateral cervical incision after the foreign bodies were accurately located by MPR and/or corrected MPR, 1 foreign body was removed by incision of the pharyngeal mucosa under suspension laryngoscope, 1 foreign body was removed by tracheoscopy. Compared with patients with intraluminal foreign bodies ( n=308) treated in the same period, intake of fishbone [19 (19/23) vs. 133 (82.6% (43.2%, 133/308), OR=7.31] and first visit was more than 24 hours [20(87.0%, 20/23) vs. 77(25.0%, 77/308), OR=17.2] were the significant risk factors of migratory esophageal foreign bodies. Conclusions:MPR and the corrected MPR can accurately locate the migrating pharyngeal and cervical esophageal foreign bodies, by providing more intuitive imaging evidence for doctors, which provide imaging basis for formulation of surgical programs. Foreign bodies in pharyngeal and cervical esophagus need to be treated as soon as possible, otherwise they are easy to migrate, leading lead to serious complications.

RNA modifications affect many biological processes and physiological diseases. The 5-methylcytosine (m⁵C) modification regulates the progression of multiple tumors. However, its characteristics and functions in hepatocellular carcinoma (HCC) remain largely unknown. Here, we found that HCC tissues had a higher m⁵C methylation level than the adjacent normal tissues. Transcriptome analysis revealed that the hypermethylated genes mainly participated in the phosphokinase signaling pathways, such as the Ras and PI3K-Akt pathways. The m⁵C methyltransferase NSUN2 was highly expressed in HCC tissues. Interestingly, the expression of many genes was positively correlated with the expression of NSUN2, including GRB2, RNF115, AATF, ADAM15, RTN3, and HDGF. Real-time PCR assays further revealed that the expression of the mRNAs of GRB2, RNF115, and AATF decreased significantly with the down-regulation of NSUN2 expression in HCC cells. Furthermore, NSUN2 could regulate the cellular sensitivity of HCC cells to sorafenib via modulating the Ras signaling pathway. Moreover, knocking down NSUN2 caused cell cycle arrest. Taken together, our study demonstrates the vital role of NSUN2 in the progression of HCC.
Humans ; ADAM Proteins ; Apoptosis Regulatory Proteins ; Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Membrane Proteins ; Methyltransferases/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Repressor Proteins ; RNA, Messenger/metabolism* ; Sorafenib ; RNA Methylation/genetics*

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 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.

Objective To investigate the protective roles of Epigallocatechin gallate (EGCG) on liver ischemia reperfusion injury (IRI) in rats.Methods 30 healthy male SD rats were selected and equally and randomly divided into 3 groups.Sham group,IRI group and IRI-EGCG group were established to construct 70％ liver IRI rat model.Drinking water with 0.4 mg/ml EGCG was administered for 2 weeks before the experiment in IRI-EGCG group.HE staining was performed to evaluate the injury.Transaminases in serum were investigated to assess liver injury.p-p85 and p-AKT was detected by Western-blot assay.qPCR was carried out to study the mRNA expression of TNF-α,IL-6 and IL-1β in liver tissue.The secretion of TNF-α,IL-6 and IL-1 β in serum was examined with ELISA assay.Results EGCG pretreatment reduced ASTand ALT in serum [AST:(550.0 ±66.5) IU/L vs.(220.0 ±63.5) IU/L;ALT:(376.0 ± 25.7) IU/L vs.(158.0 ± 33.1) IU/L,all P ＜ 0.05] and mitigated liver tissue damage.p-p85 and p-AKT increased due to liver IRI,and IRI-EGCG group showed higher expression of p85 and AKT.The proinflammatory cytokines of TNF-α,IL-6 and IL-1 β exhibited a relatively lower mRNA expression in IRI-EGCG group comparing with IRI group.IRI-EGCG group also revealed a decreased secretion of TNF-α,IL-6 and IL-1β in serum [TNF-α:(398.0±33.4) ng/Lvs.(211.0±23.6) ng/L;IL-6:(341.0±27.3) ng/L vs.(187.0±19.6) ng/L;IL-1β:(486.0±43.7) ng/L vs.(352.0±31.5) ng/L;allP＜0.05].Conclusion EGCG pretreatment can enhance IRI-induced activation of PI3K/AKT signaling and reduce the release of proinflammatory cytokines to exert liver protective effects.

OBJECTIVETo study the CPS-II mechanism underlying the pathological process of elevated blood ammonia leading to liver injury.

METHODSAn in vitro hyperammonemia hepatocyte cell model was constructed by exposure to various concentrations of NH4Cl. The subsequent changes to cellular morphology were observed by microscopy. to cell apoptosis were determined by flow cytometry, and to mRNA and protein expression of CPS-II were examined by real-time PCR and western blotting, respectively.

RESULTSExposure to NH₄Cl led to dose-dependent morphological damage, apoptosis and necrosis of the hepatocytes. The apoptosis rate was significantly higher for the high-dose group than for the control (no exposure) group (24.7% ± 2.39% vs. 4.1% ± 0.78%, q =8.06, P less than 0.05). Expression of the CPS-II mRNA was significantly elevated in response to NH₄Cl exposure (vs. the control group; F=191.881, P < 0.05).The CPS-II mRNA expression level increased with increasing NH₄Cl concentration (grey values: 1.040 ± 0.045, 1.641 ± 0.123, 2.285 ± 0.167 and 3.347 ± 0.124, respectively). The CPS-II protein expression level was also significantly enhanced in response to the NH₄Cl exposures (CPS-II protein and internal GAPDH grey value ratios: 0.099 ± 0.0130, 0.143 ± 0.025, 0.161 ± 0.036 and 0.223 ± 0.042, respectively; t=3.825, 3.968 and 6.908, P less than 0.05).

CONCLUSIONCPS-II mRNA and protein expression levels become elevated with increase in the NH₄Cl concentrations, suggesting that in addition to the urea cycle, CPS-II may play an important role in the ammonia metabolism under the condition of hyperammonemia.