Conventional tumor culture models include two-dimensional tumor cell cultures and xenograft models. The former has disadvantages including lack of tumor heterogeneity and poor clinical relevance, while the latter are limited by the slow growth, low engraftment successful rate, and high cost. In recent years, in vitro three-dimensional (3D) tumor models have emerged as the tool to better recapitulate the spatial structure and the in vivo environment of tumors. In addition, they preserve the pathological and genetic features of tumor cells and reflect the complex intracellular and extracellular interactions of tumors, which have become a powerful tool for investigating the tumor mechanism, drug screening, and personalized cancer treatment. 3D tumor model technologies such as spheroids, organoids, and microfluidic devices are maturing. Application of new technologies such as co-culture, 3D bioprinting, and air-liquid interface has further improved the clinical relevance of the models. Some models recapitulate the tumor microenvironment, and some can even reconstitute endogenous immune components and microvasculature. In recent years, some scholars have combined xenograft models with organoid technology to develop matched in vivo/in vitro model biobanks, giving full play to the advantages of the two technologies, and providing an ideal research platform for individualized precision therapy for specific molecular targets in certain subtypes of tumors. So far, the above technologies have been widely applied in the field of colorectal cancer research. Our research team is currently studying upon the application of patient-derived tumor cell-like clusters, a self-assembly 3D tumor model, in guiding the selection of postoperative chemotherapy regimens for colorectal cancer. A high modeling success rate and satisfactory results in the drug screening experiments have been achieved. There is no doubt that with the advancement of related technologies, 3D tumor models will play an increasingly important role in the research and clinical practice of colorectal cancer.
Humans ; Organoids/pathology* ; Cell Culture Techniques ; Colorectal Neoplasms/pathology* ; Tumor Microenvironment

Objective To determine the diagnostic accuracy of the intensity of fasciculation evaluated by muscle ultrasound in the differential diagnosis of amyotrophic lateral sclerosis (ALS). Methods We prospectively recruited patients who had ALS and neuropathy-radiculopathy attending Peking Union Medical College Hospital from 2017 to 2020. Healthy adults from a community were recruited as healthy controls. Muscle strength was assessed using the Medical Research Council (MRC) scale. At the first visit to the hospital, patients were assessed for maximal grade of fasciculations, total fasciculation score, and fasciculation grade in 16 muscle groups of bilateral upper and lower limbs using ultrasonography. The sensitivity and specificity of maximal grade of fasciculations, total fasciculation score, and fasciculation grade for the diagnosis of ALS were assessed by receiver operating characteristic analyses. Results The percentage of limb muscles with a maximal fasciculation grade higher than grade 2 in ALS patients and neuropathy-radiculopathy patients was 84.9% and 9.8%, respectively (χ² = 172.436, P < 0.01). Of the 16 limb muscles detected, the total fasciculation score [median (interquartile range)] was 29 (15, 41) in ALS patients and 3 (0, 8) in neuropathy-radiculopathy patients (Z = 9.642, P < 0.001). Remarkable fasciculations were seen in ALS patients whose muscles with a MRC score ranging from 2 to 4, followed by patients with MRC score 5, and then in those with MRC score 0 and 1. The sensitivity and specificity of total fasciculation score for diagnosis of ALS were 80.6% and 93.4%, respectively (cut-off value 14). In patients with ALS, for muscles with MRC score 4 and 5, the percentage of muscles with fasciculation grades ≥ 3 was 42.3% and 24.1% respectively, while in neuropathy-radiculopathy patients, the percentage for muscles with MRC score 4 and 5 was only 1.7% and 0, respectively. Conclusion A combined analysis of fasciculation intensity and MRC score of the limb muscles may be helpful for differential diagnosis of ALS.
Adult ; Humans ; Amyotrophic Lateral Sclerosis/diagnostic imaging* ; Fasciculation/diagnostic imaging* ; Radiculopathy ; Muscle, Skeletal/diagnostic imaging* ; Ultrasonography/methods*

Hodgkin Disease/pathology* ; Humans ; Lung/pathology* ; Lymphoma, B-Cell/pathology*

This study analyzed the outcome indicators in randomized controlled trial(RCT) on Chinese medicine as adjuvant therapy for severe pneumonia in the past years, laying a foundation for the design of clinical trials on and construction of core outcome set(COS) for severe pneumonia. To be specific, related RCT was retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, Web of Science, Chinese Clinical Trial Registry, and ClinicalTrials.gov(from January 1,2011 to April 9,2022). Then data in the trials were extracted, and the quality of included RCT was assessed according to Cochrane handbook, followed by descriptive analysis of the use of outcome indicators. A total of 11 833 articles were screened out, and finally 34 RCTs were included(2 were protocols). The included trials involved 109 outcome indicators with emergence frequency of 320, which were mainly classified into 9 categories: physicochemical indicators(54, frequency 167), time to achieve the efficacy(15, frequency 38), clinical effective rate(10, frequency 36), quality of life(11, frequency 35), symptoms and signs(7, frequency 18), traditional Chinese medicine(TCM) syndrome(4, frequency 13), safety(3, frequency 8), economic evaluation(1, frequency 1), other indicators(4, frequency 4). The indicators with high frequency followed the order: total effective rate, arterial oxygen partial pressure, C-reactive protein, white blood cell count, arterial blood carbon dioxide partial pressure. A total of 5 articles(14.71%) reported the main outcome indicators and 11 articles(32.35%) adopted the efficacy on TCM syndromes as the outcome indicator. There are many problems in the selection of outcome indicators in RCT on the treatment of severe pneumonia with Chinese medicine, mainly manifested as the disregard of clinical endpoint indicators, the inappropriate selection of surrogate indicators, and the non-standard evaluation criteria for the efficacy on TCM syndrome. It is suggested that the evaluation system for the efficacy of Chinese medicine on severe pneumonia should be established in accordance with the method for international COS to improve the quality of clinical trials.
Humans ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use* ; Quality of Life ; Combined Modality Therapy ; Pneumonia/drug therapy*

Network Meta-analysis was conducted to compare the efficacy and safety of different Chinese medicine injections combined with conventional therapy in the treatment of stroke-associated pneumonia. CNKI, Wanfang, VIP, PubMed, Web of Science, and Cochrane Library were searched for the relevant literature pubslished from inception to April 1, 2022. Stata 17 was used for data analysis. After screening of 1 189 papers, 72 studies were finally selected, which involved 5 819 patients and 6 Chinese medicine injections(Tanreqing Injection, Xingnaojing Injection, Xuebijing Injection, Xiyanping Injection, Shenfu Injection, and Shenmai Injection). The network Meta-analysis ranked the injections as follows.(1) In terms of improving the total clinical effective rate, the surface under the cumulative ranking curve(SUCRA) followed the order of Xiyanping Injection + conventional therapy > Xuebijing Injection + conventional therapy > Tanreqing Injection + conventional therapy > Shenmai Injection + conventional therapy > Xingnaojing Injection + conventional therapy > Shenfu Injection + conventional therapy > conventional therapy.(2) In terms of recovering the National Institute of Health stroke scale(NIHSS) scores, the SUCRA followed the order of Xuebijing Injection + conventional therapy > Xingnaojing Injection + conventional therapy > Tanreqing Injection + conventional therapy > Shenfu Injection + conventional therapy > conventional therapy.(3) In reducing the average time to abatement of fever, the SUCRA followed the order of Xiyanping Injection + conventional therapy > Tanreqing Injection + conventional therapy > Xuebijing Injection + conventional therapy > conventional therapy.(4) In terms of reducing the mean hospital stay, the SUCRA followed the order of Xiyanping Injection + conventional therapy > Xubijing Injection + conventional therapy > Tanreqing Injection + conventional therapy > Shenmai Injection + conventional therapy > conventional therapy. The clinical efficacy of Tanreqing Injection, Xuebijing Injection, Xiyanping Injection, Xingnaojing Injection, Shenmai Injection, or Shenfu Injection combined with conventional therapy was superior to that of conventional therapy alone. However, due to the limitations of the quality and methodology of different intervention measures, this conclusion needs to be verified by more high-quality and rigorously designed randomized controlled trial.
Humans ; Medicine, Chinese Traditional ; Network Meta-Analysis ; Drugs, Chinese Herbal/therapeutic use* ; Pneumonia/drug therapy* ; Injections ; Stroke/drug therapy*

Objective Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are major public health and social issues worldwide. The long-term follow-up of COVID-19 with pulmonary TB (PTB) survivors after discharge is unclear. This study aimed to comprehensively describe clinical outcomes, including sequela and recurrence at 3, 12, and 24 months after discharge, among COVID-19 with PTB survivors. Methods From January 22, 2020 to May 6, 2022, with a follow-up by August 26, 2022, a prospective, multicenter follow-up study was conducted on COVID-19 with PTB survivors after discharge in 13hospitals from four provinces in China. Clinical outcomes, including sequela, recurrence of COVID-19, and PTB survivors, were collected via telephone and face-to-face interviews at 3, 12, and 24 months after discharge. Results Thirty-two COVID-19 with PTB survivors were included. The median age was 52 (45, 59) years, and 23 (71.9％) were men. Among them, nearly two-thirds (62.5％) of the survivors were moderate, three (9.4％) were severe, and more than half (59.4％) had at least one comorbidity (PTB excluded). The proportion of COVID-19 survivors with at least one sequela symptom decreased from 40.6％ at 3 months to 15.8％ at 24 months, with anxiety having a higher proportion over a follow-up. Cough and amnesia recovered at the 12-month follow-up, while anxiety, fatigue, and trouble sleeping remained after 24 months. Additionally, one (3.1％) case presented two recurrences of PTB and no re-positive COVID-19 during the follow-up period. Conclusion The proportion of long symptoms in COVID-19 with PTB survivors decreased over time, while nearly one in six still experience persistent symptoms with a higher proportion of anxiety. The recurrence of PTB and the psychological support of COVID-19 with PTB after discharge require more attention.

Cheezheng Xiaotong Tiegao is a Tibetan traditional prescription,which has the functions of promoting blood circulation,relieving swelling and relieving pain. It has been widely used in various clinical departments such as orthopedics department,rheumatology department,pain management department,and rehabilitation department to treat all types of acute and chronic skeletal muscle pain. However,duet to the lack of detailed description of the specific use of various diseases in its manual,and in the published guidelines,monographs,and clinical reports,the introduction of the dominant clinical disease,usage,treatment,safety,etc. of Cheezheng Xiaotong Tiegao is not detailed. Therefore,this experts consensus statement has been prepared based on the research and analysis of clinicians and patients,evidence-based medical research and evaluation,combined with the experience of clinical experts. The experts consensus statement regulates usage,dosage,combination,safety,etc. in the treatment of acute and chronic contusion( soft tissue injury),osteoarthritis,low back pain,frozen shoulder,cervical spondylosis postoperative recovery pain and other pain relief and other skeletal muscle system diseases to provide evidence and reference for the rational and safety using of Cheezheng Xiaotong Tiegao.
Consensus ; Edema ; Humans ; Pain

Objective Few studies are reported on the prevention and management of oral mucositis(OM) induced by post-operative radiotherapy in patients with oral cavity cancer.This study aimed to investigate the therateutic effect of the recombinant human epidermal growth factor(rhEGF) gel on radiation-induced OM. Methods Sixty-eight cases of radiation-induced OM after surgery for oral cavity cancer were randomly divided into an experimental and a control group of equal number,the former treated with rhEGF gel while the latter with borax mouthwash. Comparisons were made between the two groups of patients in the severity of oral cavity mucous membrane injury,the intensity of radiation-induced oral pain,the in-cidence of oral cavity infection, and the duration of radiotherapy. Results At 3 weeks of radiotherapy,the patients of the experimental group showed mainly mild and moderate OM while the controls chiefly moderate and severe OM,and at 6 weeks,the former exhibited mainly moderate while the latter chiefly severe OM, with statistically significant differences in the incidence rate between the two groups (P<0.01). The experimental group, compared with the controls, had a significantly higher incidence rate of grade-Ⅰ radiation-induced pain (47.1% vs 20.6%,P<0.01),but lower rates of grade-Ⅱ(17.6% vs 32.4%,P<0.01) and grade-Ⅲpain(2.9% vs 20.6%,P<0.01).The rates of oral infection and antibiotics medication were remarkably lower in the experimental group than in the controls(23.5% vs 38.2% and 11.8% vs 26.5%,P<0.05),and the duration of radiotherapy was markedly shorter in the former than in the latter ([42.37±3.14] d vs [48.47±4.39] d, P<0.05). Conclusion The rhEGF gel can significantly reduce the severity of radiation-induced oral mucositis,improve its symptoms,and shorten the time of postoperative radiotherapy for patients with oral cavity cancer.

Cellular therapy in acute ischemic stroke (AIS) is a research hotspot in the field of neu-roscience in recent years. Compared with other cells,bone marrow mononuclear cells (BMMNCs) are one of the most attractive therapeutic cells because BMMNCs can be rapidly isolated from bone marrow,are enriched with stem cells and permit autologous applications. Numerous basic researches showed that BMMNCs trans-plantation can decrease infarct volume and promote neurological outcomes in animal stroke model,indicating BMMNCs transplantation may has therapeutic values in acute ischemic stroke,and the transformation from basic research to clinical applications is on the key phase. In this paper,the progress of BMMNCs transplan-tation is reviewed in acute ischemic stroke on the aspects of BMMNCs component,methods of purification, route of transplantation,therapeutic mechanisms and problems from basic research to clinical application.

OBJECTIVETo explore the inhibitory effect of migration-inducing gene 7 (Mig-7) gene silencing induced by retroviral-mediated small hairpin RNA (shRNA) on vasculogenic mimicry (VM), invasion and metastasis of human hepatocellular carcinoma (HCC) cells in vitro.

METHODSTwo target sequences (Mig-7 shRNA-1 and Mig-7 shRNA-2) and one negative control sequence (Mig-7 shRNA-N) were synthesized. The recombinant retroviral vectors carrying Mig-7 shRNA were constructed, and HCC cell line MHCC-97H were transfected with Mig-7 shRNA-1, Mig-7 shRNA-2, Mig-7 shRNA-N, or the empty vector, or treated with 125 µg/mL recombinant human endostatin (ES). Mig-7 expression in the treated cells was detected using semi-quantitative PCR and Western blotting. The inhibitory effect of Mig-7 silencing on VM formation was investigated in a 3-dimensional cell culture system; the changes in cell adhesion, invasion and migration were assessed with intercellular adhesion assay, Transwell invasion assay and Transwell migration assay, respectively.

RESULTSThe expression of Mig-7 at both mRNA and protein levels decreased significantly, VM formation, invasion and metastasis were suppressed, while intercellular adhesion increased significantly in MHCC-97H cells in Mig-7 shRNA-1 and Mig-7 shRNA-2 groups (P<0.05); such changes were not observed in cells transfected with Mig-7 shRNA-N or the empty vector, nor in cells treated with ES.

CONCLUSIONSMig-7 silencing by retroviral-mediated shRNA significantly inhibits VM formation, invasion and metastasis and increases the intercellular adhesion of the HCC cells, while ES does not have such inhibitory effects.