Multi-strain probiotics ameliorate Alzheimer's-like cognitive impairment and pathological changes through the AKT/GSK-3ß pathway in senescence-accelerated mouse prone 8 mice.

BACKGROUND: Alzheimer's disease (AD), the most prevalent type of dementia, still lacks disease-modifying treatment strategies. Recent evidence indicates that maintaining gut microbiota homeostasis plays a crucial role in AD. Targeted regulation of gut microbiota, including probiotics, is anticipated to emerge as a potential approach for AD treatment. However, the efficacy and mechanism of multi-strain probiotics treatment in AD remain unclear. METHODS: In this study, 6-month-old senescence-accelerated-mouse-prone 8 (SAMP8) and senescence-accelerated-mouse-resistant 1 (SAMR1) were utilized. The SAMP8 mice were treated with probiotic-2 (P2, a probiotic mixture of Bifidobacterium lactis and Lactobacillus rhamnosus) and probiotic-3 (P3, a probiotic mixture of Bifidobacterium lactis, Lactobacillus acidophilus, and Lactobacillus rhamnosus) (1 × 109 colony-forming units) once daily for 8 weeks. Morris water maze (MWM) and novel object recognition (NOR) tests were employed to assess the memory ability. 16S sequencing was applied to determine the composition of gut microbiota, along with detecting serum short-chain fatty acids (SCFAs) concentrations. Neural injury, Aß and Tau pathology, and neuroinflammation level were assessed through western blot and immunofluorescence. Finally, potential molecular mechanisms was explored through transcriptomic analysis and western blotting. RESULTS: The MWM and NOR test results indicated a significant improvement in the cognitive level of SAMP8 mice treated with P2 and P3 probiotics compared to the SAMP8 control group. Fecal 16S sequencing revealed an evident difference in the α diversity index between SAMP8 and SAMR1 mice, while the α diversity of SAMP8 mice remained unchanged after P2 and P3 treatment. At the genus level, the relative abundance of ten bacteria differed significantly among the four groups. Multi-strain probiotics treatment could modulate serum SCFAs (valeric acid, isovaleric acid, and hexanoic acid) concentration. Neuropathological results demonstrated a substantial decrease in neural injury, Aß and Tau pathology and neuroinflammation in the brain of SAMP8 mice treated with P3 and P2. Transcriptomic analysis identified the chemokine signaling pathway as the most significantly enriched signaling pathway between SAMP8 and SAMR1 mice. Western blot test indicated a significant change in the phosphorylation level of downstream AKT/GSK-3ß between the SAMP8 and SAMR1 groups, which could be reversed through P2 and P3 treatment. CONCLUSIONS: Multi-strain probiotics treatment can ameliorate cognitive impairment and pathological change in SAMP8 mice, including neural damage, Aß and Tau pathology, and neuroinflammation. This effect is associated with the regulation of the phosphorylation of the AKT/GSK-3ß pathway.

CRISPR-Cas9 systems: versatile cancer modelling platforms and promising therapeutic strategies.

The RNA-guided nuclease CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-CRISPR associated nuclease 9) and its variants such as nickase Cas9, dead Cas9, guide RNA scaffolds and RNA-targeting Cas9 are convenient and versatile platforms for site-specific genome editing and epigenome modulation. They are easy-to-use, simple-to-design and capable of targeting multiple loci simultaneously. Given that cancer develops from cumulative genetic and epigenetic alterations, CRISPR-Cas9 and its variants (hereafter referred to as CRISPR-Cas9 systems) hold extensive application potentials in cancer modeling and therapy. To date, they have already been applied to model oncogenic mutations in cell lines (e.g., Choi and Meyerson, Nat Commun 2014;5:3728) and in adult animals (e.g., Xue et al., Nature 2014;514:380-4), as well as to combat cancer by disabling oncogenic viruses (e.g., Hu et al., Biomed Res Int 2014;2014:612823) or by manipulating cancer genome (e.g., Liu et al., Nat Commun 2014;5:5393). Given the importance of epigenome and transcriptome in tumourigenesis, manipulation of cancer epigenome and transcriptome for cancer modeling and therapy is a promising area in the future. Whereas (epi)genetic modifications of cancer microenvironment with CRISPR-Cas9 systems for therapeutic purposes represent another promising area in cancer research. Herein, we introduce the functions and mechanisms of CRISPR-Cas9 systems in genome editing and epigenome modulation, retrospect their applications in cancer modelling and therapy, discuss limitations and possible solutions and propose future directions, in hope of providing concise and enlightening information for readers interested in this area.

Competitive assessments of pulmonary embolism: Noninvasiveness versus the golden standard.

Diagnosis of suspected pulmonary embolism (PE) is crucial as undiagnosed and over-diagnosis can both lead to serious consequences. Contemporary diagnostic approach of PE is a sequential combination assessment beginning with clinical assessment, validated with D-dimer measurement and confirmed with pulmonary angiography or imaging. Since the invasive pulmonary angiography is risky and costly, imaging is a warranted tool in the diagnosis procedure. CT pulmonary angiography is a less-invasive method with general availability, studies provide favorable evidences for CT pulmonary angiography as a stand-alone test for excluding PE, and it has become the first choice of tests in emergency department for suspected PE in most centers. Ventilation/perfusion single-photon emission CT signifies a new era in nuclear medicine. It has excellent sensitivity and specificity, fast procedure, low radiation exposure, few complications and contradictions. Besides, MR angiography is another possible and promising approach for diagnosis of suspected PE with much safer contrast agents than CT and no ionizing radiation. With wide availability and less invasive effects, imaging becomes a firsthand tool to obtain optimal accuracy in the diagnosis work up in clinic nowadays. This review summarizes the current methods in diagnosing PE and the update of imaging assessments of the disease.

Comparison of MIS vs. open PLIF/TLIF with regard to clinical improvement, fusion rate, and incidence of major complication: a meta-analysis.

PURPOSE: Meta-analysis was conducted to estimate whether MiTLIF could reduce the complication rate while maintaining the similar clinical result to that of open procedures. METHODS: A search of the literature was conducted on pubmed or EMBASE. A database including patient clinical information was created. A systematic review of eligible studies with multivariate regression analysis was performed to quantitatively review the correlation of VAS improvement rate and the performance of MiTLIF. RESULTS: Fourteen articles with a minimum of 12-month follow-up met our inclusion criteria. The hypothesis of homogeneity could be accepted. The fixed-effects model was used to calculate the summary risk ratio (odds ratio). In the pooled analysis, the summary risk ratio (odds ratio) in patients with MiTLIF against those with open procedure for fusion rate, complication rate and revision/readmission rate was 0.99 (p = 0.36), 1.15 (p = 0.5) and 2.59 (p = 0.003), respectively, suggesting that MiTLIF was a risk factor for revision/readmission. Multivariate regression analysis showed that the percentage of male patients and the length of surgery exert a significant impact on VAS improvement rate. The selection of MiTLF was not significant. CONCLUSION: Fusion rate and complication rate for both open and MiTLIF were similar. Moreover, the MiTLIF group tended to have a higher revision/readmission rate, which might be associated with the deep learning curve. Therefore, to achieve the level of surgical skill required of an MiTLIF surgeon, many years of training and experience are necessary. Otherwise, MiTLIF may yield unsatisfactory result upon patients.

Comparison of efficacy of dexmedetomidine combined with sufentanil versus oxycodone for percutaneous transforaminal endoscopic surgery / 中华麻醉学杂志

Objective:To compare the efficacy of dexmedetomidine combined with sufentanil versus oxycodone for percutaneous transforaminal endoscopic surgery. Methods:Eighty patients with lumbar disc herniation undergoing percutaneous transforaminal endoscopic discectomy, aged 18-65 yr, were selected and divided into 2 groups ( n=40 each) according to the random number table method: dexmedetomidine combined with sufentanil group and dexmedetomidine combined with oxycodone group. Dexmedetomidine was given as a loading dose of dexmedetomidine 0.8 μg/kg (10-15 min) before surgery, followed by an intravenous infusion of 0.4-0.6 μg/kg until 10 min before the end of surgery. At 5 min before surgery, sufentanil was intravenously injected as a bolus of 0.1 μg/kg, followed by an intravenous infusion of 0.1 μg/kg until 10 min before the end of surgery in dexmedetomidine combined with sufentanil group, and oxycodone was intravenously injected as a bolus of 0.05 μg/kg, followed by an intravenous infusion of 0.05 mg/kg until 10 min before the end of surgery in dexmedetomidine combined with oxycodone group. The Ramsay sedation score, mean arterial pressure and heart rate were recorded before administration, before skin incision, at 10 min after the start of surgery, at polishing facet joints and at the end of surgery. Bispectral index value was also recorded before skin incision, at 10 min after the start of surgery, at polishing facet joints and at the end of surgery. The emergence time was recorded, and the emergence quality was evaluated using Steward score. The visual analog scale score was recorded before surgery and at 1, 6 and 24 h after surgery. Peripheral venous blood samples were taken before administration and at 1 h after surgery for determination of concentrations of serum angiotensin Ⅱ and endothelin by radioimmunoassay. The perioperative adverse reactions were recorded. Results:Compared with dexmedetomidine combined with sufentanil group, the Ramsay sedation score before skin incision, at 10 min after the start of surgery, at polishing facet joints and at the end of surgery was significantly increased, and the mean arterial pressure, heart rate and bispectral index value were decreased, and the visual analog scale score at each time point after surgery and serum angiotensin Ⅱ and endothelin concentrations at 1 h after surgery were decreased, the incidence of adverse reactions was decreased( P<0.05), and no significant change was found in Steward score and emergence time in dexmedetomidine combined with oxycodone group( P>0.05). Conclusions:Compared with sufentanil, dexmedetomidine combined with oxycodone has a better analgesia efficacy with fewer adverse reactions in the patients undergoing percutaneous transforaminal endoscopic surgery.

Systematic review and Meta-analysis of Biling Weitong Granules in treatment of stomach ache disorder / 中国中药杂志

This study aimed to evaluate the efficacy and safety of Biling Weitong Granules in the treatment of stomach ache disorder. Randomized controlled trial(RCT) of Biling Weitong Granules in the treatment of digestive diseases with stomach ache disorder as the primary symptom was retrieved from Chinese and English electronic databases and trial registration platforms from database inception to June 10, 2022. Two investigators conducted literature screening and data extraction according to the screening criteria. The Cochrane risk-of-bias tool(v 2.0) was used to assess the risk of bias in the included studies. Analyses were performed using RevMan 5.4 and R 4.2.2, with summary estimates measured using fixed or random effects models. The primary outcome indicators were the visual analogue scale(VAS) scores and stomach ache disorder symptom scores. The secondary outcome indicators were clinical recovery rate, Helicobacter pylori(Hp) eradication rate, and adverse reaction/events. Twenty-seven RCTs were included with a sample size of 2 902 cases. Meta-analysis showed that compared with conventional western medicine treatments or placebo, Biling Weitong Granules could improve VAS scores(SMD=-1.90, 95%CI[-2.18,-1.61], P<0.000 01), stomach ache disorder symptom scores(SMD=-1.26, 95%CI[-1.71,-0.82], P<0.000 01), the clinical recovery rate(RR=1.85, 95%CI[1.66, 2.08], P<0.000 01), and Hp eradication rate(RR=1.28, 95%CI[1.20, 1.37], P<0.000 01). Safety evaluation revealed that the main adverse events in the Biling Weitong Granules included nausea and vomiting, rash, diarrhea, loss of appetite, and bitter mouth, and no serious adverse events were reported. Egger's test showed no statistical significance, indicating no publication bias. The results showed that Biling Weitong Granules in the treatment of digestive system diseases with stomach ache disorder as the primary symptom could improve the VAS scores and stomach ache disorder symptom scores of patients, relieve stomach ache disorder, and improve the clinical recovery rate and Hp eradication rate, with good safety and no serious adverse reactions. However, the quality of the original studies was low with certain limitations. Future studies should use unified and standardized detection methods and evaluation criteria of outcome indicators, pay attention to the rigor of study design and implementation, and highlight the clinical safety of the medicine to provide more reliable clinical evidence support for clinical application.

Systematic review and Meta-analysis of efficacy and safety of Fengliao Changweikang prescription in treatment of acute gastroenteritis / 中国中药杂志

This study systematically evaluated the clinical efficacy and safety of Fengliao Changweikang prescription for treating acute gastroenteritis(AGE). The databases of CNKI, Wanfang, VIP, SinoMed, Medline, Cochrane Library and two clinical trial registration platforms were retrieved from inception to August 30, 2022, to collect randomized controlled trial(RCT) on Fengliao Changweikang prescription treating AGE. Two researchers independently conducted literature screening, data extraction, and risk of bias assessment according to pre-established inclusion and exclusion criteria. RevMan 5.4.1 was used for data analysis. Finally, 18 RCTs were included, involving 3 489 patients. Meta-analysis showed that compared with conventional western medicine, Fengliao Changweikang prescription improved the relief rate of abdominal pain(RR=1.27, 95%CI[1.17, 1.38],P<0.000 01); Fengliao Changweikang prescription + conventional western medicine increased the cure rate(RR=1.43, 95%CI[1.12, 1.82], P=0.004), shortened the duration of diarrhoea(RR=-1.65, 95%CI[-2.44,-0.86], P<0.000 1), abdominal pain(RR=-1.46, 95%CI[-2.00,-0.92], P<0.000 01), vomiting(RR=-2.16, 95%CI[-2.51,-1.81], P<0.000 01) and fever(RR=-2.61, 95%CI[-4.00,-1.23], P=0.000 2), down-regulated the level of interleukin-8(IL-8)(RR=-1.07, 95%CI[-1.26,-0.88], P<0.000 01), IL-6(RR=-8.24, 95%CI[-8.99,-7.49], P<0.000 01) and hypersensitive C-reactive protein(hs-CRP)(RR=-3.04, 95%CI[-3.40,-2.69], P<0.000 01) and recurrence of AGE(RR=0.20, 95%CI[0.05, 0.90], P<0.04). In conclusion, Fengliao Changweikang prescription was safe in clinical application. It was beneficial to alleviate the clinical symptoms of diarrhea, abdominal pain, vomiting, and fever, and down-regulate the levels of some serum inflammatory factors in AGE patients. However, considering that few high-quality studies have evaluated the efficacy and safety of Fengliao Changweikang prescription in treatment of AGE, further evidence is needed in the future.

Rapid health technology assessment of four oral Chinese patent medicines in treatment of functional gastrointestinal disorders / 中国中药杂志

To provide proof of the evidence-based medicine and decision-making information for the clinical decision of functional gastrointestinal disorders(FGIDs), this study evaluated and compared the efficacy, safety, and economy of four oral Chinese patent medicines(CPMs) in the treatment of FGIDs using the method of rapid health technology assessment. The literature was systematically retrieved from CNKI, Wanfang, VIP, SinoMed, EMbase, PubMed, Cochrane Library and ClinicalTrials.gov from the establishment of the databases to May 1, 2022. Two evaluators screened out the literature, extracted data, evaluated the quality of the literature, and descriptively analyzed the results according to the prepared standard. Eventually, 16 studies were included, all of which was rando-mized controlled trial(RCT). The results showed that Renshen Jianpi Tablets, Renshen Jianpi Pills, Shenling Baizhu Granules, and Buzhong Yiqi Granules all had certain effects on the treatment of FGIDs. Renshen Jianpi Tablets treated FGIDs and persistent diarrhea. Shenling Baizhu Granules treated diarrhea with irritable bowel syndrome and FGIDs. Buzhong Yiqi Granules treated diarrhea with irritable bowel syndrome, FGIDs, and chronic diarrhea in children. Renshen Jianpi Pills treated chronic diarrhea. The four oral CPMs all have certain effects on the treatment of FGIDs and have specific advantages for specific patients. Compared with other CPMs, Renshen Jianpi Tablets have higher clinical universality. However, there are problems such as insufficient clinical research evidence, generally low quality of evidence, lack of comparative analysis among medicines, and lack of academic evaluation. More high-quality clinical research and the economic research should be carried out in the future, so as to provide more evidence for the evaluation of the four CPMs.

Comparative analysis of clinical efficacy between posterior percutaneous endoscopic discectomy and anterior cervical discectomy and fusion in the treatment of cervical spondylotic radiculopathy / 中国骨伤

OBJECTIVE@#To explore the clinical efficacy of posterior percutaneous endoscopic discectomy(PPECD) in the treatment of cervical spondylotic radiculopathy.@*METHODS@#A total of 56 patiens with single segment cervical spondylotic radiculopathy from December 2017 to October 2020, were randomly divided into observation group and control group. In observation group, there were 16 males and 11 females, including 8 cases of C4,5, 13 cases of C5,6 and 6 cases of C6,7 performed posterior percutaneous endoscopic discectomy, aged from 34 to 61 years old with an average of (51.15±6.29) years old. In control group, there were 19 males and 10 females with single segment cervical spondylotic radiculopathy including 10 cases of C4,5, 14 cases of C5,6 and 5 cases of C6,7 performed anterior cervical discectomy and fusion, aged from 40 to 65 years old with an average of (53.24±5.31) years old. The operative time, intraoperative blood loss, postoperative time of lying in bed and length of postoperative hospital stay were recorded. Visual analogue scale(VAS) and neck disability index(NDI) were used to evaluate the clinical efficacy. Cervical plain films or MRIs, CTs were taken for re-visiting patients.@*RESULTS@#All patients were followed up more than 2 years. The observation group patients were followed up, the duration ranged from 24 to 42 months with an average of (30.48±4.91) months. The control group patients were followed up, the duration ranged from 25 to 47 months, with an average of (32.76±4.53) months. Compared with control group, operative time, intraoperative blood loss, postoperative time of lying in bed and length of postoperative hospital stay were decreased(P<0.05). Compared with pre-operation, VAS of neck and upper limb and NDI at the latest follow-up between two groups were significantly improved(P<0.05). Compared with control group, VAS of neck and upper limb at 1 day after operation in observation group were significantly reduced(P<0.05). There was no significant difference in VAS of neck and upper limb and NID at 1, 3 months and the latest follow-up after operation between two groups(P>0.05). In the observation group, one patient's deltoid muscle strength was weakened to grade 4 after operation, and returned to normal after 12 weeks of conservative treatment. In control group, there was 1 case of postoperative adjacent spondylosis with symptoms of spinal compression after 2 years operation, then underwent cervical artificial intervertebral disc replacement. And there was 1 case of dysphagia after operation in control group and improved after 1 year. There was no significant difference in incidence of complications between two groups.@*CONCLUSION@#PPECD has advantages of shortening operative time, decreasing intraoperative blood loss, reducing postoperative time of lying in bed and length of postoperative hospital stay. However, applicable age range of patients and long-term clinical efficacy needs further study.

Effect of acupuncture combined with low frequency rTMS on comorbid mild-to-moderate depressive disorder and insomnia: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the impacts of acupuncture on depressive mood and sleep quality in patients with comorbid mild-to-moderate depressive disorder and insomnia, and explore its effect mechanism.@*METHODS@#A total of 60 patients with comorbid mild-to-moderate depressive disorder and insomnia were randomly divided into an observation group (30 cases, 1 case dropped off) and a control group (30 cases, 2 cases dropped off). In the observation group, acupuncture and low frequency repeated transcranial magnetic stimulation (rTMS) were combined for the intervention. Acupuncture was applied to Baihui (GV 20), Yintang (GV 24+), Neiguan (PC 6) and Yanglingquan (GB 34), etc., the needles were retained for 30 min; and the intradermal needles were embedded at Xinshu (BL 15) and Danshu (BL 19) for 2 days. After acupuncture, the rTMS was delivered at the right dorsolateral prefrontal cortex (R-DLPFC), with 1 Hz and 80% of movement threshold, lasting 30 min in each treatment. In the control group, the sham-acupuncture was adopted, combined with low frequency rTMS. The acupoint selection and manipulation were the same as the observation group. In the two groups, acupuncture was given once every two days, 3 times weekly; while, rTMS was operated once daily, for consecutive 5 days a week. The duration of treatment consisted of 4 weeks. Hamilton depression scale-17 (HAMD-17) and Pittsburgh sleep quality index (PSQI) scores were observed before and after treatment, as well as 1 month after the treatment completion (follow-up period) separately. Besides, the levels of nerve growth factor (BDNF) and γ-aminobutyric acid (GABA) in the serum were detected before and after treatment in the two groups.@*RESULTS@#After treatment and in follow-up, the HAMD-17 scores were lower than those before treatment in the two groups (P<0.05), and the scores in the observation group were lower than the control group (P<0.05). After treatment, the total scores and the scores of each factor of PSQI were reduced in the two groups in comparison with those before treatment except for the score of sleep efficiency in the control group (P<0.05); the total PSQI score and the scores for sleep quality, sleep latency, sleep efficiency and daytime dysfunction in the observation group were all lower than those in the control group (P<0.05). In the follow-up, except for the scores of sleep duration and sleep efficiency in the control group, the total PSQI score and the scores of all the other factors were reduced compared with those before treatment in the two groups (P<0.05); the total PSQI score and the scores of sleep quality, sleep latency, sleep duration, sleep efficiency and daytime dysfunction in the observation group were lower than the control group (P<0.05). After treatment, the levels of serum BDNF and GABA were increased in comparison with those before treatment in the observation group (P<0.05), and the level of serum BDNF was higher than that in the control group (P<0.05).@*CONCLUSION@#Acupuncture relieves depressive mood and improves sleep quality in patients with comorbid mild-to-moderate depressive disorder and insomnia. The effect mechanism may be related to the regulation of BDNF and GABA levels and the promotion of brain neurological function recovery.

Novel variants in DNAH6 cause male infertility associated with multiple morphological abnormalities of the sperm flagella (MMAF) and ICSI outcomes / 亚洲男科学杂志(英文版)

Variations in the dynein axonemal heavy chain gene, dynein axonemal heavy chain 6 (DNAH6), lead to multiple morphological abnormalities of the flagella. Recent studies have reported that these deficiencies may result in sperm head deformation. However, whether DNAH6 is also involved in human acrosome biogenesis remains unknown. The purpose of this study was to investigate DNAH6 gene variants and their potential functions in the formation of defective sperm heads and flagella. Whole-exome sequencing was performed on a cohort of 375 patients with asthenoteratozoospermia from the First Affiliated Hospital of Anhui Medical University (Hefei, China). Hematoxylin and eosin staining, scanning electron microscopy, and transmission electron microscopy were performed to analyze the sperm morphology and ultrastructure. Immunofluorescence staining and Western blot analysis were conducted to examine the effects of genetic variants. We identified three novel deleterious variants in DNAH6 among three unrelated families. The absence of inner dynein arms and radial spokes was observed in the sperm of patients with DNAH6 variants. Additionally, deficiencies in the acrosome, abnormal chromatin compaction, and vacuole-containing sperm heads were observed in these patients with DNAH6 variants. The decreased levels of the component proteins in these defective structures were further confirmed in sperm from patients with DNAH6 variants using Western blot. After intracytoplasmic sperm injection (ICSI) treatment, the partner of one patient with a DNAH6 variant achieved successful pregnancy. Overall, novel variants in DNAH6 genes that contribute to defects in the sperm head and flagella were identified, and the findings indicated ICSI as an effective clinical treatment for such patients.

Comparing Arsenic-Containing Qinghuang Powder and Low-Intensity Chemotherapy in Elderly Patients with Acute Myeloid Leukemia / 中国结合医学杂志

OBJECTIVE@#To compare the clinical effect of arsenic-containing Qinghuang Powder (QHP) and low-intensity chemotherapy (LIC) in treatment of elderly acute myeloid leukemia (eAML) patients.@*METHODS@#Clinical data of 80 eAML patients treated at Xiyuan Hospital of China Academy of Chinese Medical Sciences from January 2015 to December 2020 were retrospectively analyzed. The treatment scheme was designed by real world study according to patients' preference, and patients were divided into a QHP group (35 cases) and a LIC group (45 cases). The median overall survival (mOS), 1-, 2-, and 3-year OS rates, and incidence of adverse events were compared between the two groups.@*RESULTS@#The mOS of 80 patients was 11 months, and the 1-, 2-, and 3-year OS rates were 45.51%, 17.96%, and 11.05%, respectively. The QHP and LIC groups demonstrated no significant difference in mOS (12 months vs. 10 months), 1- (48.57% vs. 39.65%), 2- (11.43% vs. 20.04%), and 3-year OS rates (5.71% vs. 13.27%, all P>0.05). Moreover, the related factors of mOS demonstrated no significant difference in patients with age>75 years (11 months vs. 8 months), secondary AML (11 months vs. 8 months), poor genetic prognosis (9 months vs. 7 months), Eastern Cooperative Oncology Group performance status score ⩾ 3 (10 months vs. 7 months) and hematopoietic stem cell transplant comorbidity index ⩾ 4 (11 months vs. 7 months) between the QHP and LIC groups (all P>0.05). However, the incidence of myelosuppression was significantly lower in the QHP group than that in the LIC group (28.57% vs. 73.33%, P<0.01).@*CONCLUSIONS@#QHP and LIC had similar survival rates in eAML patients, but QHP had a lower myelosuppression incidence. Hence, QHP can be an alternative for eAML patients who do not tolerate LIC.

Clinical efficacy of totally laparoscopic pylorus-preserving gastrectomy with preservation of the first branch of the right gastroepiploic vein in the treatment of early gastric cancer / 中华消化外科杂志

Objective:To investigate the clinical efficacy of totally laparoscopic pylorus-preserving gastrectomy (TLPPG) with preservation of the first branch of the right gastroepiploic vein in early gastric cancer (EGC).Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 38 EGC patients who were admitted to the Subei Hospital Affiliated to Yangzhou University from July 2018 to May 2021 were collected. There were 18 males and 20 females, aged 60 (range, 39?73) years. All patients underwent TLPPG with preservation of the first branch of the right gastroepiploic vein.Observation indicators: (1) surgical and postoperative condi-tions; (2) postoperative histopathological examination. (3) follow-up. Follow-up was conducted using outpatient examination, WeChat interview and medical record review to detect the nutritional status, residual stomach function, cholecystolithiasis, tumor recurrence and metastasis and death of patients. Follow-up was up to July 2022. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1) Surgical and postoperative conditions. All 38 patients underwent TLPPG with preservation of the first branch of the right gastroepiploic vein successfully, without laparotomy conversion. The operation time, volume of intraoperative blood loss, time to postoperative first flatus, time to postoperative first liquid food intake and duration of postoperative hospital stay of the 38 patients were (180±28)minutes, (58±38)mL, (2.7±0.6)days, (3.4±0.7)days and (10.3±2.8)days, respectively. Of the 38 patients, there were 6 cases with postoperative complications ≥grade Ⅱ of Clavien-Dindo classification. (2) Postoperative histopatho-logical examination. The tumor diameter, distance from proximal resection margin to tumor and distance from distal resection margin to tumor of the 38 patients were (1.8±0.5)cm, (3.4±0.2)cm and (4.3±0.4)cm, respectively. Both of proximal and distal resection margin was negative. Numbers of lymph node examined and numbers of lymph node examined in the No.6 lymph node of the 38 patients were 23.3±3.9 and 3.4±1.1, respectively. There were 38 cases with pathological T1 stage including 23 cases of T1a stage and 15 cases of T1b stage. There were 36 cases with pathological N0 stage and 2 cases with pathological N1 stage. There were 36 cases with pathological ⅠA stage and 2 cases with pathological ⅠB stage of TNM staging. (3) Follow-up. All 38 patients were followed up for 18(range, 12?48)months. The hemoglobin, serum albumin and total serum protein of the 38 patients were (125.4±5.8)g/L, (42.4±2.3)g/L and (71.6±2.1)g/L, respectively, at postoperative 6 month. Endo-scopy was used to evaluate the function of residual stomach of patients at postoperative 12 month. There were 4 patients with moderate amount of food remaining in the residual stomach. No patient suffered reflux esophagitis, reflux gastritis and bile reflux. None of the 38 patients received post-operative chemotherapy, and there was no tumor recurrence and metastasis or death occured in patient.Conclusion:TLPPG with preservation of the first branch of the right gastroepiploic vein is safe and feasible for the treatment of EGC patients with tumor located at 1/3 of the middle segment of stomach.

A Breakthrough Point in Integrative Medical Research: Challenge of Treating Overlapping Symptoms in Functional Gastrointestinal Disorders / 中国结合医学杂志

Functional gastrointestinal disorders (FGIDs) are common disorders that are characterized by persistent and recurring gastrointestinal symptoms. Many patients with FGIDs have overlapping symptoms, which impaired the quality of life and ability to work of patients, and left a considerable impact on health-care systems and society. Chinese medicines (CMs) are commonly utilized by many patients with FGIDs. This article discusses the current status of diagnosis and treatment of FGIDs, the advantages and characteristics of CM treatment, and how integrated medicine can make a breakthrough in FGIDs diagnosis and treatment.

Experimental investigation of early assessment of corpora cavernosa fibrosis with two-dimensional shear wave elastography / 亚洲男科学杂志(英文版)

This study explored the usefulness of two-dimensional shear wave elastography (2D-SWE) in the early assessment of corpora cavernosa fibrosis (CCF). New Zealand male rabbits were randomly assigned to an experimental group or a control group. Recombinant human transforming growth factor beta 1 (TGF-β1) was injected into the dorsal penis tissue of rabbits in the experimental group. Conventional ultrasound and 2D-SWE examinations were performed before and 20 days after injection. Penile histological analysis was performed by hematoxylin-eosin staining, sirius red staining, and immunohistochemistry. Measurement of 2D-SWE examination results was performed using shear wave elastography quantitative measurement (SWQ). Histological analysis outcomes were the proportion of smooth muscle cells (SMCs), collagen fibers (CFs), collagen type I (Col I), and collagen type III (Col III), as well as the SMCs/CFs ratio, measured by sirius red staining. Other histological analysis outcomes were the positive area proportion (PAP) of TGF-β1 (PAPT), fibronectin (PAPF), and Col III (PAPC), measured by immunohistochemistry. After recombinant human TGF-β1 injection, SWQ was higher in the experimental group than that in the control group (P < 0.001); however, there were no differences in conventional ultrasound results. There were significant differences in histological outcomes between the two groups (all P < 0.05). These results indicated that 2D-SWE was superior for identifying early histological changes in CCF.

Extraperitoneal sigmoid colostomy combined with pelvic peritoneal reconstruction in laparoscopic abdominoperineal resection for locally advanced low rectal cancer / 中华普通外科杂志

Objective:To evaluate the role of permanent sigmoid colostomy created through the extraperitoneal route combined with pelvic floor peritoneal reconstruction after laparoscopic Miles surgery for lower rectal cancer.Methods:A total of 88 patients undergoing laparoscopic Miles surgery at Gastrointestinal Center of Northern Jiangsu People's Hospital from Apr 2016 to Apr 2020 were divided into extraperitoneal ostomy group(40 cases) and transperitoneal ostomy group (48 cases).Results:There were no significant differences in operating time, stoma-forming time, intraoperative blood loss, first exhausting time, first defecation time and hospital stay between the two groups (all P>0.05). There were 17 cases of complications in observation group vs. 16 cases in control group ( χ2=0.782， P=0.376). After 12 months, the complications in observation group were significantly less than control group ( χ2=8.601， P=0.003). There was no parastoma hernia in observation group vs.7 in control group ( χ2=4.502， P=0.034). The satisfaction rate of ostomy control defecation in observation group (70%) was significantly higher than that in control group (38%) after 12 months ( P=0.001). Conclusion:A permanent sigmoid colostomy created through the extraperitoneal route combined with pelvic floor peritoneal reconstruction during laparoscopic Miles surgery is safe and feasible, with fewer complications and better defecation function than that of the stoma through transperitoneal approach.

MicroRNA-34a promotes cell cycle arrest and apoptosis and suppresses cell adhesion by targeting DUSP1 in osteosarcoma.

MicroRNAs are often deregulated in most cancer types and have important functions in carcinogenesis and cancer progression. Here, we studied the function of microRNA-34 (miR-34a) in osteosarcoma MG63 and U-2OS cells by expressed with pre-miR-34a, anti-miR-34a and corresponding negative controls, respectively. Cells proliferation, cell cycle and apoptosis was measured by MTT and flow cytometry assay. The effect of miR-34a on DUSP1 expression was evaluated by luciferase assays, real-time PCR and western blot assay. The data showed that miR-34a reduced the proliferation of MG63 cells through prompting cell cycle arrest at G0/G1 phase, cell apoptosis, and suppressed cell adhesion ability. Whereas anti-miR-34a increases U-2OS cell proliferation by preventing cell apoptosis, and promotes cell adhesion. Finally, we identified Dual-specificity phosphatase 1 (DUSP1) as the target gene of miR-34a in osteosarcoma cells and confirmed that DUSP1 enhanced the proliferation through inhibiting cell cycle arrest at G0/G1 phase and apoptosis, and inhibits the decreased cell adhesion induced by miR-34a. However, inhibition of DUSP1 resulted in substantially decreased proliferation and adhesion, and cell cycle arrest in G0/G1 phase and cell apoptosis similar to that observed with miR-34a in U-2OS cells. Our findings find out an important function of miR-34a as a novel tumor-suppressor in osteosarcoma pathogenesis through inhibition of DUSP1.

Anti-inflammatory effects of aucubin in cellular and animal models of rheumatoid arthritis / 中国天然药物

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease. It is known that aucubin (AU) exerts anti-inflammatory activity, but its effects and mechanisms in RA are unclear. This study investigated the anti-inflammatory effects and mechanisms of AU in vivo and in vitro. Human fibroblast-like synoviocyte cells from patients with RA (HFLS-RA), RAW264.7 cells, and MC3T3-E1 cells were used to evaluate the effects of AU on migration, invasion, apoptosis, osteoclast differentiation and production. Immunofluorescence was used to observe nuclear translocation of nuclear factor (NF)-κB, the double luciferase reporter gene method was used to observe NF-κB-p65 activity in AU-treated MC3T3-E1 cells. RT-qPCR was used to measure expression of bone metabolism and inflammation-related genes, and western blot was used to measure bone metabolism and NF-κB protein expression levels. Collagen-induced arthritis (CIA) rat model was used for pharmacodynamics study. Arthritis indexes were measured in the ankle and knee, histological staining and Micro-computed tomography were performed on the ankle joints. Also, inflammatory factor gene expression and the levels of NF-κB-related proteins were detected as in vitro. AU effectively inhibited HFLS-RA cell migration and invasion, promoted apoptosis, and inhibited RAW264.7 cell differentiation into osteoclasts, as well as inhibited NF-κB-p65 activity in MC3T3-E1 cells. Notably, AU significantly reduced the gene expression levels of three cell-related inflammatory factors and bone metabolism factors, effectively inhibited the expression of p-Iκκα β, p-IκBα, and p-p65 proteins. In vivo, AU relieved joint inflammation, reduced related inflammatory factors, and inhibited NF-κB signaling. It could be used to treat RA-related synovial inflammation and bone destruction through the NF-κB pathway.

Effect of Xiangsha Liu Junzitang on Gastric Motility and CRF and UCN2 Expression in Rats with Functional Dyspepsia Due to Spleen Deficiency / 中国实验方剂学杂志

ObjectiveTo observe the effects of Xiangsha Liu Junzitang （XSLJZ） on gastric emptying rate and expression levels of corticotropin-releasing factor （CRF） and urocortin 2 （UCN2） in rats with functional dyspepsia （FD） due to spleen deficiency. MethodForty-eight 10-day-old male SD rats were randomly divided into the normal group （n=8） and iodoacetamide （IA） group （n=40）， and they separately received 2% sucrose solution and 0.1% sucrose solution containing IA for six successive days. Following the removal of mother rats， the three-week-old IA-treated rats were randomized into five groups， namely the model group， mosapride group， and low-， middle-， and high-dose XSLJZ groups， with eight rats in each group. At the age of six weeks， rats in all groups expert for the normal group were modeled by the modified multiple platform method for 14 d. Afterwards， the ones in normal group and model group were treated with 10 mL·kg-1 distilled water， and those in the treatment groups with 1.6×10-3 g·kg-1 mosapride and 2.8， 5.6， and 11.2 g·kg-1 XSLJZ by gavage， respectively， for 14 d. The grasping ability and gastric emptying rate were determined. The histological changes in gastric antrum were observed by hematoxylin-eosin （HE） staining. The protein and mRNA expression levels of CRF and UCN2 in gastric antrum were detected by Western blot and real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）. ResultNo obvious change or organic lesion was observed in gastric antrum of rats in each group. Compared with the normal group， the model group exhibited lowered gastric emptying rate and grasping ability （P<0.01）， up-regulated CRF protein and mRNA expression in gastric antrum （P<0.01）， and down-regulated UCN2 protein and mRNA expression （P<0.05， P<0.01）. Compared with the model group， XSLJZ at the middle and high doses enhanced the grasping ability and gastric emptying rate （P<0.05， P<0.01） and down-regulated CRF mRNA expression to varying degrees （P<0.05， P<0.01）. XSLJZ at the high dose decreased CRF protein expression （P<0.05） and up-regulated UCN2 protein and mRNA expression （P<0.01）. ConclusionThe mechanism of XSLJZ in invigorating spleen and promoting gastric motility of FD rats may be related to its reduction of CRF and elevation of UCN2 in gastric antrum.

Effect of light on refractive development / 国际眼科杂志(Guoji Yanke Zazhi)

@#In modern society, children and adolescents are experiencing an increasing incidence of myopia, resulting from the combined influence of genetic factor and environmental factor. Despite the influence of genetic factor, a great number of researches indicate that environmental factor has been playing a crucial role. Outdoor activity proves to be a major protective factor to reduce the incidence of children's myopia. Sunlight is one of the important ones among various factors of outdoor activity. The intensity, wavelength and rhythm of sunlight may all affect eyeball's refraction development. Varied sunlight environment may have different influences on eyeball's refraction development. The paper has summarized clinical and trial and animal experiment research results on how sunlight affects eyeball's refraction development, and it has offered references to further study on refractive error development mechanism and prevention strategy.