BACKGROUND:Spleen has the functions of blood storage,hematopoiesis,and immunity.With the increase of age,the structural degeneration and functional decline of spleen lead to the impairment of immune system function,thus accelerating the aging process of the body.The treatment of spleen aging in tree shrews with highly active umbilical cord mesenchymal stem cells has not been reported. OBJECTIVE:To explore the intervention effect and mechanism of highly active umbilical cord mesenchymal stem cells on spleen aging in tree shrews. METHODS:Highly active umbilical cord mesenchymal stem cells were isolated,cultured,and obtained from the umbilical cord tissue of newborn tree shrews by caesarean section.The differentiation abilities of adipogenesis,osteogenesis,and chondrogenesis were detected by three-line differentiation kit.Cell cycle and surface markers were detected by flow cytometry.The second generation of highly active umbilical cord mesenchymal stem cells were transfected with Genechem Green Fluorescent Protein with infection complex values of 100,120,140,160,180,and 200,respectively,to screen the best transfection conditions.After transfection,the fourth generation of highly active umbilical cord mesenchymal stem cells was injected into the tail vein of tree shrews in the elderly treatment group.The young control group and the aged model group were not given special treatment.After 4 months of treatment,the spleen tissue was taken and the structure of the spleen was observed by hematoxylin-eosin staining.β-Galactosidase staining was used to detect the activity of aging-related galactosidase.Immunohistochemical staining was used to detect the expression levels of p21 and p53 proteins.Ki67 and PCNA immunofluorescence staining was used to detect cell proliferation activity.Immunofluorescence staining was used to detect the expression levels of spleen autophagy protein molecules Beclin 1 and APG5L/ATG5.Reactive oxygen species fluorescence staining was used to detect the content of reactive oxygen species in spleen tissue.CD3 immunofluorescence staining was used to detect the change of the proportion of total T lymphocytes.The secretion levels of interleukin 1β and transforming growth factor β1 in spleen were detected by enzyme linked immunosorbent assay.The distribution of highly active umbilical cord mesenchymal stem cells labeled with green fluorescent protein in spleen tissue was observed by DAPI double staining of nucleus. RESULTS AND CONCLUSION:(1)Highly active umbilical cord mesenchymal stem cells grew in a short spindle shape with fish-like growth,with a large proportion of G0/G1 phase,and had the potential to differentiate into adipogenesis,osteogenesis,and chondrogenesis.(2)Multiplicity of infection=140 and transfection for 72 hours were the best conditions for labeling tree shrews highly active umbilical cord mesenchymal stem cells with Genechem Green Fluorescent Protein.(3)Compared with the aged model group,in the aged treatment group,the spleen tissue cells of tree shrews were arranged closely,and the area of white pulp was increased(P<0.01);the boundary between red pulp and white pulp was clear;the proportion of germinal centers did not show statistically significant difference(P>0.05).The activity level of galactosidase related to spleen tissue aging was decreased(P<0.001),and the expression levels of aging protein molecules p21 and p53 were down-regulated(P<0.001).The expression levels of proliferation-related molecules Ki67 and PCNA were up-regulated(P<0.001,P<0.05);expression levels of autophagy-related molecules Beclin 1 and APG5L/ATG5 were up-regulated(P<0.001),and the content of reactive oxygen species decreased(P<0.001),and the proportion of CD3+T cells increased(P<0.05).The secretion level of interleukin 1β in the aging-related secretion phenotype decreased(P<0.001);no significant difference was found in transforming growth factor β1 level(P>0.05).Compared with the young control group,the above indexes were significantly different in the elderly treatment group(P<0.05).(4)Green fluorescent cells labeled with green fluorescent protein were observed in spleen tissue of tree shrews the elderly treatment group by frozen tissue section observation.The results show that intravenous infusion of highly active umbilical cord mesenchymal stem cells can migrate to spleen tissue,inhibit the production of reactive oxygen species,down-regulate the expression of aging-related proteins,induce autophagy,promote cell proliferation,reduce chronic inflammation,and then improve the structure and function of spleen tissue.

The connotation of the "four-dimensional pivot-earth" qi transformation mode is a dialectical system of the ascending and descending of yin-yang qi movement， which presented as "the middle Jiao showing earth qi mediating， the left wheel showing water and wood ascending， and the right wheel showing fire and metal converting and descending". Based on this dialectical thinking， it is believed that the core pathogenesis of myasthenia gravis is deficiency of center qi and transportation failure to pivot-earth； the middle-stage characteristics of the disease progression are the loss of mediation of the central qi， resulting in water coldness and wood constraint， and clear yang failing to ascend； the final outcome of this disease is the loss of astringeing of lung metal and qi sinking. The treatment should be based on the rule of qi movement， so for the start-stage， Buzhong Yiqi Decoction （补中益气汤） should be used as the basis to nourish the earth and consolidate the root， and restrengthen the middle qi； for the middle-stage， herbs like Yingyanghuo （Epimedium brevicornu Maxim.）， Bajitian （Morinda officinalis How） could be combined to warm the water and soothe the wood， raise yang and boost qi； for the final stage， plus Sini Decoction （四逆汤） to astringe metal to stop collapse， and powerfully supplement original qi. All these medicinals can promote pivot-earth re-transportation， four-dimensional transformation， and regular circulation of qi movement， so as to provide thoughts for improving the clinical effectiveness of myasthenia gravis.

ObjectiveTo evaluate the clinical efficacy of Fuzheng Huaji Formula （扶正化积方） for chronic hepatitis B to reduce the incidence of liver cirrhosis and hepatocellular carcinoma. MethodsA retrospective cohort study was conducted， collecting medical records of 118 patients with chronic hepatitis B and 234 patients with hepatitis B-related cirrhosis who visited the hospital between January 1， 2014， and December 31， 2018. The use of Fuzheng Huaji Formula was designated as the exposure factor. Patients receiving antiviral treatment for hepatitis B without concurrent Fuzheng Huaji Formula therapy were included in the western medicine group， while those receiving antiviral treatment combined with Fuzheng Huaji Formula for a cumulative treatment lasting longer than 3 months were included in the combined treatment group. The follow-up observation period was five years. Kaplan-Meier survival analysis was used to assess the cumulative incidence of cirrhosis in patients with chronic hepatitis B and the cumulative incidence of hepatocellular carcinoma in patients with hepatitis B-related cirrhosis. Univariate and multivariate Cox regression analyses were employed to examine the factors influencing the occurrence of cirrhosis and hepatocellular carcinoma. ResultsAmong patients with chronic hepatitis B， there were 55 cases in the combined treatment group and 63 cases in the western medicine group； among patients with hepatitis B-related cirrhosis， there were 110 cases in the combined treatment group and 124 cases in the western medicine group. Five-year follow-up outcomes for chronic hepatitis B patients showed that the cumulative incidence of cirrhosis was 5.45% （3/55） in the combined treatment group and 17.46% （11/63） in the western medicine group， with a statistically significant difference between groups （Z = 2.003， P = 0.045）. Five-year follow-up outcomes for hepatitis B-related cirrhosis patients showed that the cumulative incidence of hepatocellular carcinoma was 8.18% （9/110） in the combined treatment group and 22.58% （28/124） in the western medicine group， also showing a statistically significant difference （Z = 3.007， P = 0.003）. Univariate and multivariate Cox regression analyses indicated that treatment with Fuzheng Huaji Formula is an independent protective factor in preventing the progression of chronic hepatitis B to cirrhosis and the progression of hepatitis B-related cirrhosis to hepatocellular carcinoma （P＜0.05）. ConclusionCombining Fuzheng Huaji Formula with antiviral therapy for hepatitis B can effectively intervene in the disease progression of chronic hepatitis B， reducing the incidence of cirrhosis and hepatocellular carcinoma.

ObjectiveThrough qualitatively and quantitatively analysis of the differences in chemical composition between the combined decoction and single decoction of Huaganjian and comparison of their core efficacy， to explore the rationality of the flexible clinical application of Huaganjian compound preparations and single-flavored dispensing granules. MethodsUltra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS） was used to qualitatively analyze the combined decoction and single decoction samples of Huaganjian， and meanwhile， the contents of four index components（geniposide， paeoniflorin， hesperidin and paeonol） were quantitatively analyzed by high performance liquid chromatography（HPLC）. Nonalcoholic fatty liver disease（NAFLD） rat model induced by high-fat diet was applied to compare the efficacy of combined decoction and single decoction of Huaganjian. A total of 30 male SD rats were randomly divided into the control group， model group， lovastatin group（1.8 mg·kg^-1）， combined decoction group（1.26 g·kg^-1） and single decoction group（1.18 g·kg^-1）. After successful modeling， lovastatin group， combined decoction group and single decoction group were given corresponding doses of drugs by intragastric administration every day， and the control group and model group were given equal amounts of normal saline by intragastric administration， after 4 weeks of administration， the serum and liver tissues were collected， and the contents of alanine aminotransferase（ALT）， aspartate aminotransferase（AST）， total cholesterol（TC）， triglyceride（TG）， low-density lipoprotein cholesterol（LDL-C） and high-density lipoprotein cholesterol（HDL-C） in serum of rats were detected， and the liver pathological examination was carried out by hematoxylin-eosin（HE） staining and oil red O staining， so as to compare differences of their efficacy. ResultsSeventy chemical components were initially identified and attributed from the lyophilized powder of the combined decoction and single decoction samples of Huaganjian， and there was no obvious difference in composition between the two. Further quantitative analysis showed that the contents of geniposide， paeoniflorin， hesperidin and paeonol in the combined decoction samples were significantly increased when compared with those of the single decoction samples（P<0.01）. The pharmacodynamic results showed that compared with the model group， both the combined and single decoction groups of Huaganjian could improve the liver index of NAFLD rats， reduce the serum levels of AST， ALT， TC， TG and LDL-C， increase the serum level of HDL-C， and ameliorate the pathological changes of liver cell steatosis and fat accumulation. However， there was no significant difference in pharmacodynamic effects between the combined decoction group and the single decoction group. ConclusionThere is no significant difference between the combined decoction and single decoction of Huaganjian in terms of chemical composition， but the contents of the four index components show significantly difference. Both of them can significantly improve the fat accumulation and liver function in NAFLD rats. This study provides a reference basis for the rational clinical application and evaluation of famous classical formula compound preparations and single-flavored dispensing granules.

OBJECTIVE To establish HPLC fingerprint for Jianpi hewei formula （JPHWF）， conduct chemical pattern recognition analysis， and determine the contents of seven components in the formula， aiming to provide a scientific basis for quality control and further research of JPHWF. METHODS Taking 15 batches of standard decoctions of JPHWF as samples， the HPLC fingerprint was established using the Similarity Evaluation System of TCM Chromatographic Fingerprint （2012 edition）. Subsequently， similarity evaluation， as well as identification and attribution analysis of chromatographic peaks， were conducted. Using the common peak areas from the 15 batches of samples as variables， chemical pattern recognition analyses were performed on the samples through hierarchical cluster analysis， principal component analysis， and orthogonal partial least squares-discriminant analysis. The contents of adenine， 5-hydroxymethylfurfural， tetrahydropalmatine， naringin， dehydrocorydaline， neohesperidin and glycyrrhizic acid in 15 batches of samples were determined by HPLC. RESULTS There were 19 common peaks in the characteristic chromatograms for 15 batches of samples with the similarities of more than 0.95. Results of chemical pattern recognition analysis showed that 15 batches of samples could be clustered into 3 categories， and 3 differential compounds were found [peak 7 （5- hydroxymethylfurfural）， peak 17 （neohesperidin）， and peak 15 （naringin）]. The 7 components were linearly good in the respective concentration ranges （R2≥0.999 4）； RSDs of precision， stability and repeatability tests were less than 2% （n＝6）； the average recovery rate of 98.95%-103.81%， RSD of 0.61%-2.75% （n＝6）； the contents of them were 0.031-0.106， 0.267-0.824， 0.089- 0.144， 1.344-2.091， 0.089-0.178， 1.328-2.028， 0.040-0.150 mg/g， respectively. CONCLUSIONS Established HPLC fingerprinting method coupled with multi-index content determination is validated to be accurate and reliable， and its combination with chemical pattern recognition analysis can be applied to the quality control of JPHWF.

Hereditary angioedema (HAE) is a rare autosomal dominant genetic disorder characterized by recurrent episodes of subcutaneous and submucosal edema, which can be life-threatening in severe cases. Lanadelumab, a recombinant human monoclonal antibody against kallikrein, has been recommended as a first-line option for long-term prophylaxis of HAE. This paper analyzed the clinical data of four patients with HAE diagnosed and treated with lanadelumab for long-term prophylaxis in our department since 2020. It also reviewed relevant literature, summarizing the clinical manifestations of HAE, as well as the efficacy and safety of lanadelumab in treating HAE, to provide therapeutic references for clinicians.

Primary liver cancer is one of the most common malignant tumors of the digestive system， and the “inflammation-to-cancer transformation” （ICT） of chronic hepatitis is the core pathological process of the progression of chronic hepatitis to liver cancer. Persistent and uncontrolled liver inflammation in patients with chronic hepatitis often leads to repeated liver tissue damage and repair， which gradually develops into liver fibrosis and cirrhosis， eventually leading to malignant transformation through the mechanisms such as gene mutation and microenvironment imbalance. ICT in chronic hepatitis is the key link between chronic hepatitis and liver cancer， and its dynamic evolution involves various pathogenic factors such as dampness， heat， deficiency， toxin， and stasis； among which damp-heat and vital energy deficiency are the initiating factors for ICT of chronic hepatitis， while intermingled stasis and toxin are the key pathological products that promote malignant transformation. Based on the concept of preventive treatment， traditional Chinese medicine can effectively delay and even block the ICT of chronic hepatitis by regulating inflammation， metabolism， and abnormal cell proliferation through multiple targets， which provides important strategies and research directions for the prevention and treatment of liver cancer.

Objective:To analyze the evaluation of the application effect and deficiency of nurses acting as standardized parents in the graduation examination of standardized residency training of pediatrics and further improve and promote the level of standardized parents.Methods:A questionnaire survey was used to collect the scores of nurse standardized parents by students and examiners who took part in the graduation examination of standardized residency training of pediatrics in 2021. And the self-evaluation scores of standardized parents were collected. Counting data were represented by the number of cases and composition ratio. A Chi-square test was used to compare the rates.Results:A total of 125 questionnaires from students and 37 questionnaires from nurse standardized parents were collected, and the overall satisfaction (very satisfied + satisfied) of standardized parents reached 121 (96.80%). In the three dimensions of simulation ability, compliance with question-and-answer rules, and simulated attitude, students believed that the consistency between standardized parents and actual parents in simulated altitude was lower than that in the simulation ability and compliance with question-and-answer rules ( P=0.007, P=0.001). The overall satisfaction of standardized parents (very satisfied + satisfied) reached 87.38% (388/444). There were 26 (70.27%) nurse standardized parents who had the lowest satisfaction with their own performance ability, followed by 28 (75.68%) cases of imitation ability and 30 (81.08%) cases of adaptability. Conclusions:It is feasible to adopt nurse standardized parents in the assessment of standardized residency training of pediatrics, and both students and examiners have higher satisfaction. The next step is to improve the training of nurses standardized parents in the attitude of simulation and, at the same time, enhance the training of imitation ability and adaptability, so as to further expand the construction of standardized parents.

Objective:To establish an automated labeling method of 18F-AlF-1, 4, 7-triazocyclohexane-1, 4, 7-triacetic acid- D-Phe1-Tyr3-Thr8-octreotide (NOTATATE) and perform neuroendocrine tumor (NET) imaging. Methods:Based on the GE-FASTLab2 synthesis module, 18F-AlF-NOTATATE was automatically prepared by one-step chelation labeling with aluminum fluoride, and its labeling conditions were optimized. The product quality was analyzed. One patient (male, 47 years old) with lower rectal segment NET and one patient (female, 52 years old) with pancreatic NET underwent 18F-AlF-NOTATATE PET/CT imaging. Results:18F-AlF-NOTATATE was successfully prepared with a total synthesis time of 35 min. The optimized radiochemical yield was (23.8±3.1)% (without decay correction, n=3), the radioactivity was (4.63±0.68) GBq, and the radiochemical purity was >95%. The stability was good, and the product quality met the requirements. 18F-AlF-NOTATATE showed clear imaging in the patient with rectal segment NET, with SUV max of 13.3 and tumor/liver ratio of 3.3. Metastatic lesions in the liver, lymph nodes, and ribs showed high SUV max and tumor/liver ratios. The imaging of the pancreatic NET patient showed an abnormal increase in local radioactive uptake at the uncinate process of the pancreatic head, with SUV max of 5.6 and SUV max of 6.3 and the tumor/liver ratio of 2.3 after 2-hours imaging. Conclusions:Using the GE-FASTLab2 synthesis module, 18F-AlF-NOTATATE can be prepared with high activity. The preparation is simple, the method is stable, and the product has high radiochemical purity. 18F-AlF-NOTATATE exhibits good imaging performance in NET patients, providing valuable information for diagnosis, treatment, and prognosis evaluation.

Objective:To consolidate the current evidences regarding the efficacy of vitamin D supplementation in age-related sarcopenia.Methods:In this systemic review, a comprehensive literature search of scientific research including journal articles and academic dissertations was performed in prominent databases such as PubMed, Web of Science, China National Knowledge Infrastructure (CNKI) and Wanfang Database platforms, spanning from January 31, 2014 to January 31, 2024. Two search protocols integrating keywords and citation tracking were adopted to ensure comprehensiveness of the literature. Using “vitamin D” “ergocalciferols” “cholecalciferol” “sarcopenia” “muscle mass” “muscle strength” “myopenia” “muscle loss” “muscle reduction” “gait speed” “grip strength” “handgrip” as the main key words, focusing on the systematic reviews, meta-analyses of randomized controlled trials (RCT), and individual RCT, the scientific evidence of individual vitamin D intervention on age-related sarcopenia was evaluated and summarized. Research concerning particular disease conditions, children and adolescents, menopausal women, athletes and other specific populations were excluded.Results:A initial search yielded 2 448 articles in Chinese or English. A total of 8 systemic reviews/meta-analysis and 22 individual RCT literatures were included in the final analysis. Although some earlier lower-quality studies reported subtle improvements in skeletal muscle strength with vitamin D supplementation, high-quality systematic reviews/meta-analysis over the past three years had not shown significant positive effects of vitamin D intervention on sarcopenia and its breakdown parameters, such as skeletal muscle mass, muscle strength, and muscle function. Furthermore, the efficiency was influenced to some extent by the participants′ baseline status, such as muscle health and vitamin D nutritional status.Conclusions:Present evidence does not robustly support the efficacy of sole vitamin D supplement on age-related sarcopenia. High-quality clinical trials are imperative to accumulate more robust evidence in the future.