Chronic refractory wound （CRW） presents significant clinical treatment challenges due to pathological characteristics such as persistent inflammation， bacterial infection， oxidative stress and inadequate angiogenesis. Astragali Radix， a traditional Chinese medicinal herb， exerts multi-target pharmacological effects on CRW through its active components， including Astragalus polysaccharides， flavonoids， and astragaloside Ⅳ， etc. Fundamental studies indicate that these components promote CRW healing by modulating inflammatory responses， inhibiting pathogen growth， improving antioxidant capacity and stimulating neovascularization. Network pharmacology and bioinformatics studies have revealed that active components of Astragali Radix target and modulate key signaling nodes such as nuclear factor-κB， phosphatidylinositol 3-kinase/Akt， AMP-activated protein kinase， and vascular endothelial growth factor receptor， as well as inflammation-angiogenesis-related pathways， thereby synergistically exerting anti-inflammatory and pro-angiogenic effect. Clinical applications have demonstrated that oral formulations （e.g.， Huangqi guizhi decoction， Danggui huangqi decoction， etc.） reduce healing time of CRW and lower inflammatory marker levels， while topical preparations （e.g.， Zizhu ointment， Huangqi shengji ointment， electrostatically spun Astragalus polysaccharide composite nanofibre dressings， etc.） significantly improve healing rates of CRW and minimize complications.

OBJECTIVE To investigate the intervention effect of kushenol F （KSC-F） on ulcerative colitis （UC） mice. METHODS Totally 30 male C57BL/6J mice were randomly divided into the normal group， model group， positive drug group （sulfasalazine， 703 mg/kg）， KSC-F 50 mg/kg group （KSC-F50 group）， and KSC-F 100 mg/kg group （KSC-F100 group）， with 6 mice in each group. Except for the normal group， the mice in the remaining groups were given 3% dextran sulfate sodium solution continuously for 7 days to induce UC model. Concurrently， administration groups received corresponding drug solution intragastrically， once a day， for 10 consecutive days. During the experiment， the changes in body weight and bowel movements of the mice were observed. Disease activity index scoring was performed after the last administration. The histopathological morphology of colonic tissue was examined. The levels of inflammatory factors in the serum and colon tissue were measured. Additionally， the mRNA expression of inflammatory factors， and the protein expressions of inflammation-related proteins [interleukin-1β （IL-1β）， forkhead box O1（FOXO1）， phosphoinositide 3-kinase（PI3K）， phosphorylated PI3K（p-PI3K）， p38 mitogen-activated protein kinase（p38 MAPK）， phosphorylated p38 MAPK（p-p38 MPAK） and phosphorylated protein kinase B（p- Akt）] were determined in colonic tissue. RESULTS KSC-F could alleviate weight loss and colonic tissue damage in UC mice. KSC- F reduced the levels of IL-1β， IL-6， IL-8 and tumor necrosis factor-α （TNF-α） in serum， as well as IL-1β， IL-6， IL-17 and TNF- α in colonic tissue to varying degrees and increased the levels of IL-10 in both serum and colonic tissue （P＜0.05 or P＜0.01）. Moreover， KSC-F decreased the expression levels of IL-1β， IL-17 and TNF-α mRNA， as well as p-PI3K， p-p38 MAPK， and p- Akt proteins in colonic tissue to varying degrees， and increased the expression levels of IL-10 mRNA and FOXO1 protein in colonic tissue （P＜0.05 or P＜0.01）. CONCLUSIONS KSC-F effectively alleviates UC symptoms in mice by inhibiting PI3K， Akt and p38 MAPK activation， mitigating the release of pro-inflammatory factors such as IL-1β， IL-6， TNF- α，promoting the anti-inflammatory factor IL-10 secretion， and reducing inflammation-induced colonic tissue damage.

In the context of delayed marriage and parenthood, decreased willingness in having children, and population aging in China, maternal and child health has become an important and urgent issue. Being essential platforms for research in maternal and child health, the importance of birth cohorts has been widely recognized. In the past 20 years, tens of birth cohorts have been established in major cities and regions of China, with cohorts ranging from thousands to hundreds of thousands. These cohorts, particularly those large ones launched in recent years, have collected a wide spectrum of data and biological samples from mothers and children. Although they have made considerable preliminary achievements, there remain difficulties and challenges. The significant challenges include small and medium-sized cohorts' lacking of clear research themes; insufficient recognition of and emphasis on behavioral and social determinants of health while emphasizing biological determinants of health; variations in types of variables and quality of data collected, which make it difficult for cohorts to be merged and shared; lack of and difficulties in long-term follow-up; significant uncertainties in resources for long-term sustention of the cohorts, and so on. So, we argue that birth cohorts should focus on essential and urgent issues in maternal and child health in the country and seek recognition and support from the government and the entire society. Last but not least, the overall success of birth cohorts in the country requires scientists to be not only academically capable, but also realistic, persistent, altruistic, and collaborative.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has a clinical manifestation of hypoxic respiratory failure and acute respiratory distress syndrome. However, COVID-19 still lacks of effective clinical treatments so far. As a promising potential treatment against COVID-19, stem cell therapy raised recently and had attracted much attention. Here we review the mechanisms of mesenchymal stem cell-based treatments against COVID-19, and provide potential cues for the effective control of COVID-19 in the future. METHODS: Literature is obtained from databases PubMed and Web of Science. Key words were chosen for COVID- 19, acute respiratory syndrome coronavirus 2, mesenchymal stem cells, stem cell therapy, and therapeutic mechanism. Then we summarize and critically analyze the relevant articles retrieved. RESULTS: Mesenchymal stem cell therapy is a potential effective treatment against COVID-19. Its therapeutic efficacy is mainly reflected in reducing severe pulmonary inflammation, reducing lung injury, improving pulmonary function, protecting and repairing lung tissue of the patients. Possible therapeutic mechanisms might include immunoregulation, antiinflammatory effect, tissue regeneration, anti-apoptosis effect, antiviral, and antibacterial effect, MSC - EVs, and so on. CONCLUSION Mesenchymal stem cells can effectively treat COVID-19 through immunoregulation, anti-inflammatory, tissue regeneration, anti-apoptosis, anti-virus and antibacterial, MSC - EVs, and other ways. Systematically elucidating the mechanisms of mesenchymal stem cell-based treatments for COVID-19 will provide novel insights into the follow-up research and development of new therapeutic strategies in next step.

BACKGROUND: Early fluid resuscitation is one of the fundamental treatments for acute pancreatitis (AP), but there is no consensus on the optimal fluid rate. This systematic review and meta-analysis aimed to compare the efficacy and safety of aggressive vs. controlled fluid resuscitation (CFR) in AP. METHODS: The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and Web of Science databases were searched up to September 30, 2022, for randomized controlled trials (RCTs) comparing aggressive with controlled rates of early fluid resuscitation in AP patients without organ failure on admission. The following keywords were used in the search strategy: "pancreatitis," "fluid therapy,""fluid resuscitation,"and "randomized controlled trial." There was no language restriction. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was used to assess the certainty of evidence. Trial sequential analysis (TSA) was used to control the risk of random errors and assess the conclusions. RESULTS: A total of five RCTs, involving 481 participants, were included in this study. For primary outcomes, there was no significant difference in the development of severe AP (relative risk [RR]: 1.87, 95% confidence interval [CI] 0.95-3.68; P = 0.07; n = 437; moderate quality of evidence) or hypovolemia (RR: 0.98, 95% CI: 0.32-2.97; P = 0.97; n = 437; moderate quality of evidence) between the aggressive and CFR groups. A significantly higher risk of fluid overload (RR: 3.25, 95% CI: 1.53-6.93; P <0.01; n = 249; low quality of evidence) was observed in the aggressive fluid resuscitation (AFR) group than the controlled group. Additionally, the risk of intensive care unit admission ( P = 0.02) and the length of hospital stay ( P <0.01) as partial secondary outcomes were higher in the AFR group. TSA suggested that more studies were required to draw precise conclusions. CONCLUSION: For AP patients without organ failure on admission, CFR may be superior to AFR with respect to both efficacy and safety outcomes. REGISTRATION PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; CRD 42022363945.
Humans ; Randomized Controlled Trials as Topic ; Fluid Therapy ; Hypovolemia ; Pancreatitis/therapy*

ObjectiveTo compare the similarities and differences of material basis for improving insulin resistance （IR） in different parts of Morus alba based on liquid-mass combination combined with network pharmacology and molecular docking technology. MethodUltra-high performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS） was used to analyze the composition differences in different parts of M. alba. Sybyl-X2.1 was used to connect components with IR core targets， and the selection criterion was Total Score≥5. The "component-target-disease" network map was drawn. The total statistical moment standard similarity （TQSMSS） between the single target-component docking score data set and the total target-component docking score data set was calculated. The targets with higher TQSMSS were screened out， and the protein-protein interaction （PPI） network was constructed. The Gene Ontology （GO） functional analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed using R language. ResultForty-one active components were obtained by UPLC-Q-TOF-MS. According to the total statistical moment （similarity） method， there were 20， 23， 30， and 27 targets with TQSMSS≥0.75 in Mori Ramulus， Mori Cortex， Mori Fructus， and Mori Folium， respectively. In the four M. alba medicinal sources， the functional order of the targets by GO enrichment analysis was Mori Fructus>Mori Folium>Mori Cortex>Mori Ramulus， which were involved in biological processes such as blood glucose homeostasis， glucose metabolism， and glucose transmembrane transport. The order of the four M. alba medicinal sources by KEGG pathway enrichment analysis was Mori Fructus>Mori Ramulus>Mori Folium>Mori Cortex， which were involved in the adenosine monophosphate-activated protein kinase （AMPK） energy metabolism signaling pathway， the insulin regulation-related signaling pathway， the anti-inflammatory and anti-oxidative stress signaling pathway， and so on. ConclusionThis research demonstrates that there are differences in the material basis for improving IR by different parts of M. alba， which provides references for the development of different parts of M. alba.

【Objective】 To investigate the clinicopathological features and prognosis of clear cell papillary renal cell carcinoma (CCPRCC). 【Methods】 The clinicopathological and follow-up data of 40 CCPRCC patients treated during Jun. 2011 and Oct.2021 were retrospectively analyzed. The prognosis was compared with that of 40 cases of clear cell renal cell carcinoma (ccRCC) and 19 cases of papillary renal cell carcinoma (PRCC) treated in the same period. Survival analysis was performed by Log-rank test and Kaplan-Meier survival curves were plotted. 【Results】 Among the 40 patients, 28 were male and 12 were female, aged 31-84 years; 38 cases had unilateral and 2 cases had bilateral tumors; 3 cases had multifocal lesions. All patients received surgery. The maximum diameter of the masses ranged from 3.0 to 95.0 mm, with an average of (27.6±18.1) mm. Pathological grade was Fuhrman 1-2 in all cases. Immunohistochemical tests were positive for CK7 and CA-IX. During the follow-up of 5-129 (average 56) months, 1 case died after bone metastasis, 2 had ipsilateral recurrence, and 1 developed primary esophageal cancer. CCPRCC patients had a significantly better prognosis than CCRCC (P<0.001) and PRCC (P=0.005) patients, while there was no significant difference in the prognosis between CCRCC and PRCC patients (P=0.93). 【Conclusions】 CCPRCC has low malignancy. The diagnosis relies on characteristic pathological and immunohistochemical features. Surgery is an effective treatment. CCPRCC has a better overall prognosis than CCRCC and PRCC.

[摘 要] 目的：评价肿瘤特异性个体化多靶点树突状细胞-细胞因子诱导的杀伤细胞（DC-CIK）治疗晚期非小细胞肺癌（NSCLC）患者的临床疗效和安全性。方法：回顾性分析2019年10月1日至2022年10月31日东部战区总医院生物治疗科行肿瘤特异性个体化多靶点DC-CIK治疗晚期NSCLC患者的临床资料。统计NSCLC患者的临床疗效和不良反应，分析治疗前后血清中肿瘤标志物的变化，FCM检测患者治疗前后的淋巴细胞亚群和各种细胞因子的表达情况，用质谱仪检测治疗前后靶点的变化。结果: 共入组52例晚期NSCLC患者，其中女性21例、男性31例；年龄32~71岁，平均年龄（50.97±10.72）岁，中位年龄47.5岁。经DC-CIK治疗后，CR 0例，PR 0例，SD 27例，PD 25例。与治疗前比较，DC-CIK治疗后：（1）CEA和CYFRA21-1水平无显著改变，CA125水平显著低于治疗前（P<0.01）；（2）治疗后患者淋巴细胞亚群无显著变化；（3）治疗后患者外周血IL-2、IL-4、IFN-γ和TNF-α水平显著升高（均P<0.01），IL-6、IL-10及IL-17水平无明显变化；（4）治疗后靶点数下降明显。DC-CIK治疗过程中无严重不良反应发生。结论: 晚期NSCLC患者行肿瘤特异性个体化多靶点自体DC-CIK治疗是安全的，能使患者产生抗肿瘤免疫反应并得到一定的临床获益。

AIM: To analyze ocular wavefront aberrations and scattering parameters changes in patients with meibornian gland dysfunction(MGD)and aqueous deficient dry eye(ADDE), and assess the visual quality of patients with two types of dry eye syndromes.METHODS:There were 25 patients with MGD, 25 patients with ADDE and 25 healthy controls treated in our hospital from January to October 2018 were included in this study. Ocular surface disease index questionnaire(OSDI)and tear film correlation examination were performed in three groups. The tear film correlation examination included tear break-up time(TBUT), Schirmer test( SⅠt )and cornea fluorescein staining(FL). The root mean square of total high order aberration(HO), comatic aberration(CA), trefoil aberration(TA)and spherical aberration(SA)were recorded with i-Trace visual function analyzer. The scattering values were recorded by the double-pass Optical Quality Analysis System(OQAS Ⅱ), including the modulation transfer function(MTF cutoff ), Strehl ratio(SR)and objective scattering index( OSI ). Three groups of subjects kept their eyes open for 20s, the mean value of OSI was recorded using OQAS Ⅱ tear film analysis program.RESULTS:The OSDI score in MGD group was significantly higher than that in ADDE group(38.2±5.6 vs 32.2±7.2, P<0.01). The SⅠT score in ADDE group was significantly lower than that in MGD group(1.98±0.92 vs 12.52±6.80mm/5min, P<0.001). The TBUT and FL staining score were lower in MGD group than those in ADDE group(TBUT: 3.27±1.91 vs 6.02±1.05s, FL:3.27±2.18 vs 6.23±2.19, all P<0.001). There was no significant difference in HO, CA, TA and SA between MGD Group and ADDE group(HO: 0.385±0.081 vs 0.344±0.092, CA:0.210±0.062 vs 0.175±0.075, TA:0.107±0.056 vs 0.086±0.042, SA:0.322±0.078 vs 0.273±0.097, HO:t=1.67, P>0.05; CA: t=1.80, P>0.05; TA: t=1.50, P>0.05; SA: t=1.97, P>0.05). There was no statistically significant differences between MGD group and ADDE group with the value of MTF cutoff, SR and OSI(MTF cutoff: 33.28±8.28 vs 37.12±9.53, SR: 0.19±0.06 vs 0.22±0.08, OSI:1.30±0.32 vs 1.12±0.52, MTF cutoff: t=1.52, P>0.05; SR: t=1.50, P>0.05; OSI: t=1.47, P >0.05). In the condition of not blinking, the mean value of OSI in MGD group was significantly higher than that in ADDE group(2.386±0.118 vs 1.554±0.058, P<0.001).CONCLUSION:In the treatment of symptoms of patients with dry eye, improving the visual quality of patients should also be considered. The visual quality in patients with MGD is more serious than those with ADDE. The OSI related parameters seem to be sensitive indicators indexes to evaluate the dynamic changes of tear film-related visual quality in dry eye patients.

ObjectiveTo explore the material basis for the difference in the efficacy of different parts of mulberry based on molecular connectivity index （MCI）. MethodBy referring to the relevant literature at home and abroad and traditional Chinese medicine systems pharmacology database and analysis platform （TCMSP） database， the chemical composition database of mulberry-source medicinal materials was established. Venn analysis was carried out on the components among mulberry-source medicinal materials. The components in the database were divided into 10 categories， and the composition information was analyzed. According to MCI value， all components of mulberry-source medicinal materials were divided into different groups. The angle cosine method was used to calculate the MCI similarity. The average MCI values of the common component group from 0-8 orders and CI of mulberry-source medicinal materials were calculated. ResultThe components with high similarity such as （+）-cycloolivil， 1′-methoxy-2′-hydroxydihydromollugin， kuwanon， morusin and 1-deoxynojirimycin were selected as potential pharmacodynamic components. Mulberry-source medicinal materials could be divided into five component groups. The similarity between component groups and total components was 0.760-0.999， and the similarity between component groups was 0.248-0.999. In Mori Ramulus， Mori Folium， Mori Cortex and Mori Fructus， the average MCI values of their flavonoids from 0-8 orders were 4.57， 4.59， 6.41， 4.24， respectively. The average MCI values of alkaloids from 0-8 orders were 2.65， 4.55， 2.58， 2.78， respectively. The average CI values from 0-8 orders were 5.51， 5.49， 5.44 and 2.88， respectively. ConclusionIt is preliminarily concluded that there are differences in the flavonoids and pathways of hypoglycemic effects between Mori Cortex and the other three mulberry-source medicinal materials. The MCI values of alkaloids from 0-8 orders in Mori Folium and Mori Fructus were higher， but their inhibitory activity of α-glucosidase were lower than those of Mori Ramulus and Mori Cortex. The structural characteristics of the total components of Mori Fructus represented by CI were quite different from the other three mulberry-source medicinal materials.