lncRNA ZFP36-AS1 regulates proliferation and immune escape of bladder cancer cell through miR-221 / 国际外科学杂志

Objective:To investigate the expression of long non-coding RNA(lncRNA) ZFP36-AS1 in bladder cancer and the effect of ZFP36-AS1/miR-221 axis on the proliferation and immune escape of bladder cancer cells.Methods:The expression difference of ZFP36-AS1 in bladder cancer tissues was analyzed by cBioPortal database. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to analyze the expression difference of ZFP36-AS1 in bladder cancer cell lines (J82, RT-4, MGH-U3, 5637). MGH-U3 cells were randomly divided into negative control (NC) group and ZFP36-AS1 group, which were transfected with pcDNA3.1-NC plasmid and pcDNA3.1-ZFP36-AS1 plasmid, respectively. Colony formation assay and flow cytometry were used to analyze the proliferation activity and cell cycle of MGH-U3 cells, respectively. T lymphocytes were co-cultured with MGH-U3 cells in each group, and the levels of interleukin-10 (IL-10), γ-interferon (IFN-γ), and interleukin-4 (IL-4) in the supernatants of each group were detected by enzyme-linked immunosorbent assay (ELISA). The dual-luciferase reporter gene assay verified the targeting relationship between ZFP36-AS1 and miR-221. The effect of ZFP36-AS1 on the expression of miR-221 in MGH-U3 cells was detected by RT-qPCR. Western blotting was used to detect the effect of ZFP36-AS1/miR-221 axis on the protein expression of CDK3, Cyclin C, CDK5, Cyclin D1 and Cyclin D3 in MGH-U3 cells.Results:Compared with normal bladder tissue, ZFP36-AS1 was abnormally low-expressed in bladder cancer tissue ( P<0.01). Compared with SV-HUC-1 cells, ZFP36-AS1 was abnormally low-expressed in bladder cancer cell lines (J82, RT-4, MGH-U3, 5637) ( P<0.01), and the expression was lowest in MGH-U3 cells ( P<0.01). The number of MGH-U3 cell colonies formed in the NC group and the ZFP36-AS1 group were (220.80±34.65) and (77.84±19.11), respectively, and the number of MGH-U3 cell colonies formed in the ZFP36-AS1 group was significantly down-regulated, the difference was statistically significant ( P<0.01). The proportions of G 0/G 1 phase cells in NC group and ZFP36-AS1 group were (48.04±2.89)% and (72.89±3.46)%, respectively, and the proportion of S phase cells were (35.38±2.98)% and (20.62±2.56)%, respectively. The proportion of G 2/M stage cells was (16.59±1.46)% and (6.48±1.50)%, respectively. The proportion of cells in G 0/G 1 phase were up-regulated in ZFP36-AS1 group ( P<0.01), and the proportion of cells in S phase and G 2/M phase were both down-regulated ( P<0.01). Compared with the NC group, the levels of IL-4 and IFN-γ in the ZFP36-AS1 group were significantly up-regulated ( P<0.01), and the level of IL-10 was significantly down-regulated ( P<0.01). ZFP36-AS1 can target miR-221 ( P<0.01). The relative expression of miR-221 in the NC group and the ZFP36-AS1 group was 6.84±1.35 and 1.00±0.21, respectively. Compared with the NC group, overexpression of ZFP36-AS1 could significantly inhibit the expression of miR-221 ( P<0.01). Compared with the NC group, the expressions of CDK3, Cyclin C, CDK5, Cyclin D1, and Cyclin D3 in the ZFP36-AS1 group were significantly decreased. Conclusion:ZFP36-AS1 is abnormally low-expressed in bladder cancer, and it reduces the proliferation activity of bladder cancer cells and inhibits their immune escape by inhibiting the expression of miR-221.

ROBO3 deficiency promotes chemotherapy-induced transition of macrophage to foam cell / 实用医学杂志

Objective To explore the effect of chemotherapeutic drugs doxorubicin or cisplatin on lipid metabolism of macrophages and its regulatory mechanism.Methods Macrophage RAW264.7 was treated with doxorubicin or cisplatin,and intracellular lipid level was detected by oil red O and ELISA;RNA sequence screen-ing and Western blot were used to confirm the changes of gene expression after chemotherapeutic drug treatment;The effects of silencing ROBO3 on cellular lipid metabolism were explored,and changes in key target genes of lipid metabolism were detected by Q-PCR and western blot.Results Adriamycin or cisplatin induced disturbances in macrophage cholesterol metabolism and exacerbated macrophage foaminess.Further studies showed that the expression of the axon guidance factor receptor,ROBO3,increased and then decreased during the chemotherapeutic drug-induced macrophage foaming process.Further intervention with ROBO3 exacerbates oxldl-induced cholesterol accumulation and foam formation in macrophages.Mechanistically,ROBO3 deficiency promotes the expression of cholesterol synthesis-related gene DHCR24 and inhibits the expression of cholesterol elimination-related gene ABCG1,resulting in cholesterol accumulation in macrophages.Conclusion This study found that ROBO3 plays an important regulatory role in the disruption of cholesterol metabolism and its foaming process in macrophages induced by chemotherapeutic drugs,which may provide new targets and ideas for the prevention and treatment of chemotherapy-related atherosclerosis.

Recent advances in small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase / 药学学报

Influenza virus causes serious threat to human life and health. Due to the inherent high variability of influenza virus, clinically resistant mutant strains of currently approved anti-influenza virus drugs have emerged. Therefore, it is urgent to develop antiviral drugs with new targets or mechanisms of action. RNA-dependent RNA polymerase is directly responsible for viral RNA transcription and replication, and plays key roles in the viral life cycle, which is considered an important target of anti-influenza drug design. From the point of view of medicinal chemistry, this review summarizes current advances in diverse small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase, hoping to provide valuable reference for development of novel antiviral drugs.

Advances in peripheral defocus and myopia prevention and control / 国际眼科杂志(Guoji Yanke Zazhi)

The global prevalence of myopia is increasing year by year, leading to many ocular health issues and social problems. In recent years, it has been confirmed that peripheral defocus is closely related to the occurrence and development of myopia. Alteration of the state of peripheral defocus can significantly influence the progression of myopia and emmetropization, but the exact mechanisms are still unclear. At present, there is no method that can completely control myopia. Nowadays, the main controlling methods, including orthokeratology lens, peripheral defocus lens and multi-focal soft lens, have been confirmed to be closely related to peripheral defocus. In this paper, we will review and summarize the development and effect of these peripheral defocus relating control methods. In addition, the researches on the related mechanisms of peripheral retinal defocus and myopia prevention and control at home and abroad are reviewed, as well as the potential mechanisms of peripheral defocus, with a view to further improving the controlling effects of existing methods, developing new prevention and control methods and reducing the incidence and progression of myopia.

Research progress of anti-gout small molecules targeting the NLRP3 inflammasome / 药学学报

Currently, clinically used drugs for the treatment of gout inflammation, such as colchicine, nonsteroidal anti-inflammatory drugs, and glucocorticoids, can only relieve the pain of joint inflammation and have severe hepatorenal toxicity and multiple organ adverse reactions. The NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome is a key complex that induces the onset of gout inflammation and has become a crucial target in the development of anti-gout drugs. This article reviews the research progress of anti-gout small molecules targeting the NLRP3 inflammasome and their bioactivity evaluation methods in the past five years, in order to provide information for the development of specific drugs for the treatment of gout inflammation.

Recent advances in drug screening methods of SARS-CoV-2 spike protein / 药学学报

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a serious impact on global public health and the economy. SARS-CoV-2 infiltrates host cells via its surface spike protein, which binds to angiotensin-converting enzyme 2 on the host cell membrane. As a result, small molecules targeting spike protein have emerged as a hotspot in anti-SARS-CoV-2 drug research. Activity screening is an important step in seeking small molecule drugs. Therefore, this article aims to review the biological activity evaluation methods of small molecule inhibitors targeting SARS-CoV-2 spike protein, with the goal of laying the foundation for the discovery of new anti-SARS-CoV-2 drugs.

Identification and expression analysis of TCP family members in tobacco (Nicotiana tabacum L.) / 生物工程学报

TCP family as plant specific transcription factor, plays an important role in different aspects of plant development. In order to screen TCP family members in tobacco, the homologous sequences of tobacco and Arabidopsis TCP family were identified by genome-wide homologous alignment. The physicochemical properties, phylogenetic relationships and cis-acting elements were analyzed by bioinformatics. The homologous genes of AtTCP3/AtTCP4 were screened, and RT-qPCR was used to detect the changes of gene expression upon 20% PEG6000 treatment. The results show that tobacco contains 63 TCP family members. Their amino acid sequence length ranged from 89 aa to 596 aa, and their protein hydropathicity grand average of hydropathicity (GRAVY) ranged from -1.147 to 0.125. The isoelectric point (pI) ranges from 4.42 to 9.94, the number of introns is 0 to 3, and the subcellular location is all located in the nucleus. The results of conserved domain and phylogenetic relationship analysis showed that the tobacco TCP family can be divided into PCF, CIN and CYC/TB1 subfamilies, and each subfamily has a stable sequence. The results of cis-acting elements in gene promoter region showed that TCP family genes contain low docile acting elements (LTR) and a variety of stress and metabolic regulation related elements (MYB, MYC). Analysis of gene expression patterns showed that AtTCP3/AtTCP4 homologous genes (NtTCP6, NtTCP28, NtTCP30, NtTCP33, NtTCP42, NtTCP57, NtTCP63) accounted for 20% PEG6000 treatment significantly up-regulated/down-regulated expression, and NtTCP30 and NtTCP57 genes were selected as candidate genes in response to drought. The results of this study analyzed the TCP family in the tobacco genome and provided candidate genes for the study of drought-resistance gene function and variety breeding in tobacco.

Predictors of Difficult Laryngeal Exposure in Suspension Laryngoscopy: A Systematic Review and Meta-Analysis

Objectives@#. Considerable research has been focused on independent predictors of difficult laryngeal exposure (DLE) during suspension laryngoscopy. However, previous studies have yielded inconsistent results and conclusions. Consequently, we performed a meta-analysis of the existing literature with the aim of identifying significant parameters for a standardized preoperative DLE prediction system. @*Methods@#. We systematically retrieved articles from the PubMed, Embase, Web of Science, China National Knowledge Infrastructure, and Wanfang databases up to October 2022. Data from eligible studies were extracted and analyzed using the R programming language. The effect measures included odds ratios (ORs) with 95% confidence intervals (CIs) for dichotomous variables and mean differences (MDs) with 95% CIs for continuous variables. @*Results@#. The search yielded 1,574 studies, of which 18 (involving a total of 2,263 patients) were included. Pooled analysis demonstrated that patients with DLE during microsurgery tended to be male (OR, 1.73; 95% CI, 1.16–2.57); were older (MD, 5.47 years, 95% CI, 2.44–8.51 years); had a higher body mass index (BMI; MD, 1.19 kg/m2; 95% CI, 0.33–2.05 kg/m2); had a greater neck circumference (MD, 2.50 cm; 95% CI, 1.56–3.44 cm); exhibited limited mouth opening (MD, −0.52 cm; 95% CI, −0.88 to −0.15 cm); had limited neck flexibility (MD, −10.05 cm; 95% CI, −14.10 to −6.00 cm); displayed various other anatomical characteristics; and had a high modified Mallampati index (MMI) or test score (OR, 3.37; 95% CI, 2.07–5.48). @*Conclusion@#. We conducted a comprehensive and systematic analysis of the factors relevant to DLE. Ultimately, we identified sex, age, BMI, neck circumference, MMI, inter-incisor gap, hyomental distance, thyromental distance, sternomental distance, and flexion-extension angle as factors highly correlated with DLE.

Value of FAST combined with serum CRP,PCT,and IL-6 detection in predicting the clinical outcome of patients with acute chest and abdominal trauma / 中国医科大学学报

Objective To investigate the value of emergency physician-led focused assessment with sonography for trauma(FAST)combined with serum C-reactive protein(CRP),procalcitonin(PCT),and interleukin-6(IL-6)testing in predicting the clinical outcome of patients with acute chest and abdominal trauma.Methods Ninety-six patients with acute thoracoabdominal trauma,who had been admitted to the Department of Emergency in our hospital from February 2019 to February 2022,were selected for this study.The patients were grouped according to their clinical outcomes,with the individuals who died after 48 h of treatment classified to the death group(n = 14)and all the others to the survival group(n = 82).The general clinical indicators(sex,age,body mass,trauma type,smoking history,alcohol consumption history,and previous chest and abdominal surgery history),CRAMS scores,inferior vena cava-collapse index(IVC-CI),and serum CRP,PCT,and IL-6 levels at 0,24,and 48 h after admission were compared between the two groups.Logistic regression analysis was used to identify the factors that influence the outcomes of patients with acute thoracoabdominal trauma based on statistically significant differences(P＜0.05)between the two groups.Receiver operating characteristic(ROC)curves of the IVC-CI combined with serum CRP,PCT,and IL-6 detection were plotted to evaluate the value in predicting clinical outcomes.Results The serum CRP,PCT,and IL-6 levels,CRAMS score,and IVC-CI in the death group were higher than those in the survival group at 0,24,and 48 h after admis-sion(all P＜0.001).The serum CRP,PCT,and IL-6 levels in patients in the death group gradually increased from 0,24,and 48 h after admission,and the differences between each time point were statistically significant(all P＜0.05).In the patients in the survival group,these serum protein levels increased from 0 to 24 h after admission and peaked at 48 h,and the differences between each time point were statistically significant(all P＜0.05).The logistic regression analysis showed that the CRAMS score,IVC-CI,and serum CRP,PCT,and IL-6 levels were risk factors affecting the outcome of patients with acute chest and abdominal trauma(all P＜0.05).The area under the ROC curve for the IVC-CI combined with serum CRP,PCT,and IL-6 detection was greater than that for each individual assessment type alone(all P＜0.05),and the use of the IVC-CI combined with serum CRP,PCT,and IL-6 detection to predict the clinical outcome of patients with acute chest and abdominal trauma had net clinical benefit.Conclusion The IVC-CI and serum CRP,PCT,and IL-6 levels were associ-ated with the clinical outcomes of patients with acute thoracoabdominal trauma.Therefore,emergency physician-led bedside ultrasound FAST combined with 48 h serum CRP,PCT,and IL-6 testing has good value for predicting the clinical outcomes of patients with acute chest and abdominal trauma.

Feasibility of Deep Learning Algorithm to Optimize the Noise and Texture of Children's Head CT / 中国医学影像学杂志

Purpose To evaluate the image quality improvement of deep learning iterative reconstruction(DLIR)on pediatric head CT images of head injury and to evaluate the performance of DLIR and conventional adaptive statistical iterative reconstruction-veo(ASIR-V)of noise and image texture of CT image in children's head trauma.Materials and Methods A total of 80 cases in Beijing Children's Hospital,Capital Medical University from December 7th to 11th 2020 of children's head low-dose CT were retrospectively selected.Scan voltage was 120 kV.Scan current was 150-220 mA.The raw data were reconstructed into 5 mm thick slice and 0.625 mm thin slice brain window and bone window images.50%ASIR-V and high weight DLIR images(DL-H)were reconstructed,respectively.A 4-point system was used to subjectively evaluate the display of sulcus,brain matter and bone.The number of lesions in each group was counted.The CT value and image noise values of gray matter and white matter were measured,and the contrast to noise ratio was calculated,then measured the blur metric index was measured in the same slice.The differences between the two image reconstruction methods were compared.Results Compared to 50%ASIR-V images,DL-H significantly improved the display ability of the sulcus and ventricles,as well as the display ability of the brain parenchyma(W=5.5-22.2,all P<0.05)in both slice thickness.There was no statistically significant difference in the display ability of the sulcus and ventricles between 5 mm 50%ASIR-V and 0.625 mm DL-H images(W=0.9,2.0,P=0.32,0.05,respectively).In terms of bone display ability,all images could achieve a maximum score of 4.0.A total of 35 lesions were found in 80 patients via 5 mm 50%ASIR-V and DL-H images,including 12 hemorrhagic lesions,1 intracranial gas,9 fractures,and 13 soft tissue swelling.In terms of objective evaluation,the noise level of DL-H images was significantly lower than that of 50%ASIR-V images(t=21.4-35.7,all P<0.05),and there was no statistically significant difference in noise and contrast noise ratio between 5 mm 50%ASIR-V and 0.625 mm DL-H images(t=1.7-2.2,all P≥0.05).The blur metric index showed that DL-H was superior to 50%ASIR-V images(t=6.1,10.0,both P<0.05),and there was no statistically significant difference in blur metric index between 0.625 mm DL-H and 5 mm 50%ASIR-V images(t=2.6,P=0.28).Conclusion DLIR can improve the CT image quality and image texture of children's head trauma,0.625 mm DL-H image quality is close to 5 mm 50%ASIR-V image,which can meet the diagnostic requirements,and possible to further reduce the radiation dose.

Study of synovial mesenchymal stem cells combined with PRP in cartilage repair / 中国医学装备

Objective:To compare the repair effects of three kinds of treatment methods included synovial mesenchymal stem cells(SMSCs),platelet rich plasma(PRP)and the combination of them with knee joint cavity injection on cartilage injury of rabbit.Methods:A total of 24 New Zealand rabbits were selected to establish a cartilage injury model of knee joint by using surgery in knee joint of them.The rabbits with cartilage injury model were divided into four groups using a random number table method,which included blank group,single SMSCs with joint cavity injection group(SMSCs group),PRP with joint cavity injection group(PRP group)and the combination of SMSCs and PRP with joint cavity injection group(SMSCs+PRP group),with 6 rabbits in each group.The synovium of four groups of rabbits were scraped off their joints to conduct in vitro culture of SMSCs,as well as the morphological observation and identification of SMSCs.The venous bloods of rabbits were extracted to prepare PRP by centrifugation.The contents of PRP,platelet and growth factor in blood were compared.The SMSCs and PRP were injected into the knee joint cavity of three groups of rabbits with model.After 2,4 and 6 weeks of injection treatment,the repair statuses of cartilages at defection area of different groups were evaluated according to cartilage repair scoring table of International Association for Cartilage Repair(ICRS).Results:The primary synovial cells of rabbit knee joint synovium were initially round in shape after isolation,but almost all of them were spindle shaped after passage.The positive detection rates of SMSCs surface antigen CD73,CD90 and CD105 of 4 group were respectively 100%,99.22%and 99.99%.The CD45 detection was 0.5%,which indicated that they possessed the property of stem cell.The platelet count of 4 groups showed that the platelet concentration in PRP was approximate 6 times of that in whole blood.The concentrations of platelet derived growth factor(PDGF),transforming growth factor-β(TGF-β)and vascular endothelial growth factor(VEGF)were respectively(569.15±57.48)ng/mL,(633.56±63.90)ng/mL and(1 243.55±106.04)ng/mL in PRP,which were approximately 5 times,6 times and 7 times of that in whole blood,respectively.After 2 weeks of injection treatment for joint cavity,there was no significant statistical difference in the scores of cartilage repair among 4 groups(P>0.05).At 4 and 6 weeks of injection treatment,the morphological and histological score of cartilage repair of the SMSCs+PRP group were significantly higher than those of the blank group,and the differences were significant(t4 week=6.35,9.15,t6 week=8.16,8.60,P<0.05),respectively.Conclusion:The repair effect of SMSCs combined with PRP on cartilage injury of rabbit is significantly better than that of single PRP and single SMSCs,respectively,and all of them are better than those without treatment.SMSCs combined with PRP can significantly improve the effect of self-repair of cartilage injury.

Survey of Disease Cognition in Patients with Endometriosis and Effect Evaluation of TCM Chronic Disease Management / 中国中医药信息杂志

Objective To understand cognition level and treatment intention of patients with endometriosis(EMs);To evaluate the effects of TCM chronic disease management on EMs patients.Methods The disease cognition level and treatment intention of 1 895 EMs patients from October 2020 to December 2021 in 19 provinces,autonomous regions and municipalities were analyzed through cross-sectional investigation.The cognitive effect of chronic disease management of TCM on 801 patients with EMs from 6 Grade A hospitals in Beijing was evaluated by self-control study.Results The cognition level of EMs patients for the disease was improved with the increase of educational background.Patients generally believed that EMs was a chronic disease,requiring regular review and long-term management.The proportion of patients with high school education or below,junior college education,bachelor degree or above who knew the possibility of malignant changes in EMs was less,only 32.3%,41.6%and 47.7%,respectively.The awareness rate of patients with high school education or below for recurrence after EMs conservative surgery was 46.9%,lower than that of those with junior college education(66.8%)and bachelor degree or above(72.7%).Among the patients with dietary contraindications,the proportion of patients with high school education or below,junior college education,bachelor degree or above who knew the contraindication of the forest frog oil was less,only 20.7%,30.3%and 32.9%,respectively.In the aspect of life adjustment,the awareness of patients was generally high.EMs patients mainly recognized the disease through face-to-face communication with gynecologists.Only 34.4%of patients with high school education or below learned about EMs through WeChat public accounts,APPs and other new media,which was lower than those with junior college education(48.6%)and bachelor degree or above(55.4%).EMs patients generally tend to be treated in comprehensive hospitals,with high acceptance of TCM treatment,mainly TCM decoction,and low acceptance of TCM appropriate technology.After 1 year of TCM chronic disease management,the disease awareness of EMs patients was significantly improved compared with before management,with statistical significance(P<0.05).Conclusion EMs patients with different educational backgrounds have different cognition of the disease,and each has different emphasis.Education and popularization should be carried out according to their knowledge blind spots.Chronic disease management of TCM can improve the disease cognition level of EMs patients.

Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults (version 2024) / 中华创伤杂志

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

Effect of self-efficacy-based intelligent walking training on function of lower extremities of stroke patients / 中国康复理论与实践

ObjectiveTo investigate the effect of self-efficacy-based intelligent walking training on function of lower extremities of stroke patients. MethodsFrom December, 2021 to December, 2022, 44 stroke inpatients from Zhejiang Provincial People's Hospital were randomly divided into control group (n = 22) and experimental group (n = 22). Both groups accepted routine rehabilitation, while the control group accepted routine gait training, and the experimental group accepted self-efficacy-based intelligent walking training on the gait training system (Walker View), for six weeks. They were assessed with Fugl-Meyer Assessment-Lower Extremities, 10-Meter Walk Test, Timed 'Up and Go' Test, stride length and average walking velocity, Functional Ambulation Category and General Self-Efficacy Scale before and after treatment. ResultsThree cases dropped down in the experimental group. All the indexes improved in two groups after treatment (|t| > 5.808, |Z| > 2.961, P < 0.01), and improved more in the experimental group than in the control group (|t| > 2.049, Z = -2.572, P < 0.05). ConclusionThe self-efficacy-based intelligent walking training can promote the recovery of motor function of lower extremities and walking ability in stroke patients.

Screening methods of SARS-CoV-2 main protease inhibitors and current applications / 药学学报

COVID-19 epidemic continues to spread around the world till these days, and it is urgent to develop more safe and effective new drugs. Due to the limited P3 biosafety laboratories for directly screening inhibitors of virulent viruses with high infectivity, it is necessary to develop rapid and efficient screening methods for viral proteases and other related targets. The main protease (Mpro), which plays a key role in the replication cycle of SARS-CoV-2, is highly conserved and has no homologous proteases in humans, making it an ideal target for drug development. From two different levels, namely, molecular level and cellular level, this paper summarizes the reported screening methods of SARS-CoV-2 Mpro inhibitors through a variety of representative examples, expecting to provide references for further development of SARS-CoV-2 Mpro inhibitors.

Effect of transcutaneous auricular vagus nerve stimulation combined with bilateral arm training on upper limb motor function of stroke patients / 中国康复理论与实践

ObjectiveTo investigate the effects of transcutaneous auricular vagus nerve stimulation (taVNS) combined with bilateral arm training (BAT) on upper limb motor function of hemiplegic stroke patients. MethodsFrom January, 2021 to January, 2022，105 stroke patients from Zhejiang Provincial People's Hospital were randomly divided into taVNS group (n = 35), BAT group (n = 35) and combined group (n = 35). All the patients received routine rehabilitation, while taVNS group received taVNS, BAT group received BAT, and the combined group received both taVNS and BAT, for eight weeks. The root mean square (RMS) of surface electromyography in deltoid, triceps brachii and extensor carpi was measured, and the scores of Box and Block Test (BBT), and Fugl-Meyer Assessment-Upper Extremities (FMA-UE) were obtained before and after treatment. ResultsThe RMS of all these muscles, and the scores of BBT and FMA-UE improved in all the three groups after treatment (|t| > 6.124, P < 0.001), and they were improved the most in the combined group (F > 18.162, P < 0.001). ConclusionBoth taVNS and BAT can enhance the muscle strength on the affected upper limb, increase the hand flexibility, and improve upper limb motor function of stroke patients, while the combination of both methods is more effective.

Risk factors for residual cancer or lymph node metastasis after endoscopic noncurable resection of early colorectal cancer / 中华肿瘤杂志

Objective: Risk factors related to residual cancer or lymph node metastasis after endoscopic non-curative resection of early colorectal cancer were analyzed to predict the risk of residual cancer or lymph node metastasis, optimize the indications of radical surgical surgery, and avoid excessive additional surgical operations. Methods: Clinical data of 81 patients who received endoscopic treatment for early colorectal cancer in the Department of Endoscopy, Cancer Hospital, Chinese Academy of Medical Sciences from 2009 to 2019 and received additional radical surgical surgery after endoscopic resection with pathological indication of non-curative resection were collected to analyze the relationship between various factors and the risk of residual cancer or lymph node metastasis after endoscopic resection. Results: Of the 81 patients, 17 (21.0%) were positive for residual cancer or lymph node metastasis, while 64 (79.0%) were negative. Among 17 patients with residual cancer or positive lymph node metastasis, 3 patients had only residual cancer (2 patients with positive vertical cutting edge). 11 patients had only lymph node metastasis, and 3 patients had both residual cancer and lymph node metastasis. Lesion location, poorly differentiated cancer, depth of submucosal invasion ≥2 000 μm, venous invasion were associated with residual cancer or lymph node metastasis after endoscopic (P<0.05). Logistic multivariate regression analysis showed that poorly differentiated cancer (OR=5.513, 95% CI: 1.423, 21.352, P=0.013) was an independent risk factor for residual cancer or lymph node metastasis after endoscopic non-curative resection of early colorectal cancer. Conclusions: For early colorectal cancer after endoscopic non-curable resection, residual cancer or lymph node metastasis is associated with poorly differentiated cancer, depth of submucosal invasion ≥2 000 μm, venous invasion and the lesions are located in the descending colon, transverse colon, ascending colon and cecum with the postoperative mucosal pathology result. For early colorectal cancer, poorly differentiated cancer is an independent risk factor for residual cancer or lymph node metastasis after endoscopic non-curative resection, which is suggested that radical surgery should be added after endoscopic treatment.

Risk factors analysis and prediction model construction of submucosal deep infiltration of early colorectal tumor / 中华肿瘤杂志

Objective: To investigate the risk factors for the development of deep infiltration in early colorectal tumors (ECT) and to construct a prediction model to predict the development of deep infiltration in patients with ECT. Methods: The clinicopathological data of ECT patients who underwent endoscopic treatment or surgical treatment at the Cancer Hospital, Chinese Academy of Medical Sciences from August 2010 to December 2020 were retrospectively analyzed. The independent risk factors were analyzed by multifactorial regression analysis, and the prediction models were constructed and validated by nomogram. Results: Among the 717 ECT patients, 590 patients were divided in the within superficial infiltration 1 (SM1) group (infiltration depth within SM1) and 127 patients in the exceeding SM1 group (infiltration depth more than SM1). There were no statistically significant differences in gender, age, and lesion location between the two groups (P>0.05). The statistically significant differences were observed in tumor morphological staging, preoperative endoscopic assessment performance, vascular tumor emboli and nerve infiltration, and degree of tumor differentiation (P<0.05). Multivariate regression analysis showed that only erosion or rupture (OR=4.028, 95% CI: 1.468, 11.050, P=0.007), localized depression (OR=3.105, 95% CI: 1.584, 6.088, P=0.001), infiltrative JNET staging (OR=5.622, 95% CI: 3.029, 10.434, P<0.001), and infiltrative Pit pattern (OR=2.722, 95% CI: 1.347, 5.702, P=0.006) were independent risk factors for the development of deep submucosal infiltration in ECT. Nomogram was constructed with the included independent risk factors, and the nomogram was well distinguished and calibrated in predicting the occurrence of deep submucosal infiltration in ECT, with a C-index and area under the curve of 0.920 (95% CI: 0.811, 0.929). Conclusion: The nomogram prediction model constructed based on only erosion or rupture, local depression, infiltrative JNET typing, and infiltrative Pit pattern has a good predictive efficacy in the occurrence of deep submucosal infiltration in ECT.

Association Between Constipation and a Reduction in Lower Limb Muscle Strength in Preoperative Patients with Thoracic Spinal Tumors / 中国医学科学杂志(英文版)

Objective To investigate the clinical symptoms experienced by patients with thoracic spinal tumors and verify the associated symptoms that are predictive of a decline in muscle strength in the lower limbs. Methods A single-center, retrospective cross-sectional study was conducted on in-patients diagnosed with epidural thoracic spinal tumors between January 2011 and May 2021. The study involved a review of electronic medical records and radiographs and the collection of clinical data. The differences in clinical manifestations between patients with constipation and those without constipation were analyzed. Binary logistic regression analyses were performed to identify risk factors associated with a decline in muscle strength in the lower limbs.Results A total of 227 patients were enrolled, including 131 patients with constipation and 96 without constipation. The constipation group had a significantly higher proportion of patients who experienced difficulty walking or paralysis compared to those without constipation prior to surgery (83.2% vs. 17.7%, χ2 = 99.035,P < 0.001). Constipation (OR = 9.522, 95%CI: 4.150-21.849, P < 0.001) and urinary retention (OR = 14.490, 95%CI: 4.543-46.213, P < 0.001) were independent risk factors for muscle strength decline in the lower limbs. Conclusions The study observed that patients with thoracic spinal tumors who experienced constipation symptoms had a higher incidence of lower limb weakness. Moreover, the analysis revealed that constipation and urinary retention were independent risk factors associated with a preoperative decline in muscle strength of lower limbs.

Analysis of CNNM2 gene variant in a child with Hypomagnesemia, seizures, and mental retardation syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic etiology of a child with Hypomagnesemia, epilepsy and mental retardation syndrome (HSMR).@*METHODS@#A child who was admitted to the Children's Hospital of Shandong University on July 9, 2021 due to repeated convulsions for 2 months was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his pedigree members were collected for the extraction of genomic DNA. Whole exome sequencing was carried out, and candidate variant was verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The child, a 1-year-and-7-month-old male, had presented with epilepsy and global developmental delay. Serological testing revealed that he has low serum magnesium. Genetic testing showed that the child has harbored a heterozygous c.1448delT (p.Val483GlyfsTer29) variant of the CNNM2 gene, which was de novo in origin. The variant has caused substitution of the Valine at position 483 by Glycine and formation of a termination codon after 29 amino acids at downstream. As predicted by Swiss-Model online software, the variant may alter the protein structure, resulting in a truncation. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.1448delT (p.Val483GlyfsTer29) was predicted as a pathogenic variant (PVS1+PS2+PM2_Supporting+PP4).@*CONCLUSION@#The heterozygous c.1448delT variant of the CNNM2 gene probably underlay the HSMR in this child. Above finding has enriched the phenotype-genotype spectrum of the CNNM2 gene.