ObjectiveThis paper aims to investigate the effects and mechanism of Mimenghua prescription in modulating the mitogen-activated protein kinase kinase （MEK）/rat sarcoma viral oncogene homolog （Ras）/rapidly accelerated fibrosarcoma kinase （Raf）/extracellular signal-regulated kinase （ERK） signaling pathway to inhibit inflammatory responses in a dry eye animal model. MethodsA total of 60 C57BL/6J mice （eight weeks old， half male and half female） were used in the experiment. Ten mice were randomly selected as the blank control group， while the remaining 50 were exposed to a controlled dry system and received instillation of 0.2% benzalkonium chloride （BAC） into the eyes for four weeks to establish a dry eye mouse model. After successful modeling， the mice were randomly divided into five groups： Model group， sodium hyaluronate group， and Mimenghua prescription groups with low dose （4.83 g·kg^-1）， medium dose （9.67 g·kg^-1）， and high dose （19.34 g·kg^-1）. The mice in the model group received an equal volume of normal saline via gavage for four weeks. The mice in the sodium hyaluronate group received instillation of sodium hyaluronate eye drops twice daily for 14 consecutive days. The tear secretion volume， tear film break-up time （TBUT）， and corneal fluorescein staining were evaluated once every two weeks. After four weeks of administration， mice were euthanized， and their lacrimal gland tissues and corneas were harvested. Hematoxylin-eosin （HE） staining was used to assess histopathological morphology. Western blot was performed to detect the protein expression levels of MEK， Ras， Raf， and ERK. Enzyme-linked immunosorbent assay （ELISA） was used to measure the contents and expressions of MEK， Ras， Raf， ERK， and interleukin （IL）-1β in lacrimal gland and corneal tissues of the mice in each group. Quantitative real-time polymerase chain reaction （Real-time PCR） was employed to determine mRNA expression levels of MEK， Ras， Raf， and ERK. ResultsThe Mimenghua prescription groups and the sodium hyaluronate group exhibited significantly increased tear secretion volume （P<0.05） and prolonged TBUT （P<0.05） after treatment. Ocular surface damage of mice was visibly recovered. Western blot results indicated that protein expression levels of MEK， Ras， Raf， and ERK in the lacrimal gland and corneal tissues were significantly downregulated in the sodium hyaluronate group and Mimenghua prescription group with high dose （P<0.05）. ELISA results showed that IL-1β levels were highest in the model group but significantly reduced in the sodium hyaluronate group and Mimenghua prescription groups （P<0.05）. Both ELISA and Real-time PCR results demonstrated that the expression levels of MEK， Ras， Raf， and ERK in the lacrimal glands and corneal tissues were significantly elevated in the model group （P<0.05）， but markedly downregulated in the sodium hyaluronate group and Mimenghua prescription groups （P<0.05）， suggesting that Mimenghua prescription can decrease the expressions of MEK， Ras， Raf， and ERK in the lacrimal glands and corneal tissues. ConclusionMimenghua prescription can reduce inflammatory responses， increase tear secretion， prolong TBUT， and promote corneal recovery by inhibiting the MEK， Ras， Raf， and ERK signaling pathways in lacrimal gland and corneal tissues.

Objective To analyze the virus subtypes, molecular evolutional and molecular transmission network features of the first confirmed mpox case in Huai’an City, Jiangsu Province, so as to provide insights into understanding of the transmission and evolution dynamics of mpox virus and formulation of the mpox control strategy in the city. Methods Genomic DNA was extracted from swabs of the first confirmed mpox case’s skin lesions in Huai’an City, and the amplicon sequencing library was constructed using the hypersensitive mpox virus whole-genome capture kit. High-throughput sequencing was performed using the GridION X5 nanopore sequencer on the Nanopore sequencing platform, and single nucleotide polymorphism (SNP) analysis of mpox virus genome sequences was performed following sequence assembly. In addition, phylogenetic analysis, genetic genealogy and molecular traceability analysis were performed. Results The virus whole genome sequence of the first confirmed mpox case was successfully obtained by high-throughput sequencing, with a full length of 197 182 bp, and was named hMpxV/China/JS-HA01/2023, which belonged to the clade IIb (West African clade) lineage B.1.3. Compared with the mpox virus reference sequence MPXV-M5312_HM12_Rivers-001 (GenBank accession number: NC_063383), the genome sequence of the Huai’an virus isolate carried 86 SNPs, including 40 SNPs in the coding region as non-synonymous mutations and 73 SNPs as nucleotide mutations caused by APOBEC3 (APOBEC3). Of the 97 mpox virus gene sequences, 79 sequences were included in the molecular network (81.44%), and the threshold of the genetic distance accessed to the network was 0.35/10⁵. There were two large molecular transmission clusters and one scattered cluster in the molecular transmission network of the mpox virus, andthehMpxV/China/JS-HA01/2023 sequence was located in the large cluster. The 97 gene sequences formed 92 haplotypes, including three shared haplotypes Hap_4, Hap_6 and Hap_38, and an exclusive haplotype Hap_1 of hMpxV/China/JS-HA01/2023 generated from mutation of the exclusive haplotype Hap_43, while the exclusive haplotype Hap_43 was generated from mutation of the shared haplotype Hap_38. Conclusions The whole genome sequence of the mpox virus isolated from the first confirmed mpox case in Huai’an City has been successfully obtained, and the molecular evolutionary and molecular transmission network characteristics of the virus have been preliminarily understood.

Objective To predict the potential suitability distribution of Vitex negundo in China;To analyze the key environmental factors influencing its suitability distribution.Methods Based on the geographic distribution data of Vitex negundo from 196 sites across China and 55 environmental variables,the Maximum Entropy(MaxEnt)model and ArcGIS 10.2 were employed to predict the potential distribution of suitable habitats for Vitex negundo in China.Results The constructed MaxEnt prediction model demonstrated high reliability.The primary environmental factors influencing the suitable distribution of Vitex negundo included the average temperature from June to October,precipitation in April and November,the mean temperature of the warmest season,soil type,and vegetation type.The predicted suitable habitats for Vitex negundo would be widely distributed,primarily concentrated in Jiangxi,central and southern Anhui,northwestern Zhejiang,eastern and northeastern Hunan,as well as eastern and southeastern Hubei.Conclusion The predicted potential distribution of Vitex negundo in China can provide a valuable reference for the conservation and sustainable utilization of this medicinal resource.

Objective To observe the value of artificial intelligence iterative reconstruction(AIIR)for improving image quality of 80 kVp low-dose CT enterography(CTE)for Crohn disease(CD).Methods Totally 59 patients with CD who underwent 80 kVp low-dose CTE were retrospectively enrolled,and CTE images were reconstructed with hybrid iterative reconstruction(HIR)(HIR group)and AIIR(AIIR group),respectively.Then subjective and objective scores of image quality were evaluated and compared between groups,and the value of AIIR was analyzed.Results Compared with HIR group,AIIR group clearly displayed the intestinal wall,intestinal lumen,mesenteric vessels and peri-intestinal soft tissue,and displayed typical CD signs more obviously,with higher subjective scores of imaging quality(all P＜0.001).The standard deviation(SD)was lower,while signal-to-noise ratio(SNR)of intestinal walls without disease,SNR and contrast-to-noise ratio(CNR)of diseased intestinal walls in AIIR group were all higher than those in HIR group(all P＜0.001).The effective dose of 80 kVp CTE examination was(2.82±0.54)mSv.Conclusion AIIR was helpful for improving image quality of 80 kVp low-dose CTE for CD.

Objective:To examine the funding landscape of the National Natural Science Foundation of China(NSFC)concerning research focused on the elderly as a specific demographic group.It seeks to analyze prevailing research hotspots and to offer insightful research ideas for scholars in this field.Methods:The study employed a retrospective research design.It involved retrieving data on approved projects related to the elderly from the NSFC's official database, covering the period from 2000 to 2020.The data set included variables such as funding year, project title, project category, supporting institution, and funding amount(application codes: H1901, H1902, H1903).Statistical analysis was conducted using Excel software, while visual analysis was performed using CiteSpace software.Results:Between 2000 and 2020, a total of 710 projects focused on geriatrics received funding, amounting to RMB 361, 032, 300, 000.This period exhibited a fluctuating upward trend in both the number of projects and the total funding amount.The primary funding categories were face-to-face projects and youth science fund projects, which together accounted for 44.4%(315/710), 34.4%(244/710)respectively.The distribution of project-relying units demonstrated significant regional imbalance, with Beijing, Zhejiang, Jiangsu, and Shanghai being the predominant areas.Notably, Nanjing Medical University, Peking University, and Shanghai Jiao Tong University ranked as the top three institutions, with funding percentages of 5.9%(42/710), 5.4%(38/710), and 4.5%(32/710), respectively.The research themes encompassed nucleoplasmic interactions, brain networks, and bioinformatics, among others.Conclusions:The NSFC has consistently provided funding for in-depth research in the critical field of geriatrics.The primary research directions focus on aspects such as the mechanisms of aging and the pathogenesis of neurological diseases associated with aging.With the application of innovative technologies and methodologies, significant breakthroughs and achievements are anticipated in geriatrics, contributing to the improvement of health outcomes and the enhancement of the quality of life for the elderly.

Objective:To develop a modified University of Wisconsin preservation solution (UW solution) containing α 2-adrenergic receptor agonists (dexmedetomidine) and noble gases (argon) and investigate its protective effect on the isolated amputated skeletal muscle of rats. Methods:Sixty male SD rats were selected to establish a hindlimb cold preservation/perfusion model and were divided into blank control group, hypothermic storage group, UW solution perfusion group, and modified UW solution perfusion group using a random number table, with 15 rats in each group. Simultaneously, a cold preservation model of rat skeletal muscle myoblasts (L6 cells) was established and the rats were also divided into four groups in the same way. Animal models were prepared in different ways: In the blank control group, the hindlimbs received no special treatment; In the hypothermic storage group, the amputated hindlimbs were stored in a dry centrifuge tube at 4℃ for 18 hours; In the UW solution perfusion group, the amputated hindlimbs were perfused with UW solution and then stored in a centrifuge tube containing UW solution at 4℃ for 18 hours; In the modified UW solution perfusion group, the amputated hindlimbs were perfused with modified UW solution (containing 0.1 nmol/L dexmedetomidine and 50% volume fraction of argon) and then stored in a centrifuge tube containing the modified UW solution at 4℃ for 18 hours. Cell models were treated as follows: In the blank control group, L6 cells were cultured under standard conditions; In the hypothermic storage group and UW solution group, L6 cells were treated with conventional culture medium or UW solution, stored in argon-filled sealed bags at 4℃ for 8 hours, and then rewarmed and cultured for 6 hours; In the modified UW solution group, L6 cells were treated with the modified solution, stored in argon-filled sealed bags at 4℃ for 8 hours, and then rewarmed and cultured for 6 hours. After sample collection, skeletal muscle morphology, tissue edema and ultrastructure features were assessed by HE staining, wet-to-dry weight ratio, and transmission electron microscopy, respectively. Additionally, L6 cell morphology was examined by light microscopy. L6 cell viability was determined by cell counting kit-8 (CCK-8) assay (expressed as absorbance A value). Expression levels of glutathione peroxidase 4 (GPX4) protein in both skeletal muscle tissue and L6 cells were evaluated by immunofluorescence staining and Western blot, respectively.Results:After 18 hours of in vitro preservation of rat isolated amputated limbs, the following results were obtained: (1) HE staining results showed that the muscle fiber morphology of the modified UW solution perfusion group was close to that of the blank control group. Moreover, the area ratio of skeletal muscle cells in the modified UW solution perfusion group was significantly higher than that in the hypothermic storage group and UW solution perfusion group ( P<0.05). (2) The wet-dry weight ratio results showed that there was no statistically significant difference among the modified UW solution perfusion group, the blank control group and UW solution group ( P>0.05), with significantly lower ratios in all three groups than that in the hypothermic storage group ( P<0.05). (3) Transmission electron microscopy results revealed that the modified UW solution perfusion group showed no statistically significant differences in ultrastructural metrics, including myofiber diameter, sarcomere length, mitochondrial short-axis/long-axis ratio, and mitochondrial cristae count, compared with those in the blank control group ( P>0.05), and performed significantly better than both the hypothermic storage group and UW solution perfusion group ( P<0.05). (4) Morphological observation of L6 cells showed that the cellular morphology was regular in the modified UW solution perfusion group, close to that in the blank control group, while it was severely damaged in the hypothermic storage group. Moreover, the cells were reduced in number and partially damaged in the UW solution group. The sequence of cell viability expressed as absorbance A value was blank control group >modified UW solution perfusion group > UW solution perfusion group > hypothermic storage group, with statistically significant differences among the four groups ( P<0.05). (5) Immunofluorescence staining showed that there was no statistically significant difference in fluorescence intensity of GPX4 protein expression between the modified UW solution perfusion group and blank control group ( P>0.05), while the fluorescence intensity was higher in the modified UW solution perfusion group than that in the hypothermic storage group and UW solution perfusion group ( P<0.05). Western blot analysis showed that the relative expression level of GPX4 in the modified UW solution group was significantly lower than that in the blank control group ( P<0.05), but higher than that in the hypothermic storage group and UW solution perfusion group ( P<0.05). Conclusion:The modified UW solution can stabilize the expression level of GPX4 protein, thereby inhibiting ferroptosis and alleviating cold preservation injury in both rat amputated isolated limb skeletal muscle tissue and L6 cells.

Objective To investigate the value of nutritional status control(CONUT)score,platelet to albumin ratio(PAR)and mean platelet volume to lymphocyte ratio(MPVLR)before treatment on immunotherapy efficacy and immune-related adverse reactions(irAEs)in advanced gastric cancer patients.Methods A total of 113 patients with advanced gastric cancer admitted to the hospital from January 2020 to June 2023 were selected as the gas-tric cancer group,and 113 healthy volunteers were selected as the control group.According to the efficacy of immunotherapy,the patients with advanced gastric cancer were divided into effective group(70 cases)and in-effective group(43 cases),and divided into irAEs group(51 cases)and non-irAEs group(62 cases)according to whether irAEs occurred.The factors influencing the occurrence of irAEs in advanced gastric cancer were analyzed,and the value of CONUT score,PAR and MPVLR before treatment in predicting the efficacy of im-munotherapy and irAEs in advanced gastric cancer was analyzed.Results The CONUT score,PAR and MPV-LR in gastric cancer group before treatment were higher than those in control group(P＜0.05).The CONUT score,PAR and MPVLR before treatment in the ineffective group were higher than those in the effective group(P＜0.05).The area under the curve(AUC)of CONUT score,PAR and MPVLR alone in predicting the ineffective immunotherapy in advanced gastric cancer patients before treatment were 0.779,0.739 and 0.766,respectively,the AUC predicted by combined detection was 0.889,which was higher than that predic-ted by alone(P＜0.05).The CONUT score,PAR and MPVLR before treatment in irAEs group were higher than those in non-irAEs group(P＜0.05).The age of irAEs group was lower than that of non-irAEs group(P＜0.05),and the proportion of Ki-67 index,CD4+T lymphocytes and Treg cells was lower than that of non-irAEs group(P＜0.05).The increase of CONUT score,PAR and MPVLR before treatment were risk factors for irAEs in advanced gastric cancer patients(P＜0.05),and the increase of Treg cell proportion was a protective factor(P＜0.05).The AUC of CONUT score,PAR and MPVLR alone in predicting the occurrence of irAEs in advanced gastric cancer patients before treatment was 0.816,0.798 and 0.783,respectively,the AUC predic-ted by combined detection was 0.887,which was higher than that predicted alone(P＜0.05).Conclusion The CO-NUT score,PAR and MPVLR before treatment are significantly increased in advanced gastric cancer patients,and are associated with ineffective immunotherapy and the occurrence of irAEs.The combined detection of the three indicators can effectively predict the immunotherapy efficacy and irAEs in advanced gastric cancer pa-tients.

Objective To analyze the influencing factors of hepatic encephalopathy(HE)after transjugular intrahepatic portosystemic shunt(TIPS)and construct a nomogram prediction model based on these factors.Methods A total of 290 patients with cirrhotic portal hypertensive variceal gastrointestinal bleeding in the Yuncheng Central Hospital Affiliated to Shanxi Medical University from January 2019 to December 2023 were selected and randomly divided into training set of 145 cases and validation set of 145 cases.All patients underwent TIPS treatment,and the incidence of HE within 3 months after TIPS was recorded.In the training set,patients were divided into HE group(n=42)and non-HE group(n=103)based on the occurrence of HE.Clinical materials were compared between the two groups,and Lasso-Logistic regression analysis was applied to explore the influencing factors of HE after TIPS.A nomogram prediction model was constructed based on the influencing factors and validated in both the training set and the validation set for its clinical value in predicting HE after TIPS.Results The overall incidence of HE was 29.31％,with incidence rates of 28.97％and 29.66％respectively in the training set and the validation set.In the training set,the HE group had significantly higher age,C grading of preoperative Child-Pugh ratio,diabetes mellitus ratio,total bilirubin(TBIL),prothrombin time(PT),serum sodium,serum creatinine,interleukin-6(IL-6),interleukin-18(IL-18),blood ammonia,monocyte chemotactic protein-1(MCP-1),postoperative portal venous pressure,and intestinal flora disturbance ratio when compared to the non-HE group,while the preoperative glial fibrillary acidic protein(GFAP)level was significantly lower in the HE group(P＜0.05).Lasso-Logistic regression analysis showed that preoperative C grading of Child-Pugh grading,diabetes mellitus,TBIL,PT,IL-6,IL-18,blood ammonia,GFAP,MCP-1 level,and postoperative intestinal flora disturbance were influencing factors for HE after TIPS(P＜0.05).A nomogram prediction model was constructed based on ten influencing factors selected by Lasso-Logistic regression analysis.The area under the curve(AUC)of this model for predicting HE after TIPS was 0.933(95％CI,0.889 to 0.976)in the training set and 0.944(95％CI,0.893 to 0.995)in the valida-tion set,with good consistency between the model's prediction and actual observation.Conclusion The nomogram prediction model for HE after TIPS,constructed based on the influencing factors selected by Lasso-Logistic regression analysis,has high predictive efficacy and accuracy.

Objective:To investigate the influence of cytochrome P450 2A6 (CYP2A6) gene polymorphisms on liver function injury in patients with hyperthyroidism treated with methimazole.Methods:The study selected 90 patients with hyperthyroidism who were treated with methimazole in the Department of Thyroid Surgery at the First Affiliated Hospital of Zhengzhou University from Sept. 2023 to Aug. 2024 as the research subjects. Based on the occurrence of liver injury, they were divided into a liver injury group ( n=36) and a non-liver injury group (n=54). Peripheral blood DNA was extracted from the patients, and the CYP2A6 gene genotypes (rs8192725, rs8192720, and rs28399433) were detected using the polymerase chain reaction (PCR) amplification method. The association between CYP2A6 gene polymorphisms and liver injury induced by methimazole treatment in hyperthyroidism was analyzed. Results:The comparison of genotype distribution frequencies at the rs8192725 locus between the liver injury group and the non-liver injury group showed a statistically significant difference ( P<0.05). The AG and GG genotypes at the rs8192725 locus were protective factors against liver injury in patients with hyperthyroidism (AG vs. AA, OR: 0.21; 95% CI: 0.08-0.57; P<0.05; GG vs. AA, OR: 0.24; 95% CI: 0.06-0.89; P<0.05; AG+GG vs. AA, OR: 0.22; 95% CI: 0.09-0.54; P<0.05). The frequency of the G allele of rs8192725 in the liver injury group was significantly lower than that in the non-liver injury group (G vs. A, OR: 0.36; 95% CI: 0.19-0.70; P<0.05), indicating that it is a protective factor for liver injury in hyperthyroid patients receiving methimazole treatment. Conclusions:The CYP2A6 gene polymorphism at the rs8192725 locus is associated with the occurrence of liver injury in patients with hyperthyroidism treated with methimazole. The G allele may be a protective factor against liver injury in patients with hyperthyroidism, suggesting that individualized treatment plans can be developed based on the patient's genotype.

Objective To analyze the performances of electronic portal imaging device (EPID) in mechanical and dosimetry responses,and to investigate the feasibility of adopting EPID as a daily quality assurance (QA) equipment. Methods The EPID of Trilogy linear accelerator was tested for mechanical position repeatability and dose linear response. Then,a group of special fields were edited manually for simulations of field translation and symmetry deviations,and the sensitivities of EPID and MyQA Daily to field translation and symmetry deviations were evaluated,and moreover,the linear correlation between the set value and the measured value was analyzed. Finally,daily QA was conducted with EPID and MyQA Daily for 30 consecutive days,and the measurement results and time consumption were analyzed. Results The maximum deviation of EPID position repeatability was 0.4 mm,and the dose response was linearly correlated (R2>0.999). The symmetry deviation test results showed that both of EPID and MyQA Daily were capable to effectively detect the 0.2％ offset in symmetry,and a linear correlation was demonstrated between the set value and the measured results (R2>0.995). In translation test,the linear correlation of EPID was more explicit than that of MyQA Daily (R2=0.992 vs R2=0.976). In daily QA,all the measured results of EPID and MyQA Daily were within the clinic acceptance tolerance. Moreover,the mean value of Y-directional symmetry and flatness measured by EPID was approximately 1.00％ larger than MyQA Daily. The average time required by EPID was 50 s less than MyQA Daily[(129.97±4.16) s vs (184.53±4.23) s]. Conclusion EPID can be served as a reliable and efficient daily QA equipment for linear accelerator. However,it is not capable to be used as a criterion for evaluating linear accelerator performance.