eIF3a is a N ⁶-methyladenosine (m⁶A) reader that regulates mRNA translation by recognizing m⁶A modifications of these mRNAs. It has been suggested that eIF3a may play an important role in regulating translation initiation via m⁶A during infection when canonical cap-dependent initiation is inhibited. However, the death of animal model studies impedes our understanding of the functional significance of eIF3a in immunity and regulation in vivo. In this study, we investigated the in vivo function of eIF3a using eIF3a knockout and knockdown mouse models and found that eIF3a deficiency resulted in splenic tissue structural disruption and multi-organ damage, which contributed to severe sepsis induced by Lipopolysaccharide (LPS). Ectopic eIF3a overexpression in the eIF3a knockdown mice rescued mice from LPS-induced severe sepsis. We further showed that eIF3a maintains a functional and healthy immune system by regulating B cell function and quantity through m⁶A modification of mRNAs. These findings unveil a novel mechanism underlying sepsis, implicating the pivotal role of B cells in this complex disease process regulated by eIF3a. Furthermore, eIF3a may be used to develop a potential strategy for treating sepsis.

Objective:To investigate the impact of serum vitamin A levels on all-cause mortality risk in diabetes patients.Methods:Diabetes patients aged 20 years and above who participated in the US National Health and Nutrition Examination Survey during 2003-2004 and 2005-2006 were enrolled as the study population,with death data up to 2019 as the endpoint.Cox proportional hazards regression models were employed to calculate the hazard ratios of all-cause mortality in diabetes patients with different serum vitamin A levels,both unadjusted and adjusted for confounders.Restricted cubic spline methods were used to analyze the dose-response relationship between serum vitamin A levels and all-cause mortality risk in diabetes patients.Results:A total of 484 diabetes patients were included,with a median follow-up period of 13.7 years,during which 211 deaths occurred.Cox proportional hazards analysis showed that compared to the lowest quartile of serum vitamin A,higher quartiles of serum vitamin A were not associated with all-cause mortality risk in diabetes patients without adjusting for confounders.However,after adjusting for confounders,higher quartiles of serum vitamin A significantly reduced the all-cause mortality risk.The dose-response analysis indicated a significantly increased risk of all-cause mortality in diabetes patients with lower serum vitamin A levels.As the vitamin A levels increased,the mortality risk gradually decreased.A significant reduction in all-cause mortality risk was observed when serum vitamin A levels were between 2.17 and 2.50 μmol/L.Beyond this range,there was a tendency for increased all-cause mortality risk with further increases in vitamin A levels.Conclusion:Lower serum vitamin A levels increase the all-cause mortality risk in diabetes patients,while moderate serum vitamin A levels help reduce the all-cause mortality risk in diabetes patients.

AIM To study the secondary metabolites from the endophytic fungi Candida sp.of Berberis atrocarpa Schneid.METHODS The ethyl acetate fraction and petroleum ether fraction from the secondary metabolites of Candida sp.fermentation extract were separated and purified by silica gel,Sephadex LH-20 and preparative liquid chromatography,then the structures of obtained compounds were identified by physicochemical properties and spectral data.RESULTS Eighteen compounds were isolated and identified as 1-phenyl-1,2-ethanediol(1),4-hydroxyphenethyl alcohol(2),4-hydroxybenzoic acid(3),4-hydroxyphenylacetic acid(4),3-hydroxyphenylacetic acid(5),3-methylsulfinyl propionic acid(6),phenylacetic acid(7),(S)-N-nitroso-1-amino-p-hydroxy phenylethanol(8),2-phenylacetamide(9),p-hydroxybenzaldehyde(10),ethyl 2-(4-hydroxyphenyl)acetate(11),dibutyl phthalate(12),5,5'-dimethoxybiphenyl-2,2'-diol(13),3-indolealdehyde(14),N-acetyl-L-phenylalanine(15),9-hydroxy-10E,12Z-octadecadienoic acid(16),9-hydroxy-10E,12E-octadecadienoic acid(17),(6E)-5-methylene-6-tetradecenoic acid(18).CONCLUSION Compounds 1,3-8 and 10-18 are isolated from Candida sp for the first time.

Abstract： Objective　To analyze the value and influencing factors of cross-primer isothermal amplification technology(CPA) in clinical screening and diagnosis of tuberculosis (TB). Methods　We collected 543 inpatients in the Second Affiliated Hospital of Hainan Medical College from January 1, 2018 to December 31, 2021, including 179 patients with tuberculosis, 187 patients with pneumonia and 177 patients with other diseases. The patients' sputum, alveolar lavage fluid, pleural effusion and midstream urine were detected by CPA, smear microscopy, culture method and gene detection. The value of CPA detection in the diagnosis of tuberculosis and its influencing factors were evaluated. Statistical analysis was performed using SPSS 26.0. Results　The total positive rate of CPA was 14.4% (78/543), and the positive rate of sputum samples accounted for 29.1% (39/134). Among the 78 cases of CPA positive patients, the tuberculosis group accounted for 69.2% (54/78), followed by pneumonia group 21.8% (17/78), and other diseases group accounted for 9.0% (7/78). Taking CPA test as the reference method, the "sensitivity" of smear microscopy was lower than that of genetic testing and culture, while the "specificity" was higher than that of culture and gene testing, and the "missed diagnosis rate" of smear microscopy was higher than that of genetic testing and culture. CPA test positive was related to gender, ESR and pneumonia. There is a good agreement between CPA test and culture method and gene test (Kappa>0.9), and a moderate agreement between CPA test and smear microscopy (Kappa=0.616). Conclusions　Sputum specimen is the best choice for CPA detection, while the value of pleural effusion detection is relatively limited. Sputum, alveolar lavage fluid and midcourse urine can be used as clinical specimens for screening and diagnosis of "tuberculosis group and other disease group", while sputum can be used for screening and diagnosis of "tuberculosis group and pneumonia group". Gender, ESR and pneumonia are the influencing factors of CPA positive patients. Therefore, CPA testing is worthy of clinical promotion, but more clinical research data are needed.

In this study, according to TCM theory of "liver qi stagnation forming fire", emotional stress mice model was employed to evaluate the protective effects of Qingre Xiaoyanning on herpes simplex virus type 1 (HSV-1) induced reactivation. The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Jinan University, in compliance with the Institutional Animal Care Guidelines. BALB/c mice were divided into six groups, including mock group, HSV-1 latency group, HSV-1 reactivation group (HSV-1 latency + stress), low (0.658 g·kg^-1·day^-1) and high dose (1.316 g·kg^-1·day^-1) of Qingre Xiaoyanning groups and positive control group (acyclovir, 0.206 g·kg^-1·day^-1). Except for the normal group and HSV-1 latency group, all mice in other groups received a daily 12-h restraint stress for 4 days. After 7-day treatment of drugs, body weight and recurrent eye infections of mice were recorded. Brain tissues were harvested to monitor HSV-1 antigen distribution by immunohistochemical staining and detect virus titer by plaque assay. In the meantime, the mRNA and protein levels of infected cell polypeptide (ICP27) and glycoprotein B (gB) in the brain tissues were detected by RT-PCR and Western blot, respectively. The level of 4-hydroxynonenal (4-HNE) and expressions of ferroptosis-related proteins were measured by Western blot. The evaluation of malondialdehyde (MDA) content in the brain tissues was conducted by MDA assay commercial kit. The results showed that Qingre Xiaoyanning significantly retarded the decline of body weight of mice induced by HSV-1 reactivation, reduced the activation rate of HSV-1 and recurrent eye infections, declined virus titer of HSV-1, down-regulated gene and protein expressions of ICP27 and gB, and hindered the distribution of HSV-1 antigen in the brain of mice. Meanwhile, Qingre Xiaoyanning also decreased the protein expression of ferroptosis-related proteins, including DMT1, TFR1 and ALOX15 in the brain tissue of HSV-1 reactivated mice. The levels of lipid peroxidation products, 4-HNE and MDA, were also reduced by Qingre Xiaoyanning treatment. All the above results indicate that Qingre Xiaoyanning significantly inhibited HSV-1 reactivation by restraint stress, which might be related to the regulation of ferroptosis. Our findings provide a theoretical basis for the application of "clearing liver-fire" TCM on treatmenting HSV-1 reactivation-related symptoms.

In this study, emotional stress-induced herpes simplex virus type 1(HSV-1) susceptibility model was employed to simu-late the pathological state of " depression-induced liver fire", and the protection effect of Qingre Xiaoyanning(QX) in clearing liver fire was investigated. BALB/c mice were randomly divided into a normal group, a HSV-1 group, a restraint stress + HSV-1 group,low-(0. 658 g·kg~(-1)) and high-dose(1. 316 g·kg~(-1)) QX groups, and an acyclovir group. Except for the normal group and the HSV-1 group, the mice in other groups received daily restraint stress for 6 h from day 3 of medication. On day 9 of medication, mice were anesthetized by isoflurane and infected intranasally with HSV-1. Survival rate, weight change, encephalitis symptoms, and eye injury of mice were recorded for 14 d after virus infection. Hematoxylin-eosin(HE) staining and immunohistochemical staining were used to detect pathological changes and HSV-1 antigen distribution. Plaque assay was performed to detect the titer of HSV-1. The protein ex-pression of ICP27 in the mouse brain was detected by Western blot. The experimental results showed that QX could increase the survival rate of HSV-1-infected mice loaded with emotional stress(P<0. 001), reduce the titer of HSV-1 in the mouse brain(P<0. 01), relieve brain inflammation(P<0. 05) and eye injury(P<0. 05), down-regulate the expression of ICP27 related to HSV-1(P<0. 05), and decrease the distribution of HSV-1 antigen in the mouse brain. The results demonstrated that QX significantly reduced the susceptibility to HSV-1 induced by emotional stress, which is expected to provide a theoretical basis for the treatment and preven-tion of HSV-1 infection and promote the clinical development and application of Chinese medicine effective in clearing liver fire.
Animals ; Capsules ; Herpes Simplex ; Herpesvirus 1, Human ; Mice ; Mice, Inbred BALB C ; Psychological Distress

Objective: To investigate the prevalence of allergic rhinitis (AR) in 3 central cities (Chifeng, Hohhot, Ordos) and the surrounding rural areas of Inner Mongolia region, and to look for possible risk factors related to the disease. Methods: From March to October of 2019, a multi-stage stratified random sampling epidemiological survey was conducted in Chifeng, Hohhot, Ordos and rural areas. The AR-related factors of the population were obtained in the form of face-to-face questionnaire survey, and the skin prick test (SPT) was taken for the participants. AR disease was diagnosed according to the "Guidelines for the Diagnosis and Treatment of Allergic Rhinitis (2015, Tianjin)". The daily airborne pollen situation in the three regions was monitored during the same period. SPSS 23.0 was used to analyze all survey results. Results: A total of 6 818 questionnaires were recovered, with 6 393 valid questionnaires. The self-reported prevalence of AR was 27.72% (1 772/6 393) and the confirmed prevalence of AR was 17.10% (1 093/6 393). The prevalence of perennial AR was 1.83% (117/6 393) while the prevalence of seasonal AR was 15.27% (976/6 393). The prevalence of AR diagnosed in females was higher than that in males (19.19% vs 15.34%, χ²=16.594, P<0.001) and the prevalence of females in the two age groups of 36-45 years and 46-55 years was significantly higher than that of males (18.17% vs 9.73%, 14.13% vs 7.25%, χ² value was 23.848, 18.772, respectively, all P<0.001). The prevalence of confirmed diagnoses in ethnic minorities was higher than that of Han nationality, and the prevalence of confirmed diagnoses in urban areas was higher than that in rural areas (23.13% vs 16.20%, 27.27% vs 9.71%, χ² value was 24.516, 336.024, respectively, all P<0.001). The main nasal symptoms of AR patients were sneezing (91.31%), nasal congestion (85.91%) and nasal itching (85.00%). The most common concomitant disease of AR was allergic conjunctivitis (73.99%). Asthma (OR=6.629), food allergy (OR=3.236), drug allergy (OR=1.786), application of antibiotics (OR=1.553), recent home decoration (OR=2.307), and smoking (OR=1.322) were the AR related risk factors. The highest proportion of SPT positive reactions was Artemisia annua (80.15%). The peak period of clinical symptoms of AR patients in Inner Mongolia region was July to September, which was consistent with the second peak period of airborne pollen monitoring. Conclusions: The prevalence of AR in central cities and the surrounding rural areas of Inner Mongolia region is 17.10%, and Artemisia species is the most important pollen allergen in this area. History of asthma, food allergy, drug allergy, antibiotic use, home decoration and smoking history are the related risk factors for AR.
Adult ; Allergens ; China/epidemiology* ; Female ; Humans ; Male ; Middle Aged ; Pollen ; Prevalence ; Rhinitis, Allergic/epidemiology* ; Rhinitis, Allergic, Seasonal ; Urbanization

Objective:To explore the diagnosis, surgical methods and therapeutic effect of primary duodenal malignant tumor.Methods:The clinical data of 116 patients with primary duodenal malignant tumor from January 2010 to December 2018 were retrospectively analyzed.Results:Among 116 patients, adenocarcinoma was in 74 cases, interstitial tumor was in 25 cases, carcinoid was in 9 cases, the others was in 8 cases. Before operation, duodenoscopy was performed in 107 cases, and CT examination was performed in 76 cases. There were 57 cases of pancreaticoduodenectomy, 15 cases of duodenal segmental resection, 13 cases of subtotal gastrectomy and duodenal bulbar resection, 13 cases of duodenal partial resection, and 18 cases of palliative short circuit operation. The total incidence of postoperative complication was 31.9% (37/116), including pancreatic fistula in 8 cases (grade B 5 cases, grade C 3 cases), biliary fistula in 6 cases, abdominal infection in 5 cases, pulmonary infection in 4 cases, intestinal fistula in 3 cases, delayed gastric emptying in 3 cases, and hemorrhage in 8 cases. Four cases (3.4%) died during the perioperative period. Single factor Cox regression analysis result showed that the postoperative survival time was related to the tumor differentiation degree, operation method, tumor infiltration degree and lymphatic metastasis ( P<0.05 or <0.01); multi-factor Cox regression analysis results showed that the operation method, tumor infiltration degree and lymphatic metastasis were the independent risk factors for the postoperative survival time of patients with primary duodenal malignant tumor ( P<0.05). The patients were followed up until June 2021, and 9 cases were lost to follow-up. Kaplan-Meier survival curve analysis result showed that the postoperative overall 1-,3- and 5-year survival rates were 82.11%, 57.56% and 33.11%, respectively. Conclusions:Adenocarcinoma is the main primary malignant tumor of duodenum. Duodenoscopy and CT are the main examination methods. Radical resection is the most effective treatment for primary duodenal malignant tumor, and pancreaticoduodenectomy is the first choice. Surgical method, tumor infiltration degree and lymphatic metastasis are the independent risk factors affecting the prognosis of patients.

Objective To investigate the correlation of body mass index (BMI) on pathological complete response (pCR) and prognosis of breast cancer patients receiving neoadjuvant chemotherapy.Methods A retrospective analysis was performed on 98 cases of breast cancer patients in the Tumor Hospital Affiliated to Zhengzhou University from December 2013 to November 2015.Patients were divided into normal or underweight (N/U,BMI ＜25.0 kg/m2) group,overweight (OW,BMI 25.0-29.9 kg/m2)group and obese (OB,BMI ≥30.0 kg/m2) group according to BMI.A total number of 50 (51.0％) patients were N/U,32 (32.6％) patients were OW,and 16 (16.3％) patients were OB.The pathological complete remission after neoadjuvant chemotherapy was observed,and the prognostic evaluation index was disease-free survival rates.Univariate analysis of BMI and pCR correlations was performed by Chi-square test or Fisher exact test,and logistic regression for multivariate analysis.Kaplan-Meier analysis and log-rank test were used to analyze survival status,and Cox proportional hazard model analysis for multivariate analysis.Results In this study,A statistically significant difference was found in the molecular subtypes of the three groups(P ＜ 0.05).Twenty-nine(29.6％) patients achieved pCR,pCR rates in N/U group,OW group and OB group were 36.0％ (18/50),25.0％ (8/32),and 18.8％ (3/16),respectively,but the difference was not statistically significant (P ＞ 0.05).Multivariate logistic regression analysis showed that obesity and molecular subtype were independent factors of pCR in all patients (P ＜ 0.05).The 3-year disease free survival rates of the N/U,OW,and OB groups were 84.0％,93.5％ and 80.4％,respectively (P ＞ 0.05).Multivariate survival analysis showed that the BMI was not an independent prognostic factor for the 3-year disease free survival rate (P ＞ 0.05).Conclusion Excessive BMI (obesity) is an independent predictor of pCR in breast cancer patients receiving neoadjuvant chemotherapy,but does not affect the prognosis of these patients.

Objective:To explore the inhibitory effect of moxibustion on tumor growth and metastasis, and also its possible mechanism, in gastric tumor-bearing rats by investigating the expressions of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF). Methods:Fifty healthy Sprague-Dawley (SD) rats (half male and half female) were routinely housed for 1 week. A total of 20 rats were randomly divided into a blank group and a sham operation group, with 10 rats in each group. The remaining 30 rats were used to make gastric cancer models by implantation of ascites-type Walker-256 cancer cells. After successful modeling, rats were randomly divided into a model group, a moxibustion group and an infrared group, with 10 rats in each group. From the day of modeling, the body weight of each group was weighed every 4 days. Warm moxibustion was alternately performed at two-group acupoints [Zhongwan (CV 12), Guanyuan (CV 4) and bilateral Zusanli (ST 36) in one group, and bilateral Pishu (BL 20) and Weishu (BL 21) in another group] in the moxibustion group. The body surface projection area of the stomach was irradiated with short-wave infrared rays in the infrared group, once a day, 20 min per time for 21 d. At the end of the treatment, the gastric tumor was completely dissected, and the tumor volume and tumor growth inhibition rate were calculated. Then the gastric tumor cell metastasis was recorded. The levels of VEGF and EGF in rat gastric tumor tissues were determined by enzyme-linked immunosorbent assay (ELISA). Results:Compared with the blank group, the body weight of the model group decreased significantly after modeling (P<0.05); compared with the model group, the rats in the moxibustion group had increased body weight during the middle and late stages (bothP<0.05). The tumor volumes of rats in the moxibustion group and the infrared group were smaller than the volume in the model group (bothP<0.05). The tumor growth inhibition rate in the moxibustion group was significantly higher than that in the infrared group (P<0.05). The case number of tumor metastasis in the moxibustion group was smaller than that in the model group and the infrared group. The VEGF level in the tumor tissues of the model group was statistically significantly higher than that in the blank group (P<0.05). Compared with the model group, the VEGF levels in the moxibustion group and the infrared group were statistically significantly lower (bothP<0.05). The EGF levels in the tumor tissues of the model group was statistically significantly lower than that in the blank group (P<0.05); compared with the model group, the EGF levels in the moxibustion group and the infrared group were statistically significantly increased (bothP<0.05). Conclusion:Moxibustion can increase the body weight, inhibit the tumor growth, invasion and metastasis in gastric tumor-bearing rats, which may be related to the regulation of VEGF and EGF expressions in tumor tissues.