ObjectiveTo investigate the effects of three traditional Chinese medicine formulas for nourishing kidney Yin on the occurrence of breast cancer， including Zuoguiwan（ZGW）， Liuwei Dihuangwan（LWDHW） and Erzhiwan（EZW）， and to explore their preventive mechanisms from the phagocytic function of macrophages. MethodsTen-month-old post-breeding female mice were randomly divided into the blank group， soy isoflavone group（0.13 g·kg^-1·d^-1， mixed with feed）， ZGW group（2.34 g·kg^-1·d^-1）， LWDHW group（0.56 g·kg^-1·d^-1）， and EZW group（4.68 g·kg^-1·d^-1）. The mice were palpated every 3 d until the age of 18 months， and those with detected lumps were confirmed for tumor development through hematoxylin-eosin（HE） staining， and the incidence of breast cancer in mice was calculated. A total of 40 SPF-grade female SD rats were randomly divided into the blank serum group（physiological saline）， ZGW drug-containing serum group（16.20 g·kg^-1·d^-1of ZGW）， LWDHW drug-containing serum group（3.89 g·kg^-1·d^-1 of LWDHW） and EZW drug-containing serum group（32.40 g·kg^-1·d^-1 of EZW）， each group was orally administered 3 times a day for 5 consecutive days. On the 5^th day， blood was collected from the abdominal aorta 1 h after the last gavage to prepare drug-containing serum. The effect of drug-containing serum with different concentrations on the viability of RAW264.7 cells was assessed by cell counting kit-8（CCK-8）. Taking 20% of drug-containing serum concentration as the research object， its effect on the expression levels of major histocompatibility complex-Ⅱ（MHC-Ⅱ）， CD80 and CD86 on the surface of RAW264.7 cells was detected by immunofluorescence（IF）， the phagocytic function of RAW264.7 cells was examined by flow cytometry， and the levels of interleukin-6（IL-6） and nitric oxide（NO） in RAW264.7 cells in the conditioned medium（CM） co culture system of 4T1 cells were detected by enzyme-linked immunosorbent assay（ELISA） and Griess assay. ResultsAfter prophylactic administration， the tumor incidence rates in the soy isoflavone group（4%）， ZGW group（4%）， LWDHW group（4%）， and EZW group（6%） were lower than that in the blank group（8%）. Compared with the blank serum group， the drug-containing serum of the three nourishing kidney Yin formulas could enhance the expression levels of MHC-Ⅱ， CD80 and CD86 on the surface of RAW264.7 cells， enhance phagocytic ability towards tumor cells， and reduce the content of IL-6 and increase the level of NO（P<0.05， P<0.01）. ConclusionThe three nourishing kidney Yin formulas can reduce the incidence of tumor in mice， the mechanism may be related to activating RAW264.7 cells， increasing their phagocytosis to breast cancer cells， and regulating the secretion of IL-6 and NO.

BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

To investigate the mechanism of action of Syngnathus extract in treating knee osteoarthritis of rats, forty-eight male SD rats were randomly divided into the blank group, model group, positive drug group, as well as low-dose, medium-dose, and high-dose groups of Syngnathus extract. The rat model of knee osteoarthritis was constructed by intra-articular injection of sodium iodoacetate. After successful modeling, celecoxib(18 mg·kg~(-1)·d~(-1)) and Syngnathus extract(0.4, 0.8, and 1.6 g·kg~(-1)·d~(-1)) were given in different groups by gavage intervention for two weeks. Hematoxylin-eosin(HE) staining was used to observe the histopathological changes of cartilage in knee joints, and enzyme-linked immunosorbent assay(ELISA) was used to detect the expression level of inflammatory factors in serum. Real-time fluorescence quantitative PCR, Western blot, and immunohistochemistry were used to detect the levels of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target protein of rapamycin(mTOR) pathway-related mRNA and protein expression. The results showed that, comparied with the blank group, the cartilage surface of the knee joints of rats in the model group was uneven, with disorganized levels and defective cartilage tissue. The serum levels of interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) and the mRNA levels of PI3K, Akt, and mTOR in cartilage tissue, as well as the protein expression levels of phosphorylated PI3K(p-PI3K)/PI3K, phosphorylated Akt(p-Akt)/Akt, phosphorylated mTOR(p-mTOR)/mTOR, and P62 were significantly increased. Beclin1 protein expression was decreased. Comparied with the model group, the number of chondrocytes in the knee joint of rats in each group of Syngnathus extract increased, and the arrangement of chondrocytes was relatively neat. The cartilage layer was restored, and the serum levels of IL-1β, IL-6, and TNF-α, as well as the mRNA expression levels of PI3K, Akt, and mTOR in cartilage tissue were significantly reduced. The protein expression levels of p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR, and P62 were significantly reduced in the rats in the middle-dose and high-dose groups of Syngnathus extract, and the Beclin1 protein expression was significantly increased. The protein expression levels of p-PI3K/PI3K, p-Akt/Akt, and P62 in rats in the low-dose group of Syngnathus extract were significantly reduced. In summary, Syngnathus extract may be used to treat knee osteoarthritis by inhibiting the expression of PI3K/Akt/mTOR signaling pathway, so as to alleviate the inflammatory response in the organism, enhance the autophagy activity of chondrocytes, and reduce the apoptosis of chondrocytes.
Animals ; TOR Serine-Threonine Kinases/genetics* ; Male ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/genetics* ; Rats ; Osteoarthritis, Knee/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Phosphatidylinositol 3-Kinases/genetics* ; Humans

This study predicts the potential mechanism of Hippocampus in the treatment of knee osteoarthritis(KOA) through network pharmacology, with preliminary verification using molecular docking and animal experiments. The database was used to screen the active chemical components of Hippocampus and the targets of KOA, and Gene Ontology(GO) functional analysis, Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis, and molecular docking were performed on the relevant core targets to preliminarily explore the potential targets and mechanisms of Hippocampus in the treatment of KOA. A rat KOA model was constructed by intra-articular injection of sodium iodoacetate, and the rats were intervened with different doses of Hippocampus decoction and celecoxib. The expression of relevant targets was detected through hematoxylin-eosin(HE) staining, enzyme-linked immunosorbent assay(ELISA), RT-qPCR, and Western blot to further validate the network pharmacology results. A total of 23 drug-like components of the Hippocampus were screened, and 128 common targets with KOA were identified, involving interleukin-17(IL-17) signaling pathway, transcription factor(FoxO) signaling pathway, tumor necrosis factor(TNF) signaling pathway. Molecular docking results showed that the screened core chemical components exhibited good affinity with key targets. HE staining demonstrated that Hippocampus improved the morphology of the cartilage layer. ELISA confirmed that Hippocampus significantly reduced the levels of IL-6 and TNF-α in the serum of KOA rats. Western blot and RT-qPCR analysis showed that Hippocampus significantly reduced the expression of IL-6, TNF-α, matrix metalloproteinase(MMP) 13, IL-17A, nuclear factor κB activator 1(ACT1), tumor necrosis factor receptor-associated factor 6(TRAF6) and nuclear factor κB(NF-κB) in cartilage tissue. The results suggest that Hippocampus can alleviate the degree of joint damage in the KOA rat model induced by sodium iodoacetate. The mechanism of action is related to the inhibition of the IL-17 signaling pathway, reduction of inflammation, and inhibition of extracellular matrix(ECM) degradation.
Animals ; Molecular Docking Simulation ; Rats ; Drugs, Chinese Herbal/administration & dosage* ; Network Pharmacology ; Male ; Osteoarthritis, Knee/metabolism* ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; Humans ; Interleukin-17/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Disease Models, Animal ; Hippocampus/chemistry*

The structure of intestinal tissue is complex. In vitro simulation of intestinal structure and function is important for studying intestinal development and diseases. Recently, organoids have been successfully constructed and they have come to play an important role in biomedical research. Organoids are miniaturized three-dimensional (3D) organs, derived from stem cells, which mimic the structure, cell types, and physiological functions of an organ, making them robust models for biomedical research. Intestinal organoids are 3D micro-organs derived from intestinal stem cells or pluripotent stem cells that can successfully simulate the complex structure and function of the intestine, thereby providing a valuable platform for intestinal development and disease research. In this article, we review the latest progress in the construction and application of intestinal organoids.
Organoids/cytology* ; Intestines/physiology* ; Humans ; Animals ; Pluripotent Stem Cells

Objective To explore the effect of modified Shaoyao Gancao Decoction combined with acupuncture on Oswestry Disability Index(ODI)of patients after surgery for osteoporotic vertebral compression fracture(OVCF).Methods A total of 94 patients with OVCF of liver-kidney deficiency and yin-blood deficiency type were randomly divided into an observation group and a control group,with 47 cases in each group.Both groups were treated with surgical treatment by percutaneous balloon kyphoplasty or percutaneous vertebroplasty.After the operation,the control group was given acupuncture therapy,and the observation group was treated with modified Shaoyao Gancao Decoction combined with acupuncture therapy.Both groups were treated for 12 weeks(3 months in total).The changes of pain visual analogue scale(VAS)score,ODI score,bone mineral density(BMD)of lumbar vertebrae 2-4(L2-4),femoral neck,Wards triangle and total hip,and serum levels of bone metabolism indicators of type I collagen C-terminal peptide(CTX-1),bone alkaline phosphatase(BALP)and blood calcium in the two groups at different observation time points after operation were observed.After treatment,the clinical efficacy of the two groups was evaluated.Results(1)After 3 months of treatment,the total effective rate of the observation group was 100.00%(47/47),and that of the control group was 87.23%(41/47).The intergroup comparison(tested by Fisher's exact test)showed that the clinical efficacy of the observation group was significantly superior to that of the control group(P＜0.01).(2)On the seventh day,first month and third month after operation,the pain VAS score and thoracolumbar function of ODI scores of the two groups were significantly lower than those at the previous observation time point(P＜0.05),and the decrease of VAS score and thoracolumbar ODI score in the observation group was significantly superior to that in the control group on the seventh day,first month and third month after operation(P＜0.05 or P＜0.01).(3)After treatment(one month after operation),the BMD values of L2-4,femoral neck,Wards triangle and total hip in the two groups were significantly higher than those before treatment(P＜0.05),and the increase of BMD values in the observation group was significantly superior to that in the control group(P＜0.01).(4)After treatment(one month after operation),the serum levels of bone metabolism indicators of CTX-1,BALP and calcium of the two groups were significantly lower than those before treatment(P＜0.05),and the decrease of serum CTX-1,BALP and calcium levels in the observation group was significantly superior to that in the control group(P＜0.01).Conclusion Modified Shaoyao Gancao Decoction combined with acupuncture exerts certain effect for the treatment of OVCF patients with liver-kidney deficiency and yin-blood deficiency type.The combined therapy can significantly relieve postoperative pain symptoms,improve BMD and bone metabolism,promote the recovery of thoracolumbar function,and effectively enhance the overall efficacy.

Objective To investigate the benefits of using a stapler tractor in the treatment of segmental bronchus during lung segmentectomy through detailed video replay analysis of surgical procedures. Methods We collected data from patients who underwent segmentectomy performed by the same surgical team in the Department of Thoracic Surgery, the First Affiliated Hospital of Nanjing Medical University, from November 2020 to August 2023. After excluding data that lacked analysis parameters, the remaining patients were divided into four groups based on the methods used for dissociating segmental bronchus: a stapler tractor group (group A), a stapler with bronchial stretching group (group B), a stapler only group (group C), and a silk ligature group (group D). Then, we compared baseline data and videotaped surgical details across all groups. Surgical details included the success rate of one-time segmental bronchus dissociation and severance, the time taken for successful one-time dissociation and severance of the segmental bronchus, the incidence of bleeding during bronchus dissociation, the conversion rate to thoracotomy during surgery, and surgical outcomes such as total operative time, postoperative hospitalization days, postoperative thoracic drainage volume, and pulmonary air leakage rate. Results The study included 325 patients (203 in the group A, 62 in the group B, 29 in the group C, and 31 in the group D). There was no statistically significant difference in baseline data among the four groups. However, significant differences were found in terms of total operation time, postoperative hospitalization days, intraoperative blood loss, segmental bronchial stump length, postoperative air leakage rate, hemorrhage rate during segmental bronchial dissociation, and conversion to thoracotomy rate among the four groups (P<0.05). Conclusion Using a stapler tractor for dissociating segmental bronchus in lung segmentectomy results in shorter operative time, less risk of intraoperative bleeding, and less surgical complications. This study provides valuable evaluation methodologies through the analysis of video replay surgical details, contributing to the improvement of lung segmentectomy quality.

Objective To propose a method for abdominal multi-organ segmentation assisted by multi-phase CT synthesis.Methods Multi-phase CT synthesis for synthesizing high-quality CT images was used to increase the information details for image segmentation.A transformer block was introduced to help to capture long-range semantic information in cooperation with perceptual loss to minimize the differences between the real image and synthesized image.Results The model was trained using multi-phase CT dataset of 526 total cases from Nanfang Hospital.The mean maximum absolute error(MAE)of the synthesized non-contrast CT,venous phase contrast-enhanced CT(CECT),and delay phase CECT images from arterial phase CECT was 19.192±3.381,20.140±2.676 and 22.538±2.874,respectively,which were better than those of images synthesized using other methods.Validation of the multi-phase CT synthesis-assisted abdominal multi-organ segmentation method showed an average dice coefficient of 0.847 for the internal validation set and 0.823 for the external validation set.Conclusion The propose method is capable of synthesizing high-quality multi-phase CT images to effectively reduce the errors in registration between different phase CT images and improve the performance for segmentation of 13 abdominal organs.

A quartz crystal microbalance(QCM)-systematic evolution of ligands by the exponential en-richment(SELEX)technique was developed to screen out aptamers with high affinity for arsenic(Ⅲ).A random single strand DNA library was designed and fixed on the mercaptoethylamine-modified crystal plate with arsenic(Ⅲ)as the target,and the free aptamer was captured in the solution,and the QCM-SELEX screening method was constructed.After 6 rounds of screening,the secondary library was se-quenced with high throughput method,and the 6S1 dissociation coefficient Kd value was 0.36 μmol/L based on QCM resonance frequency.Using 6S1 as a probe,the QCM biosensor was constructed for the detection of arsenic(Ⅲ).The sensor has a good linear relationship in the range of 0.01 μmol/L～0.2μmol/L,and the detection limit of arsenic(Ⅲ)is 5.2 nmol/L(3σ),indicatinggood selectivity.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]