Bladder neck contracture following transurethral surgery of prostate: a retrospective single-center study.

PURPOSE: Bladder neck contracture (BNC) is a rare but intolerant complication after transurethral surgery of prostate. The present study aims to investigate the incidence and risk factors of BNC in patients diagnosed benign prostate hyperplasia (BPH) and following transurethral resection or enucleation of the prostate (TURP/TUEP). METHODS: This retrospective study included 1008 BPH individuals who underwent transurethral surgery of the prostate between January 2017 and January 2022. Patients' demographics, medical comorbidities, urologic characteristics, perioperative parameters, and the presence of BNC were documented. Univariate and multivariate analyses were conducted to identify the risk factors. RESULTS: A total of 2% (20/1008) BPH patients developed BNC postoperatively and the median occurring time was 5.8 months. Particularly, the incidences of BNC were 4.7% and 1.3% in patients underwent Bipolar-TURP and TUEP respectively. Preoperative urinary tract infection (UTI), elevated PSA, smaller prostate volume (PV), bladder diverticulum (BD), and B-TURP were significantly associated with BNC in the univariate analysis. Further multivariate logistic regression demonstrated preoperative UTI (OR 4.04, 95% CI 2.25 to 17.42, p < 0.001), BD (OR 7.40, 95% CI 1.83 to 31.66, p < 0.001), and B-TURP (OR 3.97, 95% CI 1.55 to 10.18, p = 0.004) as independent risk factors. All BNC patients were treated with transurethral incision of the bladder neck (TUIBN) combined with local multisite injection of betamethasone. During a median follow-up of 35.8 months, 35% (7/20) of BNC patients recurred at a median time of 1.8 months. CONCLUSION: BNC was a low-frequency complication following transurethral surgery of prostate. Preoperative UTI, BD, and B-TURP were likely independent risk factors of BNC. TUIBN combined with local multisite injection of betamethasone may be promising choice for BNC treatment.

Analytical strategies to identify multicomponent quality markers for commercial Hua-ju-hong using multidimensional chemical analysis.

Hua-ju-hong (HJH) is a Chinese medicinal material obtained from Citrus grandis 'Tomentosa' (CGT) and Citrus grandis (L.) Osbeck (CG) with various commercial specifications. It is known for relieving cough and dispelling phlegm. To reveal the quality marker for distinguishing the various HJH, 215 batches of commercial HJH were studied systematically using multidimensional chemical analysis. Ten major components were identified by high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry and quantified via high-performance liquid chromatography coupled with diode array detection. In this study, a rapid, efficient, and low-cost chromatographic method was established. Total coumarin-hemiterpene and total coumarin-monoterpene were first classified and analyzed in HJH. The result indicated that the main component, naringin, was not the quality marker for differentiating CGT from CG. For reflecting the unique medicinal and food value of HJH, coumarins should be the more potential quality markers. Flavonoids were the possible quality markers for distinguishing two growth stages of fruit-exocarp and young fruit. For the first time, two chemotypes of HJH were identified in CG. This study provides a convenient yet reliant chromatographic method and novel yet systematic strategies for overall quality control of commercial HJH.

Exploring the Effects of Various Early Hospital Feeding Approaches on Feeding Tolerance and Growth in Premature Infants.

Background: Feeding intolerance poses a significant risk of malnutrition in premature infants and may result in postnatal growth restriction, leading to irreversible damage to brain function and structure. Objective: This study aims to investigate the impact of various early hospital feeding methods on feeding tolerance and the early growth and development of premature infants. Design: A retrospective study design was adopted in this study. Setting: This study was conducted at Tongling Maternal and Child Health Hospital between January 2018 and June 2023. Participants: A total of premature, low birth-weight infants admitted to our hospital between January 2018 and June 2023 were selected for the study. The preterm infants were randomly assigned to either the experimental group (EG) or the control group (CG) using the random number table method. Interventions: The EG group received deep hydrolyzed protein formula (DHPF) milk for 1-3 weeks after opening, whereas the CG group received preterm infant formula milk continuously after the milk was opened. Primary Outcome Measures: (1) Growth and development, (2) Feeding tolerance, and (3) Incidence of complications. Results: Following 14 days of feeding, both study groups exhibited notable increases in body length, body weight, and head circumference (P < .05). These measurements were significantly higher in the EG compared to the CG (P < .05). Furthermore, the EG demonstrated a marked improvement in feeding tolerance relative to the CG (P < .01). Notably, there was no significant difference in the incidence of complications between the two groups (P > .05). Conclusions: The administration of deep hydrolyzed protein formula (DHPF) milk presents a promising strategy for enhancing the growth and development of premature infants while concurrently improving feeding tolerance. These findings underscore the potential clinical benefits of incorporating DHPF milk into neonatal care protocols.

[Study on changes of Styrax varieties].

Styrax is a commonly used imported traditional Chinese medicinal material in China. It was introduced to China in the Han Dynasty and was first described as a traditional Chinese medicine in Miscellaneous Records of Famous Physicians(Ming Yi Bie Lu). In this paper, by combing ancient and modern Chinese and foreign herbal medicine books and modern literature, combined with the results of field investigations on the origin of Styrax, the changes of Styrax involving the name, quality evaluation, origin, place of origin, and harvesting and processing were systematically verified. The results show that since ancient times, the origin and place of origin of Styrax have been unclear. The medical scientists of all dynasties in China have evaluated the quality of Styrax from four aspects: texture, viscosity, odor concentration, and color. The varieties of Styrax changed twice. The first change may have occurred during the Sui and Tang Dynasties, and the base changed from Styrax officinalis to Liquidambar orientalis. The second change was in modern times, and the base changed from L. orientalis to L. styraciflua. At the same time, the place of origin changed for the first time, from Turkey, Syria, and other countries in southern Asia Minor to Honduras, Guatemala, and other countries in Central America and southern North America. This paper studied the historical evolution of Styrax in terms of quality evaluation, origin, place of origin, character, and harvesting and processing. At the same time, it summarized the application of Styrax in the western countries, which can provide a historical basis for the further development and utilization of Styrax.

Identifying a distinct fibrosis subset of NAFLD via molecular profiling and the involvement of profibrotic macrophages.

BACKGROUND: There are emerging studies suggesting that non-alcoholic fatty liver disease (NAFLD) is a heterogeneous disease with multiple etiologies and molecular phenotypes. Fibrosis is the key process in NAFLD progression. In this study, we aimed to explore molecular phenotypes of NAFLD with a particular focus on the fibrosis phenotype and also aimed to explore the changes of macrophage subsets in the fibrosis subset of NAFLD. METHODS: To assess the transcriptomic alterations of key factors in NAFLD and fibrosis progression, we included 14 different transcriptomic datasets of liver tissues. In addition, two single-cell RNA sequencing (scRNA-seq) datasets were included to construct transcriptomic signatures that could represent specific cells. To explore the molecular subsets of fibrosis in NAFLD based on the transcriptomic features, we used a high-quality RNA-sequencing (RNA-seq) dataset of liver tissues from patients with NAFLD. Non-negative matrix factorization (NMF) was used to analyze the molecular subsets of NAFLD based on the gene set variation analysis (GSVA) enrichment scores of key molecule features in liver tissues. RESULTS: The key transcriptomic signatures on NAFLD including non-alcoholic steatohepatitis (NASH) signature, fibrosis signature, non-alcoholic fatty liver (NAFL) signature, liver aging signature and TGF-ß signature were constructed by liver transcriptome datasets. We analyzed two liver scRNA-seq datasets and constructed cell type-specific transcriptomic signatures based on the genes that were highly expressed in each cell subset. We analyzed the molecular subsets of NAFLD by NMF and categorized four main subsets of NAFLD. Cluster 4 subset is mainly characterized by liver fibrosis. Patients with Cluster 4 subset have more advanced liver fibrosis than patients with other subsets, or may have a high risk of liver fibrosis progression. Furthermore, we identified two key monocyte-macrophage subsets which were both significantly correlated with the progression of liver fibrosis in NAFLD patients. CONCLUSION: Our study revealed the molecular subtypes of NAFLD by integrating key information from transcriptomic expression profiling and liver microenvironment, and identified a novel and distinct fibrosis subset of NAFLD. The fibrosis subset is significantly correlated with the profibrotic macrophages and M2 macrophage subset. These two liver macrophage subsets may be important players in the progression of liver fibrosis of NAFLD patients.

The Efficacy and Safety of Tislelizumab as Adjuvant Treatment for Advanced or Metastatic Bladder Cancer in People Living With HIV: A Retrospective Multi-Center Study.

BACKGROUND: People living with HIV (PLWH) have a worse prognosis than the general population. Locally advanced or metastatic bladder cancer (BCa) in PLWH has gradually been increasing in recent years. Immune checkpoint inhibitors can improve antitumor activity in the general population, but relevant data in PLWH are unknown. We thus evaluated the efficacy and safety of tislelizumab in PLWH with locally advanced or metastatic BCa. METHODS: This retrospective study included 24 patients with locally advanced or metastatic BCa, both HIV positive or negative who underwent tislelizumab treatment (200 mg i.v. every 3 weeks, Q3W) from the multi-centers between December 2019 and March 2022. Demographic details, clinical data, and cancer status were collected. The overall survival (OS), progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), and treatment-related adverse events (TRAEs) were recorded and evaluated. RESULTS: A total of 24 individuals were chosen for this study, 10 had HIV and the other 14 did not. The median OS in the HIV-negative group was 62.3 (95% CI, 52.6 to 72.2) was no longer than that of the PLWH group 41.9 (95% CI, 32.9 to 51.0) weeks (HR .7, [95% CI, .17 to 3.30], P = .70). Furthermore, the median PFS in the HIV-negative group was 50.0 (95% CI, 36.2 to 63.9) was also no longer than that of the PLWH group 35.9 (95% CI, 25.5 to 46.3) (HR, 1.34, [95% CI, .38 to 4.69], P = .63). Of 24 patients, treatment-related adverse events, grade 3 or 4 occurred in 2 in the PLWH group and 3 in the HIV-negative group. CONCLUSION: This retrospective multi-center study suggested that tislelizumab may provide encouraging antitumor activity and could be generally well tolerated. In this retrospective analysis of patients with locally advanced or metastatic BCa, it seems that PLWH may have similar overall and progression-free survival compared to HIV-negative cases.

Quantitative and qualitative analysis of Artemisiae Verlotori Folium and Artemisiae Argyi Folium by high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry.

Artemisiae Argyi Folium (Aiye in Chinese) has been widely used since ancient times. In the Lingnan region (Southern China), the leaf of Artemisia verlotorum Lamotte, which is named Hongjiaoai (HJA) because the roots are red (Hongjiao means red foot in Chinese), has been used as a local substitute for Artemisiae Argyi Folium. The plant has a long medicinal and edible history that can be traced to the Jin Dynasty. However, there is no systematic and reliable method to control the quality of Artemisiae Verlotori Folium. In this study, a comprehensive method involving high-performance liquid chromatography coupled with diode array detection and quadrupole-time-of-flight high-definition mass spectrometry was established to identify and quantify eight constituents (including organic acids and flavonoids) in Artemisiae Verlotori Folium and Artemisiae Argyi Folium as well as high-performance liquid chromatography fingerprints of the two varieties. Moreover, dissimilarities of chemical compositions among the two varieties were further investigated by orthogonal partial least squares discrimination analysis and cluster analysis. This research not only explored the similarities and differences between Artemisiae Verlotori Folium and Artemisiae Argyi Folium in eight components but also provided a qualitative and quantitative analytical method that quickly, accurately, and comprehensively assesses the quality of Artemisiae Verlotori Folium.

Camrelizumab for cancers in patients living with HIV: one-single center experience.

OBJECTIVES: The primary objective was to evaluate the safety of the anti-PD-1 antibody camrelizumab in people living with HIV (PLWH); the secondary objective was to evaluate tumor response. METHODS: From May 8, 2018, to December 10, 2021, twenty-four patients with HIV and advanced cancer as well as a CD4+ T-cell count greater than or equal to 100 cells/µL were treated with camrelizumab in daily practice. We describe the demographic characteristics, safety, and clinical course of these 24 PLWH with cancer treated with camrelizumab. Safety was assessed using the current Common Terminology Criteria for Adverse Events (CTCAE). The tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1). RESULTS: The median number of cycles was 8 (4-26). Only two grade 3 adverse reactions were reported (no toxic deaths or immune-related deaths). Among the 24 patients, 2 (8%) complete responses and 6 (25%) partial responses were observed. 7 patients (29%) were at stable tumor status and others progressed. CONCLUSIONS: Data from the present study strongly support the use of camrelizumab (monoclonal antibodies targeting the PD-1 pathway) in this population, as it appears to be a feasible approach with no deleterious effects on PLWH and tolerability and acceptable efficacy. In addition, these findings further support the inclusion of PLWH with cancer in clinical trials evaluating the safety and efficacy of ICIs on cancer.

Simultaneous quantitative analysis of 11 constituents in Viticis Fructus by HPLC-HRMS and HPLC-DAD combined with chemometric methods.

INTRODUCTION: Viticis Fructus is the dried ripe fruit of Vitex trifolia L. (VTF) or V. trifolia subsp. litoralis Steenis (VTLF). Different botanical sources of the same herbal medicines may have different clinical efficacies, but few studies have reported the comparative identification of VTF and VTLF. OBJECTIVES: To establish a high-performance liquid chromatography (HPLC) method for the simultaneous assay of 11 constituents in Viticis Fructus, to compare the chemical compositions of VTF and VTLF, and to identify chemical markers for the discrimination and quality evaluation of the two botanical origins of Viticis Fructus. METHODOLOGY: An HPLC-diode array detection (DAD)-high-resolution mass spectrometry (HRMS) method was developed for the simultaneous separation and quantification of 11 constituents in 21 batches of Viticis Fructus samples from different sources in China. Moreover, chemometrics were performed to compare and discriminate VTF and VTLF samples. RESULTS: The results from 11 batches of VTF and 10 batches of VTLF were compared for 11 components, of which 3,4-dicaffeoylquinic acid and 3,5-dicaffeoylquinic acid were identified and quantified in Viticis Fructus for the first time. The quantitative analysis showed significantly higher chlorogenic acid and casticin contents in VTLF than in VTF, and the chemometric analysis indicated that chlorogenic acid and casticin were responsible for the significant differences between VTF and VTLF; these two compounds might be used as chemical markers to distinguish the two original plant sources of Viticis Fructus. CONCLUSIONS: The present work provides useful information for understanding the chemical differences between VTF and VTLF. This work also provides feasible methods for the quality evaluation and discrimination of herbal medicines originating from multiple botanical sources.

[Slicing specifications in general rule of processing in Chinese Pharmacopoeia from slicing development of Chinese materia medica processed product and thinking and suggestion on slicing techniques].

Slicing is critical in the processing of Chinese materia medica(CMM) processed product and the specification(thickness) is closely related to the quality of the decoction. On the basis of clarifying the concept and evolution of slicing of CMM processed product by reviewing the Chinese herbal classics of the past dynasties and general rules of local processing standards, this study discussed the development history of slicing specifications in general rules of Chinese Pharmacopoeia(2020 edition), analyzed the current situation and key problems, and proposed the thinking and suggestion on promoting the sound development of slicing of CMM processed product. Since 2000, the slicing thickness of CMM processed product in the general rules of local CMM processed product processing specifications newly revised and issued by 27 provinces, autonomous regions, and municipalities has been consistent with that in the general rules of the Chinese Pharmacopoeia(2020 edition). The standard that the thickness of extremely thin pieces is less than 0.5 mm is rarely retained, and the pieces in 0.5-1 mm thickness have not been found on the market, which is consistent with the provisions of the general rules of the Chinese Pharmacopoeia. This study can provide a historical and modern basis for the rationality of slicing of CMM processed product.

[Comparison on volatile components between Artemisiae Verlotori Folium and Artemisiae Argyi Folium based on GC-MS and chemometrics].

Artemisiae Argyi Folium is commonly used in clinical practice. Artemisiae Verlotori Folium, the dried leaves of Artemisia verlotorum, is often used as a folk substitute for Artemisiae Argyi Folium in Lingnan area. In this study, gas chromatography-triple quadrupole mass spectrometry(GC-MS) was used to detect the volatile oil components of 27 samples of Artemisiae Verlotori Folium and 13 samples of Artemisiae Argyi Folium, and the volatile components were compared between the two species. The internal standard method was combined with multi-reaction monitoring mode(MRM) to determine the content of six major volatile components. Hierarchical clustering analysis(HCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were carried out for the content data. The results showed that the Artemisiae Argyi Folium samples had higher content and more abundant volatile oils than the Artemisiae Verlotori Folium samples. Artemisiae Argyi Folium mainly had the components with lower boiling points, while Artemisiae Verlotori Folium mainly had the components with higher boiling points. Terpenoids were the main volatile components in Artemisiae Verlotori Folium(mainly sesquiterpenoids) and Artemisiae Argyi Folium(monoterpenoids). In addition, Artemisiae Argyi Folium had higher content of oxygen-containing derivatives than Artemisiae Verlotori Folium. Furthermore, the stoichiometric analysis showed that the two species could be distinguished by both HCA and OPLS-DA, indicating that the volatile components of the two were significantly different. This study can provide a scientific basis for the quality evaluation and data support for the local rational application of Artemisiae Verlotori Folium in Lingnan.

[Textual research on Bungarus Parvus].

Bungarus Parvus, a precious animal Chinese medicinal material used in clinical practice, is believed to be first recorded in Ying Pian Xin Can published in 1936. This study was carried out to analyze the names, geographical distribution, morphological characteristics, ecological habits, poisonousness, and medicinal parts by consulting ancient Chinese medical books and local chronicles, Chinese Pharmacopeia, different processing standards of trditional Chinese medicine(TCM) decoction pieces, and modern literatures. The results showed that the earliest medicinal record of Bungarus Parvus was traced to 1894. In 1930, this medicinal material was used in the formulation of Annao Pills. The original animal, Bungarus multicinctus, was recorded by the name of "Bojijia" in 1521. The morphological characteristics, ecological habits, and poisonousness of the original animal are the same in ancient and modern records. The geographical distribution is similar between the ancient records and modern documents such as China Medicinal Animal Fauna. The dried body of young B. multicinctus is used as Bungarus Parvus, which lack detailed references. As a matter of fact, it is still inconclusive whether there are differences between young snakes and adult snakes in terms of active ingredients, pharmacological effects, and clinical applications. This study clarified the medicinal history and present situation of Bungarus Parvus. On the basis of the results, it is suggested that systematic comparison on young and adult B. multicinctus should be carried out to provide references for revising the medicinal parts of B. multicinctus.

Long-term outcome of renal cell carcinoma in patients with HIV who undergo surgery.

BACKGROUND: People living with HIV (PLWH) have a higher risk for cancer compared to the general population. The prevalence of renal cell carcinoma (RCC) in PLWH has gradually increased in recent years, but relevant data on outcomes after surgery are scarce. We thus evaluated long-term outcomes after surgery in RCC patients with and without HIV. METHODS: This retrospective study included 67 patients with RCC, both HIV positive or negative, who underwent surgical treatment in our hospital between January 2012 and January 2021. Demographic details, clinical data, and cancer status were collected. We set the day of surgery as the baseline. The co-primary end points in this time-to-event analysis were overall survival and progression-free survival. We used a multivariate Cox model to compare the prognosis of PLWH and HIV-negative patients and present Kaplan-Meier curves for the co-primary end points. RESULTS: Of 261 consecutive patients, 18 patients who forwent treatment before surgery, 133 cases with incomplete data, 16 patients classified as clinical stage IV, 11 PLWH patients did not received antiretroviral therapy and 16 patients with metastasis were excluded from the main analysis. Of the remaining 67 patients, 33 individuals had HIV and the other 34 did not. The median overall survival was 74.9 months (95% confidence interval [CI] = 64.6 to 85.2) in PLWH and 96.4 months (95% CI = 90.0 to 102.9) in the HIV-negative group. Progression-free survival was 66.4 months (95% CI = 53.5 to 79.3) and 90.6 months (95% CI = 81.1 to 100.1), respectively. RCC patients with HIV who underwent surgery had a shorter survival time (hazard ratio [HR] = 2.8, 95% CI = 1.1 to 7.0, p = 0.016) and an increased incidence of tumor progression (HR = 2.7, 95% CI = 1.1 to 6.8, p = 0.028). Univariate and multivariate Cox regression analyses showed that a lower ratio of CD4+ T cells to CD8+ T cells (adjusted odds ratio = 0.092, 95% CI = 0.01 to 0.70, p = 0.022) was associated with worse survival among PLWH. CONCLUSION: In this retrospective analysis of RCC patients who underwent surgery, PLWH had worse overall survival and shorter progression-free survival compared to HIV-negative cases.

Simultaneous qualitative and quantitative analysis of eight alkaloids in Corydalis Decumbentis Rhizoma (Xiatianwu) and Corydalis Rhizoma (Yanhusuo) by high-performance liquid chromatography and high-resolution mass spectrometry combined with chemometric methods.

In this study, we established a comprehensive high-performance liquid chromatography coupled with diode array detection and high-resolution mass spectrometry method to identify 10 and quantified eight constituents in Corydalis Decumbentis Rhizoma ("Xiatianwu" in Chinese) and Corydalis Rhizoma ("Yanhusuo" in Chinese). Chemometric methods were applied to distinguish the botanical origins of the Xiatianwu and Yanhusuo samples. Chromatographic separation was achieved using an Agilent Poroshell EC-C18 column with mobile phases A (1000 ml of 0.2% acetic acid solution containing 2.8 ml of triethylamine) and B (acetonitrile) and stepwise gradient elution. The analytical method was fully validated in terms of linearity, sensitivity, intra- and interday precision and repeatability, the limit of detection, the limit of quantitation, and recovery. Twenty-six Xiatianwu samples and 10 Yanhusuo samples were analyzed for quality evaluation. In addition, hierarchical clustering analysis and principal component analysis were used to discriminate among samples of different botanical origins. The results showed that the contents of eight alkaloids in Xiatianwu and Yanhusuo were significantly different. Moreover, it was found that chemometric methods could be applied to accurately distinguish these two often conflated Chinese medicinal materials. In conclusion, this study provides a relatively comprehensive method for botanical origin identification and Xiatianwu and Yanhusuo quality control.

Role of pyroglutamic acid in cumulus cells of women with polycystic ovary syndrome.

PURPOSE: Polycystic ovary syndrome is a complex heterogeneous endocrine disorder associated with established metabolic abnormalities and is a common cause of infertility in females. Glutathione metabolism in the cumulus cells (CCs) of women with PCOS may be correlated to the quality of oocytes for infertility treatment; therefore, we used a metabolomics approach to examine changes in CCs from women with PCOS and oocyte quality. METHODS: Among 135 women undergoing fertility treatment in the present study, there were 43 women with PCOS and 92 without. CCs were collected from the two groups and levels of pyroglutamic acid were measured using LC-MS/MS followed by qPCR and Western blot analysis to examine genes and proteins involved in pyroglutamic acid metabolism related to glutathione synthesis. RESULTS: Women with PCOS showed increased levels of L-pyroglutamic acid, L-glutamate, and L-phenylalanine and decreased levels of Cys-Gly and N-acetyl-L-methionine. Gene expression of OPLAH, involved in pyroglutamic synthesis, was significantly increased in women with PCOS compared with those without. Gene expression of GSS was significantly decreased in women with PCOS and synthesis of glutathione synthetase protein was decreased. Expression of nuclear factor erythroid 2-related factor 2, involved in resistance to oxidative stress, was significantly increased in women with PCOS. CONCLUSIONS: CCs of women with PCOS showed high concentrations of pyroglutamic acid and reduced glutathione synthesis, which causes oxidative stress in CCs, suggesting that decreased glutathione synthesis due to high levels of pyroglutamic acid in CCs may be related to the quality of oocytes in women with PCOS.

Simultaneous qualitative and quantitative analysis of 10 bioactive flavonoids in Aurantii Fructus Immaturus (Zhishi) by ultrahigh-performance liquid chromatography and high-resolution tandem mass spectrometry combined with chemometric methods.

INTRODUCTION: Aurantii Fructus Immaturus (Zhishi in Chinese) is the dried young fruit of Citrus aurantium L. (CA) and its cultivated varieties or Citrus sinensis Osbeck (CS). The content of flavonoids in different varieties of Zhishi may be significantly different. However, there is confusion about the botanical origin of Zhishi, and there is no reliable and systematic method to control Zhishi quality. OBJECTIVES: We aimed to establish an ultrahigh-performance liquid chromatography method coupled with diode-array detection and high-resolution tandem mass spectrometry (UPLC-DAD-HRMS/MS) for the quantitative analysis of 10 flavonoids in Zhishi that could be used for quality control and botanical origin identification. METHODOLOGY: A UPLC-DAD-HRMS/MS method was established for simultaneous identification and quantification of 10 flavonoids. Separation was performed on a Waters Acquity UPLC HSS T3 column (100 mm × 2.1 mm, 1.8 µm) with 0.1% formic acid and acetonitrile as mobile phase under gradient elution. MS was performed in positive and negative ionisation modes. The flavonoids in 41 batches were isolated and quantified. Zhishi of different botanical origins were identified by chemometrics. RESULTS: The results showed that the established method for the determination of 10 components was reliable and accurate. Chemometrics could be used to distinguish Zhishi of different botanical origins. There were significant differences in the contents of 10 flavonoids in samples of different botanical origins. CONCLUSIONS: The quantitative analysis method in this study can be used to accurately determine the content of 10 flavonoids and provide a chemical basis for quality control and botanical origin identification of Zhishi.

[Mechanism of moistening process of Rehmanniae Radix based on kinetic process].

The moistening process of Rehmanniae Radix was characterized quantitatively by moisture phase, texture properties, and component content based on water absorption kinetics and expansion kinetics. Non-linear fitting of water absorption kinetics and expansion kinetics in the moistening process of Rehmanniae Radix was carried out. Low-field nuclear magnetic resonance and imaging(LF-NMR/MRI) technology was used to investigate the phase state and distribution changes of water during the moistening process. The Texture Analyzer was used for the determination of texture properties. The correlations between water absorption rate, expansion rate, water phase state, hardness, and compression cycle work of Rehmanniae Radix at different moistening time were analyzed. The results showed that the water absorption kinetics and expansion kinetics of Rehmanniae Radix were in accordance with the first-order kinetics. Moreover, the water absorption rate and expansion rate increased with the increase in temperature but decreased with the increase in the size of the medicinal materials.In the moistening process, the moisture was transferred from the outside to the inside, and the proportion of the moisture phase changed significantly.Within 16 hours, free water increased from 0.825% to 97.7%,while bound water decreased from 99.2% to 2.33%.Within 28 hours, the texture properties, such as hardness and compression cycle work, decreased gradually with the prolongation in moistening time.At 32 hours, water was evenly distributed throughout the whole medicinal material, and the texture properties also tended to be stable.Pearson correlation bivariate analysis showed that moistening time, water absorption rate, expansion rate, the relative content of free water and bound water, hardness, and compression cycle work were significantly correlated, suggesting that water absorption kinetics and expansion kinetics, LF-NMR/MRI,and Texture Analyzer could directly and quantitatively characterize the moistening process.This study is expected to provide a scientific basis for clarifying the scientific connotation of the moistening process of Rehmanniae Radix.

Non-medullary Thyroid Cancer Susceptibility Genes: Evidence and Disease Spectrum.

BACKGROUND: The prevalence of non-medullary thyroid cancer (NMTC) is increasing worldwide. Although most NMTCs grow slowly, conventional therapies are less effective in advanced tumors. Approximately 5-15% of NMTCs have a significant germline genetic component. Awareness of the NMTC susceptibility genes may lead to earlier diagnosis and better cancer prevention. OBJECTIVE: The aim of this study was to provide the current panorama of susceptibility genes associated with NMTC and the spectrum of diseases associated with these genes. METHODS: Twenty-five candidate genes were identified by searching for relevant studies in PubMed. Each candidate gene was carefully checked using six authoritative genetic resources: ClinGen, National Comprehensive Cancer Network guidelines, Online Mendelian Inheritance in Man, Genetics Home Reference, GeneCards, and Gene-NCBI, and a validated natural language processing (NLP)-based literature review protocol was used to further assess gene-disease associations where there was ambiguity. RESULTS: Among 25 candidate genes, 10 (APC, DICER1, FOXE1, HABP2, NKX2-1, PRKAR1A, PTEN, SDHB, SDHD, and SRGAP1) were verified among the six genetic resources. Two additional genes, CHEK2 and SEC23B, were verified using the NLP protocol. Seventy-nine diseases were found to be associated with these 12 NMTC susceptibility genes. The following diseases were associated with more than one NMTC susceptibility gene: colorectal cancer, breast cancer, gastric cancer, kidney cancer, gastrointestinal stromal tumor, paraganglioma, pheochromocytoma, and benign skin conditions. CONCLUSION: Twelve genes predisposing to NMTC and their associated disease spectra were identified and verified. Clinicians should be aware that patients with certain pathogenic variants may require more aggressive surveillance beyond their thyroid cancer risk.

Simultaneous quantitative analysis of ten bioactive flavonoids in Citri Reticulatae Pericarpium Viride (Qing Pi) by ultrahigh-performance liquid chromatography and high-resolution mass spectrometry combined with chemometric methods.

INTRODUCTION: Citri Reticulatae Pericarpium Viride (Qing Pi in Chinese) is a clinically effective Chinese herb, which contains biologically valuable flavonoids. Qing Pi is divided into two commodity specifications, Si Hua Qing Pi (SHQP) and Ge Qing Pi (GQP), based on the harvesting time. The flavonoid contents in Qing Pi from different origins and commodity specifications may vary significantly, which will affect their therapeutic functions. Thus, it is crucial to set up a reliable and comprehensive quality evaluation method for flavonoid analysis in Qing Pi. OBJECTIVES: We aimed to establish a rapid and sensitive ultrahigh-performance liquid chromatography method coupled with diode-array detection and high-resolution mass spectrometry (UPLC-DAD-HRMS) for identification and quantification of ten flavonoids in Qing Pi. Chemometric methods were further applied to distinguish Qing Pi of different origins and specifications. METHODOLOGY: An UPLC-DAD-HRMS method was developed for the simultaneous separation and quantification of ten flavonoids in 46 batches of Qing Pi samples from different sources in China. Chemometric approaches were applied to discriminate Qing Pi from different origins and commodity specifications. RESULTS: The chemometric procedures (i.e., hierarchical clustering analysis and principal component analysis) were employed to identify the differences of Qing Pi samples with different origins and commodity specifications. The results showed that the contents of ten flavonoids in Qing Pi samples of different origins were significantly different, and the same results were found out between SHQP and GQP. CONCLUSIONS: This study provides a chemical basis for quality control of Qing Pi.

[Textual research of Schizonepetae Herba and Schizonepetae Spica].

Schizonepetae Herba and Schizonepetae Spica are well-known Chinese herbal medicines for wind dispersing and exterior releasing. Through textual research on Schizonepetae Herba and Schizonepetae Spica, the discrimination of their medicinal parts in history was clarified, and the processing, the property(nature and flavor), meridian tropism, functions, indications, usage, dosage, and the selection of decoction pieces were compared to provide the basis for clinical application. As a result, the whole herb of Schizonepeta tenuifolia was used as medicine in the early records. The aerial part and the dried spike of S. tenuifolia were used as medicines separately in the Song Dynasty, which was recorded in the Atlas of Materia Medica(Ben Cao Tu Jing). Some ancient classics emphasized that only the dried spike could be used as medicine. The separation of Schizonepetae Herba and Schizonepetae Spica meets the different needs of clinical medication and supports the concept of rational development and utilization of Chinese medicine resources. About ten processing methods for Schizonepetae Herba and Schizonepetae Spica have been recorded since ancient times, and raw and charred drugs were the major products. Raw Schizonepetae Herba is required to be used in sections, whereas raw Schizonepetae Spica in clean preparation. Both charred products should avoid scorching. Schizonepetae Herba and Schizonepetae Spica are similar in the property(pungent, bitter, and warm), meridian tropism(lung and liver meridians, as well as qi and blood aspects), and functions(releasing exterior, dispersing wind, regulating and stopping blood, promoting eruption, dispelling sores, promoting digestion, eliminating alcohol effect, etc.), but Schizonepetae Spica is superior in efficacy. For Schizonepetae Herba and Schizonepetae Spica in traditional Chinese medicinal prescriptions, the raw and charred products are similar in usage and dosage, while their focuses in clinical compatibility vary. The raw and charred products of Schizonepetae Herba and Schizonepetae Spica are widely applied clinically. Decoction pieces of different specifications can result in different efficacies and clinical applications, so medication should be performed with caution.