Search

This study aims to comprehensively analyze the material basis of toad visceral oil(hereafter referred to as toad oil), and explore the pharmacological effect of toad oil on atopic dermatitis(AD). Ultra-high performance liquid chromatography-linear ion trap/orbitrap high-resolution mass spectrometry(UHPLC-LTQ-Orbitrap-MS) and gas chromatography-mass spectrometry(GC-MS) were employed to comprehensively identify the chemical components in toad oil. The animal model of AD was prepared by the hapten stimulation method. The modeled animals were respectively administrated with positive drug(0.1% hydrocortisone butyrate cream) and low-and high-doses(1%, 10%) of toad oil by gavage. The effect of toad oil on AD was evaluated with the AD score, ear swelling rate, spleen index, and pathological section results as indicators. A total of 99 components were identified by UHPLC-LTQ-Orbitrap-MS, including 14 bufadienolides, 7 fatty acids, 6 alkaloids, 10 ketones, 18 amides, and other compounds. After methylation of toad oil samples, a total of 20 compounds were identified by GC-MS. Compared with the model group, the low-and high-dose toad oil groups showed declined AD score, ear swelling rate, and spleen index, alleviated skin lesions, and reduced infiltrating mast cells. This study comprehensively analyzes the chemical composition and clarifies the material basis of toad oil. Meanwhile, this study proves that toad oil has a good therapeutic effect on AD and is a reserve resource of traditional Chinese medicine for external use in the treatment of AD.

Purpose: To explore a more effective comprehensive prevention and treatment model for children's oral health by constructing a health network platform that integrates medical information evaluation, interaction, monitoring, and prevention with oral health management as the core., Methods: The database of Shaoxing Children's Oral Health Management Network Platform was established. The oral health survey and information entry of 7 042 second-grade children in primary school in Yuecheng District from 2021 to 2022 were conducted. An open randomized controlled clinical trial was designed, with 3 472 of 7 042 children randomly assigned to the platform management group and 3 570 to the control group. One year later, oral examinations were conducted again on two groups of children, and the correlation between oral examination indicators between the two groups was statistically analyzed using SPSS 25.0 software package., Results: There was significant difference between the two groups in the mean number of newly added deciduous caries decayed- missing-filled teeth(dmft), deciduous caries decayed teeth (dt), deciduous caries missing teeth(mt), and deciduous caries filled teeth(ft) after one year(P＜0.05). The newly added rates of caries, gingival bleeding, calculus detection, and malocclusion between the two groups were lower in the platform group than in the control group, with a significant difference(P＜0.05)., Conclusions: To the prevention and treatment of oral diseases, intelligence has become more and more indispensable and important. Building a network platform for oral health is an effective way to promote oral health level.

Objective: To comprehensively evaluate the effectiveness of preventive measures for acute kidney injury (AKI) in children and identify the effective strategies. Methods: Databases were systematically searched including CNKI, Wanfang, VIP, China Biology Medicine National Knowledge Infrastructure, PubMed, Embase, Cochrane Library databases, and the reference lists of relevant papers for randomized controlled trials on preventing pediatric AKI up to December 2023. Literature screening was conducted based on the inclusion and exclusion criteria, followed by data extraction and quality assessment of included studies. Traditional and network meta-analyses were performed, along with trial sequential analysis (TSA). Results: A total of 21 studies involving 3 483 children were included. Traditional and network meta-analysis showed that dexmedetomidine was effective in preventing AKI in children undergoing cardiac surgery or cardiac angiography ( OR= 0.26, 0.27; 95% CI 0.11-0.64, 0.13-0.58). Remote ischemic preconditioning (RIPC) was effective in preventing AKI in children after cardiac surgery ( OR= 0.43, 0.44; 95% CI 0.24-0.79, 0.23-0.83). Traditional and network meta-analysis specific to children with sepsis or septic shock showed that balanced solution was effective in preventing pediatric AKI ( OR= 0.58, 0.52; 95% CI 0.42-0.79, 0.37-0.73). TSA indicated that the total sample sizes of dexmedetomidine (348 cases) and RIPC (666 cases) both reached the required information size (320 and 534 cases); additionally, the Z -curve for balanced solution (cumulative Z= 3.38) crossed the TSA monitoring boundary ( Z= 3.29). Conclusion: Dexmedetomidine reduces the risk of AKI in children undergoing cardiac surgery or cardiac angiography, RIPC decreases the risk of AKI in children after cardiac surgery, and balanced solution lowers the risk of AKI in children with sepsis or septic shock.

Objective: To explore the effect of the "internet + health education system" in nursing care after stapler circumcision., Methods: A total of 260 patients underwent stapler circumcision in the Outpatient Department of our hospital from January 2022 to July 2022, of whom 130 received routine nursing after operation (the control group), and the other 130 internet + medical nursing service based on the internet + health education system (the experimental group). We followed up the patients on the 1st, 3rd, 7th and 30th day after surgery, recorded their Visual Analogue Scale (VAS) scores within 24 hours postoperatively, their satisfaction scores with surgery and nursing, the incidence of complications and falloff of the stapler nails, and compared them between the two groups., Results: The postoperative VAS scores of the patients and the incidences of postoperative edema, bleeding, infection and other complications were significantly lower (P < 0.05), the falloff of the stapler nails markedly sooner, and the patients' satisfaction scores with surgery and nursing service remarkably higher (P < 0.05) in the experimental than in the control group (P < 0.05)., Conclusion: The application of the internet + health education system in nursing care after stapler circumcision can impart relevant knowledge to the patients, enhance their self-care ability, effectively reduce postoperative complications, and improve the patients' satisfaction with surgery and nursing service.

Dihuang Baoyuan Granules is a prescription endorsed by HU Tianbao, a renowned and elderly Chinese medicine practitioner from Beijing, and has demonstrated definite clinical efficacy. The composition of this prescription is intricate as it includes 7 distinct herbal medicines. This study aims to analyze the chemical composition of Dihuang Baoyuan Granules, evaluate its efficacy in the treatment of diabetes and analyze the distribution of the drug components in the plasma, liver, and kidney after administration. The findings will serve as a reference for future research on pharmacodynamic substances of this prescription. UHPLC-LTQ-Orbitrap MS was employed to analyze the main chemical components of Dihuang Baoyuan Granules. A Waters ACQUITY Premier HSS T3 column(2.1 mm×100 mm, 1.8 μm) was used for chromatographic separation with 0.1% formic acid(A)-acetonitrile(B) as the mobile phases in a gradient elution at a flow rate of 0.3 mL·min~(-1). Electrospray ionization(ESI) source was used to acquire data in positive and negative ion modes. Furthermore, a rat model of diabetes mellitus was established by feeding with a high-sugar high-fat diet, and injection with streptozocin at a dose of 35 mg·kg~(-1), and the modeled rats were then administrated with Dihuang Baoyuan Granules. The fasting blood glucose, hemoglobin A1c, and other relevant indicators were measured, and the substances present in the plasma, liver, and kidney were identified. By reference to quasi-molecular ions, MS/MS fragment ions, MS spectra of reference substances, and compound information in available reports, 191 components were identified in Dihuang Baoyuan Granules, including 29 alkaloids, 24 flavonoids, 22 organic acids, 16 amino acids, 12 terpenes, 11 steroid saponins, 9 sugars, 8 phenylethanoid glycosides, 8 nucleosides, 2 phenylpropanoids, and 49 others compounds. Eighty-three chemical components were identified in rat plasma, 109 in the liver, and 98 in the kidney. Component identification and characterization of Dihuang Baoyuan Granules in vitro and in vivo provide efficacy information and guidance for the basic research on the pharmacodynamic substances and further clinical application of this prescription.

This study aimed to investigate the effects of microtubule associated tumor suppressor 1 (MTUS1) on hemeoxygenase 1 (HMOX1) expression and hemin-induced apoptosis of vascular endothelial cells and its regulatory mechanism. RNA sequencing, RT-qPCR and Western blot were used to assess altered genes of hemin binding proteins, the expression of cAMP response element-binding protein (CREB) and nuclear respiratory factor 2 (NRF2), hemin-induced HMOX1 expression in MTUS1 knockdown human umbilical vein endothelial cells (HUVEC), and the effect of overexpression of CREB and NRF2 on HMOX1 expression in MTUS1 knockdown 293T cells. The effect of MTUS1 or HMOX1 knockdown on hemin-induced apoptosis in HUVEC, and the overexpression of NRF2 on hemin-induced apoptosis in MTUS1 knockdown 293T cells were assayed with CCK8 and Western blot. The results showed that MTUS1 was knocked down significantly in HUVEC by siRNA (P < 0.01), accompanied by decreased HMOX1 expression (P < 0.01). The increased HMOX1 expression induced by hemin was also inhibited by MTUS1 knockdown (P < 0.01). And the apoptosis of HUVEC induced by hemin was amplified by MTUS1 or HMOX1 knockdown (P < 0.01). Moreover the expression of CREB and NRF2 were both inhibited by MTUS1 knockdown in HUVEC (P < 0.01). The decreased HMOX1 regulated by MTUS1 knockdown could be rescued partly by overexpression of NRF2 (P < 0.01), however, not by overexpression of CREB. And the MTUS1 knockdown mediated decreased 293T cells viability induced by hemin could be partly rescued by NRF2 overexpression (P < 0.01). These results suggest that MTUS1 can inhibit hemin-induced apoptosis of HUVEC, and the mechanism maybe related to MTUS1/NRF2/HMOX1 pathway.

Objective To establish a model for predicting the growth of pulmonary ground-glass nodules (GGN) based on the clinical visualization parameters extracted by the 3D reconstruction technique and to verify the prediction performance of the model. Methods A retrospective analysis was carried out for 354 cases of pulmonary GGN followed up regularly in the outpatient of pulmonary nodules in Zhoushan Hospital of Zhejiang Province from March 2015 to December 2022.The semi-automatic segmentation method of 3D Slicer was employed to extract the quantitative imaging features of nodules.According to the follow-up results,the nodules were classified into a resting group and a growing group.Furthermore,the nodules were classified into a training set and a test set by the simple random method at a ratio of 7∶3.Clinical and imaging parameters were used to establish a prediction model,and the prediction performance of the model was tested on the validation set. Results A total of 119 males and 235 females were included,with a median age of 55.0 (47.0,63.0) years and the mean follow-up of (48.4±16.3) months.There were 247 cases in the training set and 107 cases in the test set.The binary Logistic regression analysis showed that age (95% CI =1.010-1.092, P =0.015) and mass (95% CI =1.002-1.067, P =0.035) were independent predictors of nodular growth.The mass (M) of nodules was calculated according to the formula M=V×(CT mean +1000)×0.001 (where V is the volume,V=3/4πR 3 ,R:radius).Therefore,the logit prediction model was established as ln[ P /(1- P )]=-1.300+0.043×age+0.257×two-dimensional diameter+0.007×CT mean .The Hosmer-Lemeshow goodness of fit test was performed to test the fitting degree of the model for the measured data in the validation set ( χ 2 =4.515, P =0.808).The check plot was established for the prediction model,which showed the area under receiver-operating characteristic curve being 0.702. Conclusions The results of this study indicate that patient age and nodule mass are independent risk factors for promoting the growth of pulmonary GGN.A model for predicting the growth possibility of GGN is established and evaluated,which provides a basis for the formulation of GGN management strategies.

A non-invasive condensation collection-ion chromatography method was established for the determination of organic acids and anions including lactic acid, formic acid, acetic acid, pyruvic acid, chloride, nitrate, nitrite, and sulfate in the exhaled breath of humans. The breath exhaled was condensed and collected using a home-made exhaled breath condensation equipment. This equipment included a disposable mouthpiece as a blow-off port, one-way valve and flow meter, cold trap, disposable condensate collection tube placed in the cold trap, and gas outlet. A standard sampling procedure was used. Before collection, the collection temperature and sampling volume were set on the instrument control panel, and sampling was started when the cold-trap temperature dropped to the set value, while maintaining the balance. Subjects were required to gargle with pure water before sampling. During the sampling process, the subjects were required to inhale deeply until the lungs were full of gas and then exhale evenly through the air outlet. When the set volume was collected, the instrument made a prompt sound; then, the collection was immediately ended, the expiration time was recorded, and the average collection flow was calculated according to the expiration time and sampling volume. After collection, the disposable condensation collection tube was immediately taken out, sealed, and stored in the refrigerator at -20 ℃ away from light, and immediately used for further testing. The organic acids and anions in exhaled breath condensation (EBC) were filtered through a 0.22 μm membrane filter before injection and detected by ion chromatography with conductivity detection. Factors such as collection temperature and collection flow rate during condensation collection were optimized. The optimal cooling temperature was set at -15 ℃, and the optimal exhaled breath flow rate was set at 15 L/min. The mobile phase consisted of a mixture of sodium carbonate (1.5 mmol/L) and sodium bicarbonate (3 mmol/L). The flow rate was 0.8 mL/min, and the injection volume was 100 μL. An IC-SA3 column (250 mm×4.0 mm) was used, and the temperature was set at 45 ℃. An ICDS-40A electrodialysis suppressor was used, and the current was set at 150 mA. The linear ranges of the eight organic acids and anions were 0.1-10.0 mg/L; their correlation coefficients ( r ) were ≥0.9993. The limits of detection (LODs) for the eight organic acids and anions were 0.0017-0.0150 mg/L based on a signal-to-noise ratio of 3, and the limits of quantification (LOQs) were 0.0057-0.0500 mg/L based on a signal-to-noise ratio of 10. The intra-day precisions were 5.06%-6.33% ( n =5), and the inter-day precisions were 5.37%-7.50% ( n =5). This method was used to detect organic acids and anions in the exhaled breath of five healthy subjects. The contents of organic acids and anions in the exhaled breath were calculated. The content of lactic acid was relatively high, at 1.13-42.3 ng/L, and the contents of other seven organic acids and anions were 0.18-11.0 ng/L. During a 10 km-long run, the majority of organic acids and anions in the exhaled breath of five subjects first increased and then decreased. However, due to abnormal metabolism, the content changes of lactic acid, acetic acid, pyruvic acid and chloride in one subject were obviously different from others during exercise, showing a continuous rise. This method has the advantages of involving a simple sampling process and exhibiting good precision, few side effects, and no obvious discomfort or risk to the subjects. This study provides experimental ideas and a theoretical basis for future research on human metabolites.

This study explored the biosynthesis of bufadienolides(BDs) in Bufo bufo gargarizans to solve the dilemma of the decreasing resources of B. bufo gargarizans and provide a theoretical basis for the sustainable utilization of the resources. Ultra-high performance liquid chromatography-Orbitrap-mass spectrometry(UHPLC-Orbitrap-MS) was employed to detect the synthesis sites of BDs in B. bufo gargarizans, and the results were verified by desorption electrospray ionization-mass spectrometry imaging(DESI-MSI) and homogenate incubation experiments. BDs in B. bufo gargarizans had the highest content in the liver and the highest concentration in the gallbladder, in addition to the parotid gland and skin, which suggested that the liver could synthesize BDs. The results of DESI-MSI also showed that BDs were mainly enriched in the liver rather than the immature parotid gland. The incubation experiment of liver homogenates demonstrated the liver of B. bufo gargarizans had the ability to synthesize BDs. This study showed that the liver was a major organ for the synthesis of BDs in B. bufo gargarizans during metamorphosis, development, and growth, which provided strong theoretical support for the biosynthesis of BDs and the sustainable utilization of B. bufo gargarizans resources.

This study aims to reveal the mechanism of prenatal stress in affecting the testicular development of offspring rats and the intervention effects of Zuogui Pills via connexin 43(Cx43). Forty pregnant SD rats were randomized into a blank control group, a mo-del group, a high-dose(18.9 g·kg~(-1)) Zuogui Pills group, a low-dose(9.45 g·kg~(-1)) Zuogui Pills group, and a vitamin E(1.44 mg·kg~(-1)) group. The other groups except the blank control group was subjected to chronic unpredictable mild stress for the modeling of prenatal stress. The model was evaluated by sucrose preference test, open field test, and enzyme-linked immunosorbent assay(ELISA) of the glucocorticoid level. ELISA was employed to measure the thyroxine 4(T4), testosterone(T), and follicle-stimulating hormone(FSH) levels to assess kidney deficiency. Hematoxylin-eosin(HE) staining was employed to evaluate the status of testicular germ cells. An automatic sperm analyzer was used to measure the sperm quality. Immunofluorescence double staining was employed to detect the expression of Cx43 and follicle-stimulating hormone receptor(FSHR) in the testes of offspring rats. The mRNA and protein levels of Cx43, FSHR, phosphatidylinositol 3-kinase(PI3K), and protein kinase B(Akt) were determined by real-time fluorescence quantitative polymerase chain reaction and Western blot, respectively. Prenatal stress induced testicular development disorders in offspring rats. The HE staining results showed that on the day of birth, the model group had reduced seminiferous tubules in the testes, elevated FSH level in the serum, and lowered Cx43 level in the testicular tissue. Male offspring rats of 60 days old had reduced testicular spermatogenic function, decreased sperm quality, elevated FSH level and lowered T level in the serum, and down-regulated protein and mRNA levels of Cx43, FSHR, PI3K, and Akt in the testicular tissue. Zuogui Pills alleviated the abnormal development and dysfunction of testicles in the offspring rats caused by prenatal stress. In summary, Zuogui Pills may weaken the effects of prenatal stress on testicular development and spermatogenic function of offspring rats by activating the PI3K/Akt pathway to regulate Cx43 expression in the testicular tissue.

Objective: To evaluate the participation rate and detection of colorectal neoplasms based on annual fecal immunochemical testing (FIT) for three consecutive years in a population-based colorectal cancer screening program in China. Methods: Based on a population-based colorectal cancer screening program conducted from May 2018 to May 2021 in 6 centers in China, 7 793 eligible participants aged 50-74 were included and offered free FIT and colonoscopy (for those who were FIT-positive on initial screening). At baseline, all participants were invited to receive FIT. In subsequent screening rounds, only FIT-positive participants who did not undergo colonoscopy or FIT-negative participants were invited to have repeated FIT screening. FIT-positive participants were recommended to undertake colonoscopy and pathological examination (if abnormalities were found during colonoscopy). An overall of three rounds of annual FIT screening were conducted. The primary outcomes of the study were the participation rate of FIT screening, the compliance rate of colonoscopy for FIT-positive participants, and the detection rate of colorectal neoplasms. Results: Among the 7 793 participants included in this study, 3 310 (42.5%) were male, with age of (60.50±6.49) years. The overall participation rates for the first, second and third round of FIT screening were 94.0%(7 327/7 793), 86.8% (6 048/6 968) and 91.3% (6 113/6 693), respectively. Overall, 7 742 out of 7 793 participants (99.3%) attended at least one round of screening, and 5 163 out of 7 793 participants (66.3%) attended all three rounds of screening. The positivity rate was significantly higher in the first (14.6%, 1 071/7 327) round compared with the second (5.6%, 3 41/6 048) and third (5.5%, 3 39/6 113) screening rounds ( P <0.001). The overall compliance rates of colonoscopy examination among FIT-positive subjects were over 70% in three rounds, which were 76.3% (817/1 071), 75.7% (258/341) and 71.7% (243/339), respectively. In a multivariate logistic regression model considering factors including sex, education background, smoking, alcohol drinking, previous colonoscopy examination, colonic polyp history and family history of colorectal cancer among first-degree relatives, gender and smoking status were related factors affecting the participation rate of FIT screening, with higher rate in males and non-smokers. In addition, logistic regression analysis also found that age was negatively correlated with the compliance rate of colonoscopy in FIT positive patients. The detection rate of advanced tumors (colorectal cancer + advanced adenoma) declined from the first round to subsequent rounds [1st round: 1.15% (90/7 793); 2nd round: 0.57% (40/6 968); and 3rd round: 0.58% (39/6 693)], however, the positive predictive value for advanced neoplasms increased round by round, and was 11.02% in the first screening round, 15.50% in the second screening round, and 16.05 % in the third screening round. In each screening round, the detection rate for advanced neoplasms was higher in men than that in women, and increased with age. Conclusions: Annual repeated FIT screening has high acceptance and satisfying detection rates in the Chinese population. To optimize and improve the effectiveness of colorectal cancer screening, multi-round repeated FIT screening should be implemented while ensuring high participation rates.

Screening and early diagnosis and treatment have been proven effective in reducing the incidence and mortality of colorectal cancer. Colonoscopy combined with pathological examination is the gold standard for colorectal cancer screening. However, due to the invasiveness, high cost and the need for professional endoscopists of colonoscopy, it is not feasible to directly use this method for mass population screening. Fecal immunochemical test (FIT) is one of the screening techniques recommended by authoritative international guidelines for colorectal cancer screening, and has been widely used in population-based colorectal cancer screening programs in countries around the world. This paper elaborates on the value of FIT in colorectal cancer screening from different aspects, such as the technical principles, the screening efficiency, the screening strategies, and the population effects and benefits. Additionally, it describes the current situation of colorectal cancer screening in China and summarizes the challenges faced in colorectal cancer screening in order to optimize the FIT-based colorectal cancer screening strategies in the population and provide theoretical reference for effective colorectal cancer screening.

This study comprehensively analyzed the active components of Sanhan Huashi Formula using qualitative and quantitative mass spectrometry techniques, laying the foundation for understanding its pharmacological substance basis. UHPLC-LTQ-Orbitrap-MS and GC-MS technologies were used to analyze and identify the volatile and non-volatile components in Sanhan Huashi Formula. UHPLC-QQQ-MS/MS technology was used to simultaneously determine the content of 27 major active components in the formula. The results showed that 308 major chemical components were identified in Sanhan Huashi Formula, among which 60 compounds were identified by comparing with reference standards, mainly including alkaloids, flavonoids, coumarins, triterpenoid saponins, amino acids, and nucleosides. GC-MS technology preliminarily identified 52 volatile compounds, with γ-eudesmol and β-eudesmol as the main components. The quantitative results demonstrated good linearity(r&gt;0.99) for the 27 active components, indicating the stability, simplicity, and reliability of the established method. Among them, amygdalin, nodakenin, arecoline, ephedrine, and pseudoephedrine had relatively high content and were presumably the main pharmacologically active substances. In conclusion, this study systematically and comprehensively characterized the major chemical components and patterns in Sanhan Huashi Formula, providing a basis for understanding its pharmacological mechanisms and clinical applications.

This study aims to reveal the endogenous metabolic characteristics of acteoside in the young rat model of purinomycin aminonucleoside nephropathy(PAN) by non-targeted urine metabolomics and decipher the potential mechanism of action. Biochemical indicators in the urine of rats from each group were determined by an automatic biochemical analyzer. The potential biomarkers and related core metabolic pathways were identified by ultra-high performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS) combined with principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA). MetaboAnalyst 5.0 was used to establish the receiver operating characteristic(ROC) curve for evaluating the clinical diagnostic performance of core metabolites. The results showed that acteoside significantly decreased urinary protein-to-creatinine ratio in PAN young rats. A total of 17 differential metabolites were screened out by non-targeted urine metabolomics in PAN young rats and they were involved in phenylalanine metabolism and phenylalanine, tyrosine and tryptophan biosynthesis. Thirtten differential metabolites were screened by acteoside intervention in PAN young rats, and they were involved in phenylalanine metabolism and arginine and proline metabolism. Among them, leucylproline and acetophenone were the differential metabolites that were significantly recovered after acteoside treatment. These pathways suggest that acteoside treats PAN in young rats by regulating amino acid metabolism. The area under the curve of two core biomarkers, leucylproline and acetophenone, were both greater than 0.9. In summary, acteoside may restore amino acid metabolism by regulating endogenous differential metabolites in PAN young rats, which will help to clarify the mechanism of acteoside in treating chronic glomerulonephritis in children. The characteristic biomarkers screened out have a high diagnostic value for evaluating the treatment of chronic glomerulonephritis in children with acteoside.

The farmland ecosystem faces the emerging risk of microplastic pollution. To investigate the distribution characteristics of microplastics in agricultural soils in Guyuan City, the abundance, type, color, size, and shape of microplastics in Guyuan City agricultural soils were analyzed using field survey, microscopic observation, and Fourier transform infrared spectroscopy. In addition, the risk of microplastic pollution was assessed using the pollution load index method (PLI). The results showed that the microplastic abundance of agricultural soils (0-20 cm) in Guyuan City ranged from 186.32 to 1286.24 n·kg -1 , and the microplastic abundance of soils in facility agriculture increased significantly by 35.56% and 228.91% compared with those in non-facility agriculture with and without film, respectively, and the microplastic abundance in the arable layer was 0.31 times higher than that in the plough pan layer. PE (26.42% to 62.83%) and PP (27.64% to 42.62%) were the main microplastic polymer types, and the number of soil polymer species was significantly greater in facility agriculture than that in non-facility agriculture. Microplastics <100 μm accounted for 32.21%-42.52%, whereas >1000 μm accounted for only 0.28%-12.31%. The particle size of microplastics in the arable layer was 47.39% higher than that in the plough pan layer, and the particle size of microplastics was the largest in facility agriculture and the smallest in non-facility film-free planting. Microplastics were mostly in the form of films, fibers, fragments, and microbeads, with the greatest abundance in the form of fibers and the second largest in the form of films. A total of seven colors of microplastics were monitored, mainly white and black. The overall risk of contamination in the study area was low, and the highest risk of microplastic contamination was found in the soil of facility agriculture. The results of the study will provide data reference for the assessment of microplastic contamination in agricultural soils and microplastic soil environmental behavior in China.

Pet allergies are the type Ⅰ allergic reaction stimulated by allergens in pet dander, hair, and saliva and urine. Atopic individuals with pet allergies have mucosal and respiratory symptoms and casually severe anaphylaxis. Recently, the increasing presence of household pets in China has contributed to an increase in the prevalence of allergies to pets. Moreover, pet allergen sensitization is one of the critical risk factors for developing other allergic diseases, posing a major health problem. This article discussed the epidemiology, allergenic components, clinical features, diagnosis and management, and prevention of pet allergies, providing advice for prevention and treatment.

A method based on ultra-high performance liquid chromatography coupled with triple quadrupole linear ion trap-tandem mass spectrometry(UHPLC-QTRAP-MS/MS) was developed for the simultaneous determination of 41 bioactive constituents of flavonoids, organic acids, nucleosides, and amino acids in Lysimachiae Herba. The content of multiple bioactive constituents was compared among the samples from different habitats. The chromatographic separation was performed in a Waters XBridge®C&#95;(18) column(4.6 mm×100 mm, 3.5 μm) at 30 ℃. The gradient elution was performed with 0.4% methanol(A)-formic acid water(B) as the mobile phase at a flow rate of 0.8 mL·min~(-1), and the multiple-reaction monitoring(MRM) mode was adopted. According to the content of 41 constituents, hierarchical cluster analysis(HCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and gray relational analysis(GRA) were perfomed to comprehensively evaluate the samples from different habitats. The results showed that the 41 constituents exhibited good linear relationship within the tested concentration ranges, with the correlation coefficients(r) greater than 0.999 4. The method featured good precision, repeatability, and stability with the relative standard deviations(RSDs) less than 5.0%. The average recoveries of the 41 constituents ranged from 98.06% to 101.9%, with the RSDs of 0.62%-4.6%. HCA and OPLS-DA separated 48 batches of Lysimachiae Herba samples from different habitats into three categories: the producing areas in Sichuan and Chongqing, the producing areas in Jiangsu, Zhejiang, and Jiangxi, and the producing areas in Guizhou. The content of 41 constituents varied among the Lysimachiae Herba samples from different habitats. The GRA results revealed that the Lysimachiae Herba sample from Nanchong City, Sichuan Province had the best comprehensive quality. The method developed in this study was accurate and reliable and thus can be used for comprehensive evaluation of Lysimachiae Herba quality and provide basic information for the selection of habitats.

Microplastics are a new contaminant that are causing worldwide concern. However, an understanding of their impact on agricultural seed germination remains inadequate. To investigate the effects of combined microplastic and heavy metal contamination on crop seed germination and growth, the effects of exposure to different single and combined concentrations of lead (Pb) and three microplastics[polyethylene (PE), polypropylene (PP), and polyvinyl chloride (PVC)] on maize seed germination and growth were investigated using maize seeds. The results showed that:the inhibition of maize seed germination by Pb single exposure generally increased with Pb concentration. Compared with that in CK, 500, 1000, and 1500 mg·L -1 PE exposure significantly inhibited maize seed germination, but 100 and 300 mg·L -1 exposure had no significant effect (except at d 5). All PP concentration exposures significantly inhibited maize seed germination, with higher concentrations resulting in stronger inhibition. Compared to that under PP and PE exposure, PVC single exposure inhibited maize germination less, and 500, 1000, and 1500 mg·L -1 exposures produced a facilitative effect at the later stages of germination. The germination index, germination potential, and vigor index of maize seeds decreased with the increase in the single exposure concentration of lead and three types of microplastics, significantly decreased compared with that of CK under the combined exposure of Pb and PE, and did not change significantly under the combined exposure of PP and Pb or PVC and Pb. Among the three types of microplastics, PVC had the least effect on corn seed vigor. Both single exposures of 10 mg·L -1 Pb and 100 mg·L -1 of the three microplastics promoted maize stalk and root growth, whereas other concentrations showed mostly inhibitory effects. When the PE concentration was 500 mg·L -1 , the 10 and 20 mg·L -1 Pb exposures both promoted maize seed stalk and root growth; however, the combined PP and Pb exposures did not produce significant inhibition, whereas 500 mg·L -1 PVC and 10 mg·L -1 Pb showed the strongest inhibition of maize stalk and root growth under combined PVC and Pb exposures. The effects of combined exposure to microplastics and Pb on the germination and growth of maize seeds were essentially antagonistic, thus slowing down the toxic effects of their respective single exposures on maize seeds.

PURPOSE： To investigate the expression of tissue-active protein kinase C receptor 1 (RACK1) and epithelin glycoprotein 40 (EGP40) in oral squamous cell carcinoma (OSCC) and their relationship with clinicopathological features and prognosis., Methods: A total of 103 patients with OSCC who were admitted to Shangrao People's Hospital from January 2016 to February 2019 were prospectively selected as the research subjects. All patients underwent radical resection of OSCC and were followed up for 3 years. Immunohistochemistry was used to detect the positive expression levels of RACK1 and EGP40 in cancer tissues and adjacent tissues. The positive expression of RACK1 and EGP40 in cancer tissues and adjacent tissues were compared. The relationship between the positive expression level of RACK1 and EGP40 in cancer tissues of OSCC patients and clinicopathological parameters was analyzed. Factors affecting postoperative recurrence and metastasis in OSCC patients were analyzed. The relationship between the expression of RACK1 and EGP40 in cancer tissues and postoperative disease-free survival of OSCC patients was analyzed. SPSS 18.0 software package was used for statistical analysis of the data., Results: The positive expression rate of RACK1 and EGP40 in cancer tissues was significantly higher than those in adjacent tissues (P＜0.05). The positive expression rate of RACK1 and EGP40 in cancer tissues of OSCC patients with poorly differentiated, stage III, cervical lymph node metastasis, and infiltrating vessels was significantly higher than that in patients with moderate and high differentiation, stage II, no cervical lymph node metastasis, and no infiltrating vessels(P＜0.05). The positive expression rate of RACK1 in cancer tissue of OSCC patients in T3 stage was significantly higher than that in T2 stage(P＜0.05). Cox multivariate regression analysis showed pathological grade (RR=6.290, 95%CI: 2.588-15.287), cervical lymph node metastasis(RR=5.995, 95%CI: 2.467-14.571), RACK1 positive rate (RR=4.495, 95%CI: 1.850-10.925) and EGP40 positive rate (RR=4.559, 95%CI: 1.876-11.079) were factors affecting the recurrence and metastasis of OSCC patients after surgery(P＜0.05). The disease-free survival curve of patients with negative expression of RACK1 was significantly better than that of patients with positive expression (P＜0.05). The disease-free survival curve of patients with negative expression of EGP40 was significantly better than that of patients with positive expression (P＜0.05)., Conclusions: The expression of RACK1 and EGP40 in cancer tissues of OSCC patients is related to clinicopathological parameters and prognosis. Patients with positive expression of RACK1 and EGP40 have a high risk of recurrence and metastasis after surgery.

Objective: To explore the safety and effectiveness of the "scarless" circumcision technique (a modified sleeve-style circumcision method) that preserves the original appearance, providing a more suitable surgical option for patients with redundant prepuce., Methods: Clinical data of patients who underwent "scarless" circumcision at the Eastern Theater Command General Hospital from April 2022 to March 2023 were collected, with patients who underwent conventional circumcision (single-use stapler method) during the same period serving as the control group. The two groups were compared in terms of operation time, postoperative recovery time, incidence of postoperative complications, and patient satisfaction rates after surgery., Results: The operation time for the study group was significantly longer than that of the control group; there was no significant difference in pain scores on the day of surgery between the two groups, but the pain scores on postoperative days 1, 3, and 7 were lower in the study group than in the control group; the postoperative recovery time was significantly shorter in the study group than in the control group; regarding postoperative complications: the control group had higher rates of edema, incision infection, and wound dehiscence than the study group. A satisfaction survey conducted 30 days postoperatively showed higher satisfaction in the study group than in the control group., Conclusion: The "scarless" circumcision technique that preserves the original appearance is safe and effective for patients with simple redundant prepuce and is a new surgical method with value for widespread adoption.

Objective: To investigate the clinicopathological features, treatment, and prognosis of hepatic angiosarcoma. Methods: Clinicopathological data and prognostic conditions of 18 cases with hepatic angiosarcoma were collected retrospectively. The recurrence-free survival rate and overall survival rate were calculated by the Kaplan-Meier method. A Cox regression analysis was used to explore the survival-related risk factors. Results: There were 12 male and 6 female patients, with an average age of 57 (37 ~ 70) years. The tumor's average diameter was 8.40 (2.00 ~ 18.00) cm. Seven cases had multiple tumors, while two cases had large vessel tumor thrombuses. Microscopically, the tumor tissues were irregularly anastomosed, with vascular lacunar or solid bundle-like weaving, and the tissue morphology mimicked capillary hemangioma, cavernous hemangioma, or angioepithelioma, while tumor cells were spindle-shaped or epithelioid, lined with hobnails in the lumen, or formed papillary structures in the lumen. The proportion of highly, moderately, and poorly differentiated tumors was 4:8:6, with six cases having clear tumor boundaries, eight having microvascular tumor thrombi, and sixteen having blood lake formation. Different levels of expression of CD31, CD34, erythroblast transformation-specific related genes, and Fli-1 markers were demonstrated in all of the cases. Four cases had a P53 mutation, and six cases had Ki-67 > 10%. During the follow-up period of 0.23-114.20 months, the five-year recurrence-free survival rate and overall survival rate were 16.7% and 37.2%, respectively. Cox regression multivariate analysis showed that preoperative symptoms and multiple tumors were significant risk factors for recurrence-free survival, while preoperative symptoms and Ki-67 > 10% were significant risk factors for overall survival. Conclusion: Hepatic angiosarcoma is a rare hepatic mesenchymal tumor with high malignancy and a poor prognosis. Pathological morphology and immunohistochemical marker combinations are needed for a definite diagnosis. However, the complexity of angiosarcomas' histological and cytological conformations and the overlap of pathological features with benign vascular tumors, sarcomas, and carcinomas pose difficulties in the differential diagnosis. Thus, the only effective ways to prolong survival are early detection and radical surgical resection.

Objective: To investigate the regulatory effects and mechanism of Nocardia rubra cell wall skeleton (Nr-CWS) on the biological function of human neutrophils. Methods: The experimental research method was used. Fifteen healthy adult volunteers (7 males and 8 females, aged 24 to 45 years) were recruited from Suzhou Physical Examination Center for physical examination from May to October 2022, the peripheral venous blood was collected, and neutrophils were extracted by immunomagnetic bead sorting. The cells were divided into normal control group without any treatment, Nr-CWS alone group treated with Nr-CWS of final mass concentration 60 ng/mL alone, endotoxin/lipopolysaccharide (LPS) alone group stimulated with LPS of final mass concentration 1 μg/mL alone, and LPS+Nr-CWS group stimulated with LPS first and then treated with Nr-CWS as before. After 1 h of culture, the chemotaxis distance, chemotactic cell percentage, chemotactic index, maximum chemotactic speed, and chemotactic function score of neutrophils were detected using the modified agarose chemotactic model; the proportion and fluorescence intensity of phagocytosis cells, the level of reactive oxygen species (ROS), the protein expression levels of granular protein CD35, CD66b, and CD63, and the concentrations of inflammatory cytokines of interleukin 2 (IL-2), IL-4, IL-6, IL-10, IL-17A, tumor necrosis factor alpha (TNF-α), and interferon-γ in cell culture supernatant were detected by flow cytometry. The number of samples in each group in the above experiments was 15. Data were statistically analyzed with analysis of variance for factorial design and independent sample t test. Results: After 1 h of culture, the chemotactic function score of cells in normal control group, Nr-CWS alone group, LPS alone group, and LPS+Nr-CWS group were 15.0, 14.5±0.5, 1.5±0.5, 12.0±1.5, respectively. Compared with those in normal control group, the chemotaxis distance, chemotactic cell percentage, chemotactic index, maximum chemotactic speed, and chemotactic function score of cells were significantly decreased in LPS alone group and LPS+Nr-CWS group (with t values of 18.36, 18.88, 54.28, 18.36, 46.77, 10.58, 14.74, 6.84, 10.58, and 4.24, respectively, P <0.05); compared with those in LPS alone group, the five chemotactic function indexes as above in LPS+Nr-CWS group were significantly increased (with t values of 11.47, 14.65, 11.62, 11.47, and 13.75, respectively, P <0.05). After 1 h of culture, compared with those in normal control group, the proportion and fluorescence intensity of phagocytosis cells were significantly increased in Nr-CWS alone group (with t values of 6.86 and 6.73, respectively, P <0.05), and the above two indexes were significantly decreased in LPS alone group (with t values of 7.35 and 22.72, respectively, P <0.05) and LPS+Nr-CWS group (with t values of 21.37 and 13.10, respectively, P <0.05). After 1 h of culture, compared with that in normal control group, the level of ROS of cells in LPS alone group was significantly increased ( t =6.64, P <0.05); compared with that in LPS alone group, the level of ROS of cells in LPS+Nr-CWS group was significantly decreased ( t =5.46, P <0.05). After 1 h of culture, compared with those in normal control group, the protein expressions of CD35, CD66b, and CD63 of cells were significantly increased in LPS alone group and LPS+Nr-CWS group (with t values of 16.75, 17.45, 10.82, 5.70, 19.35, and 15.37, respectively, P <0.05); compared with those in LPS alone group, the protein expressions of CD35, CD66b, and CD63 of cells were significantly decreased in LPS+Nr-CWS group (with t values of 4.92, 5.72, and 3.18, respectively, P <0.05). After 1 h of culture, compared with those in normal control group, the concentrations of IL-2, IL-4, IL-6, IL-10, IL-17A, TNF-α, and interferon-γ in cell culture supernatant were significantly increased in LPS alone group (with t values of 22.10, 9.50, 7.21, 10.22, 24.88, 8.43, and 47.48, respectively, P <0.05), and the concentrations of IL-6, IL-10, IL-17A, TNF-α, and interferon-γ in cell culture supernatant were significantly increased in LPS+Nr-CWS group (with t values of 4.68, 5.12, 8.02, 5.58, and 7.13, respectively, P <0.05); compared with those in LPS alone group, the concentrations of IL-2, IL-4, IL-6, IL-10, IL-17A, TNF-α, and interferon-γ in cell culture supernatant were significantly decreased in LPS+Nr-CWS group (with t values of 5.39, 2.83, 5.79, 2.90, 5.87, 4.88, and 39.64, respectively, P <0.05). Conclusions: Nr-CWS can enhance the phagocytosis ability of neutrophils in normal condition and improve the chemotactic function, ROS level, degranulation protein level, and inflammatory factor level of human neutrophils in infectious condition. Nr-CWS can enhance the anti-infection ability of human neutrophils by regulating its biological behavior in innate immunity.

A comprehensive analytical method based on ultra-fast liquid chromatography coupled with triple quadrupole/linear ion trap tandem mass spectrometry(UFLC-QTRAP-MS/MS) was established for simultaneous determination of the content of 45 bioactive constituents including flavonoids, alkaloids, amino acids, phenolic acids, and nucleosides in Epimedium brevicornum. The multiple bioactive constituents in leaves, petioles, stems and rhizomes of E. brevicornum were analyzed. The gradient elution was performed at 30 ℃ in an XBridge~® C&#95;(18) column(4.6 mm×100 mm, 3.5 μm) with 0.4% formic acid aqueous solution-acetonitrile as the mobile phase at a flow rate of 0.8 mL·min~(-1). Single factor experiment and response surface methodology were employed to optimize the extraction conditions. Multivariate statistical analyses including systematic cluster analysis(SCA), principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and one-way analysis of variance(One-way ANOVA) were carried out to classify the samples from different parts and identify different constituents. Grey relation analysis(GRA) and entropy weight-TOPSIS analysis were performed to build a multi-index comprehensive evaluation model for different parts of E. brevicornum. The results showed that there was a good relationship between the mass concentrations of 45 constituents and the corresponding peak areas, with the correlation coefficients(r) not less than 0.999 0. The precision, repeatability, and stability of the established method were good for all the target constituents in this study, with the relative standard deviations(RSDs) less than 5.0%(0.62%-4.9%) and the average recovery of 94.51%-105.7%. The above results indicated that the bioactive constituents varied in different parts of E. brevicornum, and the overall quality followed the trend of leaves &gt; petioles &gt; rhizomes &gt; stems. This study verified the rationality of the Chinese Pharmacopoeia(2020 edition) stipulating that the medicinal part of E. brevicornum is the leaf. Moreover, our study indicated that the rhizome had the potential for medicinal development. The established method was accurate and reliable, which can be used to comprehensive evaluate and control the quality of E. brevicornum. This study provides data reference for clarifying the medicinal parts and rationally utilizing the resources of E. brevicornum.

Objective: To evaluate the effectiveness of a risk-adapted colorectal cancer screening strategy constructed utilizing genetic and environmental risk score (ERS). Methods: A polygenic risk score (PRS) was constructed based on 20 previously published single nucleotide polymorphisms for colorectal cancer in East Asian populations, using 2 160 samples with MassARRAY test results from a multicenter randomized controlled trial of colorectal cancer screening in China. The ERS was calculated using the Asia-Pacific Colorectal Screening Score system. Logistic regression was used to analyze the association between PRS alone and PRS combined with ERS and colorectal neoplasms risk, respectively. We also designed a risk-adapted screening strategy based on PRS and ERS (high-risk participants undergo a single colonoscopy, low-risk participants undergo an annual fecal immunochemical test, and those with positive results undergo further diagnostic colonoscopy) and compared its effectiveness with the all-acceptance colonoscopy strategy. Results: The high PRS group had a 26% increased risk of colorectal neoplasms compared with the low PRS group ( OR =1.26, 95% CI : 1.03-1.54, P =0.026). Participants with the highest PRS and ERS were 3.03 times more likely to develop advanced colorectal neoplasms than those with the lowest score (95% CI : 1.87-4.90, P <0.001). As the risk-adapted screening simulation reached the third round, the detection rate of the PRS combined with ERS strategy was not statistically different from the all-acceptance colonoscopy strategy (8.79% vs. 10.46%, P =0.075) and had a higher positive predictive value (14.11% vs. 10.46%, P <0.001) and lower number of colonoscopies per advanced neoplasms detected (7.1 vs. 9.6, P <0.001). Conclusion: The risk-adapted screening strategy combining PRS and ERS helps achieve population risk stratification and better effectiveness than the traditional colonoscopy-based screening strategy.

The tissue distribution of Qingfei Paidu Decoction was studied by HPLC-MS/MS in vivo. Hypersil GOLD C&#95;(18) column(2.1 mm×50 mm, 1.9 μm) was used for gradient elution with acetonitrile as the mobile phase A and 0.1% formic acid solution as the mobile phase B. High-resolution liquid chromatography-mass spectrometry in both positive and negative ion scanning mode and multiple response monitoring(MRM) mode was employed to analyze the behaviors of the active components of Qingfei Paidu Decoction in diffe-rent tissues. The results showed that 19, 9, 17, 14, 22, 19, 24, and 2 compounds were detected in plasma, heart, liver, spleen, lung, kidney, large intestine, and brain, respectively. The compounds belonged to 8 groups, covering 14 herbs in the prescription. After administration with Qingfei Paidu Decoction, the compounds were rapidly distributed in various tissues, especially in the lung, liver, large intestine, and kidney. The majority of the compounds displayed secondary distribution. This study comprehensively analyzed the distribution rules of the main active components in Qingfei Paidu Decoction and provided a basis for the clinical application.

Although soil microbes play a key role in grassland ecosystem functioning, the response of their diversity to grassland degradation has not been fully investigated. Here, we used shotgun metagenomic sequencing to analyze the characteristics and influencing factors of soil microbial taxonomic and functional diversity at four different degradation stages[i.e., non-degraded (ND), lightly degraded (LD), moderately degraded (MD), and heavily degraded (HD)]of subalpine meadow in the Mount Wutai. The results showed that there were significant differences in the relative abundances of Actinobacteria, Bacteroidetes, Nitrospirae, and Parcubacteria among the four subalpine grasslands with different degradation degrees ( P <0.05).Compared with that in ND, the degraded meadows increased the proportion of genes related to carbon metabolism, biosynthesis of amino acids, pyruvate metabolism, citric acid cycle, propanoate metabolism, butanoate metabolism, and fatty acid metabolism ( P <0.05), indicating that the degradation of subalpine grassland changed the metabolic potential of energy metabolism and the nutrient cycle of the soil microbial community. Grassland degradation changed soil microbial taxonomic and functional α diversity, especially in MD and HD.Grassland degradation resulted in significant changes in the taxonomic and functional compositions of the microbial communities. The total nitrogen, pH, and soil organic carbon significantly affected the taxonomic and functional compositions of the microbial communities.The β diversity of the plant community was significantly correlated with the taxonomic and functional β diversity of the microbial community ( P <0.05), indicating strong coupling. The results of this study revealed the changes and driving mechanisms of subsurface microbial taxonomic and functional diversity during grassland degradation, which can provide a theoretical basis for subalpine meadow protection and ecological restoration.

Objective: To investigate whether admission blood pressure (BP) variability during multiple hospitalizations is associated with all-cause mortality independent of baseline BP in acute decompensated heart failure (ADHF). Methods: Patients with ADHF admitted to the Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University from September 2013 to December 2017 were retrospectively enrolled. The risk of all-cause mortality associated with indices of BP variability, including mean admission BPs, standard deviation of BP and coefficient of variation of BP during multiple hospitalizations was assessed, using Cox regression model. Results: A total of 1 006 ADHF patients (mean aged (69.3±13.5) years; 411 (40.8%) female; 670 (66.6%) with preserved ejection fraction) were enrolled. During a median follow-up of 1.54 years, 47.0% of patients died. In all ADHF patients, after adjusting for confounding factors, for every 1-standard deviation (SD) increase in SD and coefficient of variation (CV) of systolic BP, the risk of all-cause mortality increased by 10% and 11%, respectively (SD: HR , 1.10, 95% CI , 1.01-1.21, P =0.029, CV: HR , 1.11, 95% CI , 1.02-1.21, P =0.017); for every 1-SD increase in the mean of diastolic BP, the risk of all cause mortality decreased by 25% ( HR , 0.75; 95% CI , 0.65-0.87; P <0.001). In ADHF patients with preserved ejection fraction, after accounted for potential confounders, higher SD and CV of admitted systolic and diastolic BP were significantly associated with higher risk of all-cause mortality, regardless of whether confounding factors were adjusted ( P ≤0.049); After adjusting for confounding factors, the risk of all-cause mortality increased by 18% and 19% for every 1-SD increase in SD and CV of systolic BP, while the risk of all-cause mortality increased by 11% and 15% for every 1-SD increase in SD and CV of diastolic BP. In ADHF patients with reduced ejection fraction, after adjusting for confounding factors, the higher the mean admission systolic BP during multiple hospitalizations, the lower the risk of total mortality ( HR , 0.68; 95% CI , 0.47-1.00; P =0.049). Conclusions: In patients with ADHF, independent of baseline BP, BP variability during multiple hospitalizations was strong predictor of all-cause mortality.

The present study aimed to explore the main active components and underlying mechanisms of Marsdenia tenacissima in the treatment of ovarian cancer(OC) through network pharmacology, molecular docking, and in vitro cell experiments. The active components of M. tenacissima were obtained from the literature search, and their potential targets were obtained from SwissTargetPrediction. The OC-related targets were retrieved from Therapeutic Target Database(TTD), Online Mendelian Inheritance in Man(OMIM), GeneCards, and PharmGKB. The common targets of the drug and the disease were screened out by Venn diagram. Cytoscape was used to construct an &quot;active component-target-disease&quot; network, and the core components were screened out according to the node degree. The protein-protein interaction(PPI) network of the common targets was constructed by STRING and Cytoscape, and the core targets were screened out according to the node degree. GO and KEGG enrichment analyses of potential therapeutic targets were carried out with DAVID database. Molecular docking was used to determine the binding activity of some active components to key targets by AutoDock. Finally, the anti-OC activity of M. tenacissima extract was verified based on SKOV3 cells in vitro. The PI3K/AKT signaling pathway was selected for in vitro experimental verification according to the results of GO function and KEGG pathway analyses. Network pharmacology results showed that 39 active components, such as kaempferol, 11α-O-benzoyl-12β-O-acetyltenacigenin B, and drevogenin Q, were screened out, involving 25 core targets such as AKT1, VEGFA, and EGFR, and the PI3K-AKT signaling pathway was the main pathway of target protein enrichment. The results of molecular docking also showed that the top ten core components showed good binding affinity to the top ten core targets. The results of in vitro experiments showed that M. tenacissima extract could significantly inhibit the proliferation of OC cells, induce apoptosis of OC cells through the mitochondrial pathway, and down-regulate the expression of proteins related to the PI3K/AKT signaling pathway. This study shows that M. tenacissima has the characteristics of multi-component, multi-target, and multi-pathway synergistic effect in the treatment of OC, which provides a theoretical basis for in-depth research on the material basis, mechanism, and clinical application.

Sanhan Huashi formula(SHF) is the intermediate of a newly approved traditional Chinese medicine(TCM) Sanhan Huashi Granules for the treatment of COVID-19 infection. The chemical composition of SHF is complex since it contains 20 single herbal medicines. In this study, UHPLC-Orbitrap Exploris 240 was used to identify the chemical components in SHF and in rat plasma, lung and feces after oral administration of SHF, and heat map was plotted for characterizing the distribution of the chemical components. Chromatographic separation was conducted on a Waters ACQUITY UPLC BEH C&#95;(18)(2.1 mm×100 mm, 1.7 μm) using 0.1% formic acid(A)-acetonitrile(B) as mobile phases in a gradient elution. Electrospray ionization(ESI) source was used to acquire data in positive and negative mode. By reference to quasi-molecular ions and MS/MS fragment ions and in combination with MS spectra of reference substances and compound information in literature reports, 80 components were identified in SHF, including 14 flavonoids, 13 coumarins, 5 lignans, 12 amino-compounds, 6 terpenes and 30 other compounds; 40 chemical components were identified in rat plasma, 27 in lung and 56 in feces. Component identification and characterization of SHF in vitro and in vivo lay foundations for disclosure of its pharmacodynamic substances and elucidation of the scientific connotation.

Objective: To explore the characteristics of plasma Epstein-Barr virus (EBV) DNA in primary infection in pediatric cases. Methods: The laboratory and clinical data of 571 children diagnosed with EBV primary infection in Children's Hospital of Fudan University during September 1 st , 2017 to September 30 th , 2018 were retrospectively analyzed. According to the results of plasma EBV DNA, they were divided into positive group and negative group. According to the EBV DNA, they were devided into high plasma virol load group and low plasma virol load group. The Chi-square test, Wilcoxon rank sum test were used to compare the differences between groups. Results: Among the 571 children with EBV primary infection, 334 were males and 237 were females. The age of first diagnosis was 3.8 (2.2, 5.7) years. There were 255 cases in positive group and 316 cases in negative group. The percentage of cases with fever,hepatomegaly and (or) splenomegaly, elevated transaminase in the positive group were higher than those in the negative group (235 cases (92.2%) vs . 255 cases (80.7%), χ 2 =15.22, P <0.001; 169 cases (66.3%) vs. 85 cases (26.9%), χ 2 =96.80, P <0.001; and 144 cases (56.5%) vs. 120 cases (38.0%), χ 2 =18.27, P <0.001; respectively).In the positive group, 70 cases were followed up for 46 (27, 106) days, 68 cases (97.1%) turned negative within 28 days, with the exception of 2 cases (2.9%) developed chronic active EBV infection by follow-up revision.There were 218 cases in high plasma viral DNA copies group and 37 cases in low copies group. More cases presented with elevated transaminases in the high plasma viral DNA copies group than those in the low group (75.7% (28/37) vs. 56.0%(116/207), χ 2 =5.00, P= 0.025).Both the positive rate of EBV DNA in peripheral blood leukocytes (84.2% (266/316) vs . 44.7% (255/571), χ 2 =76.26, P <0.001) and the copies of EBV DNA (7.0×10 7 (1.3×10 7 , 3.0×10 8 ) vs. 3.1×10 6 (1.6×10 6 , 6.1×10 6 ) copies /L, Z =15.23, P <0.001) were higher than that of plasma. Conclusions: In immunocompetent pediatric cases diagnosed as EBV primary infection, cases with positive plasma EBV DNA were prone to have fever, hepatomegaly and (or) splenomegaly, and elevated transaminase than those with negative plasma viral DNA. The plasma EBV DNA usually turns negative within 28 days after initial diagnosis.Most cases with high viral load in plasma showed elevated aminotransferase.

A randomized, double-blind, placebo-controlled, multi-center phase Ⅱ clinical trial design was used in this study to recruit subjects who were in line with the syndrome of excess heat and fire toxin, and were diagnosed as recurrent oral ulcers, gingivitis, and acute pharyngitis. A total of 240 cases were included and randomly divided into a placebo group and a Huanglian Jiedu Pills group. The clinical efficacy of Huanglian Jiedu Pills in treating the syndrome of excess heat and fire toxin was evaluated by using the traditional Chinese medicine(TCM) syndrome scale. Enzyme-linked immunosorbent assay(ELISA) was used to determine and evaluate the levels of adenosine triphosphate(ATP), 4-hydroxynonenal(4-HNE), and adrenocorticotropic hormone(ACTH) in plasma of the two groups before and after administration and to predict their application value as clinical biomarkers. The results showed that the disappearance rate of main symptoms in the Huanglian Jiedu Pills group was 69.17%, and that in the placebo group was 50.83%. The comparison between the Huanglian Jiedu Pills group and the placebo group showed that 4-HNE before and after administration was statistically significant(P&lt;0.05). The content of 4-HNE in the Huanglian Jiedu Pills group decreased significantly after administration(P&lt;0.05), but that in the placebo group had no statistical significance and showed an upward trend. After administration, the content of ATP in both Huanglian Jiedu Pills group and placebo group decreased significantly(P&lt;0.05), indicating that the energy metabolism disorder was significantly improved after administration of Huanglian Jiedu Pills and the body's self-healing ability also alleviated the increase in ATP level caused by the syndrome of excess heat and fire toxin to a certain extent. ACTH in both Huanglian Jiedu Pills group and placebo group decreased significantly after administration(P&lt;0.05). It is concluded that Huanglian Jiedu Pills has a significant clinical effect, and can significantly improve the abnormal levels of ATP and 4-HNE in plasma caused by the syndrome of excess heat and fire toxin, which are speculated to be the effective clinical biomarkers for Huanglian Jiedu Pills to treat the syndrome of excess heat and fire toxin.

Children's fever is often accompanied by food accumulation. Traditional Chinese medicine believes that removing food stagnation while clearing heat of children can effectively avoid heat damage. To systematically evaluate the efficacy of Xiaoer Chiqiao Qingre Granules(XRCQ) in clearing heat and removing food accumulation and explore its potential mechanism, this study combined suckling SD rats fed with high-sugar and high-fat diet with injection of carrageenan to induce rat model of fever and food accumulation. This study provided references for the study on the pharmacodynamics and mechanism of XRCQ. The results showed that XRCQ effectively reduced the rectal temperature of suckling rats, improved the inflammatory environment such as the content of interleukin-1β(IL-1β), interleukin-2(IL-2), interferon-γ(IFN-γ), white blood cells, and monocytes. XRCQ also effectively repaired intestinal injury and enhanced intestinal propulsion function. According to the confirmation of its efficacy of clearing heat, the thermolytic mechanism of XRCQ was further explored by non-targeted and targeted metabolomics methods based on LTQ-Orbitrap MS/MS and UPLC-QQQ-MS/MS. Non-target metabolomics analysis of brain tissue samples was performed by QI software combined with SIMCA-P software, and 22 endogenous metabolites that could be significantly regulated were screened out. MetaboAnalyst pathway enrichment results showed that the intervention mechanism was mainly focused on tyrosine metabolism, tricarboxylic acid cycle, inositol phosphate metabolism, and other pathways. At the same time, the results of targeted metabolomics of brain tissue samples showed that XRCQ changed the vitality of digestive system, and inhibited abnormal energy metabolism and inflammatory response, playing a role in clearing heat and removing food stagnation from multiple levels.

To establish a method for the simultaneous determination of ellagic acid, quercetin, gallic acid, kaempferol, myricetin, tiliroside, salidroside, isoquercetin, chlorogenic acid, and quinic acid in the leaves, flowers, fruits, and roots of Loropetalum chinensis by ultra-performance liquid chromatography-tandem mass spectrometry, and provide references for the development and utilization of L. chinensis resources. The analysis was performed on the chromatographic column ACQUITY UPLC HSS T3(2.1 mm×100 mm, 1.8 μm) with a gradient mobile phase of acetonitrile-0.2% formic solution at the flow rate of 0.3 mL·min~(-1). Column temperature was 30 ℃ and injection volume was 2 μL. Multiple reactive ion monitoring mode(MRM) was used in the negative ion ionization mode of electrospray ion source. The 10 active components had a good linear relationship, and the established method was stable, simple, and accurate. The 10 active components existed in different parts of L. chinensis, with significant different content. The main components in different parts of L. chinensis were polyphenols, with the highest content, followed by flavonoids. The content of 10 active components was generally high in flowers. Among them, the content of quinic acid was the highest, reaching 22.539 1 mg·g~(-1). This study elucidates the differences of active components in the same part and the different parts of L. chinensis, thereby providing basis for the research on the pharmacodynamic substances of L. chinensis and references for the comprehensive development and utilization of L. chinensis resources.

Through the non-targeted metabonomics study on endogenous substances in APP/PS1 transgenic mice, this paper aimed to discover biomarkers related to APP/PS1 mice with cognitive dysfunction, and find targets of Huanglian Jiedu Decoction(HLJDD) in the treatment of Alzheimer's disease(AD) and its mechanism. The brain tissue and serum metabolic mass spectrometry of mice were analyzed by ultra-high performance liquid chromatography-Orbitrap mass spectrometry(UPLC-Orbitrap MS). Through partial least squares-discriminant analysis(PLS-DA) and orthogonal partial least squares-discriminant analysis(OPLS-DA), the metabolic data of the normal group, the model group, the high-dose and low-dose HLJDD groups, and the berberine group were compared and analyzed to screen out potential biomarkers, and the relevant metabolic pathways were constructed with the help of the Kyoto Encyclopedia of Genes and Genomes(KEGG) database. Forty-five potential endogenous metabolites were identified, including 13 in brain and 35 in serum, among which leukotriene B4, tyrosine, and adenosine were expected to be differential metabolites related to cognitive function. HLJDD recalled 22 differential metabolites, and the pathways mainly involved in aminoacyl-tRNA biosynthesis, valine, leucine and isoleucine biosynthesis, pantothenic acid and coenzyme A biosynthesis, phenylalanine, tyrosine and tryptophan biosynthesis, and arachidonic acid metabolism. These pathways suggested that the main mechanism of HLJDD in the intervention of AD was to inhibit central and peripheral inflammation, and regulate energy metabolism, fatty acid metabolism, and amino acid metabolism. HLJDD has a certain effect on the improvement of cognitive dysfunction, and regulates relative pathways by recalling endogenous differential metabolites, which helps to further discover the biomarkers of AD and clarify the intervention mechanism of HLJDD in the treatment of AD.

Autism spectrum disorder (ASD) is a serious neurodevelopmental impairment of children. Because of its difficulty of early diagnosis, length of disease course, irreversible injury and slim chance of curability, it brings heavy burdens to patients, their families and the whole society. Recent studies have shown that the pathogenic mechanism of ASD is closely related to the abnormal myelination caused by the imbalance of differentiation, proliferation and apoptosis of oligodendroglial lineage cells. This article will review on the role of oligodendroglial lineage cells in myelination and the mechanisms of ASD caused by improper differentiation, proliferation and apoptosis of oligodendroglial lineage cells, according to advanced researches. Oligodendrocytes play vital roles in neurodevelopment, and the defect in these cells has been recognized as one of the key pathogenic mechanisms leading to ASD. Elucidating the effects and disciplines which oligodendrocytes exert on the occurrence and development of ASD would provide guidance for precise prevention and control of neurodevelopmental disorders such as ASD.

The present study established an RP-HPLC method for simultaneous determination of two active components in Qingfei Paidu Granules and investigated the transfer rates of neohesperidin and naringin in the preparation process to provide references for improving the quality control standard and production of Qingfei Paidu Granules.RP-HPLC was performed on a YMC Triart C&#95;(18) column(4.6 mm×150 mm, 5 μm)with column temperature of 30 ℃, acetonitrile(A) and 0.2% phosphoric acid solution(B) as mobile phases for gradient elution at a flow rate of 1.0 mL·min~(-1) and detection wavelength of 284 nm.Good linearity was observed for naringin at 0.10-1.0 μg(R~2=0.999 9) and neohesperidin at 0.12-1.2 μg(R~2=0.999 9).The average recovery of naringin was 99.52% with an RSD of 1.2%, and that of neohesperidin was 100.8% with an RSD of 1.2%.The transfer rates of naringin and neohesperidin between medicinal materials, extracts, concentrates, and granules were measured by this method.The average transfer rate of naringin from medicinal materials to granules was 54.89%±4.38%, and that of neohesperidin was 57.63%±5.88%.The process from medicinal materials to extracts was presumedly the key link affecting the whole preparation process.The established method is simple and sensitive and can be adopted for the quality control of Qingfei Paidu Granules.Meanwhile, it can be used to investigate the transfer rate of neohesperidin and naringin in the preparation of Qingfei Paidu Granules, and further improve the quality control standard of Aurantii Fructus Immaturus in Qingfei Paidu Granules.

The production of solid preparations is a multi-unit and multi-step system and is a whole process chain. Its quality is affected by many factors such as material properties and process parameters. As an important analysis tool, multivariate models play an important role in pharmaceutical monitoring. Besides, multivariate models can comprehensively understand the multi-factor relationship between material properties, process parameters, and quality attributes of products, thereby promoting the whole process optimization and controlling the drug production quality. This paper summarized the application of commonly used multivariate models in the process of solid preparations, which provides a certain reference for the process modeling of Chinese medicinal preparations.

Quality evaluation of Chinese medicinal decoction pieces is vital for the development of the downstream industries, and is an important channel for implementing the strategy of &quot;higher quality, higher price, and priority for the high quality&quot; for traditional Chinese medicine. At the moment, the quality of Chinese medicinal decoction pieces is mainly evaluated based on chemical component examination. Considering the weak preliminary research foundation and poor research conditions, traditional experience-based evaluation is undervalued in the quality rating of Chinese medicinal decoction pieces. However, traditional experience is a summary of the quality of Chinese medicinal materials based on clinical experience, which thus can be a potential basis for the quality evaluation of the decoction pieces. It is a challenge in the evaluation of Chinese medicinal decoction pieces to objectify the traditional experience-based evaluation from multiple aspects such as chemistry, effect, and characterization via modern techniques. Therefore, this study developed the &quot;experience-ingredients-activity-electronic sensing&quot; evaluation system for Chinese medicinal decoction pieces on the basis of experience-based assessment, chemical ingredients that can truly reflect the traditional experience, biological effect assessment, and electronic sensory evaluation, which is expected to quantify the traditional experience of quality evaluation of Chinese medicinal decoction pieces via chemistry, biology, and sensory simulation. The evaluation system can serve as a reference for clinical experience-based quality evaluation of Chinese medicinal decoction pieces.

Objective: To investigate the genetic mutation types and ethnic distribution characteristics of thalassemia in Guiyang., Methods: The population underwent physical examination, antenatal examination and pre-pregnancy examination in our hospital from January 2019 to November 2019 was selected, and the thalassemia gene was detected by RDB-PCR., Results: Among the 4 572 samples, 346 were positive , and the total carrying rate was 7.57%. The carrying rate of α-thalassaemia gene was 5.42% (248 cases), while β-thalassemia was 1.99% (91 cases), and α+β-compound thalassemia was 0.15% (7 cases). α-thalassaemia genotype with the lack of right side -α 3.7 /αα (52.82%) was the most common, followed by - SEA /αα (25.00%) and -α 4.2 /αα (10.48%). β-thalassemia genotype was mainly CD17 (A→T) (51.65%), followed by CD41-42 (-TCTT) (25.27%) and IVS-2-654 (C→T) (12.09%). One case of rare αα/ααα anti3.7 and one case of rare HBB:c.-153C>A (-103 C>A) mutation were detected. Among the 346 positive samples, 264 were from the Han nationality and 82 from the ethnic minorities, among which Buyi nationality accounted for the most (35.80%), followed by Miao nationality (20.54%)., Conclusion: The gene types of thalassemia in Guiyang are complex and varied. The -α 3.7 /αα is the most common genotype of α-thalassemia, while CD17 (A→T) (51.65%) is the most common genotype of β-thalassemia. The carrying rate of thalassemia in the Buyi nationality is higher than other nations, it is necessary to carry out regular monitoring and publicity.

This study aimed to qualitatively analyze the chemical components in Xiaoer Chiqiao Qingre Granules(XRCQ) by UHPLC-LTQ-Orbitrap-MS/MS and identify its material basis. The absorbed components in plasma were combined for exploring the potential action mechanism by integrated network pharmacology. ACQUITY UPLC HSS T3(2.1 mm×100 mm, 1.8 μm) column and mobile phase system of 0.1% formic acid solution(A)-acetonitrile(B) were used for gradient elution, followed by high resolution liquid chromatography-mass spectrometry in both positive and negative ion scanning modes. According to the precise relative molecular mass and MS/MS fragment ions, a total of 124 chemical components were identified in XRCQ by the comparison with references and literature reports, among which 29 compounds were completely confirmed by comparison with reference substances. Then, the main absorbed components of XRCQ in plasma were also analyzed and clarified by UHPLC-LTQ-Orbitrap-MS/MS. BATMAN-TCM and SwissTargetPrediction were used for target prediction of absorbed components in plasma. Following the plotting of association network with Cytoscape 3.8.2, the core targets were subjected to GO and KEGG pathway enrichment analysis and a component-target-pathway network was constructed. A total of eight main targets of XRCQ against fever in children were obtained together with eight absorbed components in plasma, including glycyrhydinic acid, hesperidin, emodin, reticuline, daidzein, magnolignan C, magnolignan A, and magnolaldehyde D. It was inferred that XRCQ might improve alimentary system abnormality, inflammatory response, oxidative stress, and endocrine disorder through tumor necrosis factor, PI3 K-AKT, and other signaling pathways. The present study comprehensively expounded the chemical profiles of XRCQ and the main absorbed components in plasma and predicted the potential mechanism of XRCQ based on integrated network pharmacology, which has provided certain theoretical reference for the clinical application of XRCQ.

Objective: To investigate the effect of lysosomal-associated protein transmembrane-4 Beta(Laptm4b) deletion on hematopoietic stem/progenitor cells (HSPCs) homeostasis in mice., Methods: The hematopoietic system specific Laptm4b-deficient mice were constructed. The number and proportion of HSPCs (LSK, LT, ST, MPP, etc) in Laptm4b-deficient mice were analyzed by flow cytometry. Single SLAM-HSC cell was sorted by flow sorter and cultured in vitro to measure the effect of Laptm4b deletion on the colony forming ability of hematopoietic stem cells (HSCs). The effect of Laptm4b-deficient on the reconstitution ability of HSCs in mice was detected by competitive transplantation experiment of SLAM-HSC cells., Results: Laptm4b deficiency could moderately upregulate the proportion of T cells in the peripheral blood of the mice, but showed no significant effect on the proportion and number of HSPCs. Laptm4b deletion showed no effect on the reconstruction ability of HSCs after competitive transplantation, but it could inhibit the colony formation of HSCs in vitro., Conclusion: LAPTM4B may play a role in HSCs under the proliferation stress. Laptm4b-deficient in mice hematopoietic system showed no significant effect on the HSPCs homeostasis maintenance and reconstruction ability.

Indolealkylamines(IAAs) are the main hydrophilic substances in toad skin, mainly including free N-methyl-5-hydroxytryptamine, bufotenine, bufotenidine, dehydrobufotenine, and binding bufothionine. In this study, the LPS-activated neutrophils were used to investigate the structure-activity relationship and anti-inflammatory mechanism of the above-mentioned five monomers from the toad skin in vitro. The neutrophils were divided into the control group, model group(1 μg·mL~(-1) LPS), positive drug group(100 μg·mL~(-1) indometacin), as well as the low-(50 μg·mL~(-1)), medium-(100 μg·mL~(-1)) and high-dose(200 μg·mL~(-1)) free N-methyl-5-hydroxytryptamine, bufotenine, bufotenidine, dehydrobufotenine, and binding bufothionine groups. The levels of IL-6, TNF-α and IL-1β in the neutrophil supernatant of each group was measured by enzyme-linked immunosorbent assay(ELISA) after LPS stimulation, followed by the detection of apoptosis in each group after Annexin V/PI staining. The protein expression levels of caspase-3, Bax, Bcl-2, beclin1, LC3-I, and LC3-Ⅱ were assayed by Western blot. The results showed that IAAs reduced the excessive secretion of inflammatory cytokines caused by LPS compared with the model group. Besides, the activity of each free IAAs(N-methyl-5-hydroxytryptamine, bufotenine, bufotenidine and dehydrobufotenine), especially bufotenine, was stronger than that of the binding bufothionine. As revealed by Annexin V/PI staining, LPS delayed the early apoptosis of neutrophils compared with the control group, while bufotenine promoted the apoptosis of neutrophils in a dose-dependent manner, which might be related to the elevated expression of apoptosis-related protein Bax/Bcl-2. In addition, LPS activated the autophagy pathways in neutrophils. This study confirmed the efficacy of IAAs in reducing the secretion of inflammatory cytokines in neutrophils induced by LPS for the first time. For instance, bufotenine exerts the anti-inflammatory effect possibly by inducing the apoptosis of neutrophils.

Objective: To segment images through an unsupervised method as an alternative to manual labeling., Methods: A total of 100 whole slide image (WSI) data of HE stained and Pap stained slides were selected as the research and test objects, including 70 breast slides, 20 lung slides and 10 thyroid slides. In order to ensure the diversity of data, the breast slides included those of normal tissue, inflammation and tumor, the lung slides were mainly neoplasms in the lower lobe, including those of inflammation and tumor, and the thyroid slides were of cells, all benign, obtained through fine needle aspiration. The maximum total magnification (original magnification) of each image was 400 times, and the file format was NDPI. Each WSI was manually labeled, and the labeled area of each WSI was more than 10 fields of vision. The labeled information was to be used for validity verification. An unsupervised image segmentation technique based on superpixel and fully convolution neural network algorithms was constructed and used to segment any region of interest (ROI) of unlabeled WSI. In comparison with the region adjacency graph merging method, the segmentation effect of the two methods was assessed with the under segmentation error, the boundary recall and the mean Intersection-over-Union, and the efficiency of the two methods was also compared. In the comparison of execution efficiency, the test process included the preprocessing time of superpixel, and excluded the time of loading the deep learning engine., Results: Unsupervised automatic segmentation was implemented for any ROI region of WSI according to the texture and color. The results of the breast slides, lung slides and thyroid slides showed slight differences, and multiple tests yielded stable results. However, the performance of this method in differentiating inflammation and tumor was average. The under-segmentation error, the boundary recall and the mean Intersection-over-Union were 19.10%, 82.06% and 45.06%, respectively. The under segmentation error, the boundary recall and the mean Intersection-over-Union for the region adjacency graph merging method were 21.52%, 78.39% and 44.81%, respectively. The average time consumption of the whole process was 0.27 s in GPU mode and 1.30 s in CPU mode. The average time consumption of the region adjacency graph merging method was 10.5 s in CPU mode because the method of region adjacency graph merging was not realized in the GPU mode., Conclusion: This method produced ideal pixel level labeling results through simple human-computer interaction, which could effectively reduce the cost of digital pathology slide data labeling. Compared with the region adjacency graph merging method, this method had better performance in processing image texture and had faster processing speed., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Objective: To study the different methods of artificial intelligence (AI)-assisted Ki-67 scoring of clinical invasive ductal carcinoma (IDC) of the breast and to compare the results., Methods: A total of 100 diagnosed IDC cases were collected, including slides of HE staining and immunohistochemical Ki-67 staining and diagnosis results. The slides were scanned and turned into whole slide image (WSI), which were then scored with AI. There were two AI scoring methods. One was fully automatic counting by AI, which used the scoring system of Ki-67 automatic diagnosis to do counting with the whole image of WSI. The second method was semi-automatic AI counting, which required manual selection of areas for counting, and then relied on an intelligent microscope to conduct automatic counting. The diagnostic results of pathologists were taken as the results of pure manual counting. Then the Ki-67 scores obtained by manual counting, semi-automatic AI counting and automatic AI counting were pairwise compared. The Ki-67 scores obtained from the manual counting (pathological diagnosis results), semi-automatic AI and automatic AI counts were pair-wise compared and classified according to three levels of difference: difference ≤10%, difference of >10%-<30% and difference ≥30%. Intra-class correlation coefficient ( ICC ) was used to evaluate the correlation., Results: The automatic AI counting of Ki-67 takes 5-8 minutes per case, the semi-automatic AI counting takes 2-3 minutes per case, and the manual counting takes 1-3 minutes per case. When results of the two AI counting methods were compared, the difference in Ki-67 scores was all within 10% (100% of the total), and the ICC index being 0.992. The difference between manual counting and semi-automatic AI was less than 10% in 60 cases (60% of the total), between 10% and 30% in 37 cases (37% of the total), and more than 30% in only 3 cases (3% of the total), ICC index being 0.724. When comparing automatic AI with manual counting, 78 cases (78% of the total) had a difference of ≤10%, 17 cases (17% of the total) had a difference of between 10% and 30%, and 5 cases (5%) had a difference of ≥30%, the ICC index being 0.720. The ICC values showed that there was little difference between the results of the two AI counting methods, indicating good repeatability, but the repeatability between AI counting and manual counting was not particularly ideal., Conclusion: AI automatic counting has the advantage of requiring less manpower, for the pathologist is involved only for the verification of the diagnosis results at the end. However, the semi-automatic method is better suited to the diagnostic habits of pathologists and has a shorter turn-over time compared with that of the fully automatic AI counting method. Furthermore, in spite of its higher repeatability, AI counting, cannot serve as a full substitute for pathologists, but should instead be viewed as a powerful auxiliary tool., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

There are 18 original texts of Sun Simiao's literature quoted in the book of Bencao Tujing (, Illustration Classics for Materia Medica ) edited by Su Song in the Northern Song Dynasty, involving Qianjin Yao Fang (, Invaluable Prescriptions ), Qianjin Yi Fang (, Supplement to Invaluable Prescriptions ) and Qianjin Yueling () . They are the versions of the Northern Song Dynasty or earlier versions, which have high collation value and collection value. The Qianjin Yao Fang quoted in the book of Bencao Tujing has different versions with the current version of Qianjin Yao Fang and the ancient version of Sun Zhenren Qianjin Fang (, Immortal Sun's Invaluable Prescriptions ) . Some of these varieties are caused by Su Song's collation, while others are caused by different versions. According to the former, the latter can be corrected and supplemented. Qianjin Yi Fang quoted in Bencao Tujing is earlier than the edition in Dade period of Yuan Dynasty. According to the former, the latter can be corrected. The book of Qianjin Yueling edited by Sun Simiao has been lost. Part of the contents of the book are included in Euibangyoochui (, Classified Assemblage of Medical Prescriptions ) published in Korea. Some scholars have compiled and copied the book accordingly. The texts of Qianjin Yueling quoted in the book of Bencao Tujing can be used to correct the mistakes of the lost edition of Qianjin Yueling and make up for its incompleteness.

Thalassemia and hemophilia are common inherited blood disorders caused by genetic abnormalities. These diseases are difficult to cure and can be inherited to the next generation, causing severe family and social burden. The emergence of gene therapy provides a new treatment for genetic diseases. However, since its first clinical trial in 1990, the development of gene therapy has not been as optimistic in the past three decades as one could hope. The development of gene-editing technology, particularly the third generation gene-editing technology CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9), has given hope in such therapeutic approach for having advantages in high editing efficiency, simple operation, and low cost. Gene editing-mediated gene therapy has thus received increasing attention from the biomedical community. It has shown promises for the treatment of inherited blood disorders, such as thalassemia and hemophilia. This paper reviews the fundamental research progress of gene therapy for β-thalassemia and hemophilia based on CRISPR/Cas9 technology in the past six years. It also summarizes the CRISPR/Cas9-based clinical trials of gene therapy. The problems and possible solutions to this technology for gene therapy are also discussed, thereby providing a reference for the research on gene therapy of inherited blood disorders based on CRISPR/Cas9 technology.