Changes in serum levels of Hcy and MMP-9 and risk factor analysis in patients with coronary heart disease complicating Helicobacter pylori infection in Chengdu area / 公共卫生与预防医学

Objective To study the changes in serum homocysteine (Hcy) and matrix metalloproteinase-9 (MMP-9) levels and risk factors in patients with coronary heart disease (CHD) complicated with Helicobacter pylori (HP) infection in Chengdu area, and to provide a theoretical basis for the prevention of HP infection in patients with coronary heart disease. Methods A total of 348 CHD patients admitted to our hospital in Chengdu from 2019 to 2021 were selected. Hp infection status was detected by C14 urea breath test. Patients were classified into control group (n=197) and HP infection group (n=151) according to the detection results. Data including gender, age, body mass index and peptic ulcer history were collected, and univariate analysis and logistic regression were used to screen the risk factors affecting the occurrence of HP infection in patients with CHD. Results The prevalence rate of HP infection was 43.39% (151/348) among the selected CHD patients. Serum levels of Hcy and MMP-9 were notably elevated in HP infection group compared with control group (P<0.05). The proportion of patients with age ≥60 years old, hyperlipidemia, proton pump inhibitor use history, and frequent consumption of out-of-home food and spicy food in HP infection group was obviously larger than that in control group (P<0.05). Hyperlipidemia (OR=3.719), history of proton pump inhibitor use (OR=3.254) and frequent consumption of out-of-home food (OR=2.721) were independent risk factors for HP infection in CHD patients (P<0.05). Conclusion CHD patients in Chengdu suffer a prevalence rate of HP infection, and have elevated levels of serum Hcy and MMP-9. Furthermore, the intervention measures for patients with hyperlipidemia, proton pump inhibitor drug use history and frequent consumption of out-of-home food are of vital importance for decreasing the risk of HP infection.

Clinical value of complete lateral position endoscopic combined intra-renal surgery in treatment of staghorn kidney calculi / 中国医师进修杂志

Objective:To assess the safety and feasibility of complete lateral position endoscopic combined intra-renal surgery (ECIRS) in treatment of staghorn kidney calculi.Methods:The clinical data of 105 patients with staghorn kidney calculi from March 2016 to July 2022 in the First Hospital of Shanxi Medical University were retrospectively analyzed. Among them, 55 patients were treated with lateral position percutaneous nephrolithotomy (PCNL) (PCNL group), and 50 patients were treated with complete lateral position ECIRS (ECIRS group). The operative time, removal time of double J-tube, postoperative hospital stay, postoperative hemoglobin decrease value, operative complications (using Clavien-Dindo grading criteria), additional postoperative intervention and calculi free rate were compared between two groups.Results:Both groups of patients were successfully operated. The operative time, postoperative hemoglobin decrease value and rate of additional postoperative intervention in ECIRS group were significantly lower than those in PCNL group: (98.3 ± 19.1) min vs. (103.4 ± 16.5) min, (9.34 ± 3.04) g/L vs. (12.55 ± 4.75) g/L and 8.00% (4/50) vs. 21.82% (12/55), the calculi free rate was significantly higher than that in PCNL group: 90.00% (45/50) vs. 74.55% (41/55), and there were no statistical differences ( P<0.05 or <0.01); there were no statistical differences in the removal time of double J-tube, postoperative hospital stay, incidence of Clavien-Dindo≥ grade Ⅱ operative complications between two groups ( P>0.05). Conclusion:The complete lateral position ECIRS is a safe and effective treatment for staghorn kidney calculi, and is a good complement to the ECIRS technique because of its high stone free rate in phase Ⅰ, low complication incidence and easy dissemination.

Stem cell transplantation for mevalonic aciduria: a case report and literature review / 中华实用儿科临床杂志

Clinical data of a child with mevalonic aciduria (MA) who underwent stem cell transplantation (SCT) in the Department of Rheumatology and Immunology, Children′s Hospital, Capital Institute of Pediatrics in March 2019 were retrospectively analyzed.A girl aged 2 years and 11 months old presented with recurrent fever for 2 years and 11 months and swelling of both knees for 9 months was enrolled.The child also had specific facial features and development delay.The urinary mevalonic acid and inflammatory factor levels were increased.The whole exome sequencing showed compound heterozygous mutations c. 439G>A (p.A147T) and c. 976G>A(p.G326R) in the MVK gene.After achieving a partial remission following the treatment of Tocilizumab, the patient was treated with SCT and thus yielded the complete remission.Through literature review of a total of 39 children with MA, most of cases suffer MA since the infancy.All systems can be affected by MA.Clinical manifestations of the nervous system abnormalities, recurrent fever, hepatosplenomegaly, delayed physical development, gastrointestinal symptoms, and eye involvement were helpful for the diagnosis of MA.To date, 10 cases (including one case in this study) of MA have been reported to receive SCT after achieving a partial remission of other treatment, and 7 finally achieve a complete remission.This case report provided references that SCT is an effective treatment to children with MA who fail to achieve a complete remission after conventional treatment.

Effect of Modified Gegen Qinliantang on FXR/SHP/PPARα Signaling Pathway in Type 2 Diabetic db/db Mice / 中国实验方剂学杂志

ObjectiveTo observe the effect of modified Gegen Qinliantang on the expression levels of proteins related to the farnesoid X receptor/small heterodimer partner/peroxisome proliferator-activated receptor α （FXR/SHP/PPARα） signaling pathway in the liver tissue of db/db model mice with type 2 diabetes mellitus （T2DM） and explore the underlying mechanism of action of modified Gegen Qinliantang. MethodThirty db/db mice were randomly divided into model group， metformin group （0.2 g·kg-1）， and high-， medium-， and low-dose modified Gegen Qinliantang groups （31.9， 19.1， 6.4 g·kg-1）， with 6 mice in each group. An additional six m/m mice were assigned to the blank group. Respective drugs were administered via oral gavage for 12 weeks. Mouse body weight， fasting blood glucose （FBG）， total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） levels were measured. Oil red O staining was used to observe hepatic lipid accumulation and periodic acid-schiff （PAS） staining was used to assess hepatic glycogen deposition. Ammonium ferric sulfate staining was used to observe cholesterol deposition in intestinal tissues. Western blot was employed to detect the expression of FXR， cholesterol 7α-hydroxylase （CYP7A1）， SHP， and PPARα proteins in liver tissues， and enzyme-linked immunosorbent assay （ELISA） was used to measure serum free fatty acid （FFA） levels. ResultAt the end of the treatment， compared with the blank group， the model group exhibited significant increases in mouse body weight， FBG， FFA， TC， TG， and LDL-C levels （P<0.01）， along with significant hepatic lipid droplets， reduced hepatic glycogen， noticeable cholesterol accumulation in intestinal tissues， significantly decreased expression of FXR， SHP， PPARα proteins， and significantly increased expression of CYP7A1 protein in liver tissues （P<0.01）. Compared with the model group， the metformin group and the high- and medium-dose modified Gegen Qinliantang groups demonstrated significant reductions in mouse body weight， FBG， FFA， TC， TG， LDL-C levels （P<0.05， P<0.01）， significant increases in HDL-C levels （P<0.05， P<0.01）， decreased hepatic lipid accumulation， increased hepatic glycogen， reduced intestinal cholesterol accumulation， significantly increased expression of FXR， SHP， PPARα proteins， and significantly decreased expression of CYP7A1 protein in liver tissues （P<0.01）. ConclusionModified Gegen Qinliantang may regulate the FXR/SHP/PPARα signaling pathway to suppress FFA levels and improve lipid metabolism in T2DM mice.

Monoterpenes from an aqueous extract of the Angelica sinensis root head / 药学学报

Eleven monoterpenes including seven new chemical structures or new natural products covering two pairs of scalemic enantiomers, together with four known analogues, were isolated from an aqueous extract of the Angelica sinensis root head (Guitou) by separation techniques of column chromatography over macroporous adsorbent resin, MCI resin, silica gel, Sephadex LH-20, and Toyopearl HW-40C, together with preparative thin-layer chromatography as well as reversed phase and chiral HPLC. Their structures were determined by spectroscopic data analysis, combined with theoretic calculation of electronic circular dichroism (ECD) spectra and single crystal X-ray diffraction. The new structures or new natural products named (+)-/(-)-angelinones A and B [(+)-/(-)-1 and (+)-/(-)-2], angelinones C and D (3 and 4), and angelinol A (5), respectively, while the known analogues were 6β,9-dihydroxy-(+)-α-pinene (6), 1,1,5-trimethyl-2-hydroxymethyl-cyclohexa-2,5-dien-4-one (7), jasminol E (8), and (+)-trans-sobrerol (9). All the isolates were reported in this plant for the first time, except for the previously reported 6 from an ethanol extract of the aerial parts of A. sinensis, of which the structure was confirmed by X-ray crystallography in this study.

Differences in related indicators after Toric intraocular lens implantation in cataract patients with different axial lengths / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the differences in visual recovery, corneal astigmatism, and rotation stability of Toric intraocular lens(TIOL)implantation in cataract patients with different axial lengths.METHODS: Retrospective analysis. A total of 132 patients(132 eyes)with age-related cataract and corneal astigmatism who underwent phacoemulsification cataract extraction combined with TIOL implantation in our hospital's ophthalmology department from February 2021 to September 2022 were selected. They were divided into two groups based on the axial length: the group with axial length ≤24mm(79 cases, 79 eyes)and the group with axial length &#x003E;24mm(53 cases, 53 eyes). Compare the best corrected distance visual acuity(BCDVA), corneal astigmatism, and TIOL rotation between the two groups of patients at 3mo after surgery.RESULT: After 3mo of surgery, both groups of patients had improved BCDVA and significantly decreased corneal astigmatism compared to those before surgery(P&#x003C;0.001). However, there was no difference in BCDVA and corneal astigmatism between the two groups(P&#x003E;0.05), and there was no significant difference in TIOL rotation between the two groups [(5.24±3.72)° vs.(6.36±4.21)°, P=0.110].CONCLUSION: There is no significant difference in visual recovery, corneal astigmatism, and TIOL rotational stability after TIOL implantation in cataract patients with different axial lengths.

Effect of acupuncture on HIF-1α/NLRP3 inflammatory signaling pathway in the rats with cerebral ischemia-reperfusion injury / 中国针灸

OBJECTIVE@#To observe the effects of Xingnao Kaiqiao (regaining consciousness and opening orifices) acupuncture therapy on the expression of hypoxia-inducible factor 1α (HIF-1α) and Nod-like receptor protein 3 (NLRP3) in cerebral ischemia-reperfusion rats, and to explore the mechanism of acupuncture against cerebral ischemia-reperfusion injury.@*METHODS@#Seventy-two male SD rats were randomly divided into a sham-operation group, a model group, an acupuncture group and a non-point acupuncture group, with 18 rats in each one. Using modified Longa thread embolization method, the rat model of acute focal cerebral ischemia was prepared; and after 2 h ischemia, the reperfusion was performed to prepared the model of cerebral ischemia-reperfusion. Immediately after reperfusion, Xingnao Kaiqiao acupuncture method was applied to bilateral "Neiguan" (PC 6) and "Shuigou" (GV 26) in the acupuncture group, while in the non-point acupuncture group, acupuncture was delivered at non-points and all of the needles were retained for 30 min in these two groups. The samples were collected 24 h after reperfusion in the rats of each group. Zea-Longa neurological deficit score was used to evaluate the degree of cerebral neurological impairment, TTC staining was adopted to observe the volume percentage of cerebral infarction, HE staining was provided to observe the morphological changes of brain, and Western blot was applied for detecting the expression of HIF-1α and NLRP3 proteins in the cerebral cortex on the right side.@*RESULTS@#Compared with the sham-operation group, neurological deficit score and volume percentage of cerebral infarction were increased in the model group (P<0.01), and HIF-1α and NLRP3 protein expression was elevated (P<0.01). Compared with the model group, neurological deficit score and volume percentage of cerebral infarction were decreased (P<0.01), and HIF-1α and NLRP3 protein expression was lower (P<0.01) in the acupuncture group. There was no significant difference in above indexes in the non-point acupuncture group compared with the model group (P>0.05). Compared with the sham-operation group, the brain tissue of the rats in the model group and the non-point acupuncture group was loose and edema, and the nuclei were shriveled. The brain tissue morphology in the acupuncture group was similar to that of the sham-operation group.@*CONCLUSION@#Acupuncture can alleviate cerebral ischemia-reperfusion injury, and its mechanism may be related to the regulation of HIF-1α/NLRP3 signaling pathway to attenuate inflammatory response.

Research progress on mechanism of TLR4 in carcinogenesis of inflammatory bowel disease / 中国药理学通报

Patients with inflammatory bowel disease (IBD) have an increased risk of colorectal cancer (CRC) compared with the general population. Currently the molecular mechanism of CRC occurrence in the context of IBD is not clear. The inflammation-atypical hyperplasia-cancer process has been widely accepted. Toll-like receptor 4(TLR4) is a key receptor for pathogen recognition and immune activation, and plays a crucial role in inflammatory and carcinogenic transformation of IBD. Therefore, this paper reviews the epidemiology of colitis-associated colorectal cancer (CAC) and the main mechanisms of TLR4 in the development of IBD to CAC, which will help to further understand the carcinogenesis of IBD, detect and better describe CAC at an earlier stage, and provide more effective prevention and treatment for CAC.

Study on antidepressant effects of Nrf2/HO-l of volatile oil from Chai Dang Bo drug-group on OB model rats and its mechanism / 中国药理学通报

Aim To confirm the antidepressant effect of the volatile oil part of the disassembled prescription drugs (Chai Hu, Dang Gui and Bo He, referred to as CDB) from Xiaoyao Powder and investigate its mechanism via Nrf2/H0-1 signaling pathway on OB model rats. Methods GC-MS analysis of the main components of volatile oil part of CDB was performed. The rats were randomly divided into sham operation group, model group, fluoxetine hydrochloride group (FLX, 10 mg • kg

Comprehensive assessment of mismatch repair and microsatellite instability status in molecular classification of endometrial carcinoma / 中华妇产科杂志

Objective: To explore the concordance and causes of different mismatch repair (MMR) and microsatellite instability (MSI) detection results in endometrial carcinoma (EC) molecular typing. Methods: A total of 214 EC patients diagnosed from January 2021 to April 2023 were selected at the Department of Pathology, Peking University Third Hospital. The immunohistochemistry (IHC) results of MMR protein were reviewed. Tumor specific somatic mutations, MMR germline mutations, microsatellite scores and tumor mutation burden (TMB) were detected by next-generation sequencing (NGS) with multi-gene panel. Methylation-specific PCR was used to detect the methylation status of MLH1 gene promoter in cases with deficient MLH1 protein expression. In cases with discrepant results between MMR-IHC and MSI-NGS, the MSI status was detected again by PCR (MSI-PCR), and the molecular typing was determined by combining the results of TMB and MLH1 gene promoter methylation. Results: (1) In this study, there were 22 cases of POLE gene mutation subtype, 55 cases of mismatch repair deficient (MMR-d) subtype, 29 cases of p53 abnormal subtype, and 108 cases of no specific molecular profile (NSMP). The median age at diagnosis of MMR-d subtype (54 years old) and the proportion of aggressive histological types (40.0%, 22/55) were higher than those of NSMP subtype [50 years old and 12.0% (13/108) respectively; all P<0.05]. (2) Among 214 patients, MMR-IHC test showed that 153 patients were mismatch repair proficient (MMR-p), 49 patients were MMR-d, and 12 patients were difficult to evaluate directly. MSI-NGS showed that 164 patients were microsatellite stable (MSS; equal to MMR-p), 48 patients were high microsatellite instability (MSI-H; equal to MMR-d), and 2 patients had no MSI-NGS results because the effective sequencing depth did not meet the quality control. The overall concordance between MMR-IHC and MSI-NGS was 94.3% (200/212). All the 12 discrepant cases were MMR-d or subclonal loss of MMR protein by IHC, but MSS by NGS. Among them, 10 cases were loss or subclonal loss of MLH1 and (or) PMS2 protein. Three discrepant cases were classified as POLE gene mutation subtype. In the remaining 9 cases, 5 cases and 3 cases were confirmed as MSI-H and low microsatellite instability (MSI-L) respectively by MSI-PCR, 6 cases were detected as MLH1 gene promoter methylation and 7 cases demonstrated high TMB (>10 mutations/Mb). These 9 cases were classified as MMR-d EC. (3) Lynch syndrome was diagnosed in 27.3% (15/55) of all 55 MMR-d EC cases, and the TMB of EC with MSH2 and (or) MSH6 protein loss or associated with Lynch syndrome [(71.0±26.2) and (71.5±20.1) mutations/Mb respectively] were significantly higher than those of EC with MLH1 and (or) PMS2 loss or sporadic MMR-d EC [(38.2±19.1) and (41.9±24.3) mutations/Mb respectively, all P<0.01]. The top 10 most frequently mutated genes in MMR-d EC were PTEN (85.5%, 47/55), ARID1A (80.0%, 44/55), PIK3CA (69.1%, 38/55), KMT2B (60.0%, 33/55), CTCF (45.5%, 25/55), RNF43 (40.0%, 22/55), KRAS (36.4%, 20/55), CREBBP (34.5%, 19/55), LRP1B (32.7%, 18/55) and BRCA2 (32.7%, 18/55). Concurrent PTEN, ARID1A and PIK3CA gene mutations were found in 50.9% (28/55) of MMR-d EC patients. Conclusions: The concordance of MMR-IHC and MSI-NGS in EC is relatively high.The discordance in a few MMR-d EC are mostly found in cases with MLH1 and (or) PMS2 protein loss or MMR protein subclonal staining caused by MLH1 gene promoter hypermethylation. In order to provide accurate molecular typing for EC patients, MLH1 gene methylation, MSI-PCR, MMR gene germline mutation and TMB should be combined to comprehensively evaluate MMR and MSI status.

Effect of Modified Gegen Qinliantang on TGR5/cAMP/GLP-1 Signaling Pathway in Pancreatic Tissue of Type 2 Diabetes Mellitus db/db Mice / 中国实验方剂学杂志

ObjectiveTo discuss the effect of modified Gegen Qinliantang （MGQT） on blood glucose and lipids and Takeda G protein-coupled receptor 5 （TGR5）-related pathways in pancreatic tissue of obese type 2 diabetes mellitus （T2DM） mice. MethodA total of 10 male specific pathogen free （SPF） m/m mice （7 weeks old） and 50 male SPF （7 weeks old） were adaptively fed for one week in SPF laboratory. The m/m mice were included in the blank group. T2DM was induce d in the 50 db/db mice. The model mice were randomized into the model group， metformin group （0.2 g·kg-1）， high-dose， medium-dose， and low-dose （31.9， 19.1， 6.4 g·kg-1） MGQT groups， with 10 in each group， and the drug dose was10 mL·kg-1. The model group and the blank group received distilled water of the same volume. The administration lasted 12 weeks （once/day）. Fasting blood glucose （FBG） was detected regularly. After 12 weeks of administration， serum levels of glycated serum protein （GSP）， serum glucose （GLU）， total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were detected. Pathological changes in the pancreatic tissue were based on hematoxylin-eosin （HE） staining. Western blot was used to determine the protein expression of TGR5， protein kinase A （PKA）， phosphorylated （p）-PKA， cyclic-AMP response element binding protein （CREB）， p-CREB， proprotein convertase 1/3 （PC1/3）， and glucagon-like peptide-1 （GLP-1） in pancreatic tissues. The level of cyclic adenosine monophosphate （cAMP） in pancreatic tissue was determined by enzyme-linked immunosorbent assay （ELISA）. ResultCompared with the blank group， the model group had pathological changes in pancreatic tissue， high levels of FBG， GSP， GLU， TC， TG， and LDL-C （P<0.01）， low level of HDL-C （P<0.05）， low protein expression of TGR5， p-PKA （Thr197）/PKA， p-CREB （Ser133）/CREB， PC1/3， and GLP-1 in pancreatic tissue （P<0.01）， and low content of cAMP in the pancreas （P<0.01）. Pancreatic tissue lesion in the treatment groups were milder than that in the model group. Both the high-dose MGQT and metformin can reduce the levels of FBG， GSP， GLU， TC， TG， and LDL-C in db/db mice （P<0.05， P<0.01） and increase the level of HDL-C （P<0.01）. Except the GLP-1 protein in the medium-dose MGQT group， the protein expression of TGR5， p-PKA （Thr197）/PKA， p-CREB （Ser133）/CREB， PC1/3， and GLP-1 in the high-dose and medium-dose MGQT groups and the metformin group increased compared with that in the model group （P<0.05， P<0.01）. The content of cAMP in the pancreatic tissue of the high-dose and medium-dose MGQT groups and the metformin group was raised compared with that in model group （P<0.05， P<0.01）. ConclusionMGQT can improve the glucose homeostasis in db/db mice with T2DM by regulating TGR5/cAMP/GLP-1 signaling pathway-related protein expression.

Development and validation of a score predicting mortality for older patients with mitral regurgitation / 老年心脏病学杂志（英文版）

OBJECTIVE@#To develop and validate a user-friendly risk score for older mitral regurgitation (MR) patients, referred to as the Elder-MR score.@*METHODS@#The China Senile Valvular Heart Disease (China-DVD) Cohort Study functioned as the development cohort, while the China Valvular Heart Disease (China-VHD) Study was employed for external validation. We included patients aged 60 years and above receiving medical treatment for moderate or severe MR (2274 patients in the development cohort and 1929 patients in the validation cohort). Candidate predictors were chosen using Cox's proportional hazards model and stepwise selection with Akaike's information criterion.@*RESULTS@#Eight predictors were identified: age ≥ 75 years, body mass index < 20 kg/m2, NYHA class III/IV, secondary MR, anemia, estimated glomerular filtration rate < 60 mL/min per 1.73 m2, albumin < 35 g/L, and left ventricular ejection fraction < 60%. The model displayed satisfactory performance in predicting one-year mortality in both the development cohort (C-statistic = 0.73, 95% CI: 0.69-0.77, Brier score = 0.06) and the validation cohort (C-statistic = 0.73, 95% CI: 0.68-0.78, Brier score = 0.06). The Elder-MR score ranges from 0 to 15 points. At a one-year follow-up, each point increase in the Elder-MR score represents a 1.27-fold risk of death (HR = 1.27, 95% CI: 1.21-1.34, P < 0.001) in the development cohort and a 1.24-fold risk of death (HR = 1.24, 95% CI: 1.17-1.30, P < 0.001) in the validation cohort. Compared to EuroSCORE II, the Elder-MR score demonstrated superior predictive accuracy for one-year mortality in the validation cohort (C-statistic = 0.71 vs. 0.70, net reclassification improvement = 0.320, P < 0.01; integrated discrimination improvement = 0.029, P < 0.01).@*CONCLUSIONS@#The Elder-MR score may serve as an effective risk stratification tool to assist clinical decision-making in older MR patients.

Functional characterization and enzymatic properties of flavonoid glycosyltransferase gene CtUGT49 in Carthamus tinctorius / 中国中药杂志

Carthami Flos, as a traditional blood-activating and stasis-resolving drug, possesses anti-tumor, anti-inflammatory, and immunomodulatory pharmacological activities. Flavonoid glycosides are the main bioactive components in Carthamus tinctorius. Glycosyltransferase deserves to be studied in depth as a downstream modification enzyme in the biosynthesis of active glycoside compounds. This study reported a flavonoid glycosyltransferase CtUGT49 from C. tinctorius based on the transcriptome data, followed by bioinformatic analysis and the investigation of enzymatic properties. The open reading frame(ORF) of the gene was 1 416 bp, encoding 471 amino acid residues with the molecular weight of about 52 kDa. Phylogenetic analysis showed that CtUGT49 belonged to the UGT73 family. According to in vitro enzymatic results, CtUGT49 could catalyze naringenin chalcone to the prunin and choerospondin, and catalyze phloretin to phlorizin and trilobatin, exhibiting good substrate versatility. After the recombinant protein CtUGT49 was obtained by hetero-logous expression and purification, the enzymatic properties of CtUGT49 catalyzing the formation of prunin from naringenin chalcone were investigated. The results showed that the optimal pH value for CtUGT49 catalysis was 7.0, the optimal temperature was 37 ℃, and the highest substrate conversion rate was achieved after 8 h of reaction. The results of enzymatic kinetic parameters showed that the K_m value was 209.90 μmol·L~(-1) and k_(cat) was 48.36 s~(-1) calculated with the method of Michaelis-Menten plot. The discovery of the novel glycosyltransferase CtUGT49 is important for enriching the library of glycosylation tool enzymes and provides a basis for analyzing the glycosylation process of flavonoid glycosides in C. tinctorius.

Research progress on Rhododendron molle in treatment of rheumatoid arthritis / 中国中药杂志

Rheumatoid arthritis(RA), as a chronic autoimmune disease, has a high incidence and disability rate, causing significant suffering to patients. Due to its complex pathogenesis, it has not been fully elucidated to date, and its treatment remains a challenging problem in the medical field. Although western medicine treatment options have certain efficacy, they require prolonged use and are expensive. Additionally, they carry risks of multiple infections and adverse reactions like malignancies. The Chinese herbal medicine Rhododendron molle is commonly used in folk medicine for its properties of dispelling wind, removing dampness, calming nerves, and alleviating pain in the treatment of diseases like rheumatic bone diseases. In recent years, modern clinical and pharmacological studies have shown that the diterpenoids in R. molle are effective components, exhibiting immune-regulatory, anti-inflammatory, and analgesic effects. This makes it a promising candidate for treating RA with a broad range of potential applications. However, R. molle has certain toxic properties that hinder its clinical application and lead to the wastage of its resources. This study reviewed recent research progress on the mechanism of R. molle in preventing and treating RA, focusing on its chemical components, anti-inflammatory and analgesic properties and summarized the adverse reactions associated with R. molle, aiming to offer new ideas for finding natural remedies for RA and methods to reduce toxicity while enhancing the effectiveness of R. molle. The study seeks to clarify the safety and efficacy of R. molle and its extracts, providing a theoretical basis for its application prospects and further promoting the development and utilization of R. molle resources.

An antigen self-assembled and dendritic cell-targeted nanovaccine for enhanced immunity against cancer

The rise of nanotechnology has opened new horizons for cancer immunotherapy. However, most nanovaccines fabricated with nanomaterials suffer from carrier-related concerns, including low drug loading capacity, unpredictable metabolism, and potential systemic toxicity, which bring obstacles for their clinical translation. Herein, we developed an antigen self-assembled nanovaccine, which was resulted from a simple acryloyl modification of the antigen to induce self-assembly. Furthermore, a dendritic cell targeting head mannose monomer and a mevalonate pathway inhibitor zoledronic acid (Zol) were integrated or absorbed onto the nanoparticles (denoted as MEAO-Z) to intensify the immune response. The synthesized nanovaccine with a diameter of around 70 nm showed successful lymph node transportation, high dendritic cell internalization, promoted costimulatory molecule expression, and preferable antigen cross-presentation. In virtue of the above superiorities, MEAO-Z induced remarkably higher titers of serum antibody, stronger cytotoxic T lymphocyte immune responses and IFN-γ secretion than free antigen and adjuvants. In vivo, MEAO-Z significantly suppressed EG7-OVA tumor growth and prolonged the survival time of tumor-bearing mice. These results indicated the translation promise of our self-assembled nanovaccine for immune potentiation and cancer immunotherapy.

Neuroglobin Facilitates Neuronal Oxygenation through Tropic Migration under Hypoxia or Anemia in Rat: How Does the Brain Breathe? / 神经科学通报·英文版

The discovery of neuroglobin (Ngb), a brain- or neuron-specific member of the hemoglobin family, has revolutionized our understanding of brain oxygen metabolism. Currently, how Ngb plays such a role remains far from clear. Here, we report a novel mechanism by which Ngb might facilitate neuronal oxygenation upon hypoxia or anemia. We found that Ngb was present in, co-localized to, and co-migrated with mitochondria in the cell body and neurites of neurons. Hypoxia induced a sudden and prominent migration of Ngb towards the cytoplasmic membrane (CM) or cell surface in living neurons, and this was accompanied by the mitochondria. In vivo, hypotonic and anemic hypoxia induced a reversible Ngb migration toward the CM in cerebral cortical neurons in rat brains but did not alter the expression level of Ngb or its cytoplasm/mitochondria ratio. Knock-down of Ngb by RNA interference significantly diminished respiratory succinate dehydrogenase (SDH) and ATPase activity in neuronal N2a cells. Over-expression of Ngb enhanced SDH activity in N2a cells upon hypoxia. Mutation of Ngb at its oxygen-binding site (His64) significantly increased SDH activity and reduced ATPase activity in N2a cells. Taken together, Ngb was physically and functionally linked to mitochondria. In response to an insufficient oxygen supply, Ngb migrated towards the source of oxygen to facilitate neuronal oxygenation. This novel mechanism of neuronal respiration provides new insights into the understanding and treatment of neurological diseases such as stroke and Alzheimer's disease and diseases that cause hypoxia in the brain such as anemia.

Analysis of the characteristics of SPTB gene variants among 16 children with Hereditary spherocytosis / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical characteristics and spectrum of SPTB gene variants among 16 Chinese children with Hereditary spherocytosis (HS) and explore their genotype-phenotype correlation.@*METHODS@#Sixteen children who were diagnosed with HS at the Affiliated Hospital of Capital Institute of Pediatrics from November 2018 to July 2022 were selected as the research subjects. Genetic testing was carried out by whole exome sequencing. Candidate variants were verified by Sanger sequencing and subjected to bioinformatic analysis and prediction of 3D structure of the protein. Correlation between the SPTB genotypes and clinical phenotypes was analyzed using Chi-squared test.@*RESULTS@#The male-to-female ratio of the HS patients was 6 : 10, with the median age being 7-year-and-10-month. Clinical features of the patients have included anemia, reticulocytosis and gradual onset of splenomegaly. Mild, moderate and severe anemia have respectively occurred in 56.25% (9/16), 31.25% (5/16) and 12.50% (2/16) of the patients. SPTB gene variants were detected in all patients, among which 10 were unreported previously and 7 were de novo in origin. Loss of function (LOF) variants accounted for 93.75% (15/16). Only one missense variant was detected. Eleven, 4 and 1 of the variants had occurred in the repeat domain, CH1 domain, and dimerization domain, respectively. There was no significant correlation between the type or domain of the SPTB gene variants with the clinical features such as severity of anemia (x² = 3.345, P > 0.05). All of the variants were predicted to be pathogenic or likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics.@*CONCLUSION@#Mild to moderate anemia are predominant clinical features of the HS children harboring a SPTB gene variant, for which LOF variants are the main mutational type. The clinical feature of HS is unaffected by the type of the variants.

Mechanism of essential oil from Schizonepeta tenuifolia in treatment of depression based on network pharmacology and experimental verification / 中国中药杂志

This paper aimed to explore the antidepressant effect of the essential oil from Schizonepeta tenuifolia Briq.(EOST) on the treatment of depression and its mechanism by using a combination of network pharmacology and the mouse model of lipopolysaccharide(LPS)-induced depression. The chemical components in EOST were identified using gas chromatography-mass spectrometer(GC-MS), and 12 active components were selected as the study objects. The targets related to EOST were obtained by Traditional Chinese Medicines Systems Pharmacology(TCMSP) and SwissTargetPrediction database. The targets related to depression were screened out through GeneCards, Therapeutic Target Database(TTD), and Online Mendelian Inheritance in Man(OMIM) database. The Venny 2.1 was applied to screen out the common targets of EOST and depression. The targets were imported into Cytoscape 3.7.2 to generate "drug-active component-diease-target" network diagram. The protein-protein interaction(PPI) network was constructed using STRING 11.5 database and Cytoscape 3.7.2, and the core targets were screened out. DAVID 6.8 database was used for Gene Ontology(GO) func-tional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis, and subsequently the enrichment results were visualized through the bioinformatics platform. The mouse model of depression was induced by intraperitoneally injecting with LPS in mice. Before modeling, mice were administrated orally with EOST. The antidepressant effect of EOST was evalua-ted by tail suspension test(TST), forced swimming test(FST), and novelty suppressed feeding test(NSFT) after modeling. The content of interleukin(IL)-1β was determined by enzyme-linked immunosorbent assay(ELISA), and the protein expression levels of IL-1β and pro IL-1β in the hippocampus were determined by Western blot. There were 12 main components and 179 targets in EOAT, of which, 116 targets were related to depression, mainly involved in neuroactive ligand-receptor interaction, calcium signaling pathway, and cyclic adenosine monophosphate(cAMP) signaling pathway. Biological processes such as synaptic signal transduction, G-protein coupled receptor signaling pathway, and chemical synaptic transmission were involved. Molecular functions such as neurotransmitter receptor activity, RNA polymerase Ⅱ transcription factor activity, and heme binding were involved. In mice experiments, the results showed that EOST at 100 mg·kg~(-1) and 50 mg·kg~(-1) significantly shortened the immobility time in TST and FST as well as the feeding latency in NSFT compared with the model group, decreased the levels of serum IL-1β and NO, and reduced the protein expression levels of IL-1β and pro IL-1β in the hippocampus. In conclusion, EOST shows a good antidepressant effect in a multi-component, multi-target, and multi-pathway manner. The mechanism may be attributed to the fact that EOST can down-regulate the protein expression levels of IL-1β and pro IL-1β, decrease the release of inflammatory factors, and reduce neuroinflammation response.

Genetic characteristics and survival analysis of 27 cases of juvenile myelomonocytic leukemia / 中华儿科杂志

Objective: To investigate the genetic and genomic profiling of juvenile myelomonocytic leukemia (JMML) and factors affecting its survival rate. Methods: Clinical characteristics, cytogenetics, molecular biology results and survival status of children with 27 JMML cases admitted to the Hematology Department of Children's Hospital, Capital Institute of Pediatrics from December 2012 to December 2021 were analyzed retrospectively, and the outcomes of the children were followed up. Kaplan-Meier method was used for survival analysis. Univariate analysis was used for analyzing factors affecting the overall survival (OS) rates of patients who received hematopoietic stem cell transplantation (HSCT). Log-Rank test was used for comparison of survival curves. Results: Among 27 JMML cases, there were 11 males and 16 females. The age of disease onset was 28 (11,52) months. There are 20 cases of normal karyotype, 4 cases of monosomy 7, 1 case of trisomy 8,1 case of 11q23 rearrangement and 1 case of complex karyotype. A total of 39 somatic mutations were detected.Those involved in RAS signal pathway were the highest (64%(25/39)), among which PTPN11 mutation was the most frequent (44% (11/25)). A total of 17 cases (63%) received HSCT, 8 cases (30%) did not receive HSCT, and 2 cases (7%) lost follow-up. For children receiving transplantation, the follow-up time after transplantation was 47 (11,57) months. The 1-year OS rate of high-risk transplantation group (17 cases) and high-risk non transplantation group (6 cases) was (88±8)% and (50±20)% respectively, with a statistically significant difference (χ2=5.01, P=0.025). The 5-year OS rate of the high-risk transplantation group was (75±11)%. The survival time of those who relapsed or progressed to acute myeloid leukemia after transplantation was significantly shorter than that of those who did not relapse (χ2=6.80, P=0.009). The OS rate of patients with or without PTPN11 mutation was (81±12) % and (67±19)% respectively (χ2=0.85, P=0.356). Conclusions: The main pathogenesis involved in JMML is gene mutation related to RAS signaling pathway, and the most common driver gene of mutation is PTPN11. Allogeneic HSCT can significantly improve the survival rate of high-risk JMML patients. The recurrence or progression after transplantation was related to poor prognosis.

Uterine POLE mutant endometrioid carcinoma combined with human papilloma virus-associated cervical adenocarcinoma: A case report and literature review / 北京大学学报(医学版)

Independent primary uterine and cervical adenocarcinoma are rare and difficult to identify their origins, which makes treatment decision difficult. A 46-year-old female with endometrioid carcinoma and adenocarcinoma, human papilloma virus (HPV)-associated of the uterine cervix was reported. The patient presented with increased menstrual flow, contact bleeding and watery leucorrhea for more than one year, and the imaging findings showed abnormal uterine morphology, irregular margins, and multiple abnormal signals in uterine cavity and myometrium, which suggested multiple leiomyomas of the uterus. The signal intensity in the right muscle layer was markedly enhanced, suggesting a smooth muscle tumor of uncertain malignant potential. A large number of cystic hypointensity was seen in the cervix, and multiple cysts were considered. The initial preoperative diagnosis was multiple leiomyoma of the uterus, and a hysterectomy operation was planned. During the operation, the uterus was sent for frozen sections. There was a mass in the endometrium of the fundus, with a soft grayish-red cut surface and a clear border with the myometrium, and there was a grayish-white nodule in the cervix with a hard grayish-white cut surface. The two masses were well demarcated from each other, and the distance between them was 30 mm. The result of the frozen sections indicated the malignant tumor of the endometrium, and the extended hysterectomy+pelvic lymphadenectomy+partial resection of the greater omentum was performed. After the operation, the paraffin sections were sent to the Department of Pathology of the Peking University Third Hospital for histochemistry, POLE gene sequencing and HPV RNAscope tests, and the final diagnosis was a synchronous endometrioid carcinoma (POLE-mutant according to the WHO classification) and an adenocarcinoma, HPV-associated of the uterine cervix. Now the patient had been treated with 2 cycles of chemotherapy and her condition was fine. Through the analysis of the histological, immunohistochemical and molecular detection results of this case, the importance of applying HPV RNAscope and TCGA molecular typing in the diagnosis of cervical adenocarcinomas and endometrial carcinomas was emphasized. At the same time, gynecologists should not blindly rely on intraoperative frozen sections, and should pay attention to preoperative pathological examination, and make appropriate operation methods according to the results in order to prevent passivity in the surgery.