Objective: To provide reference and evidence for clinical application of neoadjuvant immunotherapy in patients with colorectal cancer through multicenter large-scale analysis based on real-world data in China. Methods: This was a retrospective multicenter case series study. From January 2017 to October 2021, data of 94 patients with colorectal cancer who received neoadjuvant immunotherapy in Peking University Cancer Hospital (55 cases), Union Hospital of Tongji Medical College of Huazhong University of Science and Technology (19 cases), Sun Yat-sen University Cancer Center (13 cases) and Changhai Hospital of Navy Medical University (7 cases) were retrospectively collected, including 48 males and 46 females. The median age was 58 years. Eighty-one cases were rectal cancer and 13 cases were colon cancer (2 cases of double primary colon cancer). Twelve cases were TNM staging II and 82 cases were stage III. Forty-six cases were well differentiated, 37 cases were moderately differentiated and 11 cases were poorly differentiated. Twenty-six patients (27.7%) with mismatch repair defects (dMMR) and microsatellite instability (MSI-H) were treated with immunotherapy alone, mainly programmed cell death protein-1 (PD-1); sixty-eight cases (72.3%) with mismatch repair proficient (pMMR) and microsatellite stability (MSS) were treated with immune combined with neoadjuvant therapy, mainly CapeOx (capecitabine+oxaliplatin) combined with PD-1 antibody plus long- or short-course radiotherapy, or PD-1 antibody combined with cytotoxic T lymphocyte associated antigen 4 (CTLA-4) antibody. Analysis and evaluation of adverse events during neoadjuvant immunotherapy were performed according to the National Cancer Institute Common Toxicity Standard version 3.0; the surgical complications were evaluated according to the Clavien-Dindo grading standard; the efficacy evaluation of neoadjuvant immunotherapy included the following indicators: major pathological remission (MPR) was defined as tumor regression induced by neoadjuvant therapy in pathology residual tumor ≤10%; pathological complete response (pCR) was defined as tumor regression induced by neoadjuvant therapy without residual tumor in pathology; the tumor response rate was disease control rate (DCR), namely the proportion of complete response (CR), partial response (PR) and stable disease (SD) in the whole group; the objective response rate (ORR) was CR+PR. Results: The median cycle of neoadjuvant immunotherapy was 4 (1-10) in whole group, and the incidence of immune-related adverse reactions was 37.2% (35/94), including 35 cases (37.2%) of skin-related adverse reactions, 21 cases (22.3%) of thyroid dysfunction and 8 cases (8.5%) of immune enteritis, of which grade III or above accounted for 1.1%. The median interval between completion of neoadjuvant therapy and surgery was 30 (21-55) days. There were 81 cases of radical resection of rectal cancer, 11 cases of radical resection of colon cancer, and 2 cases of colon cancer combined with other organ resection. The primary tumor resection of all the patients reached R0. The incidence of surgical-related complications was 22.3% (21/94), mainly anastomotic leakage (4 cases), pelvic infection (4 cases), abdominal effusion (3 cases), anastomotic stenosis (3 cases ) and abdominal and pelvic hemorrhage (2 cases). Grade I-II complications developed in 13 cases (13.8%), grade III and above complications developed in 8 cases (8.5%), no grade IV or above complications were found. During a median follow-up of 32 (1-46 ) months, DCR was 98.9% (93/94), ORR was 88.3 % (83/94), pCR was 41.5% (39/94), MPR was 60.6% (57/94). The pCR rate of 26 patients with dMMR and MSI-H undergoing simple immunotherapy was 57.7% (15/26), and MPR rate was 65.4% (17/26). The pCR rate of 68 pMMR and MSS patients undergoing combined immunotherapy was 35.3%(24/68), and MPR rate was 58.8% (40/68). Conclusions: Neoadjuvant immunotherapy has favorable tumor control rate and pathological remission rate for patients with initial resectable colorectal cancer. The incidences of perioperative adverse reactions and surgical complications are acceptable.
Colorectal Neoplasms/surgery* ; Female ; Humans ; Immunotherapy ; Male ; Middle Aged ; Neoadjuvant Therapy ; Rectal Neoplasms/surgery* ; Retrospective Studies

OBJECTIVE: To investigate the clinical characteristics of lower extremity arterial disease (LEAD) and its risk factors in patients with diabetic foot ulcer (DFU). METHODS: We retrospectively collected the clinical and follow-up data of 650 patients with DFU treated in the Department of Endocrinology and Metabolism of Nanfang Hospital between January, 2017 and December, 2019. We compared the data between patients who had LEAD and those without LEAD and used a multivariate logistic regression model to analyze the risk factors of LEAD in DFU patients. RESULTS: Among the 650 DFU patients, 470 (72.4%) had LEAD. The patients were followed up for a mean of 3.5 months, and the mean healing time of DFU was 2.55 months; healing of DFU occurred in 453 patients and 183 patients received amputation. The patients with LEAD and those without LEAD differed significantly in age, hospitalization costs, diastolic blood pressure (DBP), glycated hemoglobin, blood lipid levels, disease course, ankle brachial index, healing time, smoking history, clinical outcomes, Wagner grade and imaging results (P < 0.05). Multivariate logistic regression analysis identified age (OR=1.070, 95% CI: 1.049-1.091), smoking history (OR= 2.013, 95% CI: 1.268-3.195), and a decreased DBP (OR=0.980, 95% CI: 0.963-0.997) as independent risk factors for LEAD in DFU patients. A prolonged healing time was a prominent clinical feature of DFU complicated by LEAD. CONCLUSION DFU patients have a high incidence of LEAD, which leads to high rates of disability and mortality and is associated with an advanced age, high smoking rate and longer healing time. A decreased DBP is also a risk factor for LEAD in DFU patients.
Amputation ; Diabetes Mellitus ; Diabetic Foot/epidemiology* ; Humans ; Lower Extremity ; Retrospective Studies ; Risk Factors

OBJECTIVE: Using the CT three-dimensional reconstruction to measure the activity degree of atlanto-occipital joint and the atlantoaxial joint in different directions and its coupling movement in healthy volunteers, and three dimensional motion range of the maximum rotation position of the upper cervical spine of cervical spondylosis patients, and to analyze the differences, verifing the reliability of the method at the meantime. METHODS: From January 2014 to June 2015, 20 healthy adult subjects(healthy adult group), and 26 patients with cervieal spondylosis(cervical spondylosis group) were selected. In healthy adult group, there were 11 males and 9 females, aged from 22 to 26 years old with an average of (24.0±1.2) years, and in cervical spondylosis group, there were 24 males and 2 females, aged from 36 to 72 years old with an average of (52.8±8.6) years. Healthy adults underwent CT examination in neutral position, maximum right rotation, maximum right lateral bending, maximum flexion and extention, and cervical spondylosis patients underwent CT examination in neutral position, maximum right rotation. Then the software Mimics was used to reconstruct occiput (Oc), atlas(C1) and axial(C2) vertebral three-dimensional image. Three virtual non-collinear markers were positioned on prominent structures of foramen magnum, C1 and C2. The 3D spatial coordinates of these virtual anatomical markers entail the definition of an anatomical local coordinate system which represent the position and orientation of the bones. Segmental motions were calculated using Eulerian angle in three major planes, and the difference between cervical spondylosis group and healthy adult group were compared. Due to the inaccuracy in anatomical landmark idenrification, two groups were measured 3 times, and the reliability of the experimental metnod was verified by the intra-group correlation (intra-group ICC) and the inter-group correlation coefficient(inter-group ICC). RESULTS: Reliability verification results:the intra-group ICC and inter-group ICC results were all above 0.90, and the measurement method had high reliability. Three-dimensional activity of the upper cervical spine in healthy adults:the atlanto-occipital joint had(-6.8±1.5)° coupled left lateral bending and (8.9±2.0)° coupled extension in the maximum right rotation position, and the motion of atlanto-occipital joint had low activity[maximum was(5.3±2.6)°] in the remaining 3 positions; the rotation of atlanto-axial joint was(37.9±5.1)°, accounting for 52.34% of the total cervical spine activity[(72.4±5.0)°] in the maximum right rotation position, and rotational motion was still prominent in the remaining three positions. The relative translations of the upper cervical spine in all direction were small. The average axial rotation angle [(62.0±3.4)] ° of the total cervical spine in cervical spondylosis group was significantly lower than that in the healthy adult group, but the mean axial rotation angles of the atlanto-occipital and the atlantoaxial joint were not significantly different from those of the healthy adults(>0.05). CONCLUSIONS The three-dimensional CT reconstruction method has high reliability, which can be applied to measure the movement of spine. The upper cervical spine contributed the most to the direction of rotation, and the movement in all directions are accompanied by coupled motion in the other direction. There was no significant difference in the rotation of the upper cervical spine between cervical spondylosis patients and normal subjects.
Adult ; Aged ; Atlanto-Axial Joint ; Biomechanical Phenomena ; Cervical Vertebrae ; Female ; Humans ; Imaging, Three-Dimensional ; Male ; Middle Aged ; Range of Motion, Articular ; Reproducibility of Results ; Rotation ; Spine ; Tomography, X-Ray Computed ; Young Adult

Objective To discover antitumor drugs showing a synergistic effect with the cannabinoid receptor agonist sildenafil mesylate (WIN55212-2), so as to provide a new strategy for potential drug combinations for improving the life quality of cancer patients. Methods Firstly, the antitumor activity was tested for the combination of cannabinoid receptor 1 (CB1R) receptor agonist WIN55212-2 with each of 25 antitumor drugs using three tumor cell lines with high CB1R, HepG2, DU145 and HCT-8, by highthroughput assay. Then, the in vitro tumor colony-forming assay and 3D tumor spheroid assay were conducted to confirm the synergistic effect for the effective drug combination. Flow cytometry was used to investigate the effect of the synergistic drug combination on the apoptosis and cell cycle progression. Results Three drugs showed a synergistic inhibitory effect on the proliferation of tested tumor cells by combining with WIN55212-2, and among them, the combination of exemestane with WIN55212-2 displayed best effect, which showed a dose-dependent synergistic antitumor effect in the in vitro tumor colony-forming test and 3D tumor spheroid assay (CI＜1).Compared with the single-exemestane treatment, the combination of exemestane with WIN55212-2 significantly increased the apoptosis of HepG2 cells (P＜0.01) and caused G2/M phase arrest of the HepG2 cells. Conclusion The study is the first to report that the combination of exemestane with WIN55212-2 showed a synergistic anti-tumor activity on HepG2 cells, which was likely related to the promotion of apoptosis and induction of cell cycle arrest.

Critical ultrasonography(CUS) is different from the traditional diagnostic ultrasound,the examiner and interpreter of the image are critical care medicine physicians.The core content of CUS is to evaluate the pathophysiological changes of organs and systems and etiology changes.With the idea of critical care medicine as the soul,it can integrate the above information and clinical information,bedside real-time diagnosis and titration treatment,and evaluate the therapeutic effect so as to improve the outcome.CUS is a traditional technique which is applied as a new application method.The consensus of experts on critical ultrasonography in China released in 2016 put forward consensus suggestions on the concept,implementation and application of CUS.It should be further emphasized that the accurate and objective assessment and implementation of CUS requires the standardization of ultrasound image acquisition and the need to establish a CUS procedure.At the same time,the standardized training for CUS accepted by critical care medicine physicians requires the application of technical specifications,and the establishment of technical specifications is the basis for the quality control and continuous improvement of CUS.Chinese Critical Ultrasound Study Group and Critical Hemodynamic Therapy Collabration Group,based on the rich experience of clinical practice in critical care and research,combined with the essence of CUS,to learn the traditional ultrasonic essence,established the clinical application technical specifications of CUS,including in five parts:basic view and relevant indicators to obtain in CUS;basic norms for viscera organ assessment and special assessment;standardized processes and systematic inspection programs;examples of CUS applications;CUS training and the application of qualification certification.The establishment of applied technology standard is helpful for standardized training and clinical correct implementation.It is helpful for clinical evaluation and correct guidance treatment,and is also helpful for quality control and continuous improvement of CUS application.

Vertebral artery type cervical spondylosis is a common type of cervical spondylosis, also known as cervical vertigo. In recent years, with the increase of people's life pace and the number of office staff, the incidence rate has been rising year by year, with a trend of younger age. Because traditional Chinese medicine has unique advantages in treating cervical vertigo, it is necessary to study the regularity of the Chinese medicine for cervical vertigo. But at present, the research is mainly based on the statistics for frequency and proportion of herbs. In addition, in the process of diagnosis and treatment of Chinese medicine, personal experience also caused differences in prescription compatibility and drug dosage, which makes difficult guarantee for the safety and effectiveness of drug treatment. So, this paper is based on literatures about the traditional Chinese medicine in treatment of cervical vertigo in the past 5 years, by using association rules algorithm, complex system entropy clustering and other non supervised data mining methods. Analysis was made for the use of various drugs in the frequency, the association rules, the core drug combination and the new prescriptions. The traditional Chinese medicine inheritance support system(TCMISS) was utilized to analyze 154 drugs from the 101 prescriptions, determine the use frequency of drugs, analyze the characteristics and the compatibility of core drugs, and dig out 14 core drug combinations and 7 new prescription combinations. The prescription and medication regularities illustrates the drugs for treatment of cervical vertigo, including those for flating liver and suppressing yang, invigorating the circulation of blood to remove blood stasis, reducing water and permeating dampness, increasing qi and activating blood, and nourishing the liver and kidney mainly. Treatment rules are nourishing liver and kidney, invigorating the circulation of blood stasis Tongqiao, reducing phlegm and dampness, flating liver and suppressing yan, dredging collaterals, supplementing qi and nourishing blood. This study aims to summarize frequently used single herbs for vertebral artery type cervical spondylosis, combinations of frequently used herbs and dosage of frequently used herbs with significant efficacy, define the current prescription and medication regularities for treating cervical vertigo and give guidances for clinical mediation.

Objective To study the effect of Magnolia biondii Pamp ( MBP ) on hepatic antioxidant function and pathological histology for alcoholic liver injury in mice.Methods Fifty male KM mice were ran-domly divided into five groups as below:blank group , acute alcohol liver injury model group , MBP low -, medium -and high -dose groups (1.0, 2.0, 4.0 g· kg -1 ).The acute alcohol liver injury mouse model was set up by intragastric administration of alcohol once daily for 10 days.The activity of serum alanine aminotransferase ( ALT ) , aspartate aminotransferase ( AST ) , glutathione peroxidase ( GSH -PX ) activity and malondialdehyde ( MDA) content in liver were measured.The ex-pression of cytochrome P450 2E1 (CYP2E1) mRNA from the liver were determined by real-time fluorescent quantitative PCR.The pathological changes of liver were observed by light microscope with HE staining.Results Compared with the model group , MBP medium -and high-dose groups have little pathological damage of liver.The levels of ALT, AST, MDA and CYP2E1 mRNA were significant decreased while GSH-PX was significant increased.Conclusion MBP have a signifi-cant protective effect on acute alcohol liver injury in mice , which exerted its beneficial effects mainly through inhibiting oxidative damage and de-creased the expression of CYP 2E1 mRNA.

BACKGROUNDData on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China.

METHODSThe survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medications. BP < 140/90 mmHg and < 130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients.

RESULTSThe analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to < 140/90 mmHg and < 130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P < 0.001). When the threshold of BP < 130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P < 0.05). Using the threshold of < 140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P < 0.05).

CONCLUSIONSThe prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.

Adult ; Aged ; Awareness ; Female ; Humans ; Hypertension ; complications ; epidemiology ; therapy ; Male ; Middle Aged ; Prevalence ; Renal Insufficiency, Chronic ; complications

OBJECTIVETo evaluate the chromium (Cr) levels in blood and urine among general population in China between 2009 and 2010, and thereby to analyze its prevalent features.

METHODSFrom year 2009 to 2010, a total of 11 983 subjects of general population aged between 6 and 60 year-old were recruited from 24 districts in 8 provinces in eastern, central and western China mainland, by cluster random sampling method. The information about their living environment and health status were collected by questionnaire, and 11 983 blood samples and 11 853 urine samples were also collected. Inductively coupled plasma mass spectrometry (ICP-MS) was applied to test the Cr level both in blood and urine; and the Cr distribution in blood and urine among groups of population in different ages, genders and districts, were then analyzed.

RESULTSAmong general population in China, the geometric mean (GM) of Cr concentration in blood was 1.19 µg/L, with median at 1.74 µg /L and 95% percentile at 5.59 µg/L. The Cr concentration in blood among males and females were separately 1.18 µg/L and 1.20 µg/L(P > 0.05); while its GM in the groups of population aged 6 - 12, 12 - 16, 16 - 20, 20 - 30, 30 - 45 and 45 - 60 years old were 1.00, 1.22, 1.01, 1.40, 1.27 and 1.30 µg/L (P < 0.01), respectively; and the figures in populations from eastern, central and western China were 1.00, 1.70 and 1.98 µg/L (P < 0.01), respectively. Among general population, the GM of Cr concentration in urine was 0.53 µg/L, with median was lower than 0.42 µg/L and 95% percentile at 3.53 µg/L. The Cr concentration in urine among males and females were separately 0.52 µg/L and 0.53 µg/L (P > 0.05);while its GM in the groups of population aged 6 - 12, 12 - 16, 16 - 20, 20 - 30, 30 - 45 and 45 - 60 years old were 0.56, 0.60, 0.52, 0.50, 0.52 and 0.46 µg/L (P < 0.01), respectively;and the figures in populations from eastern, central and western China were 0.58, < 0.42 and 0.60 µg/L (P < 0.01), respectively.

CONCLUSIONThe study reported the Cr levels in blood and urine among general population in China, and thereby provided basic data evidence for the following Cr biological monitoring studies in near future.

Adolescent ; Adult ; Child ; China ; Chromium ; blood ; urine ; Female ; Humans ; Male ; Middle Aged ; Population Surveillance ; Young Adult