Screening of quantitative preparation quality markers of Zhibao Sanbian Wan / 药学学报

On the basis of the qualitative preparation quality markers of Zhibao Sanbian Wan (ZBSBW), we screened out the quantitative markers and evaluated the content consistency of ZBSBW. A method capable of simultaneously determining 34 compounds in ZBSBW was established based on HPLC-MS/MS, and 16 batches of ZBSBW were simultaneously analyzed by this method. Furthermore, we explored a general strategy for analyzing the component migration in preparation, plasma, brain tissue and cerebrospinal fluid. The methodological investigation was confirmed by linear range, recovery (85.10%-105.07%), precision (RSD: 1.37%-4.58%), stability, and repeatability (3.00%-12.45%), the established method was suitable for the detection and quantification of the compounds in ZBSBW. The contents of compounds in ZBSBW were all lower than 1 mg·g-1, and the contents and daily dose of nystose were the highest, followed by echinacoside, paeoniflorin, osthole and paeonol. The results of systematic clustering showed that the contents were consistent for ordinary preparations of ZBSBW. The principal component analysis showed that the components of berberine, ginsenoside Re, ginsenoside Rg1, pinoresinol diglucoside and tenuifolin had large variation, which contributed significantly to the grouping. The contents of echinacoside, verbascoside, polygalaxanthone Ⅲ, β-ecdysterone, osthole, alisol B 23-acetate, liquiritin and glycyrrhizic acid were stable from batch to batch. The animal experiment results showed that osthole, paeonol and liquiritin in ZBSBW could be absorbed into the blood and enter the brain tissue by passing through the blood-brain barrier. All animal studies were reviewed and approved by the Institutional Animal Care and Use Committee at Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences (No. 2020B071). The above compounds contributed the quantitative preparation quality markers of ZBSBW. In conclusion, the HPLC-MS/MS method established in this study was sensitive, accurate and rapid, and could be used for simultaneous quantification of 34 compounds and content consistency evaluation of multiple batches of preparations in ZBSBW. The result provided a methodological basis for the screening of quantitative preparation quality markers and material basis research of ZBSBW.

High expression of death-associated protein 5 promotes glucose metabolism in gastric cancer cells and correlates with poor survival outcomes / 南方医科大学学报

OBJECTIVE@#To investigate the prognostic value of death-associated protein 5 (DAP5) in gastric cancer (GC) and its regulatory effect on aerobic glycolysis in GC cells.@*METHODS@#We analyzed DAP5 expression levels in GC and adjacent tissues and its association with survival outcomes of GC patients using public databases. We collected paired samples of GC and adjacent tissues from 102 patients undergoing radical resection of GC in our hospital from June, 2012 to July, 2017, and analyzed the correlation of DAP5 expression level detected immunohistochemically with the clinicopathological parameters of the patients. Cox regression analysis, Kaplan-Meier analysis, and ROC curves were used to explore the independent risk factors and the predictive value of DAP5 expression for 5-year survival of the patients. In the cell experiments, we observed the changes in aerobic glycolysis in MGC-803 cells following lentivirus-mediated DAP5 knockdown or overexpression by measuring glucose uptake and cellular lactate level and using qRT-PCR and Western blotting.@*RESULTS@#Analysis using the public databases showed that DAP5 was highly expressed in GC and correlated with tumor progression and poor survival outcomes of the patients (P < 0.05). In the clinical samples, DAP5 expression was significantly higher in GC than in the adjacent tissues (3.19±0.60 vs 1.00±0.12; t=36.863, P < 0.01), and a high expression of DAP5 was associated with a reduced 5-year survival rate of the patients (17.6% vs 72.5%; χ2=29.921, P < 0.05). A high DAP5 expression, T3-4, N2-3, and CEA≥5 ng/mL were identified as independent risk factors affecting 5-year survival outcomes of GC (P < 0.05), for which DAP5 expression showed a prediction sensitivity, specificity and accuracy of 73.2%, 80.4% and 79.0%, respectively. In MGC-803 cells, DAP5 knockdown significantly reduced glucose uptake, lactate level and the expressions of GLUT1, HK2 and LDHA, and DAP5 overexpression produced the opposite effects (P < 0.05).@*CONCLUSION@#A high expression of DAP5 in GC, which enhances cellular aerobic glycolysis to promote cancer progression, is correlated with a poor survival outcome and may serve as a biomarker for evaluating long-term prognosis of GC patients.

FJX1 overexpression is associated with poor prognosis and promotes gastric cancer proliferation via the PI3K/AKT signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the expression of four-jointed box kinase 1 (FJX1) in gastric cancer (GC), its correlation with survival outcomes of the patients, and its role in GC progression.@*METHODS@#The expression level of FJX1 in GC tissues and normal gastric mucosal tissues and its correlation with the survival outcomes of GC patients were analyzed using TCGA and GEO database GC cohort. Immunohistochemistry was used to detect FJX1 expression level in clinical specimens of GC tissue, and its correlations with the patients' clinicopathological parameters and prognosis were analyzed. Bioinformatic analysis was performed to identify the potential pathways of FJX1 in GC. The effects of FJX1 overexpression or FJX1 silencing on GC cell proliferation and expressions of proliferation-related proteins, PI3K, AKT, p-PI3K, and p-AKT were evaluated using CCK-8 assay and Western blotting. The effect of FJX1 overexpression on GC cell tumorigenicity was evaluated in nude mice.@*RESULTS@#GC tissues showed significantly higher expressions of FJX1 mRNA and protein compared with normal gastric mucosa tissues (P < 0.05). The high expression of FJX1 was associated with poor prognosis of GC patients (P < 0.05) and served as an independent risk factor for poor survival outcomes in GC (P < 0.05). FJX1 was expressed mainly in the cytoplasm of GC cells in positive correlation with Ki67 expression (R=0.34, P < 0.05), and was correlated with CA199 levels, depth of tumor infiltration and lymph node metastasis of GC (P < 0.05). In the cell experiment, FJX1 level was shown to regulate the expressions of Ki67 and PCNA and GC cell proliferation (P < 0.05). Gene set enrichment analysis indicated that the PI3K/AKT pathway potentially mediated the effect of FJX1, which regulated the expressions of PI3K and AKT and their phosphorylated proteins. In nude mice, FJX1 overexpression in GC cells significantly promoted the growth of the transplanted tumors (P < 0.05).@*CONCLUSION@#FJX1 is highly expressed in GC tissues and is correlated with poor prognosis of GC patients. FJX1 overexpression promotes GC cell proliferation through the PI3K/AKT signaling pathway, and may serve as a potential prognostic biomarker and therapeutic target for GC.

HSDL2 overexpression promotes rectal cancer progression by regulating cancer cell cycle and promoting cell proliferation / 南方医科大学学报

OBJECTIVE@#To analyze the expression of hydroxysteroid dehydrogenase like 2 (HSDL2) in rectal cancer tissues and the effect of changes in HSDL2 expression level on proliferation of rectal cancer cells.@*METHODS@#Clinical data and tissue samples of 90 patients with rectal cancer admitted to our hospital from January 2020 to June 2022 were collected from the prospective clinical database and biological specimen database. The expression level of HSDL2 in rectal cancer and adjacent tissues was detected by immunohistochemistry, and based on the median level of HSDL2 expression, the patients were divided into high expression group (n=45) and low expression group (n=45) for analysis the correlation between HSDL2 expression level and the clinicopathological parameters. GO and KEGG enrichment analyses were performed to explore the role of HSDL2 in rectal cancer progression. The effects of changes in HSDL2 expression levels on rectal cancer cell proliferation, cell cycle and protein expressions were investigated in SW480 cells with lentivirus-mediated HSDL2 silencing or HSDL2 overexpression using CCK-8 assay, flow cytometry and Western blotting.@*RESULTS@#The expressions of HSDL2 and Ki67 were significantly higher in rectal cancer tissues than in the adjacent tissues (P < 0.05). Spearman correlation analysis showed that the expression of HSDL2 protein was positively correlated with Ki67, CEA and CA19-9 expressions (P < 0.01). The rectal cancer patients with high HSDL2 expressions had significantly higher likelihood of having CEA ≥5 μg/L, CA19-9 ≥37 kU/L, T3-4 stage, and N2-3 stage than those with a low HSDL2 expression (P < 0.05). GO and KEGG analysis showed that HSDL2 was mainly enriched in DNA replication and cell cycle. In SW480 cells, HSDL2 overexpression significantly promoted cell proliferation, increased cell percentage in S phase, and enhanced the expression levels of CDK6 and cyclinD1 (P < 0.05), and HSDL2 silencing produced the opposite effects (P < 0.05).@*CONCLUSION@#The high expression of HSDL2 in rectal cancer participates in malignant progression of the tumor by promoting the proliferation and cell cycle progress of the cancer cells.

Establishment of induced pluripotent stem cell model of Aicardi-Goutières Syndrome mutated in TREX1 / 中华预防医学杂志

To establish and identify induced pluripotent stem cells (iPSCs) derived from patients with Aicardi-Goutières syndrome (AGS) with TREX1 gene 667G>A mutation, and obtain a specific induced pluripotent stem cell model for Aicardi-Goutières syndrome (AGS-iPSCs). A 3-year-old male child with Aicardi-Goutieres syndrome was admitted to Zhongshan People's Hospital in December 2020. After obtaining the informed consent of the patient's family members, 5 ml peripheral blood samples from the patient were collected, and mononuclear cells were isolated. Then,the peripheral blood mononuclear cells(PBMCs) were transduced with OCT3/4, SOX2, c-Myc and Klf4 by using Sendai virus, and PBMCs were reprogrammed into iPSCs. The pluripotency and differentiation ability of the cells were identified by cellular morphological analysis, real-time PCR, alkaline phosphatase staining (AP), immunofluorescence, teratoma formation experiments in mice. The results showed that the induced pluripotent stem cell line of Aicardi-Goutieres syndrome was successfully constructed and showed typical embryonic stem-like morphology after stable passage, RT-PCR showed mRNA expression of stem cell markers, AP staining was positive, OCT4, SOX2, NANOG, SSEA4, TRA-1-81 and TRA-1-60 pluripotency marker proteins were strongly expressed. In vivo teratoma formation experiments showed that iPSCs differentiate into the ectoderm (neural tube like tissue), mesoderm (vascular wall tissue) and endoderm (glandular tissue). Karyotype analysis also confirmed that iPSCs still maintained the original karyotype (46, XY). In conclusion, induced pluripotent stem cell line for Aicardi-Goutières syndrome was successfully established using Sendai virus, which provided an important model platform for studying the pathogenesis of the disease and for drug screening.

The characteristics and correlations of vaginal flora in women with cervical lesions / 中华肿瘤杂志

Objective: To explore the characteristics and correlations of vaginal flora in women with cervical lesions. Methods: A total of 132 women, including 41 women diagnosed with normal cervical (NC), 39 patients with low-grade cervical intraepithelial neoplasia (CIN 1), 37 patients with high-grade cervical intraepithelial neoplasia (CIN 2/3) and 15 patients with cervical squamous cell carcinoma (SCC), who came from the gynecological clinic of Second Hospital of Shanxi Medical University during January 2018 to June 2018, were enrolled in this study according to the inclusive and exclusive criteria strictly. The vaginal flora was detected by 16S rDNA sequencing technology. Co-occurrence network analysis was used to investigate the Spearman correlations between different genera of bacteria. Results: The dominant bacteria in NC, CIN 1 and CIN 2/3 groups were Lactobacillus [constituent ratios 79.4% (1 869 598/2 354 098), 63.6% (1 536 466/2 415 100) and 58.3% (1 342 896/2 301 536), respectively], while Peptophilus [20.4% (246 072/1 205 154) ] was the dominant bacteria in SCC group. With the aggravation of cervical lesions, the diversity of vaginal flora gradually increased (Shannon index: F=6.39, P=0.001; Simpson index: F=3.95, P=0.012). During the cervical lesion progress, the ratio of Lactobacillus gradually decreased, the ratio of other anaerobes such as Peptophilus, Sneathia, Prevotella and etc. gradually increased, and the differential bacteria (LDA score >3.5) gradually evolved from Lactobacillus to other anaerobes. The top 10 relative abundance bacteria, spearman correlation coefficient>0.4 and P<0.05 were selected. Co-occurrence network analysis showed that Prevotella, Peptophilus, Porphyrinomonas, Anaerococcus, Sneathia, Atopobium, Gardnerella and Streptococcus were positively correlated in different stages of cervical lesions, while Lactobacillus was negatively correlated with the above anaerobes. It was found that the relationship between vaginal floras in CIN 1 group was the most complex and only Peptophilus was significantly negatively correlated with Lactobacillus in SCC group. Conclusions: The increased diversity and changed correlations between vaginal floras are closely related to cervical lesions. Peptophilus is of great significance in the diagnosis, prediction and early warning of cervical carcinogenesis.

The efficacy of radiotherapy based combined therapy for unresectable locally invasive bladder cancer and its associated factors analysis / 中华肿瘤杂志

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.

Treatment of neovascular glaucoma by anti-vascular endothelial growth factor combined with ultrasonic ciliary plasty / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the clinical efficacy and safety of ultrasonic ciliary plasty(UCP)combined with injection of anti-vascular endothelial growth factor(VEGF)in the treatment of neovascular glaucoma(NVG).METHODS: A total of 30 NVG patients(30 eyes)admitted to the First Affiliated Hospital of Bengbu Medical College from September 2020 to September 2021 were selected. After admission, all the eyes of the patients were injected with anti-VEGF drug(ranibizumab). After surgery, 15 patients were randomly selected for UCP treatment(UCP group), and the other 15 patients received trabeculectomy(trabeculectomy group). During the 10mo postoperative follow-up, the decrease of intraocular pressure was compared between the two groups and the changes of the degree of ocular pain and the occurrence of related complications were evaluated at each follow-up visit.RESULTS: The intraocular pressure and pain degree of the UCP and trabeculectomy groups were significantly lower than those before operation, and the complication probability of the UCP group was less than that of the trabeculectomy group.CONCLUSION: With fewer complications and high safety, UCP combined with anti-VEGF injection can effectively control intraocular pressure and pain in NVG patients.

Pharmacodynamic Mechanism of Kuanxiong Aerosol for Vasodilation and Improvement of Myocardial Ischemia / 中国结合医学杂志

OBJECTIVE@#To explore the effect of Kuanxiong Aerosol (KXA) on isoproterenol (ISO)-induced myocardial injury in rat models.@*METHODS@#Totally 24 rats were radomly divided into control, ISO, KXA low-dose and high-dose groups according to the randomized block design method, and were administered by intragastric administration for 10 consecutive days, and on the 9th and 10th days, rats were injected with ISO for 2 consecutive days to construct an acute myocardial ischemia model to evaluate the improvement of myocardial ischemia by KXA. In addition, the diastolic effect of KXA on rat thoracic aorta and its regulation of ion channels were tested by in vitro vascular tension test. The influence of KXA on the expression of calcium-CaM-dependent protein kinase II (CaMK II)/extracellular regulated protein kinases (ERK) signaling pathway has also been tested.@*RESULTS@#KXA significantly reduced the ISO-induced increase in ST-segment, interventricular septal thickness, cardiac mass index and cardiac tissue pathological changes in rats. Moreover, the relaxation of isolated thoracic arterial rings that had been precontracted using norepinephrine (NE) or potassium chloride (KCl) was increased after KXA treatment in an endothelium-independent manner, and was attenuated by preincubation with verapamil, but not with tetraethylammonium chloride, 4-aminopyridine, glibenclamide, or barium chloride. KXA pretreatment attenuated vasoconstriction induced by CaCl2 in Ca2+-free solutions containing K+ or NE. In addition, KXA pretreatment inhibited accumulation of Ca2+ in A7r5 cells mediated by KCl and NE and significantly decreased p-CaMK II and p-ERK levels.@*CONCLUSION@#KXA may inhibit influx and release of calcium and activate the CaMK II/ERK signaling pathway to produce vasodilatory effects, thereby improving myocardial injury.

Comparative study of three scores in predicting the death risk of severe burn patients / 中华烧伤杂志

Objective: To explore the predictive values of the modified Baux score, Belgian Outcome in Burn Injury score, and Ryan score on the death risk of severe burn patients. Methods: A retrospective case series study was conducted. From February 2018 to November 2019, 260 severe burn patients who met the inclusion criteria were admitted to the Department of Burns of the First Affiliated Hospital of Nanchang University, including 158 males and 102 females, aged 36 (3, 53) years. According to the final outcome, the patients were divided into survival group (n=229) and death group (n=31). Data of patients were compared and statistically analyzed with chi-square test or Mann-Whitney U test between the two groups, including the gender, age, cause of burn, site of burn, total burn area, depth of burn, combined inhalation injury, and combined underlying diseases on admission, and the modified Baux score, Belgian Outcome in Burn Injury score, and Ryan score calculated based on part of the aforementioned data. The Kendall tau-b coefficient method was used to analyze the consistency of the above-mentioned three scores in 260 severe burn patients. The receiver operating characteristic (ROC) curves of the above-mentioned three scores predicting the death risk of 260 severe burn patients were drawn, and the area under the curve (AUC), the optimal threshold, and the sensitivity and specificity under the optimal threshold were calculated. The quality of AUC of the above-mentioned three scores was compared by Delong test. Results: The gender, site of burn, and depth of burn of patients between the two groups were all similar (P>0.05). The age, total burn area, proportion of flame burn, proportion of combined inhalation injury, and proportion of combined underlying diseases of patients in death group were significantly higher than those in survival group (with Z values of 5.53 and 17.78, respectively, χ2 values of 16.23, 15.89, and 17.78, respectively, P<0.01); the modified Baux score, Belgian Outcome in Burn Injury score, and Ryan score of patients in death group were 142 (115, 155), 7 (5, 7), 2 (2, 3), all significantly higher than 64 (27, 87), 1 (0, 3), 0 (0, 1) in survival group (with Z values of 7.91, 7.64, and 7.61, respectively, P<0.01). In 260 severe burn patients, the results between the modified Baux score and Ryan score, modified Baux score and Belgian Outcome in Burn Injury score, Ryan score and Belgian Outcome in Burn Injury score were significantly consistent (with Kendall tau-b coefficients of 0.75, 0.71, and 0.86, respectively, P<0.01). The AUCs of ROC curves of the modified Baux score, Belgian Outcome in Burn Injury score, and Ryan score for predicting the death risk of 260 severe burn patients were 0.92, 0.89, and 0.85, respectively (with 95% confidence intervals of 0.86-0.98, 0.83-0.95, and 0.78-0.93, respectively, P<0.01); the optimal thresholds were 106.5, 4.5, and 1.5 points, respectively; the sensitivity under the optimal threshold were 88.5%, 76.9%, and 73.1%, respectively, and the specificity under the optimal threshold were 88.5%, 87.2%, and 86.3%, respectively. The modified Baux score was similar to Belgian Outcome in Burn Injury score in the AUC quality (z=1.25, P>0.05), which were both significantly better than the AUC quality of Ryan score (with z values of 2.35 and 2.11, respectively, P<0.05). Conclusions: The modified Baux score, Belgian Outcome in Burn Injury score, and Ryan score have good ability in predicting the death risk of severe burn patients. From the perspective of clinical practice, the modified Baux score is more suitable as a predictive tool for the prognosis of severe burn patients.

Evaluation of safety and immunogenicity of hepatitis E vaccine in maintenance hemodialysis patients / 中华预防医学杂志

Objective: To evaluate the safety and immunogenicity of hepatitis E vaccine(HEV)in Maintenance hemodialysis(MHD)patients. Methods: Based on an open-labeled controlled trial, from May 2016 to March 2018, 35 eligible MHD patients were recruited in the Hemodialysis Center of Zhongshan Hospital Affiliated to Xiamen University as the experimental group, and 70 MHD patients with matched age, gender and underlying diseases as the control group. The experimental group received HEV at 0, 1 and 6 months according to the standard vaccination procedures, while the control group received routine diagnosis and treatment without vaccine and placebo injection to observe the safety and immunogenicity of the vaccine. The safety of vaccine in MHD population was evaluated by the incidence of adverse reactions/events in the experimental and control groups. The immunogenicity of HEV in MHD patients was evaluated by comparing the data from the phase Ⅲ clinical trial. Results: The overall incidence of adverse reactions/events was 17.1% (18/105), and there were no grade 3-4 adverse reactions/events related to vaccination. In the experimental group, the incidence of local adverse reactions/events was 20.0% (7/35), and the incidence of systemic adverse reactions/events was 17.1% (6/35).There was no significant difference in the incidence of systemic adverse reactions/events between the experimental group and the control group (P>0.05). There were 23 patients receiving 3 doses with the standard schedule. The positive rate of HEV-IgG antibody was 100% and the GMC was 14.47(95%CI:13.14-15.80) WU/ml, which showed no significant difference compared with the 46 patients in Phase Ⅲ clinical trial (t=-1.04, P>0.05). Conclusion: Recombinant HEV has good safety and immunogenicity in MHD patients.

Repair impact of vibration exercise with different frequencies on articular cartilage of rats with early knee osteoarthritis and its JNK/NF-κB, SOX9 mechanisms / 中国应用生理学杂志

Objective: To investigate the repair effect and JNK/NF-κB,SOX9 mechanisms of vibration exercise with different frequencies on articular cartilage in rats with early knee osteoarthritis. Methods: Forty-eight adult male SD rats were randomly divided into six groups(n=8):model control group(MC),high frequency vibration group 1 (GP1,60 Hz),high frequency vibration 2 group (GP2,40 Hz),medium frequency vibration group (ZP,20 Hz),minor frequency group(DP,10 Hz)and normal control group(NC). Except for NC group,the rats in each group were made into early knee osteoarthritis model after six weeks of knee joint cavity injection of papain solution and 2% mixture l-cysteine on the 1st,4 th and 7th day. Each exercise group was subjected vibration to 40 minutes a day with amplitude of 2～5 mm and 5 days a week. Four weeks later, the articular cartilage of the lateral femoral condyle of the both back leg knee joints were detected by HE staining,serine O staining and Mankin scores for morphological observation. The expression levels of JNK,NF-κB p65 and Sox9 mRNA in articular cartilage of the medial femoral condyle were detected by RT-qPCR,and the protein expressions of JNK,NF-κB p65 and Sox9 were detected by Western blot. Results: Compared with the NC group,the Mankin score in other groups was significantly higher (P＜0.01). Compared with the MC group,the Mankin score of each vibration group was significantly lower(P＜0.05),the mRNA and protein expressions of JNK and NF-κB p65 in each vibration training group were significantly lower (P＜0.01),the expressions of Sox9 mRNA and protein in vibration training group were increased significantly (P＜0.01). Compared with the higher frequency group,the Mankin score,the mRNA and protein expressions of JNK and NF-κB p65 of lower frequency group were significantly lower (P＜0.05 or P＜0.01). But the expressions of Sox9 mRNA and protein were significantly higher (P＜ 0.05 or P＜0.01). Conclusion: Vibration exercise of different frequencies may present varying degrees of cartilage repair impact in rats with early knee osteoarthritis,and the cartilage repair by low-frequency vibration training is better than that by high-frequency vibration. This can be one of the mechanisms on controlling collagen synthesis by down-regulating JNK/NF-κB expression and increasing SOX9 activity of OA articular cartilage.

Risk factors of bronchopulmonary dysplasia in very preterm infants: a national multicenter study / 中国小儿急救医学

Objective:To analyze the risk factors of bronchopulmonary dysplasia(BPD)in very preterm infants(VPI), and to provide scientific basis for the prevention and treatment of BPD in VPI.Methods:A prospective multicenter study was designed to collect the clinical data of VPI in department of neonatology of 28 hospitals in 7 regions from September 2019 to December 2020.According to the continuous oxygen dependence at 28 days after birth, VPI were divided into non BPD group and BPD group, and the risk factors of BPD in VPI were analyzed.Results:A total of 2 514 cases of VPI including 1 364 cases without BPD and 1 150 cases with BPD were enrolled.The incidence of BPD was 45.7%.The smaller the gestational age and weight, the higher the incidence of BPD( P<0.001). Compared with non BPD group, the average birth age, weight and cesarean section rate in BPD group were lower, and the incidence of male infants, small for gestational age and 5-minute apgar score≤7 were higher( P<0.01). In BPD group, the incidences of neonatal respiratory distress syndrome(NRDS), hemodynamically significant patent ductus arteriosus, retinopathy of prematurity, feeding intolerance, extrauterine growth restriction, grade Ⅲ~Ⅳ intracranial hemorrhage, anemia, early-onset and late-onset sepsis, nosocomial infection, parenteral nutrition-associated cholestasis were higher( P<0.05), the use of pulmonary surfactant(PS), postnatal hormone exposure, anemia and blood transfusion were also higher, and the time of invasive and non-invasive mechanical ventilation, oxygen use and total hospital stay were longer( P<0.001). The time of starting enteral nutrition, cumulative fasting days, days of reaching total enteral nutrition, days of continuous parenteral nutrition, days of reaching 110 kcal/(kg·d) total calorie, days of reaching 110 kcal/(kg·d) oral calorie were longer and the breastfeeding rate was lower in BPD group than those in non BPD group( P<0.001). The cumulative doses of amino acid and fat emulsion during the first week of hospitalization were higher in BPD group( P<0.001). Multivariate Logistic regression analysis showed that NRDS, invasive mechanical ventilation, age of reaching total enteral nutrition, anemia and blood transfusion were the independent risk factors for BPD in VPI, and older gestational age was the protective factor for BPD. Conclusion:Strengthening perinatal management, avoiding premature delivery and severe NRDS, shortening the time of invasive mechanical ventilation, paying attention to enteral nutrition management, reaching whole intestinal feeding as soon as possible, and strictly mastering the indications of blood transfusion are very important to reduce the incidence of BPD in VPI.

Stereotactic body radiation therapy for patients with lung and liver oligometastases from colorectal cancer: a phase Ⅱ trial / 中华肿瘤杂志

Objective: To explore the safety and effectiveness of stereotactic body radiation therapy (SBRT) for oligometastases from colorectal cancer (CRC). Methods: This is a prospective, single-arm phase Ⅱ trial. Patients who had histologically proven CRC, 1 to 5 detectable liver or lung metastatic lesions with maximum diameter of any metastases ≤5 cm were eligible. SBRT was delivered to all lesions. The primary endpoint was 3-year local control (LC). The secondary endpoints were treatment-related acute toxicities of grade 3 and above, 1-year and 3-year overall survival (OS) and progression free survival (PFS). Survival analysis was performed using the Kaplan-Meier method and Log rank test. Results: Petients from 2016 to 2019 who were treated in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Forty-eight patients with 60 lesions were enrolled, including 37 liver lesions and 23 lung lesions. Forty-six patients had 1 or 2 lesions, with median diameter of 1.3 cm, the median biologically effective dose (BED(10)) was 100.0 Gy. The median follow-up was 19.5 months for all lesions. Twenty-five lesions developed local failure, the median local progression free survival was 15 months. The 1-year LC, OS and PFS was 70.2% (95% CI, 63.7%~76.7%), 89.0% (95% CI, 84.3%~93.7%) and 40.4% (95%CI, 33.0%~47.8%). The univariate analysis revealed that planning target volume (PTV) and total dose were independent prognostic factors of LC (P<0.05). For liver and lung lesions, the 1-year LC, OS and PFS was 58.7% and 89.4% (P=0.015), 89.3% and 86.5% (P=0.732), 30.5% and 65.6% (P=0.024), respectively. No patients developed acute toxicity of grade 3 and above. Conclusion: SBRT is safe and effective treatment method for oligometastases from CRC under precise respiratory motion management and robust quality assurance.

Expression comparison and clinical significance of PD-L1 (22C3) and PD-L1 (SP142) in triple negative breast cancer / 中华肿瘤杂志

Objective: To investigate the expression of programmed death ligand-1 (PD-L1, SP142) and PD-L1 (22C3) in triple-negative breast cancer (TNBC), and analyze their correlation with the clinicopathological factors and prognosis. Methods: The clinicopathologic data of 259 patients with TNBC treated in Cancer Hospital from August 2010 to December 2013 were collected. Whole section of surgical tissue samples were collected to conduct PD-L1 (SP142) and PD-L1 (22C3) immunohistochemical (IHC) staining. The PD-L1 expression in tumor cells and tumor infiltrating immune cells were visually assessed respectively, the relationship between PD-L1 expression and clinicopathologic characterizes were analyzed. Univariable and multivariable Cox proportional hazards regression models were used to test the correlations between PD-L1 expression and disease-free survival (DFS) and overall survival (OS). Results: The positive rates of SP142 (immune cell score, ICs≥1%) and 22C3 (combined positive score, CPS≥1) were 42.1%(109/259) and 41.3%(107/259) in TNBC tissues, respectively, with a total coincidence rate of 82.3%. The Kappa value of positive expression cases was 0.571 and the distribution difference of SP142 and 22C3 positive expression cases was statistically significant (P<0.001). The PD-L1 positive patients were less likely to have vascular invasion (P<0.05), but with higher histological grade and Ki-67 proliferation index (P<0.05). The recurrence/metastasis cases(8) of the patients with positive PD-L1 (SP142) was significantly lower than that of patients with negative PD-L1(SP142, 27, P=0.016). The positive expression of PD-L1 (SP142) patients were longer DFS (P=0.019). The OS of patients with positive PD-L1 (SP142) were longer than those with negative PD-L1 (SP142), but without significance (P=0.116). The positive expression of PD-L1 (22C3) was marginally associated with DFS and OS of patients (P>0.05). Conclusions: The expression of PD-L1 (22C3) is different from that of PD-L1 (SP142) in TNBC, and the two antibodies can't be interchangeable for each other in clinical tests. PD-L1 (SP142) status is an independent prognostic factor of DFS in TNBC. The DFS is significantly prolonged in patients with positive expression of PD-L1 (SP142).

Analysis of influencing factors related to the prognosis of visual acuity on myelin oligodendrocyte glycoprotein antibody positive optic neuritis after methylprednisolone pulse / 中华眼底病杂志

Objective:To analyze the prognostic factors of vision of myelin oligodendrocyte glycoprotein (MOG) antibody positive associated optic neuritis (ON) after methylprednisolone pulse therapy.Methods:A clinical observational study. A total of 32 patients (47 eyes) with MOG antibody positive ON were observed and followed up in the ophthalmology department of Beijing Tongren Hospital Affiliated to Capital Medical University and Beijing Puren Hospital from March 2019 to January 2022. Clinical data including the best corrected visual acuity (BCVA) and orbital magnetic resonance imaging were recorded. The BCVA was examined by Snellen visual acuity chart, which was finally converted into the logarithm of the minimal angle of resolution (logMAR) for statistical analysis. There were 22 case (38 eyes) with complete image data. All patients were treated with intravenous methylprednisolone pulse (IVMP) for 3-5 days. According to the intervention time (from onset to glucocorticoid treatment), the patients were divided into three groups: <7 d group, 7-14 d and> 14 d group, with 16, 13, 11 eyes, respectively. The median follow-up time was 28 months. After 1 week, 1, 3 and 6 months treatment, the same equipment and methods were used for relevant examinations to observe the changes of visual acuity and the factors influencing the prognosis of visual acuity after IVMP treatment. Logistic regression and linear regression were used to analyze the prognostic correlation factors. Receiver operating characteristic (ROC) curve was used to determine the critical cut-off point of intervention timing.Results:Among the patients, 16 were male and 16 were female. The median onset age was 26 years. The onset duration time was 5-60 days. There were 18 cases (56.3%, 18/32) with abnormal serum immune indexes. The initial symptom was decreased vision with unilateral or bilateral ON. Seventeen (53.1%, 17/32) cases had unilateral ON and 15 (46.9%, 15/32) cases with bilateral ON. Thirty-six eyes (76.6%, 36/47) got optic disc edema, 37 eyes (78.7%, 37/47) accompanied by pain of ocular movement. The nadir logMAR BCVA was mean 1.69±0.13. Long T2WI signals with segmental thickening in the orbital segment of the optic nerve were obtained in 27 eyes (71.1%, 27/38) and in 24 eyes (63.2%, 24/38) with optic nerve and sheath enhancement. During the follow-up period, there were 10 cases of relapse (31.3%, 10/32). The logMAR BCVA of attacked eyes were 0.52±0.09, 0.22±0.06, 0.12±0.06, 0.10±0.06 at 1 week and 1, 3 and 6 months after IVMP treatment, respectively. The rate of BCVA improvement was the fastest at 1 week after treatment, and BCVA returned to stability at 3 months. Logistic regression analysis showed that the timing of intervention was significantly correlated with the prognosis of vision in primary onset patients (odds ratio=12.17, P=0.006), with a negative linear regression relationship ( r=-0.48, 95% confidence interval -0.71--0.17, P=0.008). Comparing the logMAR BCVA between the intervention time >14 group with the <7 group and the 7-14 group, there were statistically significant difference ( P=0.017, 0.037), respectively. The cut-off point of ROC curve to predict the optimal intervention time was 13.5 days. Other factors such as: gender, age, predisposing factor, pain of eye motion, edema of optic disc, bilateral ON, imaging changes, abnormal autoimmune indicators were not associated with the prognosis of visual acuity. Conclusion:The timing of hormone intervention in primary onset patients is an important factor affecting the prognosis of vision and the optimal intervention time window of IVMP is two weeks.

Intra-operative mapping and language protection in glioma / 中华医学杂志(英文版)

The demand for acquiring different languages has increased with increasing globalization. However, knowledge of the modification of the new language in the neural language network remains insufficient. Although many details of language function have been detected based on the awake intra-operative mapping results, the language neural network of the bilingual or multilingual remains unclear, which raises difficulties in clinical practice to preserve patients' full language ability in neurosurgery. In this review, we present a summary of the current findings regarding the structure of the language network and its evolution as the number of acquired languages increased in glioma patients. We then discuss a new insight into the awake intra-operative mapping protocol to reduce surgical risks during the preservation of language function in multilingual patients with glioma.

Effect of Different Extracts of Thlaspi Herba on Gut Microbiota of Hyperuricemia Mice / 中国实验方剂学杂志

Objective:To explore the effect of different extracts of Thlaspi Herba on the gut microbiota of hyperuricemia mice， and to reveal the substance basis and mechanism of its hypouricemic activity. Method:Eighty-eight male Kunming mice were divided into 11 groups， including blank group， model group， allopurinol group， high and low dose groups of petroleum ether extract， high and low dose groups of ethyl acetate extract， high and low dose groups of <italic>n</italic>-butanol extract， high and low dose groups of total flavonoids extract. Mice in the blank group were given 0.5% sodium carboxymethylcellulose by gavage， and the other groups were given oteracil potassium （500 mg·kg^-1） by gavage to duplicate the hyperuricemia model. After modeling for several hours， the blank group and the model group were given distilled water by gavage， while mice in the allopurinol group were given allopurinol suspension （50 mg·kg^-1）， and mice in each treatment group were given high and low doses of corresponding extract （5， 2.5 g·kg^-1）. The serum uric acid （SUA） level and xanthine oxidase （XOD） activity were measured after 14 days. Fresh feces were collected for 16S rDNA sequencing. Result:Compared with the blank group， SUA level and XOD activity of model group were significantly increased （<italic>P</italic><0.05）. Compared with the model group， SUA level and XOD activity of the allopurinol group were significantly decreased （<italic>P</italic><0.01）. After intervention， SUA level were significantly decreased （<italic>P</italic><0.05， <italic>P</italic><0.01）， except for high dose and low dose groups of petroleum ether extract and low dose group of total flavonoids extract， XOD activity was significantly inhibited in low dose group of petroleum ether extract， high dose group of total flavonoids extract， and high and low dose groups of <italic>n</italic>-butanol extract （<italic>P</italic><0.05， <italic>P</italic><0.01）. The high dose group of total flavonoids extract was the most significant. The results of flora sequencing showed that <italic>α</italic> diversity and abundance of the model group changed significantly， and Bacteroidetes， Firmicutes and Lactobacillaceae were significantly correlated with XOD activity. After intervention， the operational taxonomic unit （OTU）， ACE， Chao1 and Shannon indexes of the high and low dose groups of total flavonoids extract were significantly increased （<italic>P</italic><0.05， <italic>P</italic><0.01）. Relative abundance of Bacteroidetes in low dose group of ethyl acetate extract， high dose group of total flavonoids extract， and high and low dose groups of <italic>n</italic>-butanol extract was significantly decreased （<italic>P</italic><0.01）， and the relative abundance of Firmicutes was significantly increased （<italic>P</italic><0.01）. The relative abundance of Lactobacillaceae in low dose group of <italic>n</italic>-butanol extract and high dose group of total flavonoids extract was significantly increased （<italic>P</italic><0.01）. Conclusion:The effective part of Thlaspi Herba for reducing uric acid is mainly flavonoids， the improvement of SUA level and XOD activity by affecting gut microbiota such as Lactobacillaceae， Bacteroidetes and Firmicutes， may be one of its mechanisms.

The Establishment and Identification of Acute Myeloid Leukemia NOD-SCID-IL2rg / 中国实验血液学杂志

OBJECTIVE@#To establish the in vivo traceable acute myeloid leukemia mice model with Luciferase-Expressing KG1a Cells.@*METHODS@#KG1a cells with stable luciferase gene expression (called as KG1a-Luc cells) were constructed by lentivirus transfection, then sifted out by puromycin. Eighteen male NOD-SCID-IL2rg@*RESULTS@#KG1a cells expressing luciferase stably were successfully obtained. The tumor luminescence wildly spread at day 17 captured by in vivo imaging. The KG1a-Luc tumor cells could be detected in the peripheral blood of the mice, with the average percentage of (16.27±6.66)%. The morphology and pathology result showed that KG1a-Luc cells infiltrate was detected in bone marrow, spleens and livers. The survival time of the KG1a-Luc mice was notably shorter as compared with those in the control group, the median survival time was 30.5 days (95%CI: 0.008-0.260).@*CONCLUSION@#The acute myeloid leukemia NOD-SCID-IL2rg

A multicenter survey of antibiotic use in very and extremely low birth weight infants in Hunan Province / 中国当代儿科杂志

OBJECTIVE@#To investigate the current status of antibiotic use for very and extremely low birth weight (VLBW/ELBW) infants in neonatal intensive care units (NICUs) of Hunan Province.@*METHODS@#The use of antibiotics was investigated in multiple level 3 NICUs of Hunan Province for VLBW and ELBW infants born between January, 2017 and December, 2017.@*RESULTS@#The clinical data of 1 442 VLBW/ELBW infants were collected from 24 NICUs in 2017. The median antibiotic use duration was 17 days (range: 0-86 days), accounting for 53.0% of the total length of hospital stay. The highest duration of antibiotic use was up to 91.4% of the total length of hospital stay, with the lowest at 14.6%. In 16 out of 24 NICUs, the antibiotic use duration was accounted for more than 50.0% of the hospitalization days. There were 113 cases with positive bacterial culture grown in blood or cerebrospinal fluid, making the positive rate of overall bacterial culture as 7.84%. The positive rate of bacterial culture in different NICUs was significantly different from 0% to 14.9%. The common isolated bacterial pathogens Klebsiella pneumoniae was 29 cases (25.7%); Escherichia coli 12 cases (10.6%); Staphylococcus aureus 3 cases (2.7%). The most commonly used antibiotics were third-generation of cephalosporins, accounting for 41.00% of the total antibiotics, followed by penicillins, accounting for 32.10%, and followed by carbapenems, accounting for 13.15%. The proportion of antibiotic use time was negatively correlated with birth weight Z-score and the change in weight Z-score between birth and hospital discharge (r=-0.095, -0.151 respectively, P<0.01), positively correlated with death/withdrawal of care (r=0.196, P<0.01).@*CONCLUSIONS@#Antibiotics used for VLBW/ELBW infants in NICUs of Hunan Province are obviously prolonged in many NICUs. The proportion of routine use of third-generation of cephalosporins and carbapenems antibiotics is high among the NICUs.