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La clorhidrorrea congénita es un trastorno genético infrecuente pero importante caracterizado por una alteración grave del balance hidroelectrolítico como resultado de un defecto en la absorción intestinal de cloruros. Los niños afectados presentan diarrea persistente, deshidratación y malnutrición; el control médico y del desarrollo son complejos. Mejorar la detección prenatal es esencial para facilitar la atención del paciente, las intervenciones tempranas y el asesoramiento genético informado. Sin embargo, a pesar de los avances de la medicina, la naturaleza compleja y la escasa frecuencia de esta entidad, constituyen un desafío para la detección prenatal. En este estudio, se reporta el caso de una embarazada donde los estudios por imágenes de resonancia magnética fetales identificaron en forma efectiva las características típicas de la clorhidrorrea congénita. Se proveen conocimientos sobre las complejidades del diagnóstico y se sugieren caminos para las estrategias de detección temprana de esta enfermedad.
Congenital chloride diarrhea (CCD) is a rare but significant genetic disorder characterized by severe electrolyte imbalances resulting from impaired intestinal chloride absorption. Affected children experience persistent diarrhea, dehydration, and malnutrition, complicating medical and developmental care. The enhancement of prenatal detection is crucial for improved patient management, early interventions, and informed genetic counseling. However, despite advancements in medicine, the complex nature and rarity of CCD make prenatal detection challenging. In this study, we report a fetal case where prenatal magnetic resonance imaging (MRI) effectively identified the distinctive characteristics of CCD, providing insights into the complexities of diagnosis and suggesting avenues for enhanced early detection strategies.
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Humans , Female , Pregnancy , Prenatal Diagnosis/methods , Diarrhea/congenital , Metabolism, Inborn Errors/diagnosis , Metabolism, Inborn Errors/genetics , Diarrhea/etiology , Genetic CounselingABSTRACT
Ulcerative colitis (UC) is a difficult intestinal disease characterized by inflammation, and its mechanism is complex and diverse. Angiopoietin-like protein 2 (ANGPT2) plays an important regulatory role in inflammatory diseases. However, the role of ANGPT2 in UC has not been reported so far. After exploring the expression level of ANGPT2 in serum of UC patients, the reaction mechanism of ANGPT2 was investigated in dextran sodium sulfate (DSS)-induced UC mice. After ANGPT2 expression was suppressed, the clinical symptoms and pathological changes of UC mice were detected. Colonic infiltration, oxidative stress, and colonic mucosal barrier in UC mice were evaluated utilizing immunohistochemistry, immunofluorescence, and related kits. Finally, western blot was applied for the estimation of mTOR signaling pathway and NLRP3 inflammasome-related proteins. ANGPT2 silencing improved clinical symptoms and pathological changes, alleviated colonic inflammatory infiltration and oxidative stress, and maintained the colonic mucosal barrier in DSS-induced UC mice. The regulatory effect of ANGPT2 on UC disease might occur by regulating the mTOR signaling pathway and thus affecting autophagy-mediated NLRP3 inflammasome inactivation. ANGPT2 silencing alleviated UC by regulating autophagy-mediated NLRP3 inflammasome inactivation via the mTOR signaling pathway.
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Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, with approximately 600,000 new cases each year. A small number of HNSCCs are caused by human papillomavirus (HPV) infection. Frizzled related protein (FRZB) has been reported in many inflammatory diseases and cancers, but it is yet unclear how FRZB affects HNSCC, as well as its role and underlying mechanism. TIMER2 database was utilized to evaluate FRZB expression in cancer tissues, and FRZB expression in HNSCC tissues was confirmed by samples obtained from Gene Expression Omnibus. To identify whether FRZB could be used as a prognostic predictor, we performed univariate and multivariate Cox regression analyses. FRZB co-expression profile was explored using the LinkedOmics database, then Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses were performed for these FRZB-related genes in HNSCC samples. Lasso regression analysis was subsequently used to screen for prognostic variables, and we determined the infiltration of immune cells in HNSCC patients to clarify the influence of FRZB on tumor immune microenvironment. At last, we assessed the association between FRZB expression and immune checkpoint gene, and compared the sensitivity of common chemotherapeutic agents. In this study, we found that FRZB was dysregulated in HNSCC tumor tissues and had a relationship with clinical parameters. The reliability and independence of FRZB as a factor in determining a patient's prognosis for HNSCC was also established. Additional investigation revealed that FRZB was linked to common immune checkpoint genes and may be implicated in immune infiltration.
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ABSTRACT Background: Triple-negative breast cancer (TNBC) is a subtype of breast cancer (BC) that lacks receptors for targeted therapy. Deeper insight into the molecular mechanisms regulating TNBC metastasis is urgently needed. The epithelial-mesenchymal transition process facilitates the metastasis of neighboring epithelial tumor cells. Protein kinase, membrane-associated tyrosine/threonine 1 (PKMYT1), a member of the Wee family of protein kinases, is upregulated in BC, and its high expression predicts poor prognosis in BC patients. Notch signaling activation is a pathognomonic feature of TNBC. PKMYT1 has been found to induce EMT in non-small cell lung cancer by activating Notch signaling. However, whether PKMYT1 exerts effects on TNBC progression by regulating Notch signaling remains unknown. Objectives: The objective of this study was to investigate whether PKMYT1 exerts effects on TNBC progression by regulating Notch signaling. Methods: Fifty cases of surgically resected BC samples (tumor and adjacent non-tumor tissue samples) were collected from patients diagnosed with BC. We measured the expression of PKMYT1 in clinical samples with real-time quantitative polymerase chain reaction (RT-qPCR). For in vitro analysis, RT-qPCR and Western blotting were conducted to evaluate PKMYT1 expression in TNBC cells. Then, the viability, migration, and invasion of TNBC cells were detected by cell counting kit-8 assays, wound healing assays, and Transwell assays. The EMT event was examined by evaluating the levels of EMT-associated proteins. For in vivo analysis, xenograft models in nude mice were established to explore PKMYT1 roles. E-cadherin and Ki67 expression in xenograft models were estimated by immunohistochemistry staining. Hematoxylin and eosin staining was performed to assess tumor metastasis. The underlying mechanisms by which PKMYT1 affected the malignant phenotypes of TNBC cells were explored by Western blotting measuring the pathway-associated proteins. Results: PKMYT1 was upregulated in BC tissues and cells, and its knockdown prevented cell proliferation, migration, invasion, and EMT event in TNBC. Mechanistically, Notch signaling was inactivated by PKMYT1 depletion, and Notch activation abolished the PKMYT1 silencing-induced inhibition in the malignant phenotypes of TNBC cells. For in vivo analysis, PKMYT1 knockdown inhibited tumorigenesis and metastasis of TNBC. Conclusion: PKMYT1 promotes EMT, proliferation, migration, and invasion of TNBC cells and facilitates tumor growth and metastasis by activating Notch signaling.
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ABSTRACT Purpose: This study aims to evaluate the safety and efficacy of ultrasound-guided balloon dilation compared to non-balloon dilation for percutaneous nephrolithotomy (PCNL). Materials and methods: A systematic review and meta-analysis were conducted by searching PubMed, EMBASE, and the Cochrane Library. Results were filtered using predefined inclusion and exclusion criteria as described and meta-analysis was performed using Review Manager 5.4 software. Results: A total of six studies involving 1189 patients who underwent PCNL were included. The meta-analysis results demonstrated that compared to non-balloon dilation, balloon dilation was associated with reduced haemoglobin drop [mean difference (MD) = -0.26, 95% CI = -0.40 ~ -0.12, P = 0.0002], decreased transfusion rate [odds ratio (OR) = 0.47, 95% CI = 0.24 ~ 0.92, P = 0.03], shorter tract establishment time (MD = -1.30, 95% CI = -1.87 ~ -0.72, P < 0.0001) and shorter operation time (MD = -5.23, 95% CI = -10.19 ~ -0.27, P = 0.04). Conclusions: Overall, ultrasound-guided balloon dilatation offered several advantages in PCNL procedures. It facilitated faster access establishment, as evidenced by shorter access creation time. Additionally, it reduced the risk of kidney injury by minimizing postoperative haemoglobin drop and decreasing the need for transfusions. Moreover, it enhanced the efficiency of surgery by reducing the operation time. However, it is important to note that the quality of some included studies was subpar, as they did not adequately control for confounding factors that may affect the outcomes. Therefore, further research is necessary to validate and strengthen these findings.
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ABSTRACT Objective: To evaluate objective treatment efficacy and safety, and subjective patient-reported outcomes in patients with complex ureteral strictures (US) undergoing minimally invasive lingual mucosal graft ureteroplasty (LMGU). Materials and Methods: We prospectively enrolled patients underwent robotic or laparoscopic LMGU between May 2020 and July 2022. Clinical success was defined as symptom-free and no radiographic evidence of re-obstruction. Patient-reported outcomes, including health-related quality of life (HRQoL), mental health status and oral health-related quality of life (OHRQoL), were longitudinally evaluated before surgery, 6 and 12 months postoperatively. Results: Overall, 41 consecutive patients were included. All procedures were performed successfully with 32 patients in robotic approach and 9 in laparoscopic. Forty (97.56%) patients achieved clinical success during the median follow-up of 29 (range 15-41) months. Although patients with complex US experienced poor baseline HRQoL, there was a remarkable improvement following LMGU. Specifically, the 6-month and 12-month postoperative scores were significantly improved compared to the baseline (p < 0.05) in most domains. Twenty-eight (68.3%) and 31 (75.6%) patients had anxiety and depression symptoms before surgery, respectively. However, no significant decrease in the incidence of these symptoms was observed postoperatively. Moreover, there was no significant deterioration of OHRQoL at 6 months and 12 months postoperatively when compared to the baseline. Conclusions: LMGU is a safe and efficient procedure for complex ureteral reconstruction that significantly improves patient-reported HRQoL without compromising OHRQoL. Assessing patients' quality of life enables us to monitor postoperative recovery and progress, which should be considered as one of the criteria for surgical success.
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Objective To systematically evaluate the diversity of oral flora in patients with pancreatic cancer. Methods A cross-sectional study was conducted, focusing on the oral flora diversity profiles of patients with pancreatic cancer. The studies were retrieved from PubMed, Web of science, EMbase, The Cochrane Library, CBM, CNKI, Wanfang, and VIP databases, and the search period was from the establishment of the database to July 15, 2023. According to the inclusion and exclusion criteria, two researchers screened intensive review literature, extracted data and information, and carried out Meta-analysis using qualitative systematic review and Review Manager 5.4. Results Seven cross-sectional studies were reviewed, including 187 patients with pancreatic cancer and 440 healthy controls. The results of meta-analysis showed that the oral microbiota diversity Simpson index of patients with pancreatic cancer was reduced compared with that of healthy controls. Qualitative analysis showed that the relative abundance of Firmicute, Prevotella, Roseburia, and Streptococcus in patients with pancreatic cancer was higher than that in healthy people. The relative abundance of Proteobacteria, Neisseria, Haemophilus, porphyromonas, and Haemophilus parainfluenza in patients with pancreatic cancer was lower than that in healthy people. Conclusion Patients with pancreatic cancer have distinct oral flora, which has high relative abundance of Firmicutes, Prevotella etc. and low relative abundance of Proteobacteria, Neisseria, etc.
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Objective@#To explore the pattern of change of axial length/curvatrue radius ratio (AL/CR) and associated factors in primary and secondary school students in Yunnan, so as to provide scientific basis and prospective guidance for early myopia intervention and control.@*Methods@#A total of 685 students from grades 2 to 3 and grade 7 in 2 cities/counties in Yunnan Province were selected by multi stage stratified random cluster sampling method in 2020. All the participants were followed up twice with questionnaire of myopia related factors, uncorrected distance visual acuity, and refractive parameter measurement from October,2021 and March,2023,respectivelty. The distribution and change of AL/CR in different classes and groups were analyzed, and the influencing factos of AL/CR cumulative progression were explored using generalized linear model.@*Results@#AL/CR ratio in primary school students was (2.95±0.09) at baseline, increased to (2.99±0.11) at the first follow up and (3.04±0.12) at the second follow up. AL/CR ratio in middle school students(3.08±0.13) at baseline, increased to (3.12±0.15) at the first follow up and (3.15±0.14) at the second follow up. The generalized linear model showed that after controlling for environmental factors, ethnicity ( β =-0.017) , cumulative progression of the SE ( β =-0.027) influenced the changes of AL/CR ratio among the primary school students, whereas the changes of AL/CR ratio were associated with baseline AL ( β =-0.005), baseline corneal curvatrue radius ( β =0.032) and cumulative progression of SE( β =-0.035) among middle school students ( P <0.05).@*Conclusions@#The AL/CR ratio of primary and secondary school students in Yunnan can be used to judge different refractive status types, but its variation is not only related to SE progression, but also affected by different ethnic groups and baseline ocular biological parameters. so the value of AL/CR application in assessing the progression of myopia needs to be further confirmed.
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AIM: To evaluate the performance of three distinct large language models(LLM), including GPT-3.5, GPT-4, and PaLM2, in responding to queries within the field of ophthalmology, and to compare their performance with three different levels of medical professionals: medical undergraduates, master of medicine, and attending physicians.METHODS: A total of 100 ophthalmic multiple-choice tests, which covered ophthalmic basic knowledge, clinical knowledge, ophthalmic examination and diagnostic methods, and treatment for ocular disease, were conducted on three different kinds of LLM and three different levels of medical professionals(9 undergraduates, 6 postgraduates and 3 attending physicians), respectively. The performance of LLM was comprehensively evaluated from the aspects of mean scores, consistency and confidence of response, and it was compared with human.RESULTS: Notably, each LLM surpassed the average performance of undergraduate medical students(GPT-4:56, GPT-3.5:42, PaLM2:47, undergraduate students:40). Specifically, performance of GPT-3.5 and PaLM2 was slightly lower than those of master's students(51), while GPT-4 exhibited a performance comparable to attending physicians(62). Furthermore, GPT-4 showed significantly higher response consistency and self-confidence compared with GPT-3.5 and PaLM2.CONCLUSION: LLM represented by GPT-4 performs well in the field of ophthalmology, and the LLM model can provide clinical decision-making and teaching aids for clinicians and medical education.
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Diseases of ocular fundus are the leading causes of severe vision impairment or even blindness in patients worldwide, and the medical treatments are seriously limited by the difficulty of therapeutic drugs entering the fundus due to the various physiological barriers. Nano-drug delivery systems, with their nanoscale size and large surface area, can be loaded with therapeutic drugs of different physicochemical properties and modified with various surface active substances, which can not only improve the solubility and penetration of the drugs, but also protect biologic drugs from degradation and improve the biological safety and bioavailability, as well as deliver therapeutic drugs to specific ocular targets. All of these make the therapeutic potential enormous. Currently, more and more studies have been carried out to take advantage of nanomaterials for the treatment of different fundus diseases, including neurodegenerative diseases, fundus neovascularization, endophthalmitis and fundus tumors. This review analyzes the challenges and barriers faced by different routes of drug administration in the treatment of fundus diseases, the physicochemical properties of common nano-drug delivery systems that have been studied in related fields, and further summarizes the progress, advantages, limitations, and future directions of the application of various nano-drug delivery systems for the treatment of ocular fundus diseases in recent years.
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AIM: To explore the relationship of miR-126 and miR-325 in serum and vitreous with the severity of proliferative vitreoretinopathy(PVR).METHODS: A total of 100 cases(100 eyes)with PVR who were treated in our hospital from October 2019 to October 2022 were selected and retrospectively studied. They were divided into a mild group(42 eyes)and a severe group(58 eyes)according to the degree of retinopathy, and another 30 cases(30 eyes)that underwent vitrectomy without retinopathy due to eye trauma in our hospital during the same period were selected as the control group. Fluorescence quantitative PCR was used to detect the expression levels of miR-126 and miR-325 in serum and vitreous; ELISA was used to detect the levels of transforming growth factor β(TGF-β), platelet-derived growth factor(PDGF), vascular endothelial growth factor(VEGF), and tumor necrosis factor α(TNF-α)in serum and vitreous; and Pearson's method was used to analyze the correlation between the serum and vitreous levels of miR-126 and miR-325 correlated with the levels of TGF-β, PDGF, VEGF, and TNF-α; Logistic multifactorial analysis was used to analyze the influencing factors for the occurrence of severe PVR.RESULTS: Compared with the control group, miR-126 levels in serum and vitreous of PVR patients were decreased and lower in the severe PVR group than in the mild PVR group(both P<0.05); miR-325 levels were increased and higher in the severe PVR group than in the mild PVR group(both P<0.05). TGF-β, PDGF, VEGF, and TNF-α levels in serum and vitreous were increased in the severe PVR group compared to the mild PVR group(all P<0.05). The miR-126 levels in serum and vitreous of patients with PVR were negatively correlated with miR-325, TGF-β, VEGF, TNF-α, and PDGF levels(all P<0.05), and miR-325 was positively correlated with TGF-β, VEGF, TNF-α, and PDGF levels(all P<0.05). Logistic regression analysis showed that miR-325, TGF-β, PDGF, and TNF-α were all independent risk factors for the development of severe PVR in serum and vitreous, and miR-126 was an independent protective factor for the development of severe PVR in serum and vitreous(P<0.05).CONCLUSION: With the aggravation of PVR, miR-126 expression in serum and vitreous decreased while miR-325 expression increased and correlated with TGF-β, TNF-α, VEGF, and PDGF.
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OBJECTIVE To investigate the improvement effect and potential mechanism of “Layers adjusting external application” paste on synovial fibrosis （SF） in rats with knee osteoarthritis （KOA）. METHODS Male SD rats were randomly divided into sham operation group， KOA group and Layers adjusting external application group， with 8 rats in each group. KOA model was induced by the anterior cruciate ligament disruption method in KOA group and Layers adjusting external application group. Fourteen days after modeling， the Layers adjusting external application group was given “Layers adjusting external application” paste [Sanse powder （8 g for every 100 cm2）， Compound sanhuang ointment （5 g for every 100 cm2）] on the knee joint， 8 h every day， for 28 d in total. After the last administration， the degree of synovitis and fibrosis in rats was observed， and Krenn scoring was performed in each group. The expressions of collagen Ⅰ， high mobility group protein B1 （HMGB1） and phosphorylated nuclear factor-κB p65 （p-NF-κB p65） were detected in the synovial membrane； the contents of interleukin-1β （IL- 1β）， IL-6 and tumor necrosis factor-α （TNF-α） in serum as well as the expressions of fibrosis-related and HMGB1/Toll-like receptor 4 （TLR4）/NF-κB signaling pathway-related proteins and mRNA were detected in synovial tissue. RESULTS Compared with the sham operation group， the synovial lining cells in the KOA group showed significant proliferation and disordered arrangement， the inflammatory cell infiltration and collagen fiber deposition were obvious； the positive expressing cells of collagen Ⅰ， HMGB1 and p-NF-κB p65 were increased significantly； the contents of IL-1β， IL-6 and TNF-α in serum， the expressions of fibrosis-related protein （transforming growth factor-β， collagen Ⅰ， tissue inhibitor of metalloproteinase 1， α-smooth muscle actin） and their mRNA as well as theexpressions of HMGB1， TLR4 protein and their mRNA， the expressions of p-NF-κB p65 protein and NF-κB p65 mRNA were all increased significantly in synovial tissues of rats （P＜0.01）. Compared with the KOA group， the pathological changes in the synovial tissue of rats in Layers adjusting external application group were significantly improved， and the above quantitative indicators were significantly reversed （P＜0.05 or P＜0.01）. CONCLUSIONS “Layers adjusting external application” paste could significantly improve SF in KOA rats， the mechanism of which may be associated with the inhibition of the activation of HMGB1/ TLR4/NF-κB signaling pathway.
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The development and application of processing technology is closely related to the quality of Chinese medicine. Currently， Chinese medicine processing is still in the mechanization stage with limited processing equipment， low levels of automation and intelligence. As a result， the imprecise control of parameters during processing leads to unstable quality of Chinese herbal pieces. However， with the arrival of the big data era and the continuous development of "Internet+"， Chinese medicine processing technology and equipment have been continuously improved and updated， and gradually shifted to the development direction of automation and intelligence. The linkage production technology of Chinese herbal pieces optimizes the separate processing equipment coupling into the production line for continuous manufacture of Chinese herbal pieces， intending to improve production efficiency. The large-scale industrialized production of Chinese herbal pieces tends towards digital technology of processing experience and online inspection technology based on machine vision， electronic nose， and electronic tongue. These technologies are crucial prerequisites for standardizing the parameters of Chinese medicine processing. And further by docking the processing process and equipment with the internet， realizing the intelligent control of the production process is an important process for the transformation and upgrading of Chinese herbal piece industry in the future. In this paper， we summarized the development characteristics of different stages of Chinese medicine processing technology， combed application and development of processing theory， the evolution of processing equipment， and problems in the current industrial development stage of Chinese medicine processing， in order to provide ideas and methods for achieving digital and intelligent innovation of processing technology as well as high-efficient and high-quality production of Chinese herbal pieces.
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Diabetic peripheral neuropathy（DPN） is a neurodegenerative disease of diabetes mellitus involving peripheral nervous system damage， which is characterized by axonal degenerative necrosis， Schwann cell apoptosis and demyelination of nerve myelin sheath as the main pathological features， this disease is highly prevalent and is a major cause of disability in diabetic patients. Currently， the pathogenesis of DPN may be related to oxidative stress， inflammatory response， metabolic abnormality， and microcirculation disorder. The treatment of DPN in modern medicine mainly starts from controlling blood glucose， nourishing nerves and improving microcirculation， which can only alleviate the clinical symptoms of patients， and it is difficult to fundamentally improve the pathological damage of peripheral nerves. Mitochondrial quality control refers to the physiological mechanisms that can maintain the morphology and functional homeostasis of mitochondria， including mitochondrial biogenesis， mitochondrial dynamics， mitochondrial oxidative stress and mitochondrial autophagy， and abnormal changes of which may cause damage to peripheral nerves. After reviewing the literature， it was found that traditional Chinese medicine（TCM） can improve the low level of mitochondrial biogenesis in DPN， maintain the balance of mitochondrial dynamics， inhibit mitochondrial oxidative stress and mitochondrial autophagy， and delay apoptosis of Schwann cells and neural axon damage， which has obvious effects on the treatment of DPN. With the deepening of research， mitochondrial quality control may become one of the potential targets for the research of new anti-DPN drugs， therefore， this paper summarized the research progress of TCM in treating DPN based on four aspects of mitochondrial quality control， with the aim of providing a theoretical research basis for the discovery of new drugs.
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ObjectiveTo objectively evaluate the clinical efficacy of multiple therapies of traditional Chinese medicine （TCM） in low-prognosis patients who received antagonist protocol for in vitro fertilization and embryo transfer （IVF-ET） again. MethodA total of 128 patients with kidney Yin deficiency， liver depression， and blood stasis who planned to receive antagonist protocol for IVF-ET in the West China Second Hospital of Sichuan University were enrolled and assigned into two groups by random number table method. The observation group （64 casces） was treated by oral administration of Chinese medicine decoction + enema of kidney-tonifying and blood-activating method + auricular point sticking + oral administration of dehydroepiandrosterone （DHEA）， while the control group （64 casces） was treated by only oral administration of DHEA. After treatment for three menstrual cycles， both groups received the antagonist protocol for IVF-ET. The TCM syndrome scores， basic sex hormone levels， antral follicle count （AFC）， the usage of gonadotropin （Gn）， endometrial receptivity indicators， embryo quality indicators， and pregnancy outcomes were compared between the two groups. ResultAfter treatment， the observation group showed decreased follicle-stimulating hormone （FSH）/luteinizing hormone （LH） ratio， lowered level of estradiol （E2）， increased AFC， decreased amount and days of Gn usage， improved endometrial receptivity indicators （endometrial thickness on trigger and ET days， proportion of endometrial type A in endometrial types and the level of E2 on trigger day） and embryo quality indicators （the rates of mature follicles， fertilization， normal fertilization， and premium embryos）， and decreased TCM syndrome scores （P<0.05， P<0.01）. Moreover， the observation group had lower FSH/LH ratio， E2 level， and amount of Gn usage， higher AFC， poorer endometrial receptivity and embryo quality indicators， and lower TCM syndrome scores than the control group after treatment （P<0.05， P<0.01）. In addition， except for 3 cases of natural pregnancy， the observation group outperformed the control group in terms of improving the clinical pregnancy rates during initiation cycle and transplantation cycle and clinical pregnancy rate and decreasing biochemical pregnancy rate and early abortion rate （P<0.05）. ConclusionCombined therapies of TCM can alleviate the clinical symptoms， reduce TCM syndrome scores， reduce the Gn usage amount， improve the number and quality of embryos and endometrial receptivity， and coordinate the synchronous development of endometrium and embryo. In this way， they can increase the clinical pregnancy rate and reduce biochemical pregnancy rate and early abortion rate in the low prognosis patients with kidney yin deficiency， liver depression， and blood stasis who are undergoing IVF-ET again.
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ObjectiveTo observe the effect of Tongxie Yaofang on the function of tumor-related natural killer （NK） cells under chronic stress and explore the possible molecular mechanism. MethodFifty SPF-grade BABL/C male mice were randomized into normal， model， and low-， medium-， and high-dose （6.825， 13.65， and 27.3 g·kg-1， respectively） Tongxie Yaofang groups， with 10 mice in each group. Other groups except the blank group were subjected to 7 days of chronic restraint stress， and then forced swimming and tail suspension tests were carried out to evaluate the modeling performance. After the successful modeling， rats in Tongxie Yaofang groups were administrated with low-， medium-， and high-doses of Tongxie Yaofang by gavage， while those in the other groups were administrated with normal saline by gavage. After 14 days， each group of mice was inoculated with subcutaneous colon cancer to establish the model of colon cancer under chronic stress. The pathological changes of the tumor tissue in each group of mice were observed using hematoxylin-eosin （HE） staining. The content of CD49b-positive cells in the peripheral blood and tumor tissue of mice was measured by flow cytometry. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the content of molecules associated with NK cell activation in the peripheral blood. Western blot was employed to determine the protein levels of major histocompatibility complex class Ⅰ polypeptide-related sequences A and B （MICA+MICB） and UL-16-binding protein 1 （ULBP1） in the tumor tissue. ResultCompared with the normal group， the model group showed a decrease in 5-hydroxytryptamine （5-HT） content and an increase in corticosterone （CORT） content in the serum （P<0.05）. Compared with the model group， Tongxie Yaofang increased the 5-HT content and decreased the CORT content （P<0.05， P<0.01）. Compared with the normal group， the modeling increased the tumor volume and weight （P<0.05）， while Tongxie Yaofang inhibited such increases with no statistical significance. The tumor cells in the model group presented neat arrangement， irregular shape， uneven size， obvious atypia， common nuclear division， and small necrotic area， and blood vessels were abundant surrounding the tumor cells. Compared with the model group， Tongxie Yaofang groups showed sparse arrangement of tumor cells， different degrees of patchy necrosis areas in the tumor， and karyorrhexis， dissolution， and nuclear debris in the necrotic part. Compared with the normal group， the model group showed reduced CD49b-positive cells in the peripheral blood and tumor tissue （P<0.01）. Compared with the model group， Tongxie Yaofang increased CD49b-positive cells （medium dose P<0.01， high dose P<0.05， P<0.01）. Compared with the normal group， the modeling lowered the serum levels of granzymes-B （Gzms-B）， perforin （PF）， interferon （IFN）-γ， and tumor necrosis factor （TNF）-α （P<0.05， P<0.01）. Compared with the model group， low-dose Tongxie Yaofang elevated the serum levels of PF， Gzms-B， and TNF-α （P<0.05， P<0.01）， and medium-dose Tongxie Yaofang elevated the serum levels of Gzms-B， PF， IFN-γ， and TNF-α （P<0.05， P<0.01）. In addition， high-dose Tongxie Yaofang elevated the serum levels of PF， IFN-γ， and TNF-α （P<0.01）. Compared with the normal group， the model group presented down-regulated protein level of ULBP1 （P<0.05）. Compared with the model group， low-， medium-， and high-dose Tongxie Yaofang up-regulated the protein level of ULBP1 （P<0.05， P<0.01）， and medium- and high-dose Tongxie Yaofang up-regulated the protein level of MICA+MICB （P<0.05， P<0.01）. ConclusionTongxie Yaofang may promote NK cell activation by up-regulating the expression of MICA+MICB and ULBP1， thereby delaying the progression of colon cancer under chronic stress.
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ObjectiveBased on the quality evaluation experience of "it is better to have a fragrant and strong aroma" summarized by materia medica of past dynasties， the chemical components of Sojae Semen Nigrum（SSN） and Sojae Semen Praeparatum（SSP） were systematically compared and analyzed， and the main fermentation products in different fermentation time were quantitatively analyzed， so as to clarify the transformation law of internal components in the processing process and provide scientific basis for the modern quality control of SSP. MethodUltra performance liquid chromatography-quadrupole tandem time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was used for the structural identification of the chemical constituents of SSN and SSP， and with the aid of Progenesis QI v2.3 software， the negative ion mode was employed for principal component analysis（PCA） pattern recognition， and the data were analyzed with the aid of orthogonal partial least squares-discriminant analysis（OPLS-DA） for two-dimensional data to obtain S-plot， and components with |P|>0.1 were selected as the differential constituents. The contents of isoflavonoids in SSP during fermentation was determined by UPLC， and the samples were taken every 8 h in the pre-fermentation period and every 2 d in the post-fermentation period， and the dynamic changes of isoflavonoid contents in different fermentation stages were analyzed. The contents of amino acids and nucleosides in SSP and SSN from different fermentation stages were quantitatively analyzed by phenyl isothiocyanate（PITC） pre-column derivatization and high performance liquid chromatography（HPLC） gradient elution， and the contribution of flavor substances to the "delicious" taste of SSP was discussed by taste intensity value（TAV）. ResultA total of 19 kinds of differential components were screened out， mainly soybean saponins and isoflavones， and their contents decreased significantly or even disappeared after fermentation. In the pre-fermentation process of SSP， glycoside bond hydrolysis mainly occurred， and isoflavone glycosides in SSN were degraded and converted into the corresponding aglycones， the content of flavor substances such as amino acids increased gradually. In the post-fermentation process， protein degradation mainly occurred， after 8 d of post-fermentation， the content of isoflavones was basically stable， while the total content of amino acids increased by 8-40 times on average. Different amino acids form the special flavor of SSP， such as the TAV of glutamate is always ahead of other flavor substances， and sweet substances such as alanine and valine have made relatively great contributions to SSP. ConclusionBased on the law of constituent transformation， combined with the traditional evaluation index of "fragrant and strong"， it is difficult to control the fermentation degree of SSP by the existing standards in the 2020 edition of Chinese Pharmacopoeia. It is suggested that description of the characteristics of SSP be refined and changed to "fragrant， delicious and slightly sweet"， and at the same time， the post-fermentation index compounds such as glutamic acid， alanine and valine should be added as the quality control indicators of SSP， so as to standardize the production process and improve the quality of SSP.
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By reviewing the research history on quality comparison between wild and cultivated Chinese crude drugs， this paper systematically combed the relevant research reports since the 1950s， and summarized and analyzed the results of existing comparative studies， and found that the existing comparative research on the quality of wild and cultivated Chinese crude drugs were mainly focused on several aspects， including characteristics， microstructures， chemical compositions， pharmacodynamic effects， and genetic diversity. Among these， comparative studies of chemical compositions have been the dominant approach， with a particular emphasis on comparing the contents of index components. However， research on pharmacodynamic effects remained relatively limited. Due to various factors such as sample quantity， sample origin， growth period and cultivation methods， the differences in quality between wild and cultivated Chinese crude drugs vary significantly. In general， most wild Chinese crude drugs exhibited higher quality than cultivated products， with significant differences in their characteristics. The contents and proportions of some chemical components underwent noticeable changes， particularly with a marked increase in the proportion of primary metabolites after cultivation. The quality of cultivated Chinese crude drugs is closely related to the cultivation practices employed. Chinese crude drugs produced through wild nurturing， simulated wild planting， ecological cultivation， and other similar methods demonstrate quality levels comparable to those of wild Chinese crude drugs. Based on the analysis results， it is recommended to explicitly specify the cultivation practices and cultivation period of cultivated Chinese crude drugs in comparative studies of the quality between wild and cultivated Chinese crude drugs. Multiple technical approaches， including characteristics， microscopy， non-targeted metabolomics combined with quantitative analysis of differential components， and bioefficacy evaluation， should be employed to comprehensively assess the quality disparities between wild and cultivated Chinese crude drugs. Moreover， research efforts should be intensified to investigate the changes in pharmacodynamic effects resulting from differences in plant cell wall composition， primary metabolites， and secondary metabolites， in order to guide the production of high-quality Chinese crude drugs.
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ObjectiveTo investigate risk factors for postoperative sore throat in patients with double-lumen endotracheal intubation. MethodsThe data used in this post-hoc analysis were prospectively collected from a randomized， controlled trial. Age from 18 to 65 years old， ASAI-Ⅲ patients undergoing general anesthesia with a double-lumen endotracheal tube were enrolled. The perioperative data collected retrospectively were as follows： gender， age， smoking history， endotracheal tube diameter， duration of endotracheal tube， dose of Sufentanil， use of Flurbiprofen Axetil， cough after extubation， etc..Dynamometer was applied to assess extubation force. According to occurrence of postoperative sore throat， patients were divided into two groups： those who experienced sore throats and those who did not. Comparative analysis and multivariate logistic regression analysis were performed to screen the risk factors. ROC curve was used for predicting the predictive value of risk factors. ResultsAmong the 163 patients ， 74 （45.4%） had postoperative sore throat vs 89 （54.6%） not had. Multivariate logistic regression showed female ［OR95%CI=3.83（1.73， 8.50）， P=0.000 1］ and extubation force ［OR95%CI=1.78（1.45， 2.17）， P＜0.001］ were independent risk factors for postoperative sore throat. AUC value showed the extubation force was 0.773［95%CI（0.701， 0.846）， P＜0.001］. Youden index was 0.447， and the cut-off valve of extubation force was 13N. ConclusionFemale and extubation force were risk factors for sore throat in patients with double lumen endotracheal intubation.
ABSTRACT
ObjectiveTo investigate the role and possible mechanism of action of rhubarb decoction （RD） retention enema in improving inflammatory damage of brain tissue in a rat model of mild hepatic encephalopathy （MHE）. MethodsA total of 60 male Sprague-Dawley rats were divided into blank group （CON group with 6 rats） and chronic liver cirrhosis modeling group with 54 rats using the complete randomization method. After 12 weeks， 40 rats with successful modeling which were confirmed to meet the requirements for MHE model by the Morris water maze test were randomly divided into model group （MOD group）， lactulose group （LT group）， low-dose RD group （RD1 group）， middle-dose RD group （RD2 group）， and high-dose RD group （RD3 group）， with 8 rats in each group. The rats in the CON group and the MOD group were given retention enema with 2 mL of normal saline once a day； the rats in the LT group were given retention enema with 2 mL of lactulose at a dose of 22.5% once a day； the rats in the RD1， RD2， and RD3 groups were given retention enema with 2 mL RD at a dose of 2.5， 5.0， and 7.5 g/kg， respectively， once a day. After 10 days of treatment， the Morris water maze test was performed to analyze the spatial learning and memory abilities of rats. The rats were analyzed from the following aspects： behavioral status； the serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） and the level of blood ammonia； pathological changes of liver tissue and brain tissue； the mRNA and protein expression levels of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （AKT）， and mammalian target of rapamycin （mTOR） in brain tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the MOD group， the RD1， RD2， and RD3 groups had a significantly shorter escape latency （all P<0.01）， significant reductions in the levels of ALT， AST， IL-1β， IL-6， TNF-α， and blood ammonia （all P<0.05）， significant alleviation of the degeneration， necrosis， and inflammation of hepatocytes and brain cells， and significant reductions in the mRNA and protein expression levels of PI3K， AKT， and mTOR in brain tissue （all P<0.05）， and the RD3 group had a better treatment outcome than the RD1 and RD2 groups. ConclusionRetention enema with RD can improve cognitive function and inflammatory damage of brain tissue in MHE rats， possibly by regulating the PI3K/AKT/mTOR signaling pathway.