ObjectiveTo optimize the processing technology of honey bran-fried Rosae Laevigatae Fructus（h-RLF）， formulate relevant quality standards， and explore its improving effect and mechanism on mice with ulcerative colitis（UC） induced by dextran sodium sulfate（DSS）. MethodsTaking the content of polysaccharides and water-soluble extract as the indexes， L₉（3⁴） orthogonal test was used to optimize parameters of the amount of honey bran， frying time and frying temperature. The quality of 15 batches of h-RLF decoction pieces was evaluated according to the optimized process， and the inspection limit standard was preliminarily drawn up. Eighty SPF male Kunming mice were randomly divided into 8 groups， including the blank group， model group， mesalazine group（0.13 g·kg^-1）， RLF group（3.77 g·kg^-1）， bran-fried RLF group（3.77 g·kg^-1）， h-RLF low， medium and high dose groups（1.89， 3.77， 7.54 g·kg^-1）， with 10 mice in each group. The mice in the blank group were free to drink pure water， and the other groups were free to drink 3% DSS solution for 7 days to prepare UC mouse model. Each treatment group was given corresponding drugs by intragastric administration， and the blank and model groups were given equal volume of normal saline. The body weight of mice was recorded daily and the disease activity index（DAI） was calculated. After the administration， the colon tissues of mice were collected to observe the pathological changes by hematoxylin-eosin（HE） staining. The levels of tumor necrosis factor（TNF）-α， interleukin（IL）-1β， IL-6 and IL-10 in the colon of mice were detected by enzyme-linked immunosorbent assay（ELISA）. Western blot was used to detect the expression levels of phosphorylation nuclear transcription factor-κB p65（p-NF-κB p65）， Toll-like receptor 4（TLR4）， p-p38 mitogen-activated protein kinase（p-p38 MAPK）， p-extracellular signal-regulated kinase（p-ERK） and p-c-Jun N-terminal kinase（p-JNK） proteins in colon tissues. ResultsThe optimum processing technology of h-RLF was 20 g honey bran per 100 g RLF， and stir-frying at 200 ℃ for 8 min. The limit standard under the examination of h-RLF was preliminarily formulated as follows：the polysaccharide content should not be less than 25% based on anhydrous glucose（C₆H₁₂O₆）， the content of water-soluble extract should not be less than 38%， the moisture content should not be more than 12.0%， the total ash content should not be more than 5.0%， and the acid-insoluble ash content should not be more than 1.0%. The cluster heat map analysis showed that the quality of RLF from Huanggang， Hubei province was better. Animal experiments showed that compared with the blank group， the DAI score of the model group was significantly increased， the levels of TNF-α， IL-1β and IL-6 in the colon tissue were significantly increased， the IL-10 level was significantly decreased， the colonic mucosa was seriously damaged， accompanied by a large number of inflammatory cell infiltration， tissue congestion and a significant reduction in glands， and the expression levels of p-NF-κB p65， TLR4， p-p38 MAPK， p-ERK and p-JNK proteins were significantly increased（P<0.01）. Compared with the model group， each administration group could alleviate the symptoms of colonic ulcer， the structure of colonic crypt was basically intact， and the glands were arranged in an orderly manner. Among them， the high-dose group of h-RLF had a better effect， which could significantly reduce the DAI score and the levels of TNF-α， IL-1β and IL-6 in colon tissue（P<0.01）， and significantly increase the level of IL-10（P<0.01）， alleviate the colonic mucosal injury， and effectively inhibit the expression levels of p-NF-κB p65， TLR4， p-p38 MAPK， p-ERK and p-JNK proteins（P<0.01）. ConclusionThe key parameters of the processing technology of h-RLF are determined， and the optimized technology is stable and feasible. The established quality standard is simple and reliable， and can be used for the quality control. h-RLF can effectively alleviate DSS-induced UC， and its mechanism may be related to inhibiting the activation of NF-κB/TLR4/MAPK pathway.

Bisphenols (BPs) are extensively used in food packaging, personal care products, and plastics, making them prevalent in both living and working environments, which has raised significant concern. As endocrine-disrupting chemicals, BPs exert toxic effects on the female reproductive system by binding to estrogen receptors, thereby activating or inhibiting the expression of genes related to reproductive functions, which disrupts the normal function of the endocrine system. This paper reviewed the effects of bisphenol A (BPA), bisphenol S (BPS), and bisphenol F (BPF) on female reproductive function, focusing on three key aspects: the effects on the female reproductive organs, the occurrence of associated reproductive disorders, and the mechanisms of toxicity. Specifically, this review highlighted the effects on ovarian function, uterine morphology and function, and fallopian tube function, as well as their correlation with polycystic ovary syndrome, endometriosis, miscarriage, and eclampsia. Additionally, the toxic mechanisms of BPs exposure were summarized, providing a scientific basis for future research on the impact of BPs on the female reproductive system, as well as for the assessment of potential health risks and the development of preventive measures.

Fermentum Rubrum（FR） is a kind of traditional Chinese medicine with dual-use functions of medicine and food， which has been used for more than 1 000 years. By referring to the ancient herbal classics and modern laws and regulations， the author sorted out the origin of FR， sorted out the development of processing， and analyzed the problems existing in the quality standard， aiming to provide a basis for further research and development of FR. There are many theories about the origin of FR. After summarizing and sorting out the relevant literature， three viewpoints are mainly drawn， including Han dynasty origin theory， Wei and Jin origin theory and Tang dynasty origin theory. After synthesizing the views of various schools， it is believed that the origin of FR should be no later than the Eastern Han dynasty. FR is made from rice by fermentation， which has the effect of strengthening the spleen， eliminating food， promoting blood circulation and removing stasis after fermentation. Although the natural fermentation in ancient times has been able to pay attention to the influence of temperature， humidity and strain on the quality of FR， due to the low level of science and technology， there are still problems such as complicated and cumbersome process， large workload and high labor cost. To the pure fermentation in modern times， the fermentation processing method of FR has been evolved， gradually improved and perfected. However， due to the lack of standardized research， there is no unified standard for the fermentation process of FR in various regions， and the quality standard lags behind seriously， which leads to the unstable product quality on the market. Among the 15 specifications for the preparation of FR， only 6 have been published in the past 5 years， and most of them have not been revised in a timely manner， and some of them have not been included in the updated version. Based on this， it is recommended to carry out a systematic study on processing technology of FR， and the best process is selected to accelerate the revision and improvement of its standardization， so as to improve the quality of FR sold in the market and promote its stable and sustainable development.

[Objective]To identify the relationship between tumor tissue interleukins(ILs)and non-small cell lung cancer(NSCLC)patients with poor response to immune checkpoint blockade(ICB)therapy,and to investigate the differ-ential expression of ILs in tumor of NSCLC patients as well as its effect on ICB response and prognosis.[Methods]A total of 61 patients diagnosed with NSCLC and treated with ICB were retrospectively collected from the data of a previous study.We obtained transcriptome sequencing data from tumor tissues and survival data of the patients before ICB treatment.Us-ing bioinformatics methods,we screened for ILs that significantly affected the efficacy and prognosis of ICB treatment.We evaluated the efficacy of ICB treatment using progressive-free survival(PFS)and assessed the prognosis using overall sur-vival(OS).The Kaplan-Meier survival curve and ROC curve were used to analyze the predictive effect and efficacy of ILs on the efficacy and prognosis of ICB in NSCLC patients.[Results]The results of the univariate Cox regression analysis in our study showed that nine ILs were found to be associated with OS of NSCLC patients treated with ICB at a significance level of P<0.1.Further multivariate analysis revealed that high expression of IL-11,IL-17D,and IL-36A was significant-ly associated with poor prognosis in these patients(P<0.05).The results from the Kaplan-Meier survival curve analysis revealed a significant negative correlation between the high expression of IL-17D and both PFS and OS in NSCLC patients.Specifically,patients with IL-17D high expression had a median PFS of 3.1 months compared with 6.5 months in low ex-pression patients[95%confidence interval(CI)(1.178,3.655),P=0.009].Similarly,the median OS was 9.8 months in the high expression group versus 21.8 months in the low expression group[95%CI(1.116,4.392),P=0.018].ROC curve showed that the prediction performance was favorable[AUCPFS=0.702,95%CI(0.562,0.842),P=0.027;AU-COS=0.684,95%CI(0.550,0.818),P=0.014].Although IL-11 and IL-36A alone were not significant predictors of PFS and OS in NSCLC patients,the median PFS and OS were notably shortened to 2.2 months(P=0.003)and 3.0 months(P<0.001),respectively,when high expression of IL-11 and IL-36A was combined with high expression of IL-17D.The ROC curve analysis demonstrated an improvement in prediction efficiency for both PFS and OS in NSCLC patients[AUCPFS=0.748,95%CI(0.615,0.880),P=0.007;AUCOS=0.703,95%CI(0.573,0.833),P=0.007].[Conclu-sion]The results suggest that high expression of IL-11,IL-17D,and IL-36A is associated with a higher risk of disease progression which correlates to poor PFS and OS in NSCLC patients.

Objective To investigate the changes in blood microbiota in patients with high altitude polycythemia(HAPC)and the correlation with the risk of HAPC.Methods A cross-sectional trial was carried out among 41 HAPC patients(HAPC group)and 41 healthy plateau individuals(control group)who took physical examination in the Health Management Department of No.953 Hospital of PLA Army in 2021.High-throughput sequencing technology was used to detect the V3-V4 variable region of the 16S ribosomal RNA(16S rRNA)gene in the blood smaples,and the composition and difference of the blood microbiota were compared and analyzed between the 2 groups.Results All the participants were male and Han people,and there were no significant differences in baseline data such as age,body mass index and plateau migration time between the 2 groups(P＞0.05).The α-diversity of blood microbiota in the HAPC group,including the Simpson index(0.931±0.005 vs 0.907±0.008,P＜0.05),Goods Coverage index(0.998±0.001 vs 0.997±0.001,P＜0.001)and Pielou index(0.597±0.011 vs 0.567±0.009,P＜0.05)were significantly higher than those in the control group.Meanwhile,obvious difference was observed in the β diversity between the 2 groups(P＜0.01).The relative abundance analysis of bacteria showed that Pelomonas(0.046±0.004 vs 0.033±0.003,P＜0.05),Azospirillum(0.046±0.006 vs 0.021±0.003,P＜0.01),Acidovorax(0.032± 0.003 vs 0.019±0.002,Azospirillum(0.046±0.006 vs 0.021±0.003,P＜0.01)and Acidovorax(0.032± 0.003 vs 0.019±0.002,P＜0.05)were statistically higher in the HAPC group than the control group.LEfSe analysis showed that the characteristic blood microbiota of the HAPC group were α-Proteobacteria,and those of control group were Trichospiridae.Conclusion Significant changes are found in diversity,relative abundance and characteristic bacteria of the blood microbiota between the HAPC patients and healthy people at the high altitude,which might be closely associated with the occurrence and development of HAPC.

Objective:To investigate the indications for prenatal diagnosis and pregnancy outcomes of fetal Turner syndrome (TS) with different karyotypes.Methods:Clinical data of TS cases diagnosed by fetal karyotyping in the Prenatal Diagnostic Center of Guangzhou Women and Children′s Medical Center from January 1, 2010, to June 30, 2021, were analyzed retrospectively. According to the karyotyping results, these cases were divided into two groups: monosomy X (45,X) and non-monosomy X groups (including karyotypes of mosaic monosomy X, isochromosome X, X deletion, X rearrangement, pseudodicentric X, and mosaicism with Y or Y deletion). Chi-square test was used to compare the detection rate, indications for prenatal diagnosis, and pregnancy outcomes of the two groups, and the Bonferroni test was conducted for further pairwise comparisons between the subgroups. The Chi-square test (or Fisher's exact test) was used to compare the abnormal ultrasound signs. Mann-Whitney U test was used to compare the nuchal translucency (NT) thickness of the two groups. Results:(1) Invasive prenatal diagnosis was performed on 27 981 pregnancies, and 205 (0.73%) of them were diagnosed with TS, including 135 cases of monosomy X and 70 cases of non-monosomy X (44 with numerical sex chromosome abnormalities, and 26 with structural sex chromosome abnormalities). (2) Out of the 205 pregnancies, 164 (80.0%) had one indication for prenatal diagnosis, and 41 (20.0%) had multiple indications. The detection rate of fetal ultrasonographic abnormalities [85.2% (115/135)] in monosomy X cases was significantly higher than that of three other indications [positive serological screening for Down's syndrome: 67.3% (35/52); positive non-invasive prenatal testing (NIPT) for sex chromosome abnormality: 60.0% (15/25); and other indications (advanced maternal age, adverse pregnancy history and thalassemia genes carried by both parents): 5.2% (7/135); all P<0.05], and also higher than the figure in non-monosomy X cases [25.7% (18/70), χ 2=71.55, P<0.001]. In non-monosomy X cases, the detection rates of TS among cases with high-risk results from serological screening for Down's syndrome and NIPT for sex chromosome abnormality [54.7% (29/53) and 68.3% (28/41)] were higher than those of the other two indications [fetal ultrasonographic abnormalities: 25.7% (18/70), other indications: 14.3% (10/70); all P<0.05]. (3) Of the 133 pregnancies with fetal ultrasonographic abnormalities as the indication, 65 (48.9%) had one abnormal ultrasound sign, and 68 (51.1%) had multiple signs. Among the 95 cases with ultrasound abnormalities in the first trimester and 38 cases in the second or third trimester, the incidence of cystic hygroma and hydrops was significantly higher in monosomy X cases than in non-monosomy X cases [in the first trimester: 71.8% (61/85) vs 1/10, 34.1% (29/85) vs 0/10; in the second or third trimester: 73.3% (22/30) vs 0/8, 50.0% (15/30) vs 0/8; Fisher's exact test, all P<0.05]. NT thickness in monosomy X cases was greater than that of non-monosomy X cases [7.5 mm (1.0-17.4 mm) vs 1.7 mm (0.8-9.5 mm), Z=－5.25, P<0.001]. (4) Among the 72 pregnancies with indications other than ultrasound abnormalities, 68 underwent Down's syndrome screening and 61 underwent NIPT. The detection rates among the cases with positive results in Down's syndrome screening, NIPT for a sex chromosome abnormality, and other indications (advanced maternal age, adverse pregnancy history, and thalassemia genes carried by both parents) were 54.4% (37/68), 59.0% (36/61) and 22.2% (16/72), respectively ( χ 2=22.40, P<0.001). The detection rates of the cases with high-risk results from Down's syndrome screening and NIPT for sex chromosome abnormality were higher than that of the cases with other indications ( χ 2=18.77 and 15.40, both P<0.001). Of the 72 pregnancies, 19 (26.4%) were monosomy X and 53 (73.6%) were non-monosomy X, including 42 (58.3%) with chromosomal mosaicism. (5) Among the 205 cases of TS, 185 were successfully followed up (123 were monosomy X and 62 were non-monosomy X). There was one live birth in monosomy X cases (0.8%, 1/123) and 17 in non-monosomy X cases (27.4%, 17/62), and the difference was statistically significant ( χ2=33.22, P<0.001). Sixty-three TS cases with normal ultrasound findings were followed up (18 were monosomy X and 45 were non-monosomy X). In these cases, all 18 pregnancies with monosomy X and 32 (71.1%, 32/45) with non-monosomy X were terminated and the other 13 (28.9%, 13/45) cases of non-monosomy X were delivered. Of the 18 live births, one (non-monosomy X) was delivered at 36 weeks of gestation and the rest were born at term. Eleven cases of them were followed up. The height of one child with monosomy X was lower than the average height of children of the same age and sex by more than 2 standard deviations (－2 SD). The height of 10 children with non-monosomy X were between－1 SD and +3 SD among the children of the same age and gender. The mental and motor development were good in the 11 cases, and no other structural abnormalities were observed. The remaining seven cases refused to be followed up. Conclusions:Ultrasonographic abnormalities are the main indications of fetal TS with monosomy X, while positive Down's syndrome screening and positive NIPT for sex chromosome abnormality are indicators of non-monosomy X. The termination rate for pregnancies with monosomy X is higher than that for non-monosomy X.

High Altitude Military Hygiene is the professional core course of high-altitude medicine, which is significant to the cultivation of military medical talents urgently needed by plateau troops. Under the background of "golden course" construction and army curriculum reform, aiming at the problems such as outdated content of course materials, single teaching mode and insufficient capacity of practical courses, we actively explored the effective path of "golden course" construction, including the renovation of the curriculum-construction concept, the optimization and reorganization of the teaching content, the expansion of case teaching and equipment teaching methods, and the implementation of curriculum ideological and political education and examination reforms. The reform has further improved the learning effect of students and the level of curriculum construction, and also provided beneficial reference for the construction of similar courses in military colleges and universities.

Objective:To investigate the effects of pre-existing antibody on seroconversion rate after influenza vaccination.Methods:This study recruited 1 900 healthy volunteers to receive influenza split vaccines in Xinjiang Uygur Autonomous region and Yunnan Province from September 2009 to October 2018. Hemagglutinin agglutination inhibition assay was used to detect the titers of specific antibodies in blood samples collected before vaccination and 28 d after vaccination and the effects of pre-existing antibody on the seroconversion to different influenza vaccine components were analyzed.Results:Trend analysis showed that with the increasing titer of pre-existing antibody, the seroconversion rates to A/H1N1, A/H3N2, B/Victoria and B/Yamagata vaccine components were gradually decreased (χ 2=121.76, P<0.001; χ 2=67.58, P<0.001; χ 2=45.25, P<0.001; χ 2=54.55, P<0.001). After adjusting for factors such as region, gender and age, multivariate logistic regression showed that pre-existing antibody titer equal to or higher than 40 was an independent factor that affected the seroconversion to A/H1N1, A/H3N2 and B/Victoria vaccine components, and the adjusted OR (95%CI) values were 2.50(2.00-3.13)、1.64(1.35-2.00) and 2.50(1.79-3.45), respectively. Conclusions:The seroconversion rate to each vaccine component was negatively correlated with the pre-existing antibody titer. The factor that pre-existing antibody titer equal to or higher than 40 was detrimental to the seroconversion to A/H1N1, A/H3N2 and B/Victoria vaccine components, but had no significant influence on B/Yamagata seroconversion.

Leptin, a peptide hormone discovered in the 1990s, arouses interest as it can regulate the body′s metabolism. In recent years, many studies have shown that leptin can promote the proliferation, activation and cytokine synthesis of various immune cells, and participate in innate and adaptive immune responses. This article reviewed the role of leptin and involved signaling pathways in immune response and the potential of leptin as a vaccine adjuvant.

Objective To explore the effect of timosaponin B-II ( TB-II) on the differentiation of neural stem cells (NSCs) into tyrosine hydroxylase (TH) positive neurons in neonatal rats. Methods The biological functions of self-proliferation and multi-differentiation of NSCs were identified by primary culture, cell proliferation counting,morphological observation and immunology. NSCs of SD rats were cultured in vitro and treated with different concentrations of TB-II (10 μg/ml,30 μg/ml ,100 μg/ml) for 7 days. Immuno-histochemistry was used to detect the effect of TB-II on the differentiation of NSCs into TH-positive neurons, and Western blot was used to detect the expression of TH protein in neurons. Results ( 1) The cultured cells had the ability to self-proliferation,expressed nestin protein and differentiated into neurons and glial cells. So the cultured cells were conformed to the biological function of neural stem cells. (2)Compared with the control group,the TH positive cell ratio of TB-II 30 μg/ml group and TB-II 100 μg/ml group increased ((10. 03± 1. 36)%),( 20. 01± 3. 37)%),(31. 32± 3. 98)%) ,the difference was significant ( t=6. 15, 16. 54,both P<0. 05). There was no significant difference between TB-II 10 μg/ml group and control group (P>0. 05). (3)Western results showed that the relative expression of TH protein in TB-II 30 g/ml group and TB-II 100 μg/ml group was higher than that in control group,the difference was statistically significant (con-trol group: (1. 02±0. 24),TB-II 30μg/ml group: (3. 64±1. 78),TB-II 100 μg/ml group: (5. 88±2. 34);t=12. 58,9. 15,both P<0. 05). There was no significant difference between TB-II 10 μg/ml group and con-trol group (P>0. 05). Conclusion TB-II can promote the differentiation of NSCs into TH-positive neurons.