lncRNA VIM-AS5 expression and its effect on proliferation and migration of human breast cancer cell lines / 基础医学与临床

Objective To explore the clinical significance of long non-coding RNA(lncRNA)VIM-AS5 expres-sion in human breast cancer tissues and its regulatory mechanism involved in cancer cell proliferation and mi-gration.Methods The Lnc2Cancer 3.0 database was used to analyze the expression of VIM-AS5 in breast cancer tissues and its correlation with the clinical stage and survival time of breast cancer patients.RT-qPCR was used to detect the expression of VIM-AS5 in breast cancer cell lines BT-549,MDA-MB-435,MDA-MB-231 and CAL-51.Plasmid with VIM-AS5 overexpression and negative control were all transfected into CAL-51 cells through liposome recorded as VIM-AS5 group and NC group,respectively.The proliferation and migration of CAL-51 cells were detected by colony formation assay and scratch healing method,respectively.Dual-lucif-erase reporter gene experiment verified the targeting relationship between VIM-AS5 and miR-500a.RT-qPCR was used to detect the expression of miR-500a in CAL-51 cells.Western blot was used to detect the expression of JAK/STAT3 pathway in CAL-51 cells.Results The expression of VIM-AS5 in breast cancer tissues was significantly lower than that in adjacent tissues(P＜0.01).VIM-AS5 expression was negatively correlated with the clinical stage of breast cancer patients(P＜0.01).The survival time of breast cancer patients with low VIM-AS5 expression was significantly shorter than that of breast cancer patients with high VIM-AS5 ex-pression(P＜0.01).Compared with mammary epithelial cell line MCF-10 A cells,VIM-AS5 expression was significantly reduced in breast cancer cells(P＜0.01).The counting number of colony formed in the VIM-AS5 group was significantly lower than that in the NC group(P＜0.01).The cell migration rate in the VIM-AS5 group was significantly lower than that in the NC group(P＜0.01).Dual-luciferase reporter gene experiment confirmed that miR-500a was the target gene of VIM-AS5(P＜0.01).VIM-AS5 can negatively regulate the expression of miR-500a(P＜0.01).Compared with the NC group,the expression of JAK/STAT3 pathway proteins JAK,p-STAT3,c-Myc,Bcl-2,and CDK3 in CAL-51 cells of the VIM-AS5 group were significantly decreased.Conclusions VIM-AS5 is low-expressed in breast cancer cells,and up-regulation of VIM-AS5 may inhibit the proliferation and migration of breast cancer cells CAL-51 by targeting at miR-500a/JAK/STAT3 pathway.

C-X3-C motif chemokine ligand 1/C-X3-C motif chemokine receptor 1 pathway in the recovery of memory function in hemorrhagic shock/resuscitation rats / 解剖学报

Objective To investigate the effect of microglia activation regulated by C-X3-C motif chemokine ligand 1(CX3CL1)-C-X3-C motif chemokine receptor 1(CX3CR1)pathway on memory function in hemorrhagic shock/resuscitation rats.Methods The experiment was divided into two parts.In the first part,the rats were randomly divided into sham group,model-0.5 hour group,model-1.5 hour group,model-3 hour group,10 rats in each group.There were differences in the time of hemorrhagic shock among each group.In the second part,rats were randomly divided into control group and CX3CL1 group,10 rats in each group.The rats in CX3CL1 group were treated with CX3CL1 protein factor(intraventricular injection),and the rats in control group were treated with saline.All rats were trained in Morris water maze experiments before model construction,and tests of Morris water maze experiments were carried out after 4 days of model construction.After completion,the whole brains were taken for HE staining and immunohistochemical staining.Cerebrospinal fluid was taken for detection of inflammatory cytokines,and hippocampus tissues were taken for Real-time PCR detection and Western blotting detection.Results Compared with the sham group,the escape latency of rats in model group increased,the number of platform crossings and the resident time in the third quadrant decreased.The neuronal state was impaired in HE staining in model group.In addition,compared with the sham group,the expression of ionized calcium binding adaptor molecule-1(Iba1)in the brain of the rats in model group increased,the contents of tumor necrosis factor-α(TNF-α)and interleukin(IL)-6 in the cerebrospinal fluid increased,and the M1-type microglia markers CD16,TNF-α,IL-1β and inducible nitric oxide synthase(iNOS)mRNA content increased.At the same time,compared with the sham group,the expressions of CX3CL1 and CX3CR1 in the brain of model group decreased,and the expressions of phosphorylated nuclear factor-κB(p-NF-κB)and nucleotide binding oligomerization domain(NOD)-like receptor protein 3(NLRP3)increased.However,compared with the control group,rats in CX3CL1 group had reduced escape latency,increased platform crossing times and quadrantⅢresident time,and recovered neuronal states.In addition,the expression of Iba1 in the brain of CX3CL1 group decreased,the contents of TNF-α and IL-6 in the cerebrospinal fluid decreased,the mRNA contents of M1-type microglia markers like CD16,TNF-α,IL-1β and iNOS decreased,and the mRNA contents of markers of M2-type microglia glial like CD206,transforming growth factor-β(TGF-β),arginase-1(Arg1),Chitinase 3-like protein 1(Ym 1)increased.Conclusion CX3CL1 can help inhibit the excessive activation of microglia,induce the polarization of microglia to M2 type,inhibit the polarization of M1 type,reduce the release of inflammatory cytokines,and alleviate the memory function damage induced by hemorrhagic shock/resuscitation.

A retrospective analysis of pathological features of papillary thyroid carcinoma with Hashimoto’s thyroiditis / 中华内分泌外科杂志

Objective:To analyze and compare the pathological data characteristics of patients with simple papillary thyroid carcinoma (PTC) and PTC combined with Hashimoto’s thyroiditis (HT), so as to provide clinical treatment ideas.Methods:A retrospective analysis was performed on the medical records of 326 PTC patients who met the requirements and underwent surgical treatment in the Department of Thyroid and Breast Surgery, Nanjing Hospital of Traditional Chinese Medicine from Jan. 2020 to May. 2022. There were 81 males and 245 females. They were divided into PTC group and HT-PTC group, according to whether they were combined with HT. Clinical data were collected and organized. The collection indicators included patient gender, age, body mass index (BMI), five preoperative thyroid function items including free triiodothyronine (FT3), free thyroxine (FT4), triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH), BRAF gene mutation, single or bilateral lesions, single or multiple lesions, largest postoperative pathological tumor lesions diameter, cervical lymph node metastasis (LNM) status, etc. At the same time, all patients were divided into CLNM group and no CLNM group according to CLNM status. The two groups were compared in terms of gender, age ≥55 years old, whether combined with HT, number of lesions, unilateral and bilateral, extraglandular invasion, microcarcinoma, and BRAF gene. Statistical software was used to analyze the results. t test, χ2 test, and logistic regression analysis were adopted. P<0.05 indicates that the difference is statistically significant. Results:The proportion of female patients in both groups was higher, and the proportion of female patients in the HT-PTC group (90/100, 90%) was higher than that in the PTC group (155/226, 69.59%). HT-PTC patients were younger than patients in the PTC group (43.03±12.72 vs. 43.70±12.63) years old, and their TSH (2.71±1.69 vs. 2.02±1.46) uIU/mL was higher. The differences were statistically significant (all P<0.05). There were no statistically significant differences in BMI, FT3, FT4, T3, or T4 (all P>0.05). The HT-PTC group had a lower proportion of BRAF gene mutations [87/100 (87%) vs. 212/226 (93.8%) ], a smaller maximum tumor diameter (1.06±0.73 vs. 1.32±0.97 cm), and a lower proportion of CLNM [37 /100 (37%) vs. 118/226 (52.2%) ]. The number of LNMs with metastasis is less (3.33±2.21 vs. 4.76±4.00), and it was more likely to be multifocal [44/100 (44%) vs. 73/226 (32.74%) ]. All differences were statistically significant (all P<0.05), and the differences in bilateral gland lobes involvement and extra-glandular invasion were not statistically significant. When accompanied by CLNM, gender (male vs. female) [55/100 (35.45%/64.52%) vs. 26/145 (15.2%/84.85%) ], age ≥ 55 years (yes vs. no) [21/134 (13.55) %/86.45%) vs. 50/121 (29.24%/70.76%) ], HT (yes vs. no) [37/118 (23.87%/76.13%) vs. 63/108 (36.84%/63.16%), number of lesions (single focus vs. multiple focus) [90/65 (41.94%/50.06%) vs. 119/52 (69.59%/30.41%) ], microcarcinoma (yes vs. no) [83/72 (53.55%/45.45%) vs. 139/32 (81.29%/18.71%) ] and extraglandular invasion (with vs. without) [38/117 (24.52%/75.48%) vs. 27/144 (17.42%/84.21%) ] had statistics significance (both P<0.05). There was no statistical significance in bilateral lesion involvement or BRAF gene mutation (all P>0.05). Multivariate logistic regression analysis showed that age, microcarcinoma, HT, gender, and number of lesions were independent risk factors for CLNM, and male gender and multifocal cancer were risk factors for CLNM. Age ≥55 years, microcarcinoma, and combined HT were negatively associated with CLNM. Conclusions:HT may promote the occurrence of PTC, but can inhibit its development. In the short term, patients with HT can have a better prognosis than those with simple PTC.

Diagnostic value of ultrasonography and CT in acute appendicitis / 实用放射学杂志

Objective To compare the diagnostic value of ultrasonography and CT in acute appendicitis.Methods A retrospective analysis was conducted on 279 patients who were diagnosed with acute appendicitis and followed emergency surgery.Patients were divided into different subgroups based on postoperative pathological results and body mass index(BMI),and the pathological results were used as the gold standard to analyze whether there were differences in the diagnostic accuracy of ultrasonography and CT examination for acute appendicitis.Results A total of 279 patients with confirmed acute appendicitis,with 64 cases of simple appendicitis,127 cases of suppurative appendicitis,and 88 cases of gangrenous appendicitis according to pathological classification.The diagnostic accuracy of ultrasonography was 68.75%(44/64),73.22%(93/127),and 81.81%(72/88),respectively.The diagnostic accuracy of CT was 71.87%(46/64),82.67%(105/127),and 90.90%(80/88),respectively.There was no statistically significant difference in diagnostic accuracy between the two examinations(P>0.05).Subgroup analysis based on patient BMI showed that there was no difference in diagnostic accuracy of the two examinations for patients with normal BMI(P>0.05),while for overweight and obese patients,the diagnostic accuracy of CT was better than that of ultrasonography,with a statistical difference(P<0.05).Conclusion There is no difference in the diagnostic accuracy of ultrasonography and CT examinations for acute appendicitis of different pathological types.But for overweight and obese acute appendicitis patients,the diagnostic accuracy of CT examination is superior to ultrasonography.

Clinical significance of miR-126 in prognosis of cerebral infarction after thrombectomy / 中国现代医生

@#Objective To detect the changes of serum microRNA-126(miR-126)before interventional thrombectomy for acute cerebral infarction,and to explore its correlation with the prognosis of patients.Methods A retrospective analysis was performed on 101 patients with cerebral infarction who underwent interventional thrombectomy in he First People's Hospital of Huzhou from January 2019 to December 2021.The patients were followed up for 2 month.According to modified Rankin scale(mRS),they were divided into good prognosis group(mRS≤2 points,56 cases)and poor prognosis group(mRS>2 points,45 cases).The clinical data of two groups and the difference of miR-126 before thrombectomy were compared,and the effect of serum miR-126 change on the prognosis of patients with cerebral infarction was analyzed.Results The serum miR-126 level before thromrectomy in good prognosis group was significantly higher than that in poor prognosis group[(9.31±2.14)vs.(1.36±0.28),P<0.01].There was a negative correlation between miR-126 and National Institute of Health stroke scale(NIHSS)score(r=-0.737,P<0.01),and a positive correlation between miR-126 and good collateral circulation(r=0.645,P<0.01).The area under the receiver operating characteristic curve for establishing miR-126 to predict prognosis after thrombolectomy for cerebral infarction was 0.818.The sensitivity and specificity were 78.9%and 86.0%at the optimal cut-off value.Conclusion The change of serum miR-126 level before thrombectomy may be related to the prognosis of patients with cerebral infarction,which can be used as a marker to predict the prognosis of cerebral infarction after interventional therapy.

I2-DMSO-Mediated Transannulation of Benzo[d]isoxazol-3-amine: Direct Access to 2,4,5-Substituted Pyrimidine Derivatives.

An I2-DMSO-mediated multicomponent [3+1+2] cascade annulation reaction using aryl methyl ketones, enaminones, and benzo[d]isoxazol-3-amine as substrates has been developed. This metal-free reaction involved the transannulation of benzo[d]isoxazol-3-amines with the formation of two C-N bonds and a C-C bond in one pot. Notably, a pyrimidine ring with a 1,4-dicarbonyl scaffold could efficiently transform into a pyrimido[4,5-d]pyridazine skeleton. The phenolic hydroxyl group of the target product could undergo further modification with pharmaceuticals, demonstrating the utility of this method.

Alternative Splicing and Expression Reduction of P450 Genes Mediating the Oxidation of Chlorpyrifos Revealed a Novel Resistance Mechanism in Nilaparvata lugens.

Cytochrome P450 enzymes metabolize various xenobiotics in insects. Compared to numerous P450s associated with insecticide detoxification and resistance, fewer have been identified to bioactivate proinsecticides in insects. Here we reported that two P450s, CYP4C62 and CYP6BD12, in Nilaparvata lugens could bioactivate chlorpyrifos, an organophosphorus insecticide, into its active ingredient chlorpyrifos-oxon in vivo and in vitro. RNAi knockdown of these two genes significantly reduced the sensitivity to chlorpyrifos and the formation of chlorpyrifos-oxon in N. lugens. Chlorpyrifos-oxon was generated when chlorpyrifos was incubated with the crude P450 enzyme prepared from N. lugens or recombinant CYP4C62 and CYP6BD12 enzymes. The expression reduction of CYP4C62 and CYP6BD12 and alternative splicing in CYP4C62 reduced the oxidation of chlorpyrifos into chlorpyrifos-oxon, which contributed importantly to chlorpyrifos resistance in N. lugens. This study revealed a novel mechanism of insecticide resistance due to the bioactivation reduction, which would be common for all currently used proinsecticides.

Clinical efficacy of endoscopic thyroidectomy by gasless unilateral axillary approach for the treatment of papillary thyroid microcar cinoma / 中华内分泌外科杂志

Objective:To compare and explore the clinical efficacy and safety of endoscopic thyroidectomy by gasless unilateral axillary approach for the treatment of papillary thyroid microcar cinoma (PTMC) .Methods:One hundred and ten patients with unilateral PTMC admitted to the Department of Thyroid and Breast Surgery, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, from Jan.3 2019 to Mar. 2022 were used as clinical study subjects, and according to the patients' choice of surgical modality, they were divided into 30 cases in the endoscopic thyroidectomy by gasless unilateral axillary approach (ETGUA) group and 80 cases in the minimally invasive video-assisted thyroidectomy (MIVAT) group. We retrospectively compared and analyzed the differences in the surgery-related indexes, aesthetic satisfaction rate at 3 months postoperatively and functional status of the anterior cervical region between the 2 groups. SPSS 26.0 statistical software was used to process the data, analyze and draw conclusions. P<0.05 was considered a statistically significant difference. Results:The number of lymph nodes cleared in the study group (6.60±4.41) was less than that in the control group (9.63±6.25) ( P<0.05) ; the total operative time (169.83±28.76) min, postoperative drainage (173.60±94.33) ml, and time to remove drainage tubes after surgery (5.73±1.86 ) d was significantly higher than the total operative time (145.56±33.89) min, postoperative drainage (107.28±53.82) ml, and time to remove drainage tubes after surgery (2.88±1.07) d in the control group ( P<0.01) ;the intraoperative bleeding, number of positive lymph nodes, and postoperative hospital stay were not statistically significant between the two groups ( P>0.05) .The aesthetic satisfaction rate of the study group had a significant advantage over the control group (90% vs 70%) ( P<0.01) .Comparing the functional status of the anterior cervical region between the two groups after surgery,the occurrence of swallowing discomfort or with pulling sensation was better in the study group than in the control group 1 week after surgery ( P<0.05), and there was no statistically significant difference between the two groups in the occurrence of neck pain score, abnormal sensory function (neck pressure, foreign body sensation, numbness and pins and needles) and vocal difficulty ( P>0.05) ; 3 months after surgery, abnormal sensory function of the neck in the study group (at 3 months postoperatively, the occurrence of abnormal neck sensory function (neck pressure, foreign body sensation, numbness and pins and needles sensation) and swallowing discomfort or pulling sensation were better in the study group than those in the control group ( P<0.05). There were no signs of local recurrence or distant metastasis in both groups at follow-up to date. Conclusions:Both minimally endoscopic thyroidectomy procedures were safe, feasible, and effective in the treatment of unilateral PTMC. Among them, the ETGUA is more suitable for patients with strong cosmetic needs within the indications because of its concealed incision and its ability to protect the function of the anterior cervical region, and can be the preferred option.

One case report of recurrent primary hyperparathyroidism caused by iatrogenic implant ectopic parathyroid adenoma / 中华内分泌外科杂志

Parathyroid adenoma (PTA) is an important cause of hyperparathyroidism (HPT) . The author reported a case of HPT caused by proliferation of parathyroid cells caused by implantation during surgery, and the formation of adenoma in sternocleidomastoid muscle was detected. The understanding of primary hyperparathyroidism (PHPT) caused by ectopic PTA was analyzed from clinical symptoms, laboratory examination, the neck Doppler ultrasound, imaging ( 99TC m-MIBI SPECT/CT fusion imaging, CT) and pathological examination results, combined with the parathyroidism of the patient during the first operation.

Management of vena cava tumor thrombus dislodgement in robot-assisted laparoscopic surgery / 现代泌尿外科杂志

Renal cancer complicated with inferior vena cava tumor thrombus has been difficult to manage in urological surgery, because it has a complex anatomical relationship and involves vascular blockage of vital organs such as kidney, liver and heart, as well as the blockage and reconstruction of inferior vena cava. In addition, tumor thrombus dislodgement may occur intraoperatively, leading to acute pulmonary embolism, which makes the surgery extremely difficult and risky. In this paper, we report the successful treatment of thrombus dislodgement in a case of right kidney tumor with inferior vena cava thrombus during robot-assisted laparoscopic surgery and explore the treatment methods, aiming to avoid lethal pulmonary embolism caused by tumor thrombus dislodgement.

Simultaneous determination of seven components and their distribution in Anoectochilus roxburghii by UHPLC-MS/MS / 药学学报

Based on ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), a rapid and simultaneous quantitative method for the measurement of seven components (kinsenoside; rutin; kaempferol-3-O-rutinoside; quercimeritrin; narcissin; isorhamnetin-3-O-glucoside; quercetin) of A. roxburghii was established. The separation was performed over 8.0 minutes on a Waters Acquity UPLC BEH Shield RP18 (2.1 mm × 100 mm; 1.7 μm) with a mobile phase consisting of acetonitrile (A) and 0.1% formic acid water solution (B) with gradient elution at a flow rate of 0.2 mL·min-1; the column temperature was 30 ℃ and the injection volume was 2 μL. Electrospray spray ionization source (ESI source) was used for mass spectrometry, and positive and negative ion modes were detected at the same time. The results showed good linearity (R2 ≥ 0.998 0), with good precision, repeatability and stability, and the average recovery was 97.71%-103.33%. Through cluster heat map and redundancy analysis, we found that kinsenoside was mainly distributed in stems, followed by leaves, and the lowest content in roots. The content of kinsenoside increased significantly in the stems of plants 6 months, but less change was evident in the roots and leaves. Flavonoids and flavonoid glycosides were mainly distributed in leaves. The UHPLC-MS/MS method established in this paper can be used for the quality control of A. roxburghii and provides a reference for establishing a more comprehensive quality detection method for this medicinal.

Computational Study of Fenestration and Parallel Grafts Used in Aortic Arch Lesion / 医用生物力学

Objective To explore hemodynamics of the aortic arch and supraarch vessels after thoracic endovascular aortic repair with fenestration and parallel grafts techniques, and compare the differences of these techniques. Methods Four patients with aortic arch lesions whose supraarch vessels were reconstructed by different surgical techniques (fenestration, chimney and periscope) were studied, and three-dimensional (3D) geometric models were established based on postoperative image data. The physiological flow obtained from two dimensional (2D) phase contrast magnetic resonance imaging were imposed on the ascending aorta inlet and the supraarch vessels outlets. The pressure waveform of 3-element Windkessel model was imposed on the descending aorta outlet. Through computational fluid dynamics ( CFD ) simulations, the hemodynamic parameters were obtained, including the pressure of supraarch vessels, the velocity vector of the stent inlet, and the relative residence time. Results The pressure change of the periscope stent was the largest, followed by the fenestration stent, and the pressure change of the chimney stent was the smallest. The velocity of the fenestration and periscope stent inlet was uneven, which might form vortex. The velocity of the chimney stent inlet was even. The high relative residence time concentrated in distal end of the fenestration stent outer wall, the ‘gutter’ part, and the place where the chimney and periscope stent adhered to the vessel wall. Conclusions The pressure difference between the inner and outer walls of the fenestration and periscope stent was high, so it was recommended to use the balloon-expandable stent. The pressure difference between the inner and outer walls of the chimney stent was low, so it was recommended to use the self-expanding stent. The predicted location of thrombosis was consistent with the clinical follow-up data, so it may be used for surgical planning and risk assessment of interventional treatment of aortic arch lesions.

I2-DMSO Mediated Multicomponent [3+2] Annulation Reaction: An Approach to Pyrrolo[2,1-a]isoquinoline Derivatives with a Quaternary Center.

An I2-DMSO mediated multicomponent [3+2] cascade annulation reaction using methyl ketones, 1,2,3,4-tetrahydroisoquinolines (THIQ) and cyclopropenones as readily available substrates has been developed. This metal-free process involves N-H/α-C(sp3)-H trifunctionalization of THIQ and C-C bond cleavage of cyclopropenone, providing a direct approach to obtain pyrrolo[2,1-a]isoquinoline derivatives with a quaternary carbon center. Two C-C bonds and one C-N bond are formed efficiently in one pot.

A crosstalk of circadian clock and alternative splicing under abiotic stresses in the plants.

The circadian clock is an internal time-keeping mechanism that synchronizes the physiological adaptation of an organism to its surroundings based on day and night transition in a period of 24 h, suggesting the circadian clock provides fitness by adjusting environmental constrains. The circadian clock is driven by positive and negative elements that regulate transcriptionally and post-transcriptionally. Alternative splicing (AS) is a crucial transcriptional regulator capable of generating large numbers of mRNA transcripts from limited numbers of genes, leading to proteome diversity, which is involved in circadian to deal with abiotic stresses. Over the past decade, AS and circadian control have been suggested to coordinately regulate plant performance under fluctuating environmental conditions. However, only a few reports have reported the regulatory mechanism of this complex crosstalk. Based on the emerging evidence, this review elaborates on the existing links between circadian and AS in response to abiotic stresses, suggesting an uncovered regulatory network among circadian, AS, and abiotic stresses. Therefore, the rhythmically expressed splicing factors and core clock oscillators fill the role of temporal regulators participating in improving plant growth, development, and increasing plant tolerance against abiotic stresses.

Efficacy and Safety of Placebo During the Maintenance Therapy of Ovarian Cancer in Randomized Controlled Trials: A Systematic Review and Meta-analysis.

Introduction: This meta-analysis evaluated the efficacy and safety of placebo during the maintenance therapy of ovarian cancer (OC) patients in randomized controlled trials (RCTs). Methods: A comprehensive literature review was performed for RCTs published up to and including August 2020 from four electronic databases. We analyzed the efficacy and safety in the control arms of the maintenance therapy in advanced OC patients. Hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) of progression-free survival (PFS) and overall survival (OS) were estimated in the placebo arms and the observation arms, respectively, using the Frequency Framework method. We also calculated the incidences of common adverse effects (AEs) in the placebo arms. Results: In total, 41 articles with 20,099 (4,787 in the placebo arms, 3,420 in the observation arms, and 11,892 in the experiment arms) patients were included in this meta-analysis. Compared with observation, placebo did not improve or reduce PFS (HR, 1.02; 95% CI, 0.87-1.20; P = 0.81) and OS (HR, 1.02; 95% CI, 0.89-1.16; P = 0.76) of OC patients, while other treatments, except for radiotherapy, significantly improved PFS and OS (all P < 0.05). The incidences of AEs produced by placebo were 94.03% in all grades and 20.22% in grade ≥3. The incidences of AEs were 29.75% in fatigue, 26.38% in nausea, 24.34% in abdominal pain, 18.92% in constipation, 16.65% in diarrhea, 14.55% in vomiting, 13.89% in hypertension, and 13.14% in headache. Conclusions: Placebo did not improve or reduce the PFS and OS benefits of OC patients in RCTs but increased the incidences of AEs.

I2-DMSO-Mediated N-H/α-C(sp3)-H Difunctionalization of Tetrahydroisoquinoline: Formal [2 + 2 + 1] Annulation for the Construction of Pyrrolo[2,1-a]isoquinoline Derivatives.

An I2-DMSO-mediated cascade reaction using methyl ketones and 1,2,3,4-tetrahydroisoquinolines (THIQs) as commercially available substrates has been developed for the construction of pyrrolo[2,1-a]isoquinoline derivatives. This metal-free process involves N-H/α-C(sp3)-H difunctionalization of THIQ. Two C-C bonds and one C-N bond are formed in one pot under mild conditions. Besides, a quaternary carbon center has been constructed in this transformation efficiently.

An overview of the development of EED inhibitors to disable the PRC2 function.

Polycomb repressive complex 2 (PRC2) catalyzes the methylation of histone H3 lysine 27 (H3K27) and the enrichment of its catalytic product H3K27me3 is responsible for the silencing of tumor suppressor genes and the blocking of transcripts related to immunity and cell terminal differentiation. Aberrations of PRC2 components, such as mutation and overexpression, have been observed in various cancers, which makes PRC2 a potential therapeutic target for cancer. Up to now, targeting the enhancer of zeste homolog 2 (EZH2), the catalytic subunit of PRC2, represents the main strategy in the development of PRC2 inhibitors. Although significant progress has been made, new problems also emerge, e.g. the drug resistance caused by secondary mutations. In recent years, more and more efforts have shifted to another new strategy - targeting embryonic ectoderm development (EED) to disrupt its major interactions with other components, which are necessary to the PRC2 function, and some promising results have been obtained. This review summarizes the recent development of EED inhibitors as possible chemotherapy for cancer treatment, which could help accelerate future related research work.

Gene cloning of a highly active phytase from Lactobacillus plantarum and further improving its catalytic activity and thermostability through protein engineering.

Phytase belongs to orthophosphate monoester hydrolase, which can catalyze the gradual hydrolysis of phytic acid to inositol phosphate. It can be added to animal feed to reduce the anti-nutritional factor of phytic acid in feed. The thermostability and specific activity of phytases are two key factors determining their potential applications. In this study, a highly active 233-aa phytase gene (LpPHY233) from Lactobacillus plantarum was cloned and expressed in Escherichia coli (E. coli), achieving 800 times higher activity than that expressed in L. plantarum. Next, the temperature characteristic and catalytic performance of LpPHY233 was improved by disulfide bond engineering and C-terminal truncation, respectively. Surprisingly, the specific activity of the C-terminal truncated mutant LpPHY200 was about 5.6 times higher than that of LpPHY233, and the optimal temperature for the mutant LpPHY233S58C/K61C introduced disulfide bond was 15 °C higher than that of LpPHY233. Moreover, these phytase mutants displayed excellent pH property and kinetic parameters, and have great application prospect in feed additives field. The molecular basis for its catalytic performance was preliminarily explained by in silico design methods. Our results provided a solid theoretical foundation for further molecular modification and industrial application of phytases.

[Locking plate fixation with fibular strut allograft versus locking plate fixation alone for the treatment of proximal humeral fractures in adults:a Meta-analysis].

OBJECTIVE: To compare the clinical efficacy of locking plate fixation with a fibular strut allograft (FA group) and locking plate fixation alone (LP group) in the treatment of proximal humeral fractures in adults by Meta-analysis. METHODS: Databases including PubMed, The Cochrane Library, Embase, Chinese BioMedical Literature Database(CBM), China National Knowledge Infrastructure(CNKI), WanFang Data, and China Science and Technology Journal Database (cpvip Database) were searched by computer from establishing to March 2020 to collect studies about locking plate fixation with fibular strut allograft versus locking plate fixation alone for proximal humeral fractures in adults. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies. The postoperative humeral head height changes, neck-shaft angle changes, Constant-Murley score, American Shoulder and Elbow Surgeons(ASES)score, visual analogue scale(VAS), varus malunion rate, and screw penetration rate were compared by RevMan 5.3 software for Meta-analysis. RESULTS: Ten cohort studies were enrolled in a total of 749 patients, 300 patients in the FA group and 449 patients in the LP group. The results of Meta-analysis showed that locking plate with fibular strut allograft was superior to locking plate fixation alone in the changes in humeral head height [MD=-2.69, 95%CI(-3.24, -2.13), P<0.000 01], the changes in neck-shaft angle [MD=-5.65, 95%CI(-7.18, -4.12), P<0.000 01], Constant-Murley score [MD=9.00, 95%CI(4.26, 13.73), P=0.000 2], the ASES score [MD=5.56, 95%CI(4.29, 6.84), P=0.000 01], VAS score [MD=-0.23, 95%CI(-0.37, -0.09), P=0.001], the varus malunion rate [RR=0.22, 95%CI(0.09, 0.53), P=0.000 7] and the screw penetration rate [RR=0.26, 95%CI(0.13, 0.55), P=0.000 3], respectively.While there was no significant difference in the rate of osteonecrosis of the humeral head [RR=1.18, 95%CI(0.57, 2.45), P=0.65]. CONCLUSION: For proximal humeral fractures in adults, current evidence shows that locking plate fixation with fibular strut allograft is superior to single locking plate fixation in improving postoperative radiological outcomes and shoulder function, relieving postoperative pain, reducing varus malunion rate and screw penetration rate. However, the efficacy in decreasing the osteonecrosis rate is not clear. Due to limited quality and quantity of the included studies, more high-quality studies are required to verify the above conclusion.