Impact of Large Language Models on Medical Education and Teaching Adaptations.

Unlabelled: This viewpoint article explores the transformative role of large language models (LLMs) in the field of medical education, highlighting their potential to enhance teaching quality, promote personalized learning paths, strengthen clinical skills training, optimize teaching assessment processes, boost the efficiency of medical research, and support continuing medical education. However, the use of LLMs entails certain challenges, such as questions regarding the accuracy of information, the risk of overreliance on technology, a lack of emotional recognition capabilities, and concerns related to ethics, privacy, and data security. This article emphasizes that to maximize the potential of LLMs and overcome these challenges, educators must exhibit leadership in medical education, adjust their teaching strategies flexibly, cultivate students' critical thinking, and emphasize the importance of practical experience, thus ensuring that students can use LLMs correctly and effectively. By adopting such a comprehensive and balanced approach, educators can train health care professionals who are proficient in the use of advanced technologies and who exhibit solid professional ethics and practical skills, thus laying a strong foundation for these professionals to overcome future challenges in the health care sector.

[Effect of No-tillage on Soil Aggregates in Farmland：A Meta Analysis].

In order to clarify the impact of no-tillage on the quality of farmland soil aggregates in China and promote the adaptive application of no-tillage practices， a Meta-analysis was conducted by collecting data from 116 published studies. The effects of no-tillage on aggregate size distribution， mean weight diameter （MWD）， and aggregate-associated C were studied. The results showed that compared with that under tillage， no-tillage significantly increased the proportion of macroaggregates （10.9%） and MWD （12.8%） and decreased the proportion of clay and silt （-15.5%） but had no significant effect on soil microaggregate and aggregate-associated C. The subgroup and Meta regression analysis showed that no-tillage significantly increased the proportion of macroaggregates in Northwest China （17.6%） and MWD in North China （15.4%）. In upland and clay loam， no-tillage increased MWD by 12.6% and 18.4%， respectively. The effect of no-tillage on increasing the proportion of macroaggregates increased with the soil pH. When straw returned， no-tillage significantly increased the proportion of macroaggregates （9.6%） and MWD （11.6%）， but no significant effect of no-tillage on aggregates was found after straw removal. Regarding test duration， short-term （ < 5 a） no-tillage could significantly increase the proportion of macroaggregates， whereas long-term （ > 10 a） no-tillage could improve the MWD. In different soil layers， no-tillage could only significantly improve the aggregate size distribution and MWD in topsoil （0-20 cm） but had no effect in subsoil （ > 20 cm）. In summary， no-tillage could improve aggregate size distribution and stability but had no effect on aggregate-associated C. Production region， soil properties， field management methods， and other factors should be fully considered in production practice to effectively improve the quality of soil aggregates.

Correlation between irritable bowel syndrome as well as its subtype and gallbladder stones / 解放军医学杂志

Objective To analyze the correlation between irritable bowel syndrome(IBS)as well as its subtypes and gallbladder stone.Methods Collected the clinical data of 556 patients who were treated in Department of Gastroenterology of the Sixth Medical Center of Chinese PLA General Hospital from January 2019 to March 2023.The patients were divided into IBS group(n=161)and non-IBS group(n=395).The subjects were investigated by questionnaire,physical examination and blood examination,and the data of gender,age,height,weight,blood pressure and blood biochemical indexes were obtained and compared between two groups.The relation between gallbladder stone and IBS were evaluated by logistic regression analysis.Results There were 90 cases of gallbladder stone in the total population,accounting for 16.2%,including 37 cases of gallbladder stone in IBS group(23.0%)and 53 cases in non-IBS group(13.4%).The prevalence rate of gallbladder stone in IBS group was significantly higher than that in non-IBS group(P<0.05).There were 6 cases of gallbladder muddy stones(3.7%)in IBS group and 3 cases(0.8%)in non-IBS group.And the prevalence rate of gallbladder muddy stones in IBS group was also significantly higher than that in non-IBS group(P<0.05).Logistic regression analysis showed that the age,BMI,total bile acids(TBA),total cholesterol(TC)and combined IBS were independently related to the occurrence of gallbladder stone(P<0.05).In the 161 IBS patients,there were 114 cases of diarrhea-predominant IBS(IBS-D group),including 26 cases(22.8%)of gallbladder stone in IBS-diarrhea(IBS-D,n=114)group and 47 cases of constipation-predominant IBS(IBS-C group),including 11 cases(23.4%)of gallbladder stone.And there were 53 cases(13.4%)of gallbladder stone in the non-IBS group(n=395).Further analysis showed that the prevalence rate of gallbladder stone in IBS-D group was significantly higher than that in non-IBS group(P<0.05).There was no significant difference in gallbladder stone prevalence rate between IBS-C group and non-IBS group(P>0.05).Conclusions There is a correlation between IBS and gallbladder stones.In addition,among the two subtypes of IBS,IBS-D patients may have an increased risk of gallbladder stone compared with non-IBS patients.

Clinical Advantages of Traditional Chinese Medicine in Treatment of Pediatric Diseases / 中国实验方剂学杂志

The traditional Chinese medicine （TCM） in pediatric care has a long history，proven efficacy，and distinctive characteristics.The China Association of Chinese Medicine has organized a series of youth salons to discuss the clinical advantages of treating diseases.Experts at this seminar proposed that the superior disease categories in pediatric TCM are significant for showcasing the unique strengths and advantages of TCM in the treatment of pediatric diseases，enhancing diagnostic and treatment levels，inheriting TCM knowledge，promoting the integration of TCM and Western medicine，and meeting patients' needs.The strengths of pediatric TCM are summed up as "having what others do not，excelling at what others have，being special in what others excel at，and ensuring safety in what others specialize in." The scope of superiority in pediatric TCM covers multiple systems，including respiratory，digestive，endocrine，psychological，and dermatological systems.This article summarized the advantages of TCM in treating 13 diseases discussed in the salon，such as upper respiratory tract infections，coughs，pneumonia，allergic rhinitis，bronchial asthma，atopic dermatitis，functional dyspepsia，functional constipation，enuresis，marginal short stature，simple obesity，attention deficit hyperactivity disorder，and tic disorders.The overall advantages were reflected in three aspects：First，the holistic concept and treatment based on syndrome differentiation in TCM highlight the advantage of treating the root causes of diseases，making the treatment methodical and precise.Second，most traditional Chinese herbs are natural and have strong safety profiles.Third，TCM treatment methods are abundant，especially the external treatment methods，which are widely used in pediatrics，highly accepted by parents，and have definite efficacy，as well as good safety and compliance.

[Effect of Biochar on Agricultural Soil Aggregates and Organic Carbon: A Meta-analysis].

As a soil amendment, biochar has been widely used to ameliorate agricultural soil. To ensure the effect of biochar on the carbon sequestration of farmlands in China, a Meta-analysis was carried out via collecting published literatures. We quantitatively analyzed the response of biochar application to soil aggregates, aggregate carbon, and soil organic carbon to different experimental conditions. The results showed that the application of biochar significantly increased the proportion of soil macroaggregates(10.8%) and MWD(13.3%) but had no significant effect on soil microaggregates and silty-clay compared with those in the non-biochar-added treatment. Moreover, biochar addition significantly increased soil organic carbon content(56.9%), with the largest increased area in North China(39.4%), and enhanced intra-aggregate carbon contents of each particle size. Biochar could significantly increase soil organic carbon content under different experimental designs. Compared with that under non-fertilization, biochar combined with fertilization could also significantly improve soil structure and soil fertility. We also found that more than two years of biochar application significantly increased the proportion of macroaggregates(15.7%), MWD(21.2%), macroaggregate carbon(31.7%), and soil organic carbon(40.0%). Meanwhile, biochar produced from crop straw had better soil improvement effects than that of wood and sawdust. Biochar applied in high-nitrogen soil was more beneficial to improve soil stability. Thus, we concluded that biochar could meliorate soil structure and promote the accumulation of soil organic carbon, which was of importance for the fertility maintenance and improvement of the farmland.

Clinical characteristics and treatment outcomes of 68 patients with spontaneous iliac vein rupture: A case report and systematic review.

Objective: Spontaneous iliac vein rupture (SIVR) is a rare but life-threatening condition with limited understanding regarding its clinical presentation, pathogenesis, diagnosis, management, and risk factors for mortality. This study aims to address this gap by providing comprehensive insights into SIVR through personal case reports and a systematic review of previous cases. Methods: We detail a case of right SIVR caused by inappropriate positioning of the stent in the inferior vena cava and systematically reviewed previous cases. Logistic regression analysis was used to identify risk factors for mortality. Results: Our SIVR case was successfully managed with percutaneous mechanical thrombectomy and covered stent placement. In the systematic review, 68 patients were included in the analysis with an average age of 62.01 ± 13.25 years; 86.76% were female, 91.17% had left iliac vein rupture, 55.88% presented hemodynamic instability, 76.47% had lower abdomen or iliac fossa pain, 67.64% had deep venous thrombosis (DVT), and 32.35% had May‒Thurner syndrome (MTS). The mortality rates of conservative treatment and open surgery were 2.94% and 17.65%, respectively. All 12 patients receiving endovascular treatment survived. The factors associated with a worse outcome were younger age (52.86 ± 12.96 years, OR: 1.085, 95% CI: 1.002-1.174) and SIVR patients without DVT (OR:10.111, 95% CI: 1.637-62.443). Conclusion: This first systematic review on SIVR shows that SIVR should be highly suspected in elderly females who develop lower extremity DVT and concurrent lower abdominal pain, particularly those with a retroperitoneal mass and unstable hemodynamics. Thrombosis secondary to MTS may be the main cause of SIVR. Angiography and endovascular therapy should be prioritized for DVT patients with unexplained retroperitoneal hematoma. This study classifies SIVR into two types: iliac vein rupture alone and iliac vein rupture with DVT. These findings provide critical insights for clinicians to accurately diagnose and manage SIVR, thereby improving patient outcomes.

[Structure and Function of Soil Fungal Community in Rotation Fallow Farmland in Alluvial Plain of Lower Yellow River].

This study was conducted to clarify the structure and function of the fungal community and the microecology change characteristics of farmland soil fertility response to different fallow rotation patterns. It aimed to provide a reference for promoting farmland ecological restoration and farmland quality improvement in the alluvial plain of the lower Yellow River. Farmland soil subject to a long-term rotation fallow experiment since 2018 was studied using Illumina MiSeq high-throughput sequencing technology, and the 'FUNGuild' fungal function prediction tool was used to analyze differences in soil fungal community structure and function under the following four rotation fallow regimes: long fallow (LF), winter wheat and summer fallow (WF), winter fallow and summer maize (FM), and annual rotation of winter wheat and summer maize (WM). The results showed that LF (fallow lasting two years) increased the richness and diversity of fungal communities in the topsoil (0-20 cm layer), whereas WF increased the richness and diversity of fungi in the deep soil (20-40 cm layer) after winter wheat harvest. A total of 2262 OTU were obtained from all soil samples, which were divided into 14 phyla, 34 classes, 75 orders, 169 families, 309 genera, and 523 species. OTU shared by the two soil layers included 420 types (0-20 cm layer) and 253 types (20-40 cm layer), respectively. The fungal community structure of the four rotation fallow soils was similar at the phylum level, mainly including Ascomycota, Basidiomycota, and Mortierellomycota. The total abundances of the three dominant bacteria were 91.69%-96.91% (0-20 cm layer) and 91.67%-94.86% (20-40 cm layer), respectively. Principal component analysis showed that the first principal component (PC1) and the second principal component (PC2) could explain the difference in community structure by 45.56% (0-20 cm layer) and 46.20% (20-40 cm layer). Additionally, the LDA results of LEfSe (threshold was 4.0) showed that there were 64 fungal evolutionary branches in LF, FM, WF, and WM with statistically significant differences (P<0.05). According to RDA analysis, total organic carbon (TOC), total phosphorus (TP), available nitrogen (AN), and soil water content (SWC) were the main environmental factors that significantly affected fungal community in the 0-40 cm soil layer (P<0.05). The functional prediction with FUNGuild showed that the main nutrient types among different treatments in different soil layers were saprotrophic, saprotrophic-symbiotrophic, pathotrophic-saprotrophic-symbiotrophic, and pathotrophic. In LF, the nutrient type of topsoil was mainly pathotrophic-saprotrophic-symbiotrophic, whereas in deep soil, the relative abundance of pathotrophic fungi was the highest. Additionally, in the treatments with planted wheat or corn (FM, WF, and WM), saprotrophic was the main type in both soil layers. Therefore, different fallow patterns were linked to variation in the structure, diversity, and nutrient types of soil fungal communities. Based on these results, seasonal fallow practices could regulate the farmland soil micro-ecological environment of intensive planting and promote the health and harmony of farmland soil ecosystems.

Prenatal Maternal Risk Factors Contributing to Atopic Dermatitis: A Systematic Review and Meta-Analysis of Cohort Studies

Background@#The gestational risk factors predispose to the manifestation of early childhood atopic dermatitis (AD). @*Objective@#We evaluated the association between modifiable and non-modifiable gestational and prenatal risk factors that affect the AD prevalence in children. @*Methods@#We performed the systematic review and meta-analysis of cohort studies (n=27) in PubMed and EMBASE (2000~2021). A meta-analysis was performed using random-effects models to estimate pooled odds ratios (OR) or hazard ratio (HR). We performed a systematic review according to Preferred Reporting Item for Systematic Review and Meta-Analyses (PRISMA) guidelines and summarized cohort studies investigating gestational and prenatal risk factor those predispose to AD in off spring. Leading modifiable and non-modifiable were identified through ORs. Meta-analysis using the random effect model was also conducted to provide an overall estimate for several significant factors. @*Results@#Among the non-modifiable risk factors gestational diabetes (7.2, 95% confidence interval [CI]: 1.4~34.5), maternal history of allergy (2.14, 95% CI: 1.54~2.97) and prenatal history of eczema (2.46, 95% CI: 1.0~5.8) were found as major determining risk factors in early manifestation of AD in children. Further, maternal exposure to industrial products (1.89, 95% CI: 1.10~3.16), exposure to antibiotics during pregnancy (3.59, 95% CI: 1.19~10.85) and passive smoking during pregnancy (2.60, 95% CI: 1.11~6.1) are leading causes of early AD manifestation. @*Conclusion@#Conclusively, both genetic and environmental factors play a pivotal role in early manifestation of AD. The better managing the environmental factors during gestational phase to the least can help curtail the prevalence of AD in children.

Systematic identification of chemical forms of key terpene synthase in Cinnamomum camphora / 中国中药杂志

Cinnamomum camphora is an important economic tree species in China. According to the type and content of main components in the volatile oil of leaf, C. camphora were divided into five chemotypes, including borneol-type, camphor-type, linalool-type, cineole-type, and nerolidol-type. Terpene synthase(TPS) is the key enzyme for the formation of these compounds. Although several key enzyme genes have been identified, the biosynthetic pathway of(+)-borneol, which has the most economic value, has not been reported. In this study, nine terpenoid synthase genes CcTPS1-CcTPS9 were cloned through transcriptome analysis of four chemical-type leaves. After the recombinant protein was induced by Escherichia coli, geranyl pyrophosphate(GPP) and farnesyl pyrophosphate(FPP) were used as substrates for enzymatic reaction, respectively. Both CcTPS1 and CcTPS9 could catalyze GPP to produce bornyl pyrophosphate, which could be hydrolyzed by phosphohydrolase to obtain(+)-borneol, and the product of(+)-borneol accounted for 0.4% and 89.3%, respectively. Both CcTPS3 and CcTPS6 could catalyze GPP to generate a single product linalool, and CcTPS6 could also react with FPP to generate nerolidol. CcTPS8 reacted with GPP to produce 1,8-cineol(30.71%). Nine terpene synthases produced 9 monoterpene and 6 sesquiterpenes. The study has identified the key enzyme genes responsible for borneol biosynthesis in C. camphora for the first time, laying a foundation for further elucidating the molecular mechanism of chemical type formation and cultivating new varieties of borneol with high yield by using bioengineering technology.

Generation of male germ cells in vitro from the stem cells / 亚洲男科学杂志(英文版)

Infertility has become a serious disease since it affects 10%-15% of couples worldwide, and male infertility contributes to about 50% of the cases. Notably, a significant decrease occurs in the newborn population by 7.82 million in 2020 compared to 2016 in China. As such, it is essential to explore the effective methods of obtaining functional male gametes for restoring male fertility. Stem cells, including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), spermatogonial stem cells (SSCs), and mesenchymal stem cells (MSCs), possess the abilities of both self-renewal and differentiation into germ cells. Significantly, much progress has recently been achieved in the generation of male germ cells in vitro from various kinds of stem cells under the specified conditions, e.g., the coculturing with Sertoli cells, three-dimensional culture system, the addition of growth factors and cytokines, and/or the overexpression of germ cell-related genes. In this review, we address the current advance in the derivation of male germ cells in vitro from stem cells based on the studies of the peers and us, and we highlight the perspectives and potential application of stem cell-derived male gametes in reproductive medicine.

Regional analysis of high risk factors of hypertensive disorders in pregnancy with organ or system impairment / 中华妇产科杂志

Objective: To explore the influencing factors of pregnancy-induced hypertensive disorders in pregnancy (HDP) with organ or system impairment in pregnant women, and to analyze and compare the differences of HDP subtypes in different regions of China. Methods: A total of 27 680 pregnant women with HDP with complete data from 161 hospitals in 24 provinces, autonomous regions and municipalities were retrospectively collected from January 1, 2018 to December 31, 2018. According to their clinical manifestations, they were divided into hypertension group [a total of 10 308 cases, including 8 250 cases of gestational hypertension (GH), 2 058 cases of chronic hypertension during pregnancy] and hypertension with organ or system impairment group [17 372 cases, including 14 590 cases of pre-eclampsia (PE), 137 cases of eclampsia, 2 645 cases of chronic hypertension with PE]. The subtype distribution of HDP in East China (6 136 cases), North China (4 821 cases), Central China (3 502 cases), South China (8 371 cases), Northeast China (1 456 cases), Southwest China (2 158 cases) and Northwest China (1 236 cases) were analyzed. By comparing the differences of HDP subtypes and related risk factors in different regions, regional analysis of the risk factors of HDP pregnant women with organ or system impairment was conducted. Results: (1) The proportions of HDP pregnant women with organ or system impairment in Northeast China (79.05%, 1 151/1 456), Central China (68.42%, 2 396/3 502) and Northwest China (69.34%, 857/1 236) were higher than the national average (62.76%, 17 372/27 680); the proportions in North China (59.18%, 2 853/4 821), East China (60.85%, 3 734/6 136) and South China (59.56%, 4 986/8 371) were lower than the national average, and the differences were statistically significant (all P<0.05). (2) Univariate analysis showed that the proportions of primiparas, non-Han, non-urban household registration, irregular prenatal examination and PE history in the hypertension with organ or system impairment group were higher than those in the hypertension group, and the differences were statistically significant (all P<0.05). Multivariate logistic regression analysis showed that primiparas, non-Han, non-urban household registration, irregular prenatal examination and PE history were independent risk factors for HDP pregnant women with organ or system impairment (all P<0.05). (3) Primipara: the rates of primipara in Northeast China, North China and Southwest China were higher than the national average level, while those in South China, Central China and Northwest China were lower than the national average level. Non-Han nationality: the rates of non-Han nationality in Northeast China, North China and Northwest China were higher than the national average, while those in East China, South China and Central China were lower than the national average. Non-urban household registration: the rates of non-urban household registration in Northeast China, North China, and Southwest China were lower than the national average, while those in East China, Central China were higher than the national average. Irregular prenatal examination: the rates of irregular prenatal examination in North China, South China and Southwest regions were lower than the national average level, while those in Northeast China, Central China and Northwest China were higher than the national average level. History of PE: the incidence rates of PE in Northeast China, North China, South China and Southwest China were lower than the national average level, while those in Central China and Northwest China were higher than the national average level. Conclusions: Primiparas, non-Han, non-urban household registration, irregular prenatal examination, and PE history are risk factors for HDP pregnant women with organ or system impairment. Patients in Northeast, Central and Northwest China have more risk factors, and are more likely to be accompanied by organ or system function damage. It is important to strengthen the management of pregnant women and reduce the occurrence of HDP.

Effect of FTY-720 on Pulmonary Fibrosis in Mice via the TGF-β1Signaling Pathway and Autophagy

We investigated whether FTY-720 might have an effect on bleomycin-induced pulmonary fibrosis through inhibiting TGF-β1 pathway, and up-regulating autophagy. The pulmonary fibrosis was induced by bleomycin. FTY-720 (1 mg/kg) drug was intraperitoneally injected into mice. Histological changes and inflammatory factors were observed, and EMT and autophagy protein markers were studied by immunohistochemistry and immunofluorescence. The effects of bleomycin on MLE-12 cells were detected by MTT assay and flow cytometry, and the related molecular mechanisms were studied by Western Blot. FTY-720 considerably attenuated bleomycin-induced disorganization of alveolar tissue, extracellular collagen deposition, and α-SMA and E-cadherin levels in mice. The levels of IL-1β, TNF-α, and IL-6 cytokines were attenuated in bronchoalveolar lavage fluid, as well as protein content and leukocyte count. COL1A1 and MMP9 protein expressions in lung tissue were significantly reduced. Additionally, FTY-720 treatment effectively inhibited the expressions of key proteins in TGF-β1/TAK1/P38MAPK pathway and regulated autophagy proteins. Similar results were additionally found in cellular assays with mouse alveolar epithelial cells. Our study provides proof for a new mechanism for FTY-720 to suppress pulmonary fibrosis. FTY-720 is also a target for treating pulmonary fibrosis.

Characteristics of the left heart structure and function in 86 term neonates with intrauterine growth restriction / 中国当代儿科杂志

OBJECTIVES@#To study the left heart structure and functional characteristics of term neonates with intrauterine growth restriction (IUGR).@*METHODS@#This study included 86 term neonates with IUGR admitted to the Neonatal Ward of Beijing Friendship Hospital, Capital Medical University from January 2019 to January 2022 as the IUGR group, as well as randomly selected 86 term neonates without IUGR born during the same period as the non-IUGR group. The clinical data and echocardiographic data were compared between the two groups.@*RESULTS@#The analysis of left heart structure and function showed that compared with the non-IUGR group, the IUGR group had significantly lower left ventricular mass, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, left atrial diameter, end-diastolic interventricular septal thickness, left ventricular posterior wall thickness, left ventricular end-diastolic volume, left ventricular end-systolic volume, and stroke volume (P<0.05) and significantly higher ratio of end-diastolic interventricular septal thickness to left ventricular posterior wall thickness, proportion of neonates with a mitral peak E/A ratio of ≥1, and cardiac index (P<0.05). The Spearman correlation analysis suggested that stroke volume was positively correlated with birth weight and body surface area (rs=0.241 and 0.241 respectively; P<0.05) and that the ratio of end-diastolic interventricular septal thickness to left ventricular posterior wall thickness was negatively correlated with birth weight and body surface area (rs=-0.229 and -0.225 respectively; P<0.05).@*CONCLUSIONS@#The left ventricular systolic function of neonates with IUGR is not significantly different from that of neonates without IUGR. However, the ventricular septum is thicker in neonates with IUGR. This change is negatively correlated with birth weight and body surface area. The left ventricular diastolic function may be impaired in neonates with IUGR.

Long non-coding RNA SNHG16 promotes human placenta-derived mesenchymal stem cell proliferation capacity through the PI3K/AKT pathway under hypoxia.

BACKGROUND: The effect of hypoxia on mesenchymal stem cells (MSCs) is an emerging topic in MSC biology. Although long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) are reported to play a critical role in regulating the biological characteristics of MSCs, their specific expression and co-expression profiles in human placenta-derived MSCs (hP-MSCs) under hypoxia and the underlying mech anisms of lncRNAs in hP-MSC biology are unknown. AIM: To reveal the specific expression profiles of lncRNAs in hP-MSCs under hypoxia and initially explored the possible mechanism of lncRNAs on hP-MSC biology. METHODS: Here, we used a multigas incubator (92.5% N2, 5% CO2, and 2.5% O2) to mimic the hypoxia condition and observed that hypoxic culture significantly promoted the proliferation potential of hP-MSCs. RNA sequencing technology was applied to identify the exact expression profiles of lncRNAs and mRNAs under hypoxia. RESULTS: We identified 289 differentially expressed lncRNAs and 240 differentially expressed mRNAs between the hypoxia and normoxia groups. Among them, the lncRNA SNHG16 was upregulated under hypoxia, which was also validated by reverse transcription-polymerase chain reaction. SNHG16 was confirmed to affect hP-MSC proliferation rates using a SNHG16 knockdown model. SNHG16 overexpression could significantly enhance the proliferation capacity of hP-MSCs, activate the PI3K/AKT pathway, and upregulate the expression of cell cycle-related proteins. CONCLUSION: Our results revealed the specific expression characteristics of lncRNAs and mRNAs in hypoxia-cultured hP-MSCs and that lncRNA SNHG16 can promote hP-MSC proliferation through the PI3K/AKT pathway.

Antibody avidity and multi-specificity combined to confer protection against SARS-CoV-2 and resilience against viral escape

SARS-CoV-2, the causative agent of COVID-19, has been responsible for a global pandemic. Monoclonal antibodies have been used as antiviral therapeutics, but have been limited in efficacy by viral sequence variability in emerging variants of concern (VOCs), and in deployment by the need for high doses. In this study, we leverage the MULTI-specific, multi-Affinity antiBODY (Multabody, MB) platform, derived from the human apoferritin protomer, to drive the multimerization of antibody fragments and generate exceptionally potent and broad SARS-CoV-2 neutralizers. CryoEM revealed a high degree of homogeneity for the core of these engineered antibody-like molecules at 2.1 [A] resolution. We demonstrate that neutralization potency improvements of the MB over corresponding IgGs translates into superior in vivo protection: in the SARS-CoV-2 mouse challenge model, comparable in vivo protection was achieved for the MB delivered at 30x lower dose compared to the corresponding IgGs. Furthermore, we show how MBs potently neutralize SARS-CoV-2 VOCs by leveraging augmented avidity, even when corresponding IgGs lose their ability to neutralize potently. Multiple mAb specificities could also be combined into a single MB molecule to expand the neutralization breadth beyond SARS-CoV-2 to other sarbecoviruses. Our work demonstrates how avidity and multi-specificity combined can be leveraged to confer protection and resilience against viral diversity that exceeds that of traditional monoclonal antibody therapies.

[Effect of Suanzaoren Decoction on molecular levels of bile acids in serum, liver, and ileum of insomnia mice].

To explore the mechanism of Suanzaoren Decoction in the treatment of insomnia from endogenous bile acid regulation, the present study investigated the hepatoprotective effect of Suanzaoren Decoction and the molecular changes of bile acids in the serum, liver, and ileum of insomnia model mice and Suanzaoren Decoction treated mice. The insomnia model in mice was established by the sleep deprivation method. After Suanzaoren Decoction(48.96 mg·kg~(-1)·d~(-1)) intervention by gavage for 7 days, the related indicators, such as water consumption, food intake, body weight, aspartate aminotransferase(AST), alanine transaminase(ALT), and total bile acid(TBA) were detected, and the pathological changes of the liver and ileum were observed. The molecular levels and distribution of 23 bile acids in the serum, liver, and ileum were analyzed by UPLC-MS/MS combined with principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA). The results showed that Suanzaoren Decoction could improve the decreased water consumption and food intake, weight loss, and increased AST and ALT in the model group, and effectively reverse the injury and inflammation in the liver and ileum. The bile acids in the liver of the insomnia model mice were in the stage of decompensation, and the bile acids in the serum, liver, and ileum of the mice decreased or increased. Suanzaoren Decoction could regulate the anomaly of some bile acids back to normal. Seven bile acids including glycoursodeoxycholic acid(GUDCA), glycodesoxycholic acid(GDCA), tauro-α-MCA(T-α-MCA), α-MCA, taurodeoxycholate(TDCA), T-ß-MCA, and LCA were screened out as the main discriminant components by PLS-DA. It is concluded that Suanzaoren Decoction possesses the hepatoprotective effect and bile acids could serve as the biochemical indicators to evaluate the drug efficacy in the treatment of abnormal liver functions caused by insomnia. The mechanism of Suanzao-ren Decoction in soothing the liver, resolving depression, tranquilizing the mind, and improving sleep may be related to the molecular regulation of bile acid signals.

Specific antitumor activity and mechanism of protonic bis-phenanthroline / 药学学报

Hepatocellular carcinoma (HCC) is a common malignant tumor worldwise. The incidence rate of HCC is high and is easy to metastasis and recurrence, which seriously affects human health. Traditional chemical drugs have some challenges such as toxicity, side effects, and multidrug resistance, thus it is urgent to find new drugs and effective targets. Here we synthesized a novel chemical, protonic bis-phenanthroline (H-BP), and the antitumor effect was investigated in the study. The results showed that H-BP could selectively inhibit the proliferation of tumor cells and cause HCC apoptosis. And also, in HCC tumor-bearing mice, H-BP could effectively prevent the growth of tumor mass, even completely eliminate the tumor at medium dose (5 mg·kg-1) and high dose (10 mg·kg-1), and meanwhile H-BP has no significant effect on the body weight of mice. The experimental protocol was approved by the Animal Ethics Committee of Southwest University, and the experimental operation was strictly carried out in accordance with the ethical principles of animal use and care. Mechanism studies showed that H-BP induced HCC apoptosis was related to down-regulation the expression of pleomorphic adenoma gene like-2 (PLAGL2), a oncogene transcription factor, resulting in the down-regulation of PLAGL2 downstream proteins hypoxia inducible factor and β-catenin. This study not only introduces the dimerization method to form novel compounds that will provide a new approach for drug design, but also suggests that PLAGL2 may be an effective target in tumor therapy.

Effect of Suanzaoren Decoction on molecular levels of bile acids in serum, liver, and ileum of insomnia mice / 中国中药杂志

To explore the mechanism of Suanzaoren Decoction in the treatment of insomnia from endogenous bile acid regulation, the present study investigated the hepatoprotective effect of Suanzaoren Decoction and the molecular changes of bile acids in the serum, liver, and ileum of insomnia model mice and Suanzaoren Decoction treated mice. The insomnia model in mice was established by the sleep deprivation method. After Suanzaoren Decoction(48.96 mg·kg~(-1)·d~(-1)) intervention by gavage for 7 days, the related indicators, such as water consumption, food intake, body weight, aspartate aminotransferase(AST), alanine transaminase(ALT), and total bile acid(TBA) were detected, and the pathological changes of the liver and ileum were observed. The molecular levels and distribution of 23 bile acids in the serum, liver, and ileum were analyzed by UPLC-MS/MS combined with principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA). The results showed that Suanzaoren Decoction could improve the decreased water consumption and food intake, weight loss, and increased AST and ALT in the model group, and effectively reverse the injury and inflammation in the liver and ileum. The bile acids in the liver of the insomnia model mice were in the stage of decompensation, and the bile acids in the serum, liver, and ileum of the mice decreased or increased. Suanzaoren Decoction could regulate the anomaly of some bile acids back to normal. Seven bile acids including glycoursodeoxycholic acid(GUDCA), glycodesoxycholic acid(GDCA), tauro-α-MCA(T-α-MCA), α-MCA, taurodeoxycholate(TDCA), T-β-MCA, and LCA were screened out as the main discriminant components by PLS-DA. It is concluded that Suanzaoren Decoction possesses the hepatoprotective effect and bile acids could serve as the biochemical indicators to evaluate the drug efficacy in the treatment of abnormal liver functions caused by insomnia. The mechanism of Suanzao-ren Decoction in soothing the liver, resolving depression, tranquilizing the mind, and improving sleep may be related to the molecular regulation of bile acid signals.

[Study on bile acid metabolism of sleep-deprived mice regulated by Jiaotai Pills based on LC-MS].

To investigate the changes of bile acid(BA) levels in mice with sleep deprivation and the regulatory effect of Jiaotai Pills(JTP) on bile acid metabolism, this study established an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method for simultaneous determination of 23 BAs in mice. A total of 24 ICR mice were randomized into normal group, model group, and JTP group. Mice in the model group and JTP group were deprived of sleep at 20 h·d~(-1) by sleep deprivation apparatus for 8 consecutive days. Mice in the JTP group were given(ig, qd) JTP 3.3 g·kg~(-1) and those in the normal group and model group received(ig) the same volume of purified water. UPLC conditions are as follows: Waters ACQUITY UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 µm), gradient elution with the mobile phase of 0.1% formic acid in water-methanol. MS conditions are as below: negative-ion electrospray ionization, multiple reaction monitoring(MRM). Thereby, the content of 23 BAs in serum, liver, and ileum was determined and methodological investigation of the method was performed. The results showed that 23 BAs could be accurately determined within 15 min and the correlation coefficients were all higher than 0.99. The precision, accuracy, specificity, reproducibility, matrix effect, and recovery of BAs all met the requirement. The levels of BAs were significantly increased in the serum, liver, and ileum of sleep-deprived mice, but JTP can significantly reduce the levels. The UPLC-MS/MS method is simple, rapid, and accurate, which can be used for the determination of 23 BAs in biological samples, and JTP can adjust the elevated BA levels of sleep-deprived mice.

[Characteristics of Bacterial Community Structure in Fluvo-aquic Soil Under Different Rotation Fallow].

The aim of this study was to provide a reference for promoting ecological restoration of farmland and the green development of agriculture in the alluvial plain of the lower Yellow River by determining the effects of different rotation fallow patterns on the bacterial community of the fluvo-aquic soil. Farmland soil subject to a long-term rotation fallow experiment since 2018 was studied using Illumina MiSeq high-throughput sequencing technology, and the 'Tax4Fun' bacterial function prediction tool was used to analyze differences in soil bacterial community structure and function under the following four rotation fallow regimes:long fallow(LF), winter wheat and summer fallow(WF), winter fallow and summer maize(FM), and annual rotation of winter wheat and summer maize(WM). The environmental factors affecting changes in the soil bacterial community structure and function were also analyzed. In total, 44 phyla, 146 classes, 338 orders, 530 families, 965 genera, and 2073 species of bacteria were detected in the soil samples from the different rotation fallow regimes, and the dominant bacterial groups were Actinobacteria, Proteobacteria, Acidobacteria, and Chloroflexi in 0-20 cm and 20-40 cm soil layers. However, the relative abundances of the dominant bacteria groups were varied between the rotation fallow regimes. In the 0-20 cm layer of the seasonal fallow soils(WF and FM), bacteria were more abundant and community diversity was higher than that of the WM and LF soils. In 20-40 cm soil layer, the WF soil was more abundant in bacterial and the community was more diverse. Based on the prediction function of the 'Tax4Fun' tool, six primary metabolic pathways, 40 secondary metabolic pathways(18 types with relative abundance greater than 1%), and 264 tertiary metabolic pathways were identified in the soil bacteria of the different rotation fallow regimes. Seasonal fallow(WF and FM) was found to increase the relative abundance of beneficial bacterial metabolic pathways involved in metabolism, environmental information processing, and genetic information processing. According to RDA analysis, the soil bacterial community in the 0-20 cm soil layer was significantly affected by soil moisture, total phosphorus, available phosphorus, available potassium, pH, and C/N ratio(P<0.05), and the soil bacterial community in 20-40 cm soil layer was significantly affected by soil total phosphorus and available phosphorus(P<0.05). Therefore, different fallow patterns were linked to variation in the structure, diversity, and metabolic functions of soil bacterial communities. Based on these results, seasonal fallow practices could promote the health and stability of farmland soil ecosystems.