Diagnóstico prenatal de clorhidrorrea congénita: reporte de caso / Prenatal diagnosis of congenital chloride diarrhea: A case report

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.

Silencing ANGPT2 alleviates ulcerative colitis by regulating autophagy-mediated NLRP3 inflammasome inactivation via the mTOR signaling pathway

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.

FRZB: a potential prognostic marker for head and neck squamous cell carcinoma

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.

PKMYT1 Promotes Epithelial-Mesenchymal Transition Process in Triple-Negative Breast Cancer by Activating Notch Signaling

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.

Comparing Balloon Dilation to Non-Balloon Dilation for Access in Ultrasound-Guided Percutaneous Nephrolithotomy: A Systematic Review and Meta-Analysis

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.

Minimally invasive ureteroplasty with lingual mucosal graft for complex ureteral stricture: analysis of surgical and patient-reported outcomes

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.

Composition Spectrum of Oral Microbiota Diversity in Patients with Pancreatic Cancer: A Systematic Review / 肿瘤防治研究

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.

Effect of Acupuncture on Endometrial Blood Flow in Women Undergoing in vitro Fertilization Embryo Transfer: A Single Blind, Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To evaluate the effect of manual acupuncture on endometrial blood flow parameters by three-dimensional (3D) power Doppler ultrasound in women undergoing in vitro fertilization embryo transfer (IVF-ET).@*METHODS@#Seventy patients undergoing IVF-ET were equally randomized into traditional or sham acupuncture treatment group for totally 4 days (from the day of oocyte aspiration to the day of embryo transfer) of treatment by random envelope method at the Reproductive Medicine Center and Outpatient Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medicine College, Huazhong University of Science and Technology from January 2013 to December 2015. Patients in the traditional acupuncture group accepted traditional acupuncture methods with manual acupuncture, and Zhongji (CV3), Qihai (CV 6), Sanyinjiao (SP6), Taichong (LR 3), Tianshu (ST 25), Guilai (ST 29) and Zusanli (ST 36) were chosen. Patients at the sham acupuncture group accepted shallow acupuncture methods at 4 non-meridian points at each shoulder and upper arm. Outcome measures included endometrial ultrasonic indices such as vascularization index (VI), flow index (FI) and vascularization flow index (VFI), endometrial thickness and volume, subendometrial VI (sVI), subendometrial FI (sFI), subendometrial VFI (sVFI), implantation rate, clinical pregnancy rate, abortion rate, live birth rate and number of live births.@*RESULTS@#Finally, 34 patients in the traditional acupuncture group and 35 in the sham acupuncture group completed this trial. VI, FI and VFI of the traditional acupuncture group were significantly higher than those in the sham acupuncture group (P<0.05). No significant differences were found in endometrial thickness, endometrial volume, sVI, sFI, sVFI, implantation rate, clinical pregnancy rate, abortion rate, live birth rate and number of live births (P>0.05).@*CONCLUSIONS@#Manual acupuncture performed after oocyte aspiration and before transplantation improved the endometrial blood flow parameters VI, RI and VFI in women who underwent IVF-ET, instead of sVI, sFI and sVFI. Therefore, acupuncture might be beneficial in women undergoing IVF-ET by increasing endometrial blood flow and endometrial receptivity. (Registration No. ChiCTR2100053354).

Alterations in nasal microbiota of patients with amyotrophic lateral sclerosis / 中华医学杂志(英文版)

BACKGROUND@#Links between alterations in gut microbiota composition and amyotrophic lateral sclerosis (ALS) have previously been reported. This study aimed to examine the microbiota in the nasal cavity of ALS.@*METHODS@#Sixty-six ALS patients and 40 healthy caregivers who live in close proximity with patients were enrolled. High throughput metagenomic sequencing of the 16S ribosomal deoxyribonucleic acid (rDNA) gene V3-V4 region of nasal microbiota was used to characterize the alpha and beta diversity and relative abundance of bacterial taxa, predict function, and conduct correlation analysis between specific taxa and clinical features.@*RESULTS@#The nasal microbiome of ALS patients showed lower alpha diversity than that of corresponding healthy family members. Genera Gaiella , Sphingomonas , Polaribacter _1, Lachnospiraceae _NK4A136_group, Klebsiella , and Alistipes were differentially enriched in ALS patients compared to controls. Nasal microbiota composition in ALS patients significantly differed from that in healthy subjects (unweighted UniFrac P = 0.001), while Linear discriminant analysis Effect Size (LEfSe) analysis indicated that Bacteroidetes and Firmicutes dominated healthy nasal communities at the phylum level, whereas Actinobacteria was the predominant phylum and Thermoleophilia was the predominant class in ALS patients. Genus Faecalibacterium and Alistipes were positively correlated with ALS functional rating scale revised (ALSFRS-R; rs = 0.349, P = 0.020 and rs = 0.393, P = 0.008), while Prevotella -9 and Bacteroides operational taxonomic units (OTUs) were positively associated with lung function (FVC) in ALS patients ( rs = 0.304, P = 0.045, and rs = 0.300, P = 0.048, respectively). Prevotella -1 was positively correlated with white blood cell counts (WBC, rs = 0.347, P = 0.021), neutrophil percentage (Neu%, rs = 0.428, P = 0.004), and neutrophil-to-lymphocyte ratio (NLR, rs = 0.411, P = 0.006), but negatively correlated with lymphocyte percentage (Lym%, rs = -0.408, P = 0.006). In contrast, Streptococcus was negatively associated with Neu% ( rs = -0.445, P = 0.003) and NLR ( rs = -0.436, P = 0.003), while positively associated with Lym% ( rs = 0.437, P = 0.003). No significant differences in nasal microbiota richness and evenness were detected among the severe and mild ALS patients.@*CONCLUSIONS@#ALS is accompanied by altered nasal microbial community composition and diversity. The findings presented here highlight the need to understand how dysbiosis of nasal microbiota may contribute to the development of ALS.

Risk Factors for Postoperative Sore Throat in Patients with a Double-lumen Endotracheal Tube / 中山大学学报(医学科学版)

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.

Protective mechanism of rhubarb decoction against inflammatory damage of brain tissue in rats with mild hepatic encephalopathy： A study based on the PI3K/AKT/mTOR signaling pathway / 临床肝胆病杂志

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.

Value of serum creatinine-to-cystatin C ratio in assessing the prognosis of hepatitis B virus-related acute-on-chronic liver failure / 临床肝胆病杂志

ObjectiveTo investigate the clinical value of serum creatinine-to-cystatin C ratio （CCR） in evaluating the prognosis of hepatitis B virus-related acute-on-chronic liver failure （HBV-ACLF）. MethodsA retrospective analysis was performed for the clinical data of 130 patients with HBV-ACLF （treatment group） who were hospitalized in Department of Infectious Diseases， The First Affiliated Hospital of Soochow University， from January 2021 to November 2022. According to the treatment outcome， they were divided into survival group with 87 patients and death group with 43 patients； according to the presence or absence of infection， they were divided into infection group with 37 patients and non-infection group with 93 patients. A total of 30 individuals who underwent physical examination during the same period of time were enrolled as control group. Routine blood test results were collected on the day of admission， including white blood cell count， platelet count， neutrophil count， and lymphocyte count； serum creatinine， cystatin C， serum albumin （Alb）， and prothrombin time （PT） were observed on the day of admission and on days 5， 10， and 15 of hospitalization， and related indicators were calculated， including CCR， neutrophil-to-lymphocyte ratio （NLR）， platelet-to-lymphocyte ratio （PLR）， prognostic nutritional index （PNI）， CCR5 （CCR on day 5 after admission）， ΔCCR5 （CCR on day 5 after admission minus CCR on the day of admission）， CCR10 （CCR on day 10 after admission）， ΔCCR10 （CCR on day 10 after admission minus CCR on day 5 after admission）， CCR15 （CCR on day 15 after admission）， and ΔCCR15 （CCR on day 15 after admission minus CCR on day 10 after admission）. The above indicators were compared between the survival group and the death group and between the infection group and the non-infection group. The Mann-Whitney U test was used for comparison of continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between multiple groups. The univariate and multivariate logistic regression analyses were used to investigate the influencing factors for disease prognosis； the receiver operating characteristic （ROC） curve was used to assess the value of CCR in predicting HBV-ACLF death events， and the DeLong test was used for comparison of the area under the ROC curve （AUC）. ResultsThere were significant differences in CCR， NLR， PNI， PT， and Alb at baseline between the treatment group and the healthy control group （all P<0.001）， and there were significant differences in CCR， NLR， and PT between the survival group and the death group on the day of admission （all P<0.05）. Among the 130 patients with HBV-ACLF， there were 25 in the precancerous stage， 48 in the early stage， 32 in the intermediate stage， and 25 in the advanced stage， and there were significant differences in baseline CCR， PLR， and PT between the patients in different stages of HBV-ACLF （all P<0.05）. There were significant differences in ΔCCR5 and NLR between the infection group and the non-infection group （P<0.05）， and there were significant differences in ΔCCR5， CCR10， and CCR15 between the survival group and the death group （all P<0.05）. The multivariate logistic regression analysis showed that ΔCCR5 （odds ratio ［OR］=1.175， 95% confidence interval ［CI］： 1.098‍ — ‍1.256， P<0.001）， NLR （OR=0.921， 95%CI： 0.880‍ — ‍0.964， P<0.001）， and PT （OR=0.921， 95%CI： 0.873‍ — ‍0.973， P=0.003） were independent influencing factors for the prognosis of HBV-ACLF patients. ΔCCR5 had an AUC of 0.774， a sensitivity of 0.687， and a specificity of 0.757， and the AUC of ΔCCR5+PT+NLR was 0.824， which was significantly higher than the AUC of ΔCCR5， NLR， or PT alone （all P<0.05）. ConclusionΔCCR5， NLR， and PT can reflect the condition and prognosis of patients with HBV-ACLF and are independent predictive indicators for death events in patients with HBV-ACLF. The combination ofΔCCR5， PT， and NLR has the best predictive efficiency.

Source and application of seed cells in bioartificial liver support system / 临床肝胆病杂志

So far， there are still no specific treatment methods for severe hepatitis and liver failure， resulting in a mortality rate of over 70%， and they are the difficulties in the treatment of critical illness in China and globally. Liver transplantation is currently the most effective treatment method for end-stage liver disease， but only 1%‍ ‍—‍ ‍2% of patients can receive the opportunity for organ transplantation. The bioartificial liver support system utilizes external mechanical， physical， and biological devices to remove various harmful substances accumulated in the patient’s body， compensate for the metabolic functions of the liver， supplement necessary substances， improve internal environment， promote the recovery of liver function， help patients get through the critical period， and save time for liver transplantation， and therefore， it is considered one of the important methods for the treatment of end-stage liver disease. Since hepatocytes are the core element of bioartificial liver， this article summarizes the sources of liver seed cells， 3D culture methods， and corresponding bioreactor culture systems and hopes to gradually solve the core issue of large-scale in vitro preparation of hepatocytes to obtain hepatocytes with adequate quantity and quality， which urgently needs to be addressed in clinical application.

Research advances in combined artificial liver / 临床肝胆病杂志

At present， in vitro artificial liver support system has achieved a good therapeutic effect in the diseases such as liver failure due to various causes， non-function state before and after liver transplantation， and severe cholestasis. Non-bioartificial liver （NBAL） is widely used in clinical practice through various combinations of modes， mainly the plasma exchange mode for improving coagulation factors and albumin combined with other modes for enhancing the elimination of toxic substances in the body. Bioartificial liver （BAL）， based on the design concept of the synthesis and transformation of hepatocytes， has achieved rapid development in recent years. Patients with liver failure can almost obtain the normal physiological function of human liver after NBAL detoxification and BAL synthesis and transformation of active substances in the body. NBAL mode combined with BAL with a stable therapeutic effect according to the conditions of the patient is the direction of in vitro support treatment for patients with severe liver disease in the future.

Casual Association Between Coffee Intake and Prostate Cancer Based on Two-sample Mendel Randomization / 肿瘤防治研究

Objective To assess the causal relationship between coffee intake and prostate cancer risk by using the two-sample Mendel randomization (MR) method. Methods The genome-wide association study (GWAS) data on coffee intake (exposure) and prostate cancer (outcome) were obtained from two independent data sets in UK Biobank. The inverse variance weighted method (IVW), weighted median estimator method (WME), and MR-Egger method were used for MR analyses. The OR value and 95%CI were used to represent the association between coffee intake and prostate cancer. In addition, the MR-Egger method was performed for pleiotropic and heterogeneity tests, and the leave-one-out method was used for sensitivity analysis. Results A total of 38 SNP were selected as instrumental variables. The IVW method showed that coffee intake might reduce the risk of prostate cancer (OR=0.994; 95%CI: 0.990-0.999; P=0.009). The WME method obtained the same conclusions (OR=0.991; 95%CI: 0.985-0.999; P=0.018), but MR-Egger regression did not find a causal relationship between coffee intake and prostate cancer (OR=0.992; 95%CI: 0.983-1.000; P=0.084). The MR-Egger method showed no pleiotropy (intercept=4.2E-5; P=0.581) or heterogeneity (Q=27.20; P=0.854) among the instrumental variables. The sensitivity analysis indicated that the conclusion was robust. Conclusion Two-sample Mendel randomization analysis reveals that coffee consumption might reduce the risk of prostate cancer.

Study on the treatment of cerebral infarction with Chinese medicine Shenmajingfu granule by network pharmacology / 药学实践杂志

Objective To explore the material basis and mechanism of the Chinese medicine Shenmajingfu granules in the treatment of cerebral infarction. Methods The potential active ingredients and targets of Shenmajingfu granules were retrieved through TCMSP, ETCM database and TCM Database. The related target genes of cerebral infarction were searched from OMIM database. The common targets of Shenmajingfu granules and cerebral infarction were obtained by the intersection method. Cytoscape was used to construct active components of Shenmajingfu granules-targets network. Protein-protein interaction network was constructed by STRING software. DAVID database was used for GO and KEGG enrichment analysis. Results The 183 potential active ingredients of Shenmajingfu granules were screened out. 1785 potential targets were screened in the TCMSP database, including 30 targets related to cerebral infarction. These target genes were mainly involved in the inflammatory response and apoptosis process, involving the TNF signaling pathway, HIF-1 signaling pathway and NF-κB signaling pathway. Conclusion The therapeutic effect of Shenmajingfu granules on cerebral infarction may be related to the regulation of inflammatory response, improvement of impaired neurological function and protection of cerebral ischemia-reperfusion injury.

Role of NLRP3 Inflammasome in IgA Nephropathy and Chinese Medicine Intervention： A Review / 中国实验方剂学杂志

IgA nephropathy is recognized as the most common primary glomerular disease， with up to 20%-40% of patients developing end-stage kidney disease within 20 years of onset. The deposition of IgA1-containing immune complexes targeting glycosylation defects in the mesangial region and the subsequent inflammation caused by T lymphocyte activation are considered as the main causes of IgA nephropathy， and innate immunity is also involved in the pathogenesis. Nucleotide-binding oligomerization domain （NOD）-like receptor protein 3 （NLRP3） is a newly discovered pattern recognition receptor expressed in renal intrinsic cells such as renal tubular epithelial cells， mesangial cells， and podocytes. Activated by external stimuli， NLRP3 can form NLRP3 inflammasomes with apoptosis-associated speck-like protein containing a caspase recruitment domain （ASC）. The NLRP3 inflammasome can activate cysteine aspartate-specific protease-1 （Caspase-1）， causing the maturation and release of interleukin-18 （IL-18） and interleukin-1β （IL-1β） involved in inflammation. Increasing evidence has suggested that NLRP3 inflammasomes are involved in the pathogenesis and progression of IgA nephropathy and associated with the damage of renal intrinsic cells such as podocytes， mesangial cells， endothelial cells， and renal tubular epithelial cells. Chinese medicine can regulate inflammatory cytokines and their signaling pathways by acting on NLRP3 inflammasomes and related molecules， exerting therapeutic effects on IgA nephropathy. This article introduces the role of NLRP3 inflammasomes in IgA nephropathy and reviews the clinical and experimental research progress of Chinese medicine intervention in IgA nephropathy via NLRP3 inflammasomes， aiming to provide a reference for further research and application of Chinese medicine intervention in the NLRP3 inflammasome as a new therapeutic target.

Promoting Innovative Development of Traditional Chinese Medicine Case Report Based on China Clinical Cases Library of Traditional Chinese Medicine / 中国实验方剂学杂志

China Clinical Cases Library of Traditional Chinese Medicine is built to promote the establishment of a scientific and technological talent evaluation system oriented on innovative value， ability and contribution in the backgroud of breaking the four only and setting new standards required by the document jointly issued by several national administrations and commissions. In the process of the construction， in order to further consolidate the foundation and ensure the quality and authority of case reports， we need to fully understand the origin and development of Chinese medical cases. Therefore， we clarified the development situation of Chinese medical cases by combing the characteristics of ancient and modern case reports， comparing the differences between Chinese and western medical case reports in terms of content and writing requirements， finally formed the main points of systematic case report norms and quality evaluation system， aiming to fully explore the unique advantages of Chinese medical cases in the fields of discipline development， scientific research innovation， clinical practice and guidance， talent evaluation and training， so as to promote its innovative development in a broader direction.

Qualitative and Quantitative Analysis of Chemical Constituents in Liu Junzitang by UPLC-Q-TOF-MS/MS and UPLC / 中国实验方剂学杂志

ObjectiveTo establish a qualitative and quantitative analysis method for chemical constituents in Liu Junzitang（LJZT）， and to clarify its material basis. MethodThe chemical constituents in LJZT were analyzed by ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， and the resulting compounds were identified by using databases， such as MassBank， PubChem， ChemSpider， Traditional Chinese Medicine Systems Pharmacology Database and Analytical Platform（TCMSP）， and by combining with relevant literature. UPLC was used to establish a quantitative method for analysis of 9 compounds in LJZT， including liquiritin， hesperidin， lobetyolin， liquiritigenin， glycyrrhizic acid， nobiletin， tangeretin， atractylenolide Ⅱ and Ⅰ. ResultBy combining the relevant literature， database and MS information， a total of 79 compounds were identified from LJZT， including 31 flavonoids， 15 terpenoids， 14 nitrogen-containing compounds， 6 phenylpropanoids， 6 organic acids and 7 other compounds. The established quantitative analytical method for the nine representative components showed good linearity within their respective linear ranges， and the precision， stability， reproducibility and recovery were in accordance with the requirements. The quantitative results showed that the contents of liquiritin， hesperidin， lobetyolin， liquiritigenin， glycyrrhizic acid， nobiletin， tangeretin， atractylenolide Ⅱ and Ⅰ in LJZT were 0.376 5， 2.602 1， 0.082 6， 0.128 1， 1.778 6， 0.015 7， 0.006 7， 0.030 4， 0.003 2 mg·g-1， respectively. ConclusionThe established method can quickly， sensitively and accurately analyze the chemical constituents in LJZT， clarify that the material basis of LJZT is mainly flavonoids， terpenoids and nitrogen-containing compounds， and simultaneously determine the contents of the 9 components， which can lay a foundation for the research on quality control， mechanism and clinical application of LJZT.

Comprehensive Clinical Evaluation of Yiqing Capsules in Treating Heat-toxin Syndrome / 中国实验方剂学杂志

ObjectiveTo systematically review the studies about Yiqing Capsules in the treatment of pharyngitis， tonsillitis， gingivitis， and oral ulcers with heat-toxin syndrome and clarify the advantages and therapeutic characteristics of Yiqing capsules， thus providing reference for the decision-making by relevant departments and clues for the clinical and basic research. MethodThe multi-criteria decision analysis （MCDA） model and CSC v2.0 were employed to comprehensively evaluate Yiqing capsules from multiple aspects. ResultThe serious adverse reactions in the spontaneous reporting system （SRS） monitoring data of Yiqing capsules included pruritus， rash， an ddiarrhea， all of which were relieved or cured， without aggravation or interhospital transfer for treatment. Literature data showed that the main clinical adverse reactions were abdominal pain， diarrhea， etc. Both acute toxicity and long-term toxicity tests showed good safety， and thus the safety of Yiqing capsules was rated as grade B. The results of Meta-analysis showed that Yiqing capsules used alone or in combination with other medicines outperformed Niuhuang Jiedu capsules or Western medicine in the treatment of pharyngitis， tonsillitis， gingivitis， and oral ulcers with heat toxin in terms of symptom alleviation， disappearance rate of main symptoms， and recurrence rate of aphtha. Pharmacological and pharmacodynamic studies showed that Yiqing capsules had antimicrobial， antiviral， and anti-inflammatory effects， with the effectiveness rated as grade B. The decision tree model was adopted to analyze the incremental cost-effectiveness ratio. With the threshold of 1 fold per capita GDP and the disappearing rate of pain in gingivitis as the indicator， Yiqing capsules had an economic advantage in the treatment of gingivitis due to heat-toxin compared with Niuhuang Jiedu capsules， and the incremental cost-effectiveness ratio was 0.39 yuan/%， which indicated acceptable cost， with the economy rated as grade B. Yiqing capsules can not only clear heat from Qi aspect but also purge blood fire， serving as the representative prescription of clearing and purging for heat-toxin syndrome. Considering the industrial service system and enterprise innovation， the comprehensive innovation of Yiqing capsules was rated as grade B. Generally， this product does not require personalized treatment plans and features convenient supply， storage， transportation， policy publicity， drug information standards， and easy operation for medical care and patients. The Chinese patent medicine information was complete and in line with national standards， and thus the suitability of Yiqing capsules was rated as grade A. With a low price and good availability and affordability， the accessibility of Yiqing capsules was rated as grade A. The Yiqing capsules prescription， Sanhuang Xiexin decoction， originated from ancient medical books， with rich real-world studies， and thus the traditional Chinese medicine characteristics of Yiqing capsules was rated as grade C. ConclusionThe clinical value of Yiqing capsules was rated as grade B from the "6+1" dimensions， suggesting that it could be conditionally converted into the relevant policy results of basic clinical drug management according to the procedure.