The influence of Hyssopus cuspidatus Boriss extract on lipid mediators metabolism network in asthmatic mice.

Current drugs do not provide an absolute cure or modify the course of asthma. Hyssopus cuspidatus Boriss extract (SXCF) has been used as Uyghur medicine for several years to treat bronchial asthma. However, very limited research has been conducted on the therapeutic mechanisms of SXCF. Disruptions in the metabolic network of lipid mediators (LMs) are closely linked to the development of asthma. Here, we explored the therapeutic mechanism of SXCF in asthma based on the metabolic network of LMs, aiming to contribute to the understanding of SXCF in asthma treatment at the molecular level. The UHPLC-MRM strategy was used for the quantitative detection of LMs in the lung tissue and in the peripheral circulatory system (serum). ELISA was used to detect IgE in serum and cytokines in BALF. The lung tissue sections were stained with H&E to observe the infiltration of inflammatory cells, and behavioural changes in mice were observed and recorded throughout the animal experiment. In contrast to the asthma group, the opposite result was observed in the SXCF groups, where the perturbed LMs metabolic network was partly restored in a dose-dependent manner with a significant elevation of anti-inflammatory metabolites, while pro-inflammatory lipids were decreased. As significant downregulation of IgE and pro-inflammatory cytokines was observed, IgE and cytokines analysis also supported the anti-inflammatory effects of SXCF. It was also noticed that SXCF treatment reduced the number of coughs and decreased the inflammatory cell infiltration around the bronchus in mice. These results suggested that SXCF has a significant ameliorative effect on ovalbumin (OVA)-induced asthma. The modulation of LMs is a possible underlying mechanism of the SXCF effects.

pH-sensitive nano-polyelectrolyte complexes with arthritic macrophage-targeting delivery of triptolide.

Since pro-inflammatory macrophages take on a critical significance in the pathophysiology of rheumatoid arthritis (RA), the therapeutics to affect macrophages may receive distinct anti-RA effects. However, the therapeutic outcomes are still significantly impeded, which is primarily due to the insufficient drug delivery at the arthritic site. In this study, the macrophage-targeting and pH stimuli-responsive nano-polyelectrolyte complexes were designed for the efficient targeted delivery of triptolide (TP/PNPs) on the arthritic site. The anionic and cationic amphiphilic copolymers, i.e., hyaluronic acid-g-vitamin E succinate (HA-VE) and the quaternized poly (ß-amino ester) (QPBAE-C18), were prepared and then characterized. The result indicated that TP/PNPs with the uniform particle size of âˆ¼ 175 nm exhibited the high drug loading capacity and storage stability based on the polymeric charge interaction, in which DLC and DEE of TP/PNPs were obtained as 11.27 ± 0.44 % and 95.23 ± 2.34 %, respectively. Mediated by the "ELVIS" effect of NPs, CD44 receptor-mediated macrophage targeting, and pH-sensitive endo/lysosomal escape under the "proton sponge" effect, TP/PNPs exhibited the enhanced cellular internalization and cytotoxicity while mitigating the inflammation of LPS-activated RAW 264.7 cells. Even after 96-hour after administration, PNPs were preferentially accumulated in the inflammatory joints in a long term. It is noteworthy that after treatment for 14 days with 100 µg/kg of TP, TP/PNPs significantly facilitated arthritic symptom remission, protected cartilage, and mitigated inflammation of antigen-induced arthritis (AIA) rats, whereas the systematic side-effects of TP were reduced. In this study, an effective drug delivery strategy was proposed for the treatment of RA.

Klotho inhibits the formation of calcium oxalate stones by regulating the Keap1-Nrf2-ARE signaling pathway.

PURPOSE: Oxidative damage is important in calcium oxalate (CaOx) stone development but occurs via multiple pathways. Studies have shown that klotho plays an essential role in ameliorating oxidative damage. This study aims to explore the role of klotho in CaOx stones and whether the underlying mechanism is related to the regulation of Keap1-Nrf2-ARE signaling. METHODS: The levels of GSH, SOD, CAT, MDA, and ROS were examined by ELISA. The klotho, Bcl-2, caspase-3, Keap1, Nrf2, HO-1, and NQO1 mRNA levels were measured by qRT‒PCR, and their protein levels were detected by Western blotting. Renal tissue apoptosis was examined by TUNEL staining, and crystal cell adherence and apoptosis in HKC cells were assessed based on the Ca2+ concentrations and by flow cytometry. The renal pathological changes and the adhesion of CaOx crystals in the kidneys were examined by hematoxylin-eosin and von Kossa staining, respectively. RESULTS: We constructed a CaOx kidney stone model in vitro. By regulating the klotho gene, klotho overexpression inhibited the CaOx-induced promotion of crystal cell adherence and apoptosis in HKC cells, and these effects were reversed by klotho knockdown. Moreover, our in vivo assay demonstrated that klotho overexpression alleviated glyoxylate administration-induced renal oxidative damage, renal apoptosis, and crystal deposition in the kidneys of mice, and these effects were also associated with activation of the Keap1-Nrf2-ARE pathway. CONCLUSION: Klotho protein inhibits the oxidative stress response of HKC cells through the Keap1-Nrf2-ARE signaling pathway, reduces the apoptosis of and adhesion of CaOx crystals to HKC cells, and decreases the occurrence of CaOx kidney stones. CLINICAL TRIAL REGISTRATION: 20220304.

Transdermal drug delivery technology for brain-targeted drug delivery / 药学学报

Intracerebral delivery of drugs for the treatment of central nervous system disorders is usually limited by the blood-brain barrier (BBB). Transdermal drug delivery systems (TDDS) have the advantage of improving patient compliance and avoiding first-pass effects compared to intravenous, oral and intranasal drug delivery, and are an emerging non-invasive drug delivery route that facilitates long-term drug delivery to patients. The discovery of direct subcutaneous targeting of lymphatic pathways to brain tissue has made TDDS a new brain-targeted drug delivery strategy. At the same time, the development of nano-delivery technology has further facilitated the application of TDDS for targeted drug delivery to the brain. This review summarizes the mechanism of transdermal drug delivery into the brain and the application of TDDS in the treatment of brain diseases, providing new ideas and methods for the treatment of central nervous system diseases.

Immunogenicity and reactogenicity of heterologous immunization schedules with COVID-19 vaccines: a systematic review and network meta-analysis / 中华医学杂志(英文版)

BACKGROUND@#Data on the immunogenicity and safety of heterologous immunization schedules are inconsistent. This study aimed to evaluate the immunogenicity and safety of homologous and heterologous immunization schedules.@*METHODS@#Multiple databases with relevant studies were searched with an end date of October 31, 2021, and a website including a series of Coronavirus disease 2019 studies was examined for studies before March 31, 2022. Randomized controlled trials (RCTs) that compared different heterologous and homologous regimens among adults that reported immunogenicity and safety outcomes were reviewed. Primary outcomes included neutralizing antibodies against the original strain and serious adverse events (SAEs). A network meta-analysis (NMA) was conducted using a random-effects model.@*RESULTS@#In all, 11 RCTs were included in the systematic review, and nine were ultimately included in the NMA. Among participants who received two doses of CoronaVac, another dose of mRNA or a non-replicating viral vector vaccine resulted in a significantly higher level of neutralizing antibody than a third CoronaVac 600 sino unit (SU); a dose of BNT162b2 induced the highest geometric mean ratio (GMR) of 15.24, 95% confidence interval [CI]: 9.53-24.39. Following one dose of BNT162b2 vaccination, a dose of mRNA-1273 generated a significantly higher level of neutralizing antibody than BNT162b2 alone (GMR = 1.32; 95% CI: 1.06-1.64), NVX-CoV2373 (GMR = 1.60; 95% CI: 1.16-2.21), or ChAdOx1 (GMR = 1.80; 95% CI: 1.25-2.59). Following one dose of ChAdOx1, a dose of mRNA-1273 was also more effective for improving antibody levels than ChAdOx1 (GMR = 11.09; 95% CI: 8.36-14.71) or NVX-CoV2373 (GMR = 2.87; 95% CI: 1.08-3.91). No significant difference in the risk for SAEs was found in any comparisons.@*CONCLUSIONS@#Relative to vaccination with two doses of CoronaVac, a dose of BNT162b2 as a booster substantially enhances immunogenicity reactions and has a relatively acceptable risk for SAEs relative to other vaccines. For primary vaccination, schedules including mRNA vaccines induce a greater immune response. However, the comparatively higher risk for local and systemic adverse events introduced by mRNA vaccines should be noted.@*REGISTRATION@#PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42021278149.

Comparative effectiveness of different hepatocellular carcinoma screening intervals or modalities: a systematic review and meta-analysis / 中华医学杂志(英文版)

BACKGROUND@#Current guidelines recommend hepatocellular carcinoma (HCC) screening in high-risk populations. However, the ideal HCC screening interval and screening modality have not been determined. This study aimed to compare the screening efficacy among different modalities with various intervals.@*METHODS@#PubMed and other nine databases were searched through June 30, 2021. Binary outcomes were pooled using risk ratio (RR) with 95% confidence intervals (CIs). Survival rates were also pooled using RR with 95% CIs because most eligible studies only provided the number of survival patients instead of hazard ratio.@*RESULTS@#In all, 13 studies were included. Two random controlled trials (RCTs) and six cohort studies compared screening intervals for ultrasonography (US) screening and found no significant differences between shorter (3- or 4-month) and longer (6- or 12-month) screening intervals in terms of early HCC proportion, HCC significant mortality, 1-year survival rate; screening at 6-month interval significantly increased the proportion of early HCC (RR = 1.17, 95% confidence interval [CI]: 1.08-1.26) and prolonged the 5-year survival rate (RR = 1.39, 95% CI: 1.07-1.82) relative to the 12-month interval results. Three other RCTs and two cohort studies compared different screening modalities in cirrhosis or chronic hepatitis B, which indicated no statistical differences in the proportion of early HCC (RR = 0.89, 95% CI: 0.40-1.96) and HCC mortality (RR = 0.69, 95% CI: 0.23-2.09) between the biannual US and annual computed tomography (CT screening). Biannual US screening showed a lower proportion of early HCC than biannual magnetic resonance imaging (MRI) (RR = 0.60, 95% CI: 0.37-0.97) and biannual US combined with annual CT (RR = 1.31, 95% CI: 1.13-1.51) screening. The proportion of early HCC in the contrast-enhanced US group was slightly higher than that in the B-mode US (RR = 1.08, 95% CI: 1.00-1.23) group.@*CONCLUSIONS@#The evidence suggests that 6 months may be the best HCC screening interval for US screening. The effectiveness of CT and MRI is better than US during same screening intervals. However, MRI and CT are more expensive than US, and CT also can increase the risk of radiation exposure. The selection of CT or MRI instead of US should be carefully considered.@*REGISTRATION@#No. CRD42020148258 at PROSPERO website ( https://www.crd.york.ac.uk/PROSPERO/ ).

The enigmatic helicase DHX9 as a candidate prognostic biomarker for resected pancreatic ductal adenocarcinoma.

Background: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, and current therapies have limited efficacy on PDAC. The DEAH-box helicase 9 (DHX9) is widely reported to influence cell biological behavior via regulating DNA replication, genomic stability, transcription, translation, and microRNA biogenesis. However, the prognostic role of DHX9 in PDAC remains unclear. Thus, the objective of this study is to investigate the prognostic value of DHX9 expression in PDAC patients. Methods: Tumor specimens from PDAC patients with surgical resection were obtained, and DHX9 was stained and analyzed in this study. Univariate and multivariate Cox regression analyses were utilized to identify independent risk factors of overall survival (OS) and recurrence-free survival (RFS). The prognostic nomograms for predicting OS and RFS were established to obtain superior predictive power. Results: Among the enrolled 110 patients, 61 patients were identified as having high expression of DHX9. The correlation analysis revealed that higher DHX9 expression in PDAC was prone to have advanced N stage (p = 0.010) and TNM stage (p = 0.017). For survival, the median OS (21.0 vs. 42.0 months, p < 0.001) and RFS (12.0 vs. 24.0 months, p < 0.001) of patients in the high DHX9 group were significantly shorter than those in the low DHX9 group. Within the univariate and multivariate analyses, American Joint Committee on Cancer (AJCC) N stage (p = 0.036) and DHX9 expression (p = 0.041) were confirmed as independent prognostic factors of OS, while nerve invasion (p = 0.031) and DHX9 expression (p = 0.005) were independent prognostic factors of RFS. Finally, the novel prognostic nomograms for OS and RFS were established and showed superior predictive accuracy. Conclusion: This study identified the independent prognostic value of DHX9 for RFS and OS in resected PDAC patients, and higher DHX9 expression was prone to have an earlier recurrence and shorter OS. Therefore, DHX9 may be a promising and valuable biomarker and a potential target for treating PDAC. More accurate and promising predictive models would be achieved when DHX9 is incorporated into nomograms.

Ultrasound Responsive Smart Implantable Hydrogels for Targeted Delivery of Drugs: Reviewing Current Practices.

Over the last two decades, the process of delivering therapeutic drugs to a patient with a controlled release profile has been a significant focus of drug delivery research. Scientists have given tremendous attention to ultrasound-responsive hydrogels for several decades. These smart nanosystems are more applicable than other stimuli-responsive drug delivery vehicles (ie UV-, pH- and thermal-, responsive materials) because they enable more efficient targeted treatment via relatively non-invasive means. Ultrasound (US) is capable of safely transporting energy through opaque and complex media with minimal loss of energy. It is capable of being localized to smaller regions and coupled to systems operating at various time scales. However, the properties enabling the US to propagate effectively in materials also make it very difficult to transform acoustic energy into other forms that may be used. Recent research from a variety of domains has attempted to deal with this issue, proving that ultrasonic effects can be used to control chemical and physical systems with remarkable specificity. By obviating the need for multiple intravenous injections, implantable US responsive hydrogel systems can enhance the quality of life for patients who undergo treatment with a varied dosage regimen. Ideally, the ease of self-dosing in these systems would lead to increased patient compliance with a particular therapy as well. However, excessive literature has been reported based on implanted US responsive hydrogel in various fields, but there is no comprehensive review article showing the strategies to control drug delivery profile. So, this review was aimed at discussing the current strategies for controlling and targeting drug delivery profiles using implantable hydrogel systems.

Current status of research on short-term urogenital function after transanal total mesorectal excision and laparoscopic total mesorectal excision / 中华胃肠外科杂志

Thanks to the new surgical approach, transanal total mesorectal excision (taTME) has a better operative field exposure than laparoscopic-assisted total mesorectal excision (laTME), especially for male patients with obesity, pelvic stenosis or prostate hypertrophy. Nevertheless, whether the urogenital function and quality of life after taTME are better as compared to laTME requires further study. According to the existing studies, taTME and laTME are not significantly different in symptoms of the urology system for male patients, but some large sample clinical studies show that the incidence of urethral mechanical injury after taTME is higher. Unfortunately, there is no elaboration on that for females. The sexual function of male patients after taTME and laTME is both impaired. The sexual function of male patients will be relieved to different degrees over time, but there is no significant difference. Compared with laTME, taTME shows advantages in the sexual function for female patients. There is no significant difference in short-term urogenital system function between taTME and laTME at present. As a new surgical approach, the impact on urogenital system function after taTME is acceptable. However, whether there is a significant difference in urogenital function between taTME and laTME needs further research. In addition, functional results still need comprehensive evaluation, and preoperative baseline evaluation also needs to be enhanced. The functional evaluation for male and female should be carried out separately rather than confused. Questionnaire for evaluation of functional results also needs to be verified.

Research progress of pyruvate kinase type M2 in hepatocellular carcinoma / 中华肝脏病杂志

Primary hepatocellular carcinoma is one of the most common high-grade malignant tumors in the world. Its incidence ranks fifth among malignant tumors in China, and various therapeutic measures have poor curative effect. Pyruvate kinase type M2 is a key enzyme in the glycolytic pathway, and its abnormal expression in liver cancer is closely related to the proliferation, metastasis, diagnosis, treatment, prognosis, as well as drug and radiation resistance. Therefore, multi-pathway targeted regulation of pyruvate kinase type M2 use is expected to become a new direction for the treatment of primary liver cancer.

Regulation of Wenjingtang on HIF-1α Expression and Mitochondrial Function of Ectopic Endometrial Stromal Cells in Patients with Endometriosis / 中国实验方剂学杂志

ObjectiveThis study investigated the mechanism of Wenjingtang in the prevention and treatment of endometriosis （EMT） from the perspective of regulating hypoxia stress and mitochondrial function. MethodPrimary human endometrial stromal cells （ESCs） form ectopic endometrial tissues were isolated and cultured， the cells were divided into control group （Control）， 5% control serum group （5% KBXQ）， 10% control serum group （10% KBXQ）， 5% Wenjingtang serum group （5% WJTXQ） and 10% Wenjingtang serum group （10% WJTXQ）. ESCs in different groups were detected for proliferation by methyl thiazolyl tetrazolium （MTT） assay， mRNA and protein expression of hypoxia inducible factor-1α （HIF-1α） by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） and Western blot analysis， mitochondrial ultrastructure by transmission electron microscope， mitochondrial function ［mitochondrial membrane potential， mitochondrial membrane potential（MMP） and cytochrome C（Cyt C） content］ and apoptosis （cell membrane permeability， nuclear fluorescence intensity， nuclear size and cell counts） by high content screening （HCS） assay， apoptosis rate by flow cytometry， and proteins of B-cell lymphoma-2 （Bcl-2） associated X （Bax）， Bcl-2 and cleaved cysteinyl aspartate specific proteinase-3 （cleaved Caspase-3） by Western blot. ResultCompared with Control group， the 5% KBXQ and 10% KBXQ groups showed increased cell viability （P<0.01）， there was no significant change in HIF-1α mRNA and protein expression， transmission electron microscopy showed that the mitochondrial cristae were obvious and the inner and outer membranes of mitochondria were clear， HCS multichannel fluorescence staining showed that there were no significant changes in the expression of MMP， Cyt C and cell membrane permeability， and the nuclei showed uniform light staining， there were no significant changes in apoptosis rate， cleaved Caspase-3 protein expression and Bax/Bcl-2 ratio. Compared with Control group and corresponding concentration KBXQ group， the 5% WJTXQ and 10% WJTXQ group showed decreased cell viability （P<0.01） and HIF-1α mRNA and protein levels （P<0.05，P<0.01）， the ultrastructure of mitochondria was destroyed， some mitochondria were swollen and the cristae were blurred， moreover， decreased MMP and up-regulated Cyt C release （P<0.05，P<0.01）， increased cell membrane permeability （P<0.01）， and apoptosis characteristics included nuclear pyknosis， DNA agglutination in nucleus and decrease of cell numbers were observed （P<0.05，P<0.01）， increased apoptosis rate （P<0.01）， which was consistent with the results of HCS analysis， and up-regulated expression levels of cleaved Caspase-3 protein and Bax/Bcl-2 ratio （P<0.05，P<0.01）. ConclusionIn conclusion， the results suggest that Wenjingtang can improve hypoxia stress via down-regulating HIF-1α expression in ectopic ESCs， and inhibit cell proliferation， reduce mitochondrial biological activity and induce apoptosis， which might be the internal mechanism of Wenjingtang in preventing and treating EMT.

Autoimmune conditions following mRNA (BNT162b2) and inactivated (CoronaVac) COVID-19 vaccination: a descriptive cohort study among 1.1 million vaccinated people in Hong Kong

BackgroundConcerns regarding the autoimmune safety of COVID-19 vaccines may negatively impact vaccine uptake. We aimed to describe the incidence of autoimmune conditions following BNT162b2 and CoronaVac vaccination and compare these with age-standardized incidence rates in non-vaccinated individuals. MethodsThis is a descriptive cohort study conducted in public healthcare service settings. Territory-wide longitudinal electronic medical records of Hong Kong Hospital Authority users ([≥]16 years) were linked with COVID-19 vaccination records between February 23, 2021 and June 30, 2021. We classified participants into first/second dose BNT162b2 groups, first/second dose CoronaVac groups and non-vaccinated individuals for incidence comparison. The study outcomes include hospitalized autoimmune diseases (16 types of immune-mediated diseases across six body systems) within 28 days after first and second dose of vaccination. Age-standardized incidence rate ratios (IRRs) with exact 95% confidence intervals (CIs) were estimated using Poisson distribution. ResultsThis study included around 3.9 million Hong Kong residents, of which 1,122,793 received at least one dose of vaccine (BNT162b2: 579,998; CoronaVac: 542,795), and 721,588 completed two doses (BNT162b2: 388,881; CoronaVac: 332,707). Within 28 days following vaccination, cumulative incidences for all autoimmune conditions were below 9 per 100,000 persons, for both vaccines and both doses. None of the age-standardized incidence rates were significantly higher than the non-vaccinated individuals, except for an observed increased incidence of hypersomnia following the first dose of BNT162b2 (standardized IRR: 1.47; 95% CI: 1.10-1.94). ConclusionsAutoimmune conditions requiring hospital care are rare following mRNA and inactivated virus COVID-19 vaccination with similar incidence to non-vaccinated individuals. The association between first dose BNT162b2 vaccination and immune-related sleeping disorders requires further research. Population-based robust safety surveillance is essential to detect rare and unexpected vaccine safety events. FundingResearch Grant from the Food and Health Bureau, the Government of the Hong Kong Special Administrative Region (Ref. No. COVID19F01).

Effectiveness of COVID-19 vaccines against SARS-CoV-2 variants of concern: a systematic review and meta-analysis

BackgroundIt was urgent and necessary to synthesize the evidence for vaccine effectiveness (VE) against SARS-CoV-2 variants of concern (VOC). We conducted a systematic review and meta-analysis to provide a comprehensive overview of the effectiveness profile of COVID-19 vaccines against VOC. MethodsPublished and preprinted randomized controlled trials (RCTs), cohort studies, and case-control studies that evaluated the VE against VOC (Alpha, Beta, Gamma, or Delta) were searched until 31 August 2021. Pooled estimates and 95% confidence intervals (CIs) were calculated using random-effects meta-analysis. VE was defined as (1- estimate). ResultsSeven RCTs (51,169 participants), 10 cohort studies (14,385,909 participants) and 16 case-control studies (734,607 cases) were included. Eight COVID-19 vaccines (mRNA-1273, BNT162b2, ChAdOx1, Ad26.COV2.S, NVX-CoV2373, BBV152, CoronaVac, and BBIBP-CorV) were included in this analysis. Full vaccination was effective against Alpha, Beta/Gamma, and Delta variants, with VE of 88.3% (95% CI, 82.4-92.2), 70.7% (95% CI, 59.9-78.5), and 71.6% (95% CI, 64.1-77.4), respectively. But partial vaccination was less effective, with VE of 59.0% (95% CI, 51.3-65.5), 49.3% (95% CI, 33.0-61.6), and 52.6% (95% CI, 43.3-60.4), respectively. mRNA vaccines seemed to have higher VE against VOC over others, significant interactions (pinteraction < 0.10) were observed between VE and vaccine type (mRNA vaccines vs. non-mRNA vaccines). ConclusionsFull vaccination of COVID-19 vaccines is highly effective against Alpha variant, and moderate effective against Beta/Gamma and Delta variants. Partial vaccination has less VE against VOC. mRNA vaccines seem to have higher VE against Alpha, Beta/Gamma, and Delta variants over others.

Upregulation of Fecal Epithelial Heparanase mRNA Is Associated with Increased Ulcerative Colitis Activity and Cancerization Risk.

BACKGROUND: Heparanase (HPSE) is considered to play an important role in the occurrence, development and carcinogenesis of ulcerative colitis (UC). There are no reports about the detection of HPSE mRNA in feces to predict UC activity and cancerization risk. AIMS: To explore the feasibility and effectiveness of fecal epithelial HPSE mRNA in monitoring patients' UC activity and predicting cancer risk. METHODS: The clinical part of the study enrolled 20 patients with UC and 20 controls. Meanwhile, a UC-induced carcinogenesis mouse model was established using a combination treatment of dimethylhydrazine and dextran sulfate sodium. Tissue expression of HPSE protein was detected by immunohistochemistry. RT-qPCR was used to detect the expression of HPSE mRNA in colonic mucosa and feces. RESULTS: In the human study, the relative expressions of HPSE mRNA in colonic mucosa and feces were positively correlated with the Mayo score (P < 0.05), and with a significant correlation between feces and colonic mucosa (P < 0.05). In the mouse model, the relative expressions of HPSE mRNA in colonic mucosa and feces in the ulcerative colitis-associated colorectal cancer group was significantly higher than that of the UC group and the normal control group (P < 0.05), and with a significant correlation between feces and colonic mucosa (P < 0.05). CONCLUSIONS: The relative level of HPSE mRNA was positively correlated with UC activity and cancerization. The relative level of HPSE mRNA in feces was correlated with that in colonic mucosa. The detection of HPSE mRNA in feces can be used as a new marker for disease monitoring and cancer risk prediction of UC.

Preparation and targeting capability of corona forming in human ovarian plasma / 药学学报

After entering the physiological environment, proteins and other biomolecules bind to the nanoparticles' surface, called protein corona. The corona establishes a new bio-interface that affects its physicochemical properties and biological behaviors. Variations in types and contents of human plasma proteins during the different physiological states can substantially change the composition and effects of the corona. With folic acid (FA)-modified polylactic acid-polyglycolic acid copolymer (PLGA) nanoparticles, the formation of protein coronas and their influence on the targeting capability are studied in healthy and ovarian human plasma. All human plasma samples were collected at the Peking University Third Hospital and this study protocol has been approved by Peking University Third Hospital Medical Science Research Ethics Committee (2019-409-1). Dynamic light scattering measurements demonstrated a 10-40 nm increase in their size distributions and a 30 mV decreased in their absolute zeta-potential since protein corona-coated PLGA-PEG and PLGA-FA were formed. The SDS-PAGE analysis showed the composition of the protein coronas from ovarian and healthy plasma in PLGA-FA were markedly distinct, particularly for proteins with molecular weight of 45, 110 and >180 kDa. Flow cytometry indicated that the absorption of ovarian plasma in PLGA-FA led to a lower cellular uptake by SKOV3 cells. Our results suggest that in vitro formed ovarian plasma protein corona could shield targeting molecules and reduced receptor-mediated internalization. The results of this pilot study will provide evidence of the effectiveness of active targeting nanoparticles under pathologic conditions. Additionally, the protein corona in different diseases is emerging as a key point; thus, a comprehensive understanding could accelerate clinical translation of functionalized nanoparticles.

Research progress of neurogenesis and repair after cerebral ischemia and effect of Chinese medicine / 中国药理学通报

Cerebral ischemia can induce weak endogenous neurogenesis, which is not enough to repair neural injury after cerebral ischemia.In the treatment of cerebral ischemic diseases with Chinese medicine, different treatment methods based on syndrome differentiation are adopted according to the pathological mechanism of the diseases, and the advantages of neural repair after cerebral ischemia are well shown through comprehen-sive regulation.And in this paper, the effects of inflammation, neurovascular units, exogenous stem cell transplantation, exo- somes and other factors on neurogenesis and repair after cerebral ischemia and the intervention of Chinese medicine are described.

Interpretation of international expert consensus guidance on indications, implementation and quality measures for transanal total mesorectal excision / 中华胃肠外科杂志

In recent years, transanal total mesorectal excision (taTME) has been a hot spot in the field of colorectal surgery. Compared with the traditional laparoscopic technique, taTME has potential advantages in the treatment of rectal diseases. However, the procedural safety and effectiveness of taTME need further verification. In order to ensure the safe and standardized implementation of this procedure, the European Society of Coloproctology, together with 14 international academic organizations related to colorectal surgery and minimally invasive surgery, has developed the international expert consensus guidance on indications, implementation and quality measures for taTME. This paper introduces the background of the international consensus guidance, and interprets its core contents, including the surgical indications (complex pelvic conditions, malignant and benign rectal diseases), surgical quality and outcome evaluation, structured training, and expert center. It is expected to provide reference and guidance for Chinese colorectal surgery colleagues performing taTME.

Clinical application and research progress of single-hole laparoscopy / 西安交通大学学报(医学版)

The minimally invasive surgery is the mainstream of the development of surgery, and the transformation of surgery from traditional open surgery to endoscopic surgery has brought great benefits to patients. However, surgeons have never stopped their exploration from porous laparoscopy to single hole or even endoscopic surgery via the natural cavity, and looking for a more minimally invasive way of surgery has always been the pursuit of clinicians. As a minimally invasive technique, single-hole laparoscopy is becoming more and more widely used in clinic, and achievements and difficulties will guide the development direction of further research in the future. This paper reviews the clinical application of single-hole laparoscopy in recent years and the status quo of its development.

[Research progress of ion channels relating to cerebral ischemic diseases and prevention and treatment with traditional Chinese medicine].

Cerebral ischemia is a series of clinical symptoms and signs of cerebral ischemia, hypoxia and neuronal damage caused by cerebral artery stenosis or occlusion due to atherosclerosis or thrombosis, which seriously affects human health and quality of life. Cerebral ischemia involves the cascade reaction of the "neurovascular unit" system, and finally affects the normal physiological function of nerve cells and produces a series of pathological changes. And the changes in the structure and function of various ion channels in the cell membrane play an important role during this process. This article illustrates the changes in the ion channel associated with ce-rebral ischemic diseases, such as the potassium ion channels, sodium ion channels, calcium channels and other relevant channels, like AQP, TRPM2, TRPM7, TRPV4, ASICs, Cl~- channel, and explores the intervention effect of traditional Chinese medicine in prevention and treatment of cerebral ischemic diseases from the perspective of ion channels, in order to provide references for potential targets involving in drug development for the future prevention and treatment of cerebral ischemic diseases.

Microdialysis sampling and HPLC-MS/MS quantification of sinomenine, ligustrazine, gabapentin, paracetamol, pregabalin and amitriptyline in rat blood and brain extracellular fluid / 药学学报

The treatment plan for chronic pain often proceeds from a single drug to drug combination therapy. Sinomenine and ligustrazine, natural alkaline substances derived from traditional Chinese medicines, are expected to provide a new choice for combination analgesic therapy strategies. Here we establish a microdialysis sampling and HPLC-MS/MS quantification method for sinomenine, ligustrazine, gabapentin, paracetamol, pregabalin and amitriptyline in rat blood and brain extracellular fluid. Blood and brain microdialysis probes were implanted in the jugular vein toward the right atrium and left corpus striatum zone (AP +0.2 mm, ML 3.0 mm, DV 3.5 mm) in rats. The blood and brain microdialysis probes were perfused with citric acid buffer solution and Ringer's solution, respectively. Blood and brain extracellular fluid microdialysate were collected at intervals of 20 min at a perfusion rate of 1.5 μL·min-1, and continuously collected for 24 h after administration. The liquid chromatographic separation used a C18-reversed phase chromatographic column (HSS T3 2.5 μm, 2.1 mm×50 mm), the mobile phase was methanol/water (containing 0.05‰ formic acid), and gradient elution was carried out at a flow rate of 0.3 mL·min-1. Mass spectrometric detection used an electrospray ion source, positive ion mode and multi-reaction monitoring method. The selected quantitative ions for sinomenine, ligustrazine, gabapentin, paracetamol, pregabalin, amitriptyline and internal standard naloxone were 330/181, 137/80, 172/154, 152/110, 160/142, 278/233 and 328/310 respectively. The specificity, linear range, matrix effect, accuracy, precision, stability and probe recovery were investigated and confirmed to be suitable for the determination of the above drugs in rat blood and brain extracellular fluid microdialysate. The calculated in vivo recovery of microdialysis probes ranged from 19.38% to 25.88%. After intravenous administration of sinomenine (50 mg·kg-1), ligustrazine (50 mg·kg-1), gabapentin (50 mg·kg-1), paracetamol (50 mg·kg-1), pregabalin (50 mg·kg-1) and amitriptyline (40 mg·kg-1) to rats, the peak concentration in the blood microdialysate was in the range of 0.2-10 μg·mL-1. Drug concentrations could also be detected in brain extracellular fluid microdialysate, however with lower levels (peak concentration: 0.1-6 μg·mL-1) than those of blood microdialysates at each time point. In conclusion, this method can be applied to microdialysis sampling and quantification of sinomenine, ligustrazine, gabapentin, paracetamol, pregabalin and amitriptyline in rats. The method will promote research in identifying herb-drug pharmacokinetic interactions, as well as safety concerns in combination-therapy strategies.