ObjectiveTo study the effect and efficacy of Nirmatrelvir tablet/Ritonavir tablet in the treatment of patients with COVID‑19 infection aged ≥90 years, to inform pharmacological treatment of patients aged ≥90 years with COVID‑19 infection. MethodsMild to moderate COVID-19 patients who were hospitalized in the Department of Geriatrics of the First Affiliated Hospital of the Naval Medical University from March 2022 to June 2024, aged ≥90 years, and who had not been vaccinated against novel coronavirus were selected as the research subjects. A total of 112 patients who received Nirmatrelvir tablet/Ritonavir tablet antiviral treatment within 5 days after the diagnosis of COVID‑19 infection were referred to the drug group, and 80 patients who were not treated with antiviral drugs were referred to as the control group. A retrospective research method was employed to gather and compare patitents’ clinical laboratory data before and after antiviral treatment, such as blood routine tests, inflammatory markers, coagulation function tests, liver and renal function tests, electrolyte levels, and blood gas analysis, between the drug group and the control group. Additionally, the time duration to negative conversion and 28-day all-cause mortality rates were compared between the two groups. Logistic regression analysis was conducted on factors associated with mortality, such as the oxyhemoglobin saturation after treatment, time duration to negative conversion, and the use of Nirmatrelvir tablet/Ritonavir tablet or not, while correlation analysis was performed to evaluate the efficacy of Nirmatrelvir tablet/Ritonavir tablet based on the level of oxyhemoglobin saturation, time duration to negative conversion, and all-cause mortality rates within 28 days. ResultsAfter treatment, oxyhemoglobin saturation increased in the drug group (t=-2.726, P=0.011), and the differences between the indicators in the control group compared to the pre-treatment period were not statistically significant (all P>0.05). The time to negative conversion and 28-day all-cause mortality of control group were higher than those in the drug group (all P<0.05). Logistic regression analysis revealed that the lower the post-treatment oxyhemoglobin saturation, the lower the use of Nirmatrelvir tablet/Ritonavir tablet, the longer the time to conversion, and the higher the mortality rate of the patients (all P<0.05). Correlation analysis showed that treatment with Nirmatrelvir tablet/Ritonavir tablet resulted in higher oxyhemoglobin saturation (r=0.425, P=0.008), shorter time to negative conversion (r=-0.398, P=0.013), and lower all-cause mortality rates within 28 days (r=-0.370, P=0.022). ConclusionNirmatrelvir tablet/Ritonavir tablet is effective in mild and moderate infection patients aged ≥90 years who have not been vaccinated against COVID‑19 infection, and can increase patients’ oxyhemoglobin saturation, shorten the time to negative conversion, and reduce 28-day all-cause mortality rate.

OBJECTIVE To explore the in vitro and in vivo inhibitory effects and mechanism of metformin on the malignant biological behavior of esophageal squamous cell carcinoma （ESCC） cells by the hypoxia inducible factor-1α （HIF-1α）/interleukin-8 （IL-8） signaling pathway. METHODS Human ESCC TE1 cells were assigned into blank group， metformin low-， medium-， and high-dose groups （0.5， 1， 2 mmol/L）， IDF-11774 （HIF-1α inhibitor） group （20 μmol/L）， and high-dose metformin+HIF-1α activator dimethyloxalylglycine （DMOG） group. After 24 h treatment， cell proliferation [measured by the positive rate of 5-ethynyl- 2′-deoxyuridine （EdU） and optical density at 450 nm （OD450 value）]， apoptosis， invasion and migration as well as mRNA expressions of proliferating cell nuclear antigen （PCNA）， Bcl-2 interacting mediator of cell death （Bim）， migration and invasion enhancer 1 （MIEN1）， and matrix metalloproteinase-9 （MMP-9）， and protein expressions of HIF-1α and IL-8 in the cells were detected. The xenograft tumor model of nude mice was established. Thirty nude mice were randomly divided into blank group， metformin low-， medium-， and high-dose groups （i.g. administration of metformin 62.5， 125， 250 mg/kg+i.p. administration of equal volume of normal saline）， IDF-11774 group （i.g. administration of 50 mg/kg IDF-11774+i.p. administration of equal volume of normal saline） and high-dose metformin+DMOG group （i.g. administration of metformin 250 mg/kg+i.p. administration of DMOG 250 mg/kg）， with 5 mice in each group. They were given relevant medicine， once a day， for 4 consecutive weeks； the mass and volume of the tumor and protein expressions of HIF-1α and IL-8 in the tumor tissue were determined. RESULTS The EdU positive rate， OD450 value， cell invasion number， scratch healing rate， mRNA expressions of PCNA， MIEN1 and MMP-9， protein expressions of HIF-1α and IL-8， as well as the mass and volume of transplanted tumors and protein expressions of HIF-1α and IL-8 in tumor tissues were decreased by metformin in concentration/dose-dependent manner （P＜0.05）. Additionally，metformin increased the apoptosis rate and mRNA expression of Bim in cells （P＜0.05）. The trend of changes in corresponding indicators in the IDF-11774 group was consistent with that in the metformin groups， whereas DMOG could significantly attenuate the aforementioned effects of high-concentration/high-dose metformin （P＜0.05）. CONCLUSIONS Metformin can inhibit the proliferation， invasion， migration of TE1 cells， and tumor growth of nude mice， and induce cell apoptosis， the mechanism of which may be related to the inhibition of HIF-1α/IL-8 signaling pathway.

Objective To analyze of the therapeutic effect of Weifuchun capsules combined with quadruple therapy on elderly patients with chronic atrophic gastritis(CAG)infected with Helicobacter pylori(Hp).Methods Elderly Hp-infected CAG patients admitted to Affiliated Hospital of Shaoxing University from April 2019 to April 2023 were divided into a control group(treated with classic quadruple therapy)and an experimental group(treated with Weifuchun capsules combined with classic quadruple therapy)according to different regimens.The clinical treatment effects of two groups of patients were compared,the clinical symptom scores,changes in serum gastrointestinal hormones,inflammatory factors levels before and after treatment,and the adverse reactions and Hp recurrence were compared.Results A totol of 300 patients were included in the study,with 150 cases in each group.After treatment,the clinical symptom score,pepsinogen(PG)Ⅱ,high-sensitivity C-reactive protein(hs-CRP),serum tumor necrosis factor-α(TNF-α),interleukin(IL)-6,and IL-8 levels in the experimental group were lower than those in the control group(P＜0.05),and the levels of PG Ⅰ,gastrin-17(GAS-17)in the serum,and total effective rate were higher than those in the control group(P＜0.05).The difference in the incidence of adverse reactions between the two groups was not statistically significant(P＞0.05),and no Hp recurrence was seen in either group.Conclusion The combination of Weifuchun capsules and classic quadruple therapy has shown good efficacy in treating elderly Hp-infected CAG patients,which can effectively improve the clinical symptoms,regulate gastrointestinal hormone secretion,and has good safety.

OBJECTIVE To elucidate the mechanisms responsible for the inhibitory effects of limonene on the proliferation of non-small cell lung cancer(NSCLC) by non-targeted metabolomics and additional approaches. METHODS The CCK-8 assay was utilized to evaluate the inhibitory effects of limonene on NSCLC A549 cell viability and to ascertain the IC50. In vitro experiments, encompassing colony formation, flow cytometry, iron content assessment, and mitochondrial staining, were conducted to assess the anti-lung cancer and iron-induced cell death effects of limonene. Metabolomic analysis was employed to identify potential pathways influenced by limonene, and Western blotting was carried out to validate pivotal proteins within these pathways. RESULTS In comparison to the control group, the limonene-treated group demonstrated a significant, dose-dependent reduction in A549 cell proliferation and colony formation. Optical microscopy revealed cellular detachment and pronounced changes in cellular morphology following exposure to limonene. Limonene induced apoptosis in A549 cells and arrested them in the G0-G1 phase of the cell cycle. Confocal microscopy unveiled diminished mitochondrial fluorescence and an augmented intracellular iron content, indicative of the classical phenomenon of ferroptosis. Metabolomic investigations unveiled divergent metabolic pathways, including glutathione(GSH) metabolism, arginine biosynthesis, D-glutamine and D-glutamate metabolism, as well as cysteine and methionine metabolism, with many of them intricately linked to intracellular GSH synthesis. Western blotting experiments underscored a marked reduction in the levels of SLC40A1, SLC7A11(xCT), and GPX4 proteins within the cells post-limonene treatment. CONCLUSION Limonene may induce ferroptosis in lung cancer cells by reducing GSH synthesis and increasing Fe2+ levels.

Objective:To investigate the features and influencing factors of language in children with various types of speech disorders.Methods:A case-control study was carried out, 262 children with speech disorder had been diagnosed at the language-speech clinic of the Center of Children′s Healthcare, Children′s Hospital, Capital Institute of Pediatrics from January 2021 to November 2023, the children with speech sound disorder as the speech sound disorder group, the children with developmental stuttering as the stuttering group. There were 100 typically-developed children who underwent physical checkups at the Center of Healthcare during the same period as the healthy group. All children experienced a standardized evaluation of language with diagnostic receptive and expressive assessment of mandarin‐comprehensive(DREAM-C) and questionnaire, One-way ANOVA and LSD test were conducted to compare the differences in overall language, receptive language, expressive language, semantics, and syntax scores among 3 groups of children. According to the results of DREAM-C, the children with speech disorder were divided into language normal group and language delay group. Chi‐square test and multivariate Logistic regression were implemented to analyze the association between the linguistic development of children with speech disorder and potential influential factors.Results:There were 145 children in the speech sound disorder group, including 110 males and 35 females respectively, with an age of (5.9±1.0) years; 117 children in the stuttering group, including 91 males and 26 females, with an age of (5.8±1.0) years; 100 children in the healthy group, including 75 males and 25 females, with an age of (5.7±1.2) years. The variations in overall language, expressive language, and syntax scores among 3 groups of children were statistically significant (92±18 vs.96±11 vs. 98±11, 81±18 vs. 84±14 vs. 88±13, 87±16 vs. 89±11 vs. 91±10, F=5.46, 4.69, 3.68, all P<0.05). Pairwise comparison revealed that the speech sound disorder group had lower scores in overall language, expressive language, and syntactic compared to the healthy group, and the differences were statistically significant (all P<0.01) and the overall language score was lower than that of children with stuttering ( P<0.05). In terms of overall language and expressive language, there was a statistically significant difference in the incidence of language delay among the three groups of children (15.9% (23/145) vs. 20.5% (24/117) vs. 7.0% (7/100), 46.2% (67/145) vs. 39.3% (46/117) vs. 26.0% (26/100); χ2=7.93, 10.28; both P<0.05). In terms of overall language, the stuttering group took up the highest proportion. In terms of expressive language, the speech sound disorder group accounted for the highest amount. The incidence of language delay in children with speech disorder was 44.3% (116/262). Non-parent-child reading, daily screen time ≥1 hour and screen exposure before 1.5 years of age are risk factors for the development of language in children with speech disorder ( OR=1.87, 2.18, 2.01; 95% CI 1.07-3.27, 1.23-3.86, 1.17-3.45; all P<0.01). Negative family history are protective factors for the progress of language ability ( OR=0.37, 95% CI 0.17-0.81, P<0.05). Conclusions:Children with speech disorder tend to have easy access to language delay, especially in expressive language and syntax. The occurrence of language delay in children with speech disorder is tightly connected with factors such as the family medical history, parent-child reading, screen time, etc. Attention should be paid to the development of language in children who suffer from speech disorder.

Objective: To provide reliable prediction models based on dentoskeletal and soft tissue variables for customizing maxillary incisor positions and to optimize digitalized orthodontic treatment planning. Methods: This study included 244 Chinese women (age, 18–40 years old) with esthetic profiles after orthodontic treatment with fixed appliances (133 in group I: 1° ≤ The angle between the nasion [N]-A point [A] plane and the N-B point [B] plane [ANB] ≤ 4°; 111 in group II: 4° < ANB ≤ 7°). Dental, skeletal, and soft tissue measurements were performed on lateral cephalograms of the participants. Correlation and multiple linear regression analyses were used to determine the influence of dentoskeletal and soft tissue variables on maxillary incisor position. Results: The ideal anteroposterior position of the maxillary incisor varied between sagittal skeletal patterns. The position of the maxillary incisor correlated with the sagittal discrepancy between the maxilla and the mandible (ANB), protrusion of the midface, nasal tip projection, development of the chin, and inclination of both the maxillary and mandibular incisors. Distance from the maxillary central incisor to nasion-pogonion plane predicted using multiple linear regression analysis was accurate and could be a practical measurement in orthodontic treatment planning. Conclusions Instead of using an average value or norm, orthodontists should customize a patient’s ideal maxillary incisor position using dentoskeletal and soft tissue evaluations.

Objective Subcutaneous transplantation Lewis lung carcinoma model is commonly used in experimental studies.Researchers often choose different transplantation sites to create the models while little attention was paid on the effect of different inoculation sites on the formation of transplanted tumors.The aim of this study was to compare the effect of tumor cell inoculation at different sites on tumor formation in mice.Methods Lewis lung adenocarcinoma (ll2-luc-m38) cells stably expressing luciferase protein were subcutaneously injected into C57 BL/6 mice at the right armpit, right groin, or footpad, respectively.An IVIS spectrum in vivo imaging system was used to observe the tumor and metastasis formation.The survival time and mortality were recorded.H-E stained pathology was performed to examine the histological changes of the lung tissues and tumor metastesis.Results The tumor formation time was earlier in the armpit and groin groups, both with a tumor formation rate of 100%, while the tumors occurred later, with a tumor formation rate of 33% in the footpad group.The pulmonary metastasis rate was 70% in the groin group, 50% in the ampit group, and 0% in the footpad group, at the 21st day after inoculation.The footpad group had a high mortality.The tumors in the groin group and armpit group can be surgically resected, with a postoperative survival rate of 100%.Conclusions In this mouse model of subcutaneously transplanted Lewis adenocarcinoma, the groin and ampit groups have advantages such as a high tumor formation rate, good tolerance of tumor resection, low surgical mortality rate, easy to monitor, simple operation and high reproducibility.The axillary group has an even higher metastasis rate.

Objective To learn the clinical features of severe pneumonia in northeast sichuan ,and to improve the diagnosis and treatment level .Methods Basic disease or concomitant diseases and it′s clinical features were retrospective analyzed in different age patients with severe pneumonia in 2011 .Results (1)basic diseases and fatality cases /deteriorated cases were increased in elderly patients with the increase of age .There were 4 patients infected with HIV (3 cases under 65 years old ,1 case over 70 year old) .(2) onset pattern was given first place to suffer from cold ,but 40% were showed for symptoms of nervous system ,heart disease and other respiratory system ;(3)The main respiratory failure types of severe pneumonia is Ⅰ (about 70% ) ,30% of patients needed support of machine ventilation ;(4)community pneumonia were main type(75% );detection rate of Fungal infections and G -bacteria were 25% -30% ,normal bacteria (Streptococcus and Neisser bacteria )were over 1/3 ,Staphylococcus aureus were about 10% ;(6) More than 70% of the patients with different degree of hypoalbuminemia ;(7)Cure accounts for 2/3 ,poor prognosis accounted for 1/3 ,in which death and voluntary discharge were each 16 .6% ,ventilator-dependent ,multi-organ failure ,infections and some com-plex social factors were the prognostic factors .Conclusion Understanding the features and treatment difficulty of the local commu-nity acquired pneumonia is helpful to improve the timely diagnosis ,treatment and rescue level of patients with severe pneumonia .

Objective To explore the changes of the amount and function of Vα24~+Vβ11~+,CD161~+Vα24~+NKT cells in the peripheral blood of systemic lupus erythematosus (SLE) patients. Methods The amount of Vα24~+Vβ~+,CD16~+Va24~+NKT cells in the peripheral blood of 30 SLE cases and 30 healthy persons were detected by flow cytometry. Results Vα24~+Vβ11~+,CD161~+Vα24~+NKT cells in the peripheral blood of SLE patients were significantly lower than that of normal control (P < 0.05). Vα24~+Vβll~+ and CD161~+Va24~+NKT cells in the pe-ripheral blood of SLE patients positively correlated with the level of the complement (C3,C4) and negatively correlated with SLE disease ac-tivity index (SLEDIA) and ESR. Conclusion Activated NKT cells decreased in the peripheral blood of SLE patients. Vα24~+Vβ11~+ and CD161~+Vα24~+NKT cells might be involved in the pathogenesis and development of SLE.

Objective To analyze the radiolngical findings of mediastinal ganglioneuroma and to improve its diagnostic accuracy. Methods Imaging data of 8 cases of pathologically proven mediastinal ganglioueuroma were restrospectively analyzed. Results These tumors could occur in the anterior mediastinum, middle mediastinum or posterior mediastinum, with a preference for the posterior mediastinum (6/8). No specific clinical symptoms and signs were observed. Well-defined enlargrment of mediastinum with homogeneous density was shown on plain X-Ray. CT scanning was performed in 7 cases, including non-contrast scan alone (n = 3 ), both non-coutrast and contrast-enhanced scans ( n = 4). Round or oval shaped, well circumscribed, homogeneous or slightly heterogeneous, hypadense masses were demonstrated on non-contrast scan. Spotty calification could be found in a few cases. Homogeneous or slightly heterogeneous enhancement was seen following the intravenous injection of contrast material. Large tumors showed a tendency of wedging into the space between adjacent organs and structures, and encasing the nearby large vessels. MR without contrast was performed in 1 case. T1 WI showed isointensity to adjacent muscle, T2WI showed homogeneous hyperintensity. Multi-planar reconstruction provided more information concerning the relationship of the mass lesions with neighboring structures. Conclusion Mediastinal ganglioneuromas have some specific characterstics on imaging studies, which could assist in pre-operative diagnosis and surgical planning.