Identification of hub genes significantly linked to tuberous sclerosis related-epilepsy and lipid metabolism via bioinformatics analysis.

Background: Tuberous sclerosis complex (TSC) is one of the most common genetic causes of epilepsy. Identifying differentially expressed lipid metabolism related genes (DELMRGs) is crucial for guiding treatment decisions. Methods: We acquired tuberous sclerosis related epilepsy (TSE) datasets, GSE16969 and GSE62019. Differential expression analysis identified 1,421 differentially expressed genes (DEGs). Intersecting these with lipid metabolism related genes (LMRGs) yielded 103 DELMRGs. DELMRGs underwent enrichment analyses, biomarker selection, disease classification modeling, immune infiltration analysis, weighted gene co-expression network analysis (WGCNA) and AUCell analysis. Results: In TSE datasets, 103 DELMRGs were identified. Four diagnostic biomarkers (ALOX12B, CBS, CPT1C, and DAGLB) showed high accuracy for epilepsy diagnosis, with an AUC value of 0.9592. Significant differences (p < 0.05) in Plasma cells, T cells regulatory (Tregs), and Macrophages M2 were observed between diagnostic groups. Microglia cells were highly correlated with lipid metabolism functions. Conclusions: Our research unveiled potential DELMRGs (ALOX12B, CBS, CPT1C and DAGLB) in TSE, which may provide new ideas for studying the psathogenesis of epilepsy.

Application value of ultrasound-guided multimodal examinations in the diagnosis of lymph node mycobacterial infection / 中国基层医药

Objective:To investigate the application value of ultrasound-guided multimodal examinations in the diagnosis of lymph node mycobacterial infection.Methods:The clinical data of 42 patients with suspected lymph node mycobacterial infection who were initially diagnosed at the Affiliated Hospital of Shaoxing University from January 2019 to December 2020 were retrospectively analyzed. All patients underwent an ultrasound-guided lymph node-negative pressure puncture. Acid-fast staining, bacterial culture, pathological examination or their combination were used to screen lymph nodes for mycobacterial infection. The results were compared with those of acid-fast staining and bacterial culture of sputum and bronchoalveolar lavage fluid smears.Results:The combined application of acid fast staining, bacterial culture, and pathological examination for the puncture fluid smear showed a positive rate of 71.4% (30/42), which was significantly higher than the positive rate [26.2% (11/42)] for acid fast staining of the puncture fluid smear, the positive rate [42.9% (18/42)] for bacterial culture of the puncture fluid, and the positive rate [50.0% (21/42)] of pathological examination ( χ2 = 17.20, 7.00, 4.04, P < 0.001, P < 0.01, P = 0.040). The positive rate for sputum smear and bacterial culture was 21.4% (9/33). The positive rate for acid fast staining and bacterial culture of the bronchoalveolar lavage fluid was 28.6% (12/30). The differences were statistically significant ( χ2 = 21.11, 15.43, both P < 0.001). Conclusion:Ultrasound-guided negative pressure aspiration and puncture biopsy of lymph nodes combined with acid fast staining, bacterial culture, and pathological examinations can markedly increase the detection rate and diagnostic rate of mycobacterial infection.

Clinical efficacy of two different internal fixations in treating femoral intertrochanteric fractures in older adult patients / 中国基层医药

Objective:To investigate the clinical efficacy of two different internal fixations in the treatment of femoral intertrochanteric fractures in older adult patients.Methods:The clinical data of 152 older adult patients with femoral intertrochanteric fractures who were treated at the Second People's Hospital of Hefei from January 2019 to December 2022 were retrospectively analyzed. All patients underwent closed reduction and internal fixation surgery. They were divided into two groups based on the different types of internal fixations used. Among them, 76 patients received internal fixation using proximal femoral intramedullary nails (group A), while 76 patients received internal fixation using Intertan nails (group B). The intraoperative blood loss volume, surgical time, postoperative complications, fracture healing time, and hip joint function score were compared between the two groups.Results:The intraoperative blood loss volume in group A was (197.11 ± 37.85) mL, which was significantly less than that in group B [(226.84 ± 54.17) mL, t = 1.62, P < 0.001]. Surgical time in group A was (71.16 ± 15.64) minutes, which was significantly shorter than that in group B [(78.49 ± 15.88) minutes, t = 1.67, P < 0.001]. The fracture healing time in group A was (13.29 ± 0.94) weeks, which was not significantly different from that in group B [(13.20 ± 0.64) weeks, t = 0.33, P > 0.05]. However, the incidence of postoperative complications in group A was 5.26% (4/76), which was significantly higher than 1.32% (1/76) in group B ( χ2 = 4.04, P = 0.048). At 1 and 3 months and 1 year after surgery, the hip joint function score in group A was (63.13 ± 2.41) points, (73.50 ± 3.99) points, and (84.13 ± 7.57) points, respectively, and it was (68.65 ± 2.65) points, (79.07 ± 3.38) points, and (89.56 ± 7.71) points, respectively, in group B. At the above-mentioned time points, the difference in hip joint function score between the two groups was statistically significant ( t = 1.89, 2.48, 2.49, all P < 0.001). Conclusion:Both internal fixation methods have significant therapeutic effects on femoral intertrochanteric fractures. Internal fixation using Intertan nails leads to higher hip joint function scores and fewer postoperative complications compared with internal fixation using proximal femoral intramedullary nails, but it results in more blood loss and a longer surgical time.

Research progress of immune checkpoint inhibitor associated pneumonia in non-small cell lung cancer and integrated TCM and Western medicine treatment / 中国免疫学杂志

Immune checkpoint inhibitors(ICIs)mainly including the CTL antigen 4(CTLA-4)and PD-1/PD-L1,which would offer a notable clinical benefit for non-small cell lung cancer(NSCLC)patients.By strengthening the antitumor immune re-sponse of the body,ICIs lead to immune-related adverse events(irAEs),including checkpoint inhibitor pneumitis(CIP).Although the clinical incidence of CIP is relatively low,some serious cases may prolong or terminate of immunotherapy,even life threateing.This article tries to summarize the clinical manifestations,pathological characteristics,biological mechanism,susceptible population,diagnosis and differential diagnosis,and integrated traditional Chinese and Western medicine treatment of CIP,in order to understand CIP more clearly.

Clinical and electrophysiological characteristics and treatment outcomes of anti-neutrophil cytoplasmic antibody ANCA-associated vasculitic neuropathy / 中华内科杂志

Objective:To investigate the clinical and electrophysiological characteristics of ANCA-associated vasculitic neuropathy (VN) and analyze the predictors of treatment outcomes.Methods:Retrospective case series. In all, 652 consecutive patients with ANCA-associated vasculitis were admitted to the First Medical Center of the Chinese PLA General Hospital between January 2006 and December 2022. Peripheral neuropathy occurred in 91 patients. Patients were excluded if other known causes of neuropathy were present. Sixty-one patients were eventually enrolled, including 17 with eosinophilic granulomatosis with polyangiitis (EGPA), 11 with granulomatosis polyangiitis (GPA), and 33 with microscopic polyangiitis (MPA). Their clinical data were collected and clinical characteristics, VN manifestations, electrophysiological findings (including interside amplitude ratio [IAR]), and treatment outcomes were compared among the three subsets of AAV. Then, factors influencing the treatment outcomes were analyzed using multivariable logistic regression analysis.Results:Peripheral neuropathy occurred in 62.1%(18/29) of EGPA, 8.3%(15/180) of GPA, and 13.1%(58/443) of MPA patients. The age at onset and examination was higher in patients with MPA than those with EGPA or GPA ( P<0.01). The occurrence of VN was later in patients with GPA than those with EGPA ( P<0.01), and the GPA group had fewer affected nerves than the other two groups ( P<0.016). The abnormal IARs of motor nerves in lower limbs were more detected in the EGPA than the MPA group ( P<0.01). Logistic regression analysis suggested that higher Birmingham vasculitis activity score-version 3 (BVAS-V3) ( OR=6.85, 95% CI 1.33-35.30) was associated with better treatment outcomes of VN. However, central nervous system involvement was a risk factor for poor treatment outcomes ( OR=0.13, 95% CI 0.02-0.89). Conclusions:The clinical and electrophysiological characteristics of VN were slightly different among subsets of AAV. Patients with GPA often presented with polyneuropathy and had fewer nerves affected; mononeuritis multiplex was more common in EGPA than GPA and MPA. Higher BVAS-V3 and central nervous system involvement might predict the treatment outcome of VN.

Research progress on the mechanism of gut microbiota participating in diabetes nephropathy / 药学实践与服务

With the increasing prevalence of diabetes, the prevention and treatment of diabetes nephropathy have become a worldwide problem. The molecular mechanism of the occurrence and development of diabetes nephropathy is still unclear, but many studies in recent years have shown that gut microbiota plays an important role in the progress on diabetes nephropathy. The research progress on the mechanism of gut microbiota participating in diabetes nephropathy was reviewed in this article.

The increasement of blood METRNL protein by insulin sensitizer rosiglitazone / 药学实践与服务

Objective To investigate the effect of insulin sensitizer rosiglitazone on blood METRNL levels. Methods After fed with high fat diet (HFD) for 3 months, obese mice were treated with rosiglitazone for 1 month. Glucose tolerance was tested with glucose tolerance test (GTT), and METRNL levels in blood were measured by ELISA. Real time fluorescence quantitative PCR was used to detect the expression of METRNL in various tissues such as muscle, liver, white fat, brown fat, brain, spleen and kidney, as well as the expression of mitochondrial proteins in brown adipose tissue. Results Glucose tolerance of animals fed a high-fat diet was improved in rosiglitazone group, and blood METRNL levels were also increased significantly in this group. Rosiglitazone treatment increased the expression of METRNL in brown fat and kidney tissue. There was no effect on METRNL expression in muscle, liver, white fat, brain and spleen. Rosiglitazone increased the expression of mitochondrial-associated proteins in brown adipose tissue. Conclusion The insulin sensitizer rosiglitazone might increase the serum METRNL level by increasing the METRNL expression in brown fat and kidney tissue, suggesting that METRNL may be involved in the therapeutic effect of rosiglitazone on diabetes.

Synovial sarcoma of the liver:a case report and literature review / 解放军医学杂志

Objective To report a case of synovial sarcoma of the liver and review the literature for improving the understanding of the disease.Methods The clinical data of a patient with liver synovial sarcoma admitted to the First Affiliated Hospital of Henan University were analyzed retrospectively.The imaging,pathological features,treatment and prognosis of this disease were summarized by searching the database(CNKI,Wanfang Data,PubMed,untill July 2022)and the literature results analyzed comprehensively.Results The patient was a 71-year-old female who was admitted to the hospital due to abdominal pain.Computed tomography(CT)scan showed a mass with mixed density in the right lobe and caudate lobe of the liver.The large cross section size was about 115 mm×87 mm and the mass showed continuous heterogeneous enhancement,being considered as malignant hepatic tumors with multiple metastasis of the liver and lung.Ultrasound-guided needle biopsy was performed,and microscopy showed the tumor cells were obvious atypical,and some were spindle-shaped.Immunohistochemistry showed that the patient was positive for vimentin(VIM),epithelial membrane antigen(EMA),methylation of histone at lysine 27(H3K27Me3),and negative for pan cytokeratin(CK-pan)and S-100,and pathological diagnosis of synovial sarcoma was made.The patient did not undergo subsequent treatment and was lost to follow-up after discharge.A total of 12 cases of hepatic synovial sarcoma were reported after searching the database.The clinical manifestations were abdominal pain or distention.The lesions were mostly located in the right lobe of the liver,usually large,heterogeneous density,and heterogeneous enhancement on enhanced CT or magnetic resonance imaging(MRI).Spindle-shaped cells were found at histopathologic examination.Immunohistochemistry showed the patient was positive for VIM,EMA,H3K27Me,B-cell leukemia/lymphoma-2(BCL-2)and transducer-like enhancer of split 1(TLE1).SS18-SSX fusion gene or SS18 gene isolation were detected.Eleven patients received surgical treatment,5 received adjuvant chemotherapy,and 4 had recurrence or metastasis during the follow-up period.Conclusions Synovial sarcoma of the liver is a rare malignant tumor of the liver.The clinical and imaging features are not specific.The diagnosis depends on pathology.At present,the main treatment is surgery,and comprehensive treatment such as adjuvant chemotherapy can be performed.The prognosis of the patient is poor.

Pyrotinib Combined with Vinorelbine in Patients with Previously Treated HER2-Positive Metastatic Breast Cancer: A Multicenter, Single-Arm, Prospective Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aims to evaluate the efficacy and safety of a new combination treatment of vinorelbine and pyrotinib in human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) and provide higher level evidence for clinical practice. @*Materials and Methods@#This was a prospective, single-arm, phase 2 trial conducted at three institutions in China. Patients with HER2-positive MBC, who had previously been treated with trastuzumab plus a taxane or trastuzumab plus pertuzumab combined with a chemotherapeutic agent, were enrolled between March 2020 and December 2021. All patients received pyrotinib 400 mg orally once daily plus vinorelbine 25 mg/m2 intravenously or 60-80 mg/m2 orally on day 1 and day 8 of 21-day cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival, and safety. @*Results@#A total of 39 patients were enrolled. All patients had been pretreated with trastuzumab and 23.1% (n=9) of them had accepted trastuzumab plus pertuzumab. The median follow-up time was 16.3 months (95% confidence interval [CI], 5.3 to 27.2), and the median PFS was 6.4 months (95% CI, 4.0 to 8.8). The ORR was 43.6% (95% CI, 27.8% to 60.4%) and the DCR was 84.6% (95% CI, 69.5% to 94.1%). The median PFS of patients with versus without prior pertuzumab treatment was 4.6 and 8.3 months (p=0.017). The most common grade 3/4 adverse events were diarrhea (28.2%), neutrophil count decreased (15.4%), white blood cell count decreased (7.7%), vomiting (5.1%), and anemia (2.6%). @*Conclusion@#Pyrotinib plus vinorelbine showed promising efficacy and tolerable toxicity as second-line treatment in patients with HER2-positive MBC.

Bioinspired Adhesive Antibacterial Hydrogel with Self-Healing and On-Demand Removability for Enhanced Full-Thickness Skin Wound Repair.

Adhesive-caused injury is a great threat for extensive full-thickness skin trauma because extra-strong adhesion can incur unbearable pain and exacerbate trauma upon removal. Herein, inspired by the mussel, we designed and fabricated an adhesive antibacterial hydrogel dressing based on dynamic host-guest interaction that enabled on-demand stimuli-triggered removal to effectively care for wounds. In contrast with most hard-to-removable dressing, this adhesive antibacterial hydrogel exhibited strong adhesion property (85 kPa), which could achieve painless and noninvasive on-demand separation within 2 s through a host-guest competition mechanism (amantadine). At the same time, the hydrogel exhibited rapid self-healing properties, and the broken hydrogel could be completely repaired within 5 min. The hydrogel also had excellent protein adsorption properties, mechanical properties, antibacterial properties, and biocompatibility. This on-demand removal was facilitated by the introduction of amantadine as a competitive guest, without any significant adverse effects on cell activity (>90%) or wound healing (98.5%) in vitro. The full-thickness rat-skin defect model and histomorphological evaluation showed that the hydrogel could significantly promote wound healing and reduce scar formation by regulating inflammation, accelerating skin re-epithelialization, and promoting granulation tissue formation. These results indicate that the developed adhesive antibacterial hydrogel offers a promising therapeutic strategy for the healing of extensive full-layer skin injuries.

A Janus supramolecular hydrogel prepared by one-pot method for wound dressing.

Despite the adhesive hydrogels have gained progress and popularity, it is still an enormous challenge to develop a smart adhesion hydrogel for clinical medicine, which is an asymmetric adhesion hydrogel with on-demand detachment. Motivated by the thermal phase transition mechanism of gelatin, we have synthesized a Janus supramolecular hydrogel dressing with skin temperature-triggered adhesion by a simple one-pot process. This hydrogel has asymmetric and controllable adhesion, which not only can become the external objects barrier but also can achieve repeated adhesion and on-demand detachment triggered by temperature in tens of seconds. This hydrogel presents great mechanical performance (compressive strain of 65 %, 1.38 MPa) owing to the presence of supramolecular interactions in the hydrogel. Additionally, this hydrogel exhibits excellent antibacterial activity and biocompatibility. The synergistic effect of modified gelatin and ionic liquid greatly facilitates wound healing of full-thickness skin with high wound healing efficiency (98.45 %). Therefore, thanks to all these advantages, the Janus supramolecular hydrogel can be applied for wound management and treatment, which has huge potential in healing skin wounds.

A novel multi-scale pressure sensing hydrogel for monitoring the physiological signals of long-term bedridden patients.

For long-term bedridden patients who need to wear diapers, the timely replacement of diapers is very important to ensure their quality of life. Therefore, it is urgent to develop a pressure sensor that can monitor the physiological conditions of patients in real time. Inspired by the multi-scale network structure of the multi-fiber protein in the muscle, a multi-scale hydrogel as a pressure sensor was prepared by introducing micron-scale hydrogel microspheres as physical crosslinking agents. Compared with the traditional polyacrylamide hydrogel (0.17 MPa of compressive strength), the multi-scale hydrogel showed a higher compressive strength of up to 1.37 MPa. Meanwhile, the hydrogel exhibited better pressure sensitivity (0.59 kPa-1) than the existing hydrogels (0.27-0.40 kPa-1). The sensor prepared by this hydrogel could monitor the patient's physiological condition (urine outflow and urinary filling) in real time through the conductivity response to ion concentration and pressure, and then transmit the signal to the caregivers in time to avoid skin damage. This multi-scale hydrogel provided a great convenience for the physiological monitoring of long-term bedridden patients by acting as a pressure sensor.

Investigation on non-radioactive behavior of an acylhydrazone-based fluorescent probe: Coexistence of PET and TICT mechanisms.

A fluorescent probe (E)-((2,4-dihydroxybenzyl)diazenyl)(pyridin-2-yl)methanone (HL) to effectively and selectively detect Al3+ was designed and synthesized in the experiment. Herein, we explained the excited state dynamics mechanism of HL by using density functional theory (DFT) and time-dependent density functional theory (TD-DFT). The potential energy surfaces (PESs) proved that the excited-state intramolecular proton transfer (ESIPT) process hardly occurs due to the high reaction barriers, so the fluorescence quenching behavior of HL was not based on ESIPT. The frontier molecular orbitals (FMOs) and spectral properties were analyzed to better understand the origination of fluorescence quenching. It was found that an electron on C = N in HL could be transferred to the fluorophore during excitation in the absence of Al3+, accompanied by the PET process. The excited state could undergo a twisted intramolecular charge transfer (TICT) process, releasing non-radiative decay. After binding to Al3+, the photo-induced electron transfer (PET) process has no longer occurred, and the TICT process is eliminated, resulting in a significant fluorescence enhancement. Therefore, the calculation results well explain the quenching and enhancement behaviors of fluorescence before and after the reaction with Al3+.

Modulating the performance of lipase-hydrogel microspheres in a "micro water environment".

In our previous work, we successfully stimulated lipase activity in an anhydrous reaction system using porous polyacrylamide hydrogel microsphere (PPAHM) as a carrier of lipase and free water. However, the effect of the existence state and content of water in lipase-porous polyacrylamide hydrogel microsphere (L-PPAHM) on the interfacial activation remained unclear. In this work, L-PPAHM with different water contents were obtained by water mist rehydration and were used to catalyze the synthesis of conjugated linoleic acid ethyl ester (CLA-EE). The results revealed that there were three existence states of water in L-PPAHM: bound water, semi-bound water and free water, and free water provided the "micro water environment" for the interfacial activation of lipase. The reusability of L-PPAHM with different water contents showed that the activity and stability of L-PPAHM could be achieved by varying the water content of L-PPAHM. The proportion of free water in L-PPAHM increased, and the activity of L-PPAHM increased, but the strength of hydrogen bond interaction between PPAHM and lipase weakened, resulting in the decrease of stability. L-PPAHM with 2/3 of water absorption could ensure sufficient immobilized lipase activity and stability, and its water absorption property could reduce the free water generated during esterification, thus increasing the yield of CLA-EE.

Pyridine pigments from functional Monascus rice / 药学学报

The trace chemical components in functional Monascus rice were studied to explore the potential bioactive substances. MCI column, Sephadex LH-20 gel, and preparative liquid chromatography were used to purified the ethyl acetate extract from functional Monascus rice. Two novel pyridine Monascus pigments were isolated and identified, named monascopyridine G (1) and monascopyridine H (2), respectively based on extensive mass spectrometry (MS), infrared radiation (IR), and nuclear magnetic resonance (NMR) analysis. The molecular docking experiments between compounds 1 and 2 and peroxisome proliferators-activated receptor-gamma (PPARγ) showed that they exhibited obvious binding force with the receptor protein. Besides, the biosynthetic pathways of the two compounds were proposed, which provide a valuable reference for the selective production of these potential bioactive substances.

Influencing factors of metabolic syndrome among adults in Nanjing， China： an analysis based on decision tree and logistic regress models / 上海预防医学

ObjectiveWe analyzed the prevalence of metabolic syndrome in adult residents of Nanjing and explored its influencing factors in order to provide technical references for the prevention of metabolic syndrome. MethodsBased on the data of the Nanjing adult chronic disease thematic survey from January 2017 to June 2018， the influencing factors of metabolic syndrome were analyzed using multifactorial logistic regression model and decision tree model. ResultsThe weighted prevalence of metabolic syndrome among people aged 18 years and over in Nanjing was 16.14%（95%CI：16.12%‒16.16%）. Prevalence of metabolic syndrome was statistically different（P<0.05）among respondents with different demographic characteristics. Logistic regression model analysis showed that age， gender， education， physical activity level， marriage status， smoking status， drinking status， weight status， diabetes and hypertension family history were the influencing factors for the prevalence of metabolic syndrome（P<0.05）. The results of the decision tree model showed that weight status was the most influential factor for metabolic syndrome， followed by age， gender， diabetes family history and smoking status. ConclusionThe prevalence of metabolic syndrome is high among the adult population in Nanjing， and special attention should be paid to middle-aged and elderly men who are overweight and obese， have a family history of diabetes and smoking.

Nutritional physical indexes, obesity status and their warning effect on hypertension among Blang, Deang and Va ethnic groups in Yunnan / 解剖学报

Objective To analyze the nutritional level, obesity status and the prevalence of frypertension in Blang, Deang and Va ethnic groups in Yunnan, to explore the relationship among nutritional physical index, obesity indicators and blood pressure, and use the cutoff value of related indicators to warn frypertension. Methods This paper was based on a statistical analysis of the 7 nutritional pfrysical indexes, 5 types of obesity status and frypertension status of 766 Blang, 570 Deang and 565 Va. Results We found that the nutritional pfrysique index of man)' items (4 items for men and 4 items for women) of Blang was significantly higher than that of Deang and Va (P Blang > Deang and the difference was statistically significant (P<0. 05). Conclusion Pelidisi' s index, WHR, and PBF all have good early warning effects on frypertension in all three ethnic groups.

Body characteristics of adults from 17 minorities of the Tibeto-Burman language group in China / 解剖学报

Objective To understand the body characteristics of adults from the Tibeto-Burman language group. Methods Totally 14 837 adults (6578 males and 8259 females) from 17 minorities were selected for investigation during 2015 to 2019 and these surveys were carried out in regions including Sichuan, Yunnan, Guizhou, Hubei, Hunan and Tibet Autonomous Region. Eight physical parameters (stature, sitting height, etc.) along with 4 corresponding indexes (stature-sitting index and the like) were carefully analyzed. The body characteristics of the Tibeto-Burman language group were then compared to those of certain minorities as well as Han in both northern and southern part of China based on our collected data. Results Among 17 minorities of the Tibeto-Burman language group, people from Pumi and Tibet were relatively tall and have longer trunk and limbs. The presence of wider trunk and thicker limbs appeared to be common in Tibetan individuals. Subjects from Lahu, Jino and Derung were in possession of shorter stature and limbs while the trunk of Naxi, Lisu and Achang people seemed wider. Compared with other ethnic groups in China, individuals from the Tibeto-Burman language group tended to own shorter stature accompanied by medium trunk width, probably sharing similar physical characteristics with those minorities in southern China, especially She and Li. Conclusion Among ethnic groups dotting in southern China, individuals from the Tibeto-Burman language group generally have medium stature, medium trunk height, and wide trunk whereas those from 3 Mon-Khmer groups, Va, Khmus and Blang, are shorter and smaller in width and height of the trunk.

Etiological diagnostic value of metagenomic next-generation sequencing in peritoneal dialysis-related peritonitis / 中华肝脏病杂志

Objective: To explore the etiological diagnostic value of metagenomic next-generation sequencing (mNGS) in peritoneal dialysis (PD)-related peritonitis. Methods: The study was a retrospective cohort study. The clinical data of patients with PD-related peritonitis who were treated and underwent microbial cultivation and mNGS test at the same time from June 2020 to July 2021 in the Affiliated Drum Tower Hospital, Medical School of Nanjing University were analyzed. The positive rate, detection time and consistency between mNGS test and traditional microbial culture were compared. Results: A total of 18 patients with age of (50.4±15.4) years old and median dialysis time of 34.0 (12.4, 62.0) months were enrolled in the study, including 11 males and 7 females. Pathogenic microorganisms were isolated in 17 patients by mNGS test, with a positive rate of 17/18, which was higher than 13/18 of microbial culture, but the difference was not statistically significant (P=0.219). Both mNGS test and microbial culture isolated positive pathogenic bacteria in 12 patients, and mNGS test isolated the same types of pathogenic bacteria as microbial cultivation did in 11 patients. In five patients with negative microbial culture, mNGS test also isolated pathogenic microorganisms, including 3 cases of Staphylococcus epidermidis, 1 case of Mycobacterium tuberculosis and 1 case of Ureaplasma urealyticum. In 1 patient, microbial culture isolated pathogenic bacteria (Escherichia coli) whereas mNGS test did not. The detection time of mNGS was 25.0 (24.0, 27.0) h, which was significantly shorter than 89.0 (72.8, 122.0) h of microbial culture (Z=3.726, P<0.001). Conclusions: mNGS test can improve the detection rate of pathogenic microorganisms in PD-related peritonitis and greatly shorten the detection time, and has good consistency with microbial culture. mNGS may provide a new approach for pathogen identification of PD-related peritonitis, especially refractory peritonitis.

Stigmasterol protects human brain microvessel endothelial cells against ischemia-reperfusion injury through suppressing EPHA2 phosphorylation / 中国天然药物

Stigmasterol is a plant sterol with anti-apoptotic, anti-oxidative and anti-inflammatory effect through multiple mechanisms. In this study, we further assessed whether it exerts protective effect on human brain microvessel endothelial cells (HBMECs) against ischemia-reperfusion injury and explored the underlying mechanisms. HBMECs were used to establish an in vitro oxygen and glucose deprivation/reperfusion (OGD/R) model, while a middle cerebral artery occlusion (MCAO) model of rats were constructed. The interaction between stigmasterol and EPHA2 was detected by surface plasmon resonance (SPR) and cellular thermal shift assay (CETSA). The results showed that 10 μmol·L-1 stigmasterol significantly protected cell viability, alleviated the loss of tight junction proteins and attenuated the blood-brain barrier (BBB) damage induced by OGD/R in thein vitro model. Subsequent molecular docking showed that stigmasterol might interact with EPHA2 at multiple sites, including T692, a critical gatekeep residue of this receptor. Exogenous ephrin-A1 (an EPHA2 ligand) exacerbated OGD/R-induced EPHA2 phosphorylation at S897, facilitated ZO-1/claudin-5 loss, and promoted BBB leakage in vitro, which were significantly attenuated after stigmasterol treatment. The rat MCAO model confirmed these protective effects in vivo. In summary, these findings suggest that stigmasterol protects HBMECs against ischemia-reperfusion injury by maintaining cell viability, reducing the loss of tight junction proteins, and attenuating the BBB damage. These protective effects are at least meditated by its interaction with EPHA2 and inhibitory effect on EPHA2 phosphorylation.