Acute high-altitude (HA) illnesses (AHAIs), including acute mountain sickness (AMS), HA cerebral edema (HACE), and HA pulmonary edema (HAPE), represent significant health challenges for individuals rapidly ascending to high altitudes. Cytokines (interleukins (ILs)) and chemokines, which are involved in inflammatory and immunological responses, regulate the response of the body to hypoxic stress. Their dysregulation can contribute to the clinical symptoms of AMS, HACE, and HAPE by increasing vascular permeability, causing edema and damaging tissue. AHAIs elevate the levels of pro-inflammatory cytokines and chemokines, such as IL-17, tumor necrosis factor α (TNF-α), IL-1, IL-6, C-X-C motif chemokine ligand (CXCL) 10, CXCL8, C-C motif ligand 2 (CCL2 (CCL2), and CCL3, exacerbating symptoms. Thus, this review focuses on the cytokines and chemokines involved in AHAIs and the molecular mechanisms that extend beyond these cytokines and chemokines in clinical and preclinical contexts. Identifying these mediators and pathways helps researchers design drugs that reduce symptoms, slow disease progression, and enhance outcomes. Cytokines and chemokines have complex functions in these disorders and may serve as prospective therapeutic targets. Finally, we discuss treatment possibilities for AHAIs (drugs, exercise, and other inhibitors). This knowledge will help us to protect and improve the health of individuals at high altitudes.

Objective To develop a gas chromatography-tandem mass spectrometry(GC-MS/MS)method for the simultaneous determination of ephedrine and pseudoephedrine in urine.Methods Urine samples containing ephedrine and pseudoephedrine components were extracted with ethyl acetate,centrifuged to collect the supernatant and evaporated to dryness under a nitrogen stream and then derivatized with heptafluorobutyric anhydride 60 μL at 70 ℃ for 30 min,and re-evaporated under nitrogen,and then solubilized with 50 μL of methanol,and then analyzed by GC-MS/MS.Results The method demonstraed excellent linearity for ephedrine(0.05～10 μg/mL,r=0.999 8)and pseudoephedrine(0.02～5 μg/mL,r=0.999 5).Extraction recoveries ranged from 89.4％～95.8％(ephedrine)and 90.3％～93.8％(pseudoephedrine).Limits of detection and quantification of ephedrine and pseudoephedrine were 0.005 μg/mL and 0.01 μg/mL,the intra-day precision and accuracy were less than 5.87％and 9.56％,respectively,and the inter-day precision and accuracy were less than 7.54％and 9.27％,respectively.The stability of ephedrine and pseudoephedrine in urine in 15 d was good under the conditions of room temperature and-20 ℃.Conclusion The GC-MS/MS analytical method for the analysis of ephedrine and pseudoephedrine components in urine established in this study is accurate,stable and sensitive,which can provide data technical support for the forensic toxicological analysis of amphetamine-type drugs or new psychoactive substances in the cathinone group.

Objective To develop a gas chromatography-tandem mass spectrometry(GC-MS/MS)method for the simultaneous determination of ephedrine and pseudoephedrine in urine.Methods Urine samples containing ephedrine and pseudoephedrine components were extracted with ethyl acetate,centrifuged to collect the supernatant and evaporated to dryness under a nitrogen stream and then derivatized with heptafluorobutyric anhydride 60 μL at 70 ℃ for 30 min,and re-evaporated under nitrogen,and then solubilized with 50 μL of methanol,and then analyzed by GC-MS/MS.Results The method demonstraed excellent linearity for ephedrine(0.05～10 μg/mL,r=0.999 8)and pseudoephedrine(0.02～5 μg/mL,r=0.999 5).Extraction recoveries ranged from 89.4％～95.8％(ephedrine)and 90.3％～93.8％(pseudoephedrine).Limits of detection and quantification of ephedrine and pseudoephedrine were 0.005 μg/mL and 0.01 μg/mL,the intra-day precision and accuracy were less than 5.87％and 9.56％,respectively,and the inter-day precision and accuracy were less than 7.54％and 9.27％,respectively.The stability of ephedrine and pseudoephedrine in urine in 15 d was good under the conditions of room temperature and-20 ℃.Conclusion The GC-MS/MS analytical method for the analysis of ephedrine and pseudoephedrine components in urine established in this study is accurate,stable and sensitive,which can provide data technical support for the forensic toxicological analysis of amphetamine-type drugs or new psychoactive substances in the cathinone group.

Objective:To investigate the clinical characteristics of non-perinatal adult patients with Listeria monocytogenes (LM) infection. Methods:Twenty-five non-perinatal adult patients who were etiologically confirmed as listeriosis in Tangdu Hospital, Fourth Military Medical University during January 2010 and July 2023 were enrolled in this study. The characteristics of demographic data, underlying diseases, clinical manifestations, laboratory indicators, cranial imaging examination, anti-microbial therapeutic schemes and clinical outcomes were retrospectively analyzed. The clinical characteristics were compared between patients with Listeria septicemia and Listerial meningoencephalitis, as well as between survival and death patients. Independent samples t test and Mann-Whitney U test were used for statistical analysis. Results:The age of enrolled patients was (52.84±12.17) years. Eighteen patients were male, and seven patients were female. The major clinical manifestations included fever (23/25(92%)), headache (15/25 (60%)), disorder of consciousness (12/25(48%)) and vomiting (8/25(32%)). Thirteen (52%) patients had underlying diseases (including hematological diseases, autoimmune disorders, solid neoplasms, and liver cirrhosis, etc). There were no significant differences in blood routine test, aminotransferase, protein levels, renal function, electrolyte, blood glucose, and inflammatory indicators between patients with Listeria septicemia and Listerial meningoencephalitis (all P>0.05). The platelet count in the death group was significantly higher than that in the recovery group ((243.10±92.96)×10 9/L vs (157.80±75.55)×10 9/L, t=2.45, P=0.022). There were also no significant differences in blood biochemical index and inflammatory indicators between these two groups (all P>0.05). Cranial imaging examination of patients with Listerial meningoencephalitis manifested as intracranial infection, cerebral edema/hydrocephalus or cerebral hernia. All nineteen patients with Listerial meningoencephalitis had elevated cerebrospinal fluid (CSF) pressure (220.0(130.0, 290.0) mmH 2O (1 mmH 2O=0.009 8 kPa)), elevated CSF total cell count (522.0(350.0, 783.0)×10 6/L), elevated CSF white blood cell count (356.0(266.0, 668.0)×10 6/L), and CSF protein level (1 817.0(822.5, 6 000.0) mg/L). Fifteen patients had reduced CSF chloride level ((111.70±8.51) mmol/L). Ten patients had decreased CSF glucose level (3.71(1.45, 7.11) mmol/L). The drug sensitivity results of blood and CSF cultures revealed that LM was sensitive to ampicillin. One case was resistance to penicillin, three cases were resistance to meropenem, while three cases were resistance to trimethoprim-sulfonamide. Thirteen cases out of seventeen recovery patients were administered with ampicillin or penicillin-based therapy. Conclusions:When patients with underlying diseases or immune dysfunction suffered with clinical symptoms such as high fever, central nervous system infection, they should be alert to the possibility of listeriosis. Early administration of ampicillin-based therapeutic strategy is beneficial for clinical recovery of the patients.

Peripheral arterial disease is one of the common complications of diabetes. At present, the pathogenesis of diabetic peripheral arterial diseases is not completely clear, and there is a lack of effective treatment methods and drugs. Adipokines have profound impact on the occurrence and development of diabetes mellitus and its complications, and are directly or indirectly involved in the progression of diabetic peripheral arterial diseases. Different adipokines may inhibit or promote the occurrence of vascular diseases with the mechanisms that are complex and controversial. Adipokines are expected to be a new target for the treatment of diabetic peripheral arterial disease, which is worthy of further study. This article mainly reviews the relationship between some common adipokines and new adipokines and diabetic vascular disease, aiming to provide new methods for the clinical treatment of diabetic peripheral arterial disease.

Objective To investigate the application value of neutrophil count(N),neutrophil percentage(N％),neutrophil to lymphocyte ratio(NLR)and neutrophil to albumin ratio(NAR)in the evaluation of ul-cerative colitis(UC)patients.Methods A total of 87 UC patients admitted to the hospital from May 2022 to July 2023 were collected as the UC group,and 42 healthy people in the same hospital during the same period were selected as the control group.Blood routine and biochemical routine related inflammatory indicators in-cluding lymphocyte count(L),N,lymphocyte percentage(L％),N％,C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),albumin(ALB)were collected,NLR and NAR were calculated.The clinical data of UC patients were collected.According to medical history,modified Mayo scoring system and Montreal classifi-cation criteria,UC patients were divided into clinical types,disease activity and lesion extent.The levels of N,N％,NLR and NAR in the control group and UC group and different subgroups of UC were evaluated.Spearman correlation analysis was used to analyze the correlation between the four indexes and ESR and CRP.The receiver operating characteristic curve was drawn to test the diagnostic efficacy of the four indicators a-lone and in combination in the detection of UC patients,and the best cut-off value,sensitivity and specificity were calculated.Results The levels of N,N％,NLR and NAR in UC group were higher than those in control group,and the differences were statistically significant(P＜0.05).There were significant differences in N,N％,NLR and NAR levels between UC patients with different activity and lesion range(P＜0.05).Spearman correlation analysis showed that CRP level was positively correlated with N,N％,NLR and NAR in UC pa-tients(r=0.392,0.343,0.354,0.503,P＜0.001).ESR level was positively correlated with N,NLR and NAR(r=0.383,0.233,0.475,P＜0.05).The area under the curve of N,N％,NLR and NAR alone and in combi-nation were 0.668,0.702,0.723,0.741 and 0.882,respectively.The sensitivity and specificity of the combina-tion of the four were higher(80.5％and 88.1％,respectively).Conclusion N,N％,NLR and NAR have cer-tain clinical value in the diagnosis,disease activity and lesion extent prediction of UC patients.

Chemoresistance to 5-fluorouracil (5-FU) is a significant challenge in treating colorectal cancer (CRC). Novel combined regimens to thwart chemoresistance are therefore urgently needed. Herein, we demonstrated that the combination of Avenanthramide A (AVN A) and 5-FU has significant therapeutic advantages against CRC. Mechanistically, AVN A directly binds to the S198 site of the histone lysine demethylase KDM4C to promote its degradation, which subsequently fosters H3K9me3 occupancy on the MIR17HG promoter to block its transcription and derepress Bim expression. AVN A enhanced the therapeutic efficacy of 5-FU via impairing the KDM4C/MIR17HG/GSK-3β negative feedback loop. Importantly, the clinical correlation of the KDM4C/MIR17HG/Bim signaling axis with 5-FU response was validated in the refractory CRC patients. We provide evidence for the enhanced effectiveness of 5-FU when combined with AVN A in chemoresistant xenografts, CRC organoids, and Apc ^Min/+ mouse model. Additionally, AVN A mitigated the systemic adverse effects of 5-FU. Overall, our findings demonstrate that combinatorial therapy with AVN A and 5-FU represents an appealing opportunity and highlights KDM4C/MIR17HG/GSK-3β negative feedback loop which confers therapeutically exploitable vulnerability to chemo-refractory CRC patients.

Objective:To evaluate the application of Moorehead-Ardelt Ⅱ questionnaire (MA Ⅱ) in assessment of the quality of life (QOL) among obese patients after bariatric surgery.Methods:One hundred and five patients with obesity were enrolled, the weight, body mass index (BMI), comorbidities and MA Ⅱ scores before and after operation were counted. The difference between the QOL of pre- and post-operation was analyzed.Results:All the patients completed the questionnaire. The Cronbach α coefficient of the questionnaire was higher than 0.7. The post-operational scores of 6 items were significantly higher than that of pre-operation. ( P<0.001). The proportion of "poor" and "very poor" QOL in the pre-operational patients was 43.8%, compared with 0 in the post-operative patients;the proportion of "good" and "very good" QOL in the pre-operatve patients was 4.7%, compared to 86.7% in the post-operative patients ( χ2=146.863, P<0.001). Conclusions:MA Ⅱ questionnaire is a professional, easy oprated tool for assessment of QOL associated with obesity.

Objective: To explore the association between the frequency of prenatal care in childbearing aged women and risk of small for gestational age (SGA) among neonatal twins in Shaanxi Province. Methods: From July to December 2013, a total of 30 027 childbearing aged women, who were pregnant from January 2010 to November 2013 and had definite outcomes, were selected from 30 districts (counties) of Shaanxi Province by using the multi-stage random sampling method. The questionnaires with a face-to-face survey method were used to retrospectively collect demographic information, pregnancy history, lifestyle during pregnancy, disease history, nutritional supplements, and health care during pregnancy. Information on the gestational age and birth weight of the newborn were obtained by consulting the medical certificate of birth and were registered as twin A and twin B by birth order. Finally, 356 childbearing aged women and their twin babies with complete data were included in the analysis. A generalized estimation equation model was used to analyze the association between the frequency of prenatal care and the risk of SGA among neonatal twins. Results: The age of childbearing aged women was (27.44±4.68) years old, of which 79.49% (283 women) were rural residents and 44.38% (158 women) had seven or more times prenatal care. The gestational age and birth weight were (37.64±2.51) weeks and (2 510±497) g, respectively. The prevalence of SGA was 51.40% (183/356) for twin A and 53.37% (190/356) for twin B, respectively. The prevalence of SGA was 44.30% (70/158) for twin A with seven or more times prenatal care and 42.41% (67/158) for twin B with seven or more times prenatal care, which was lower than that for twins with less than seven times prenatal care, respectively [57.07% (113/198) and 62.12% (123/198)] (P values were 0.017 and <0.001). The results of generalized estimation equation model suggested that compared to those with less than seven times prenatal care, after adjusting for parity, birth order, place of residence, maternal age, occupation, education, family wealth index, passive smoking, pregnancy-induced hypertension syndrome, folic acid, and iron supplement during perinatal period, and gender of the newborn, the OR (95%CI) of risk of SGA among childbearing aged women with seven or more times prenatal care was 0.60 (0.40-0.91). Conclusion Seven or more times prenatal care could reduce the risk of SGA among neonatal twins in Shanxi Province.

Objective:To investigate the predictive value of preoperative peripheral blood lymphocyte to monocyte ratio (LMR) for lymph node metastasis in gastric cancer.Methods:Data of 177 gastric cancer patients who underwent surgical treatment in Beijing Shijitan Hospital from Jan 2014 to May 2017 were retrospectively analyzed. According to the ROC curve, the optimal critical value is determined to be 3.79. By this value, patients were divided into high LMR group (LMR≥3.79) and low LMR group (LMR<3.79). Patients′ clinicopathological characteristics were collected to analyze the relationship between LMR and lymph node metastasis and lymph node N staging.Results:A comparison of LMR and N1 and N2 stage between the two groups showed no significant difference, but both N1 and N2 had statistical defference with N3 ( P<0.05), suggesting a positive correlation between low LMR and high N stage. Logistic regression analysis proves that low LMR is significantly correlated with metastatic lymph node when the number was more than 6. Conclusion:Low LMR is positively correlated with lymph node metastasis in gastric cancer patients.