Analysis of the current situation of comprehensive management at intensive diabetes treatment clinic in Peking Union Medical College Hospital / 中华临床营养杂志

Objective:To assess the goal fulfillment in terms of blood glucose, blood pressure, blood lipid, and the composite indicator of these three in patients with diabetes who received intensified treatment at Peking Union Medical College Hospital and regular follow-up for 12 months, analyze the influencing factors, and explore the comprehensive management model for intensive diabetes treatment outpatient services.Methods:This study was a prospective, observational cohort study. The diabetes patients who received long-term regular follow-up at the intensive diabetes treatment outpatient clinic of Peking Union Medical College Hospital from 2012 to 2023 were selected as the research subjects. They were followed up and clinical data were collected at the 1st, 3rd, 6th, 9th, and 12th months of follow-up. The study assessed the goal fulfillment rates in terms of blood glucose, blood pressure, blood lipid, and the composite indicator of these three, with the goals of glycated hemoglobin (HbA1c)<7%, blood pressure<130/80 mmHg, and low-density lipoprotein cholesterol (LDL-C)<2.6 mmol/L. The study also analyzed the impact of factors, including gender, age, type of diabetes, duration of diabetes, body mass index, comorbidities, complications, and treatment regimens, on the outcomes of comprehensive diabetes management.Results:A total of 232 patients were included in the study, of whom 210 were with type 2 diabetes (90.5%), 13 with type 1 diabetes (5.6%), 5 with latent autoimmune diabetes of the adult (2.2%), 3 with diabetes after total pancreatectomy (1.3%), and 1 with mitochondrial diabetes (0.4%). After 3 months of intensified management, the goal fulfillment rates of blood glucose (67.7% vs. 34.1%, Kappa=0.336, P<0.001), blood pressure (53.4% vs. 37.5%, Kappa=0.159, P=0.001), blood lipid (59.1% vs. 39.2%, Kappa=0.198, P<0.001), and the composite indicator (20.7% vs. 3.0%, Kappa=0.177, P<0.001) were significantly increased. Continued treatment at 6, 9, and 12 months showed stable and sustained increases in the goal fulfillment rates of blood glucose, blood pressure, blood lipid, and the composite indicator. Logistic regression analysis showed that baseline hyperglycemia ( P=0.002), disease duration ≥5 years ( P<0.001), smoking ( P=0.009), alcohol consumption ( P=0.038), presence of diabetic complications ( P=0.001), combination therapy with oral antidiabetic drugs and insulin ( P<0.001), and use of antiplatelet drugs ( P=0.037) were risk factors for uncontrolled HbA1c. Baseline hypertension ( P<0.001), alcohol consumption ( P=0.030), and comorbid dyslipidemia ( P=0.028) were risk factors for uncontrolled blood pressure. Baseline uncontrolled LDL-C ( P=0.020) and non-use of statins ( P<0.001) were risk factors for uncontrolled blood lipid. Conclusions:Among patients with the long-term follow-up at our intensive diabetes treatment clinic, the goal fulfillment rates of blood glucose, blood lipid, blood pressure, and the composite indicator of these three are relatively higher. However, it is still necessary to improve patient compliance as much as possible, emphasize weight management, and persist on the comprehensive diabetes treatment.

Analysis of risk factors for periprosthetic joint infection after primary total knee arthroplasty and construction of a nomogram prediction model / 中华创伤骨科杂志

Objective:To investigate the risk factors for periprosthetic joint infection (PJI) after primary total knee arthroplasty (TKA) and construct a nomogram model for prediction of such risks.Methods:In this retrospective study, we enrolled 69 patients with PJI after primary TKA (the infection group, n=69) who had been admitted to Department of Orthopedics, Nanjing Jinling Hospital, The First School of Clinical Medicine, Southern Medical University from January 2010 to December 2019. The non-infection group included the patients of the same kind but without postoperative infection during the same period who were matched according to time of admission, age, and gender in a ratio of 1∶3 ( n=207). The data on body mass index, anesthesia method, operation time, preoperative C-reactive protein, preoperative albumin, and comorbid medical conditions were collected from both groups to screen the risk factors for postoperative development of PJI using univariate and multivariate conditional logistic regression analyses. After a nomogram of the risk factors was plotted using R software, the consistency index (C-index) was calculated. The receiver operating characteristic curve, calibration curve, and clinical decision curve were drawn. Results:Multivariate conditional logistic regression analysis showed that preoperative albumin <35 g/L ( OR=7.166, 95% CI: 3.427 to 14.983, P<0.001), operation time >90 min ( OR=3.163, 95% CI: 1.476 to 6.779, P=0.003), diabetes mellitus ( OR=3.966, 95% CI: 1.833 to 8.578, P<0.001), rheumatic diseases ( OR=3.531, 95% CI: 1.362 to 9.156, P=0.009), and chronic lung diseases ( OR=4.734, 95% CI: 1.790 to 12.521, P=0.002) were risk factors for development of PJI after primary TKA. The nomogram constructed with R software visualized the model. The C-index of the nomogram was 0.809 (95% CI: 0.751 to 0.867), indicating a good predictive capability of the model. The calibration curves of the model showed that the nomogram was in good agreement with the actual observations. The decision curves showed that the threshold probabilities of the model ranged from 0.08 to 0.75, providing a good net clinical benefit. Conclusions:Preoperative low albumin, prolonged operation time, diabetes, rheumatic diseases, and chronic lung diseases may be the risk factors for PJI after primary TKA. The nomogram prediction model based on these factors can provide a reference for clinicians to prevent PJI.

Serum Uric Acid Level and Its Influencing Factors in Patients with Diabetes Insipidus / 中国医学科学院学报

Objective To investigate the level of serum uric acid in patients with diabetes insipidus (DI),summarize the clinical characteristics of central diabetes insipidus (CDI) patients with hyperuricemia (HUA),and analyze the factors affecting the level of serum uric acid in the patients with CDI. Methods The clinical data of DI patients admitted to Peking Union Medical College Hospital from 2018 to 2021 were retrospectively analyzed.The patients were assigned into a child and adolescent group (≤ 18 years old) and an adult group (>18 years old) according to their ages.The demographic and biochemical data between two groups of patients with and without HUA were compared.Spearman correlation analysis and multiple linear regression analysis were performed to analyze the correlations between serum uric acid level and other factors. Results Among the 420 DI patients,411 patients had CDI (97.9%),including 189 patients with HUA (46.0%).Thirteen (6.9%) out of the 189 CDI patients with HUA presented the disappearance of thirst.The prevalence of HUA in children and adolescents was higher than that in adults (χ2=4.193,P=0.041).The level of serum uric acid in the CDI patients with HUA and disappearance of thirst was higher than those without disappearance of thirst (U=2.593,P=0.010).The multiple linear regression predicted serum creatinine (β=0.472,95%CI=2.451-4.381,P<0.001) and body mass index (β=0.387,95%CI=6.18-12.874,P<0.001) as the independent risk factors of serum uric acid level increment in children and adolescents,while serum creatinine (β=0.361,95%CI=1.016-1.785,P<0.001),body mass index (β=0.208,95%CI=2.321-6.702,P<0.001),triglyceride (β=0.268,95%CI=12.936-28.840,P<0.001),and total cholesterol (β=0.129,95%CI=2.708-22.250,P=0.013) were the independent risk factors in adults. Conclusions The patients with CDI were more likely to have HUA,and the prevalence of HUA in children and adolescents was higher than that in adults.Body mass index,serum creatinine,triglyceride,total cholesterol,and disappearance of thirst were the risk factors for the increased level of serum uric acid in CDI patients.

Meroterpenoids from Rhododendron nivale / 中国中药杂志

To elucidate the chemical material basis of Rhododendron nivale, this study comprehensively used various chromatographic techniques to isolate and obtain five new meroterpenoid enantiomers(1a/1b-5a/5b) from the ethyl acetate extract of R. nivale. A variety of spectral analytical methods, such as high-resolution mass spectrometry(HRMS), nuclear magnetic resonance spectroscopy(NMR), and infrared(IR) spectrum, were used to evaluate the structure, combined with the measurement and calculation of electronic circular dichroism(ECD). The new compounds 1a/1b-4a/4b were named as(±)-nivalones A-B(1a/1b-2a/2b) and(±)-nivalnoids C-D(3a/3b-4a/4b), along with one known enantiomer(±)-anthoponoid G(5a/5b). Human neuroblastoma cells(SH-SY5Y cells) induced by hydrogen peroxide(H_2O_2) were used as oxidative stress models to evaluate the protective activity of the isolated compounds against oxidative damage to nerve cells. It was found that compounds 2a and 3a had a certain protective effect on nerve cells against H_2O_2-induced oxidative damage at concentrations of 50 μmol·L~(-1), which increased the cell survival rate from 44.02%±2.30% to 67.82%±1.12% and 62.20%±1.87%, respectively. Other compounds did not show a significant ability to protect cells from oxidative damage. These findings enrich the chemical constituents of R. nivale and provide valuable information for identifying the structure of its meroterpenoids.

Chemical constituents from Callicarpa kwangtungensis and their hemostatic activities / 中国中药杂志

This study aims to identify the chemical constituents from Callicarpa kwangtungensis and determine their activities. MCI, ODS, and Sephadex LH-20 chromatography and semi-preparative HPLC were employed to separate the chemical constituents. A total of 15 compounds were separated, and their structures were identified on the basis of spectroscopic analysis and comparison with the data in relevant literature. Specifically, the 15 compounds were 3-O-α-L-rhamnopyranosyl-6-O-β-D-apiofuranosyl-4-O-E-caffeoyl-D-glucopyranoside(1), 3,6-O-α-L-dirhamnopyranosyl-4-O-E-caffeoyl-D-glucopyranoside(2), β-OH-forsythoside B(3), β-OH-poliumoside(4),(+)-lyoniresinol-3α-O-β-D-apiofuranosyl-(1→2)-β-D-glucopyranoside(5),(+)-lyoniresinol-3α-O-β-D-glucopyranoside(6),(-)-lyoniresinol-3α-O-β-D-glucopyranoside(7), kelampayoside A(8), descaffeoylpoliumoside(9), acteoside(10), alyssonoside(11), poliumoside(12), isacteoside(13), acetyl forsythoside B(14), and forsythoside B(15). Compounds 1 and 2 were novel, and the NMR data of compounds 3 and 4 were reported here for the first time. Furthermore, the hemostatic activities of the extract and abundant ingredients(compounds 12 and 15) of C. kwangtungensis were determined with Yunnan Baiyao as the positive control and normal saline as the negative control. The extract and compounds 12 and 15 significantly shortened the tail tip bleeding time in mice.

Correlation between contrast-enhanced ultrasound parameters and Crohn's disease activity / 中华内科杂志

Objective: By investigating the correlation between quantitative parameters of contrast enhanced ultrasound (CEUS) and commonly used activity assessment indicators of Crohn's disease (CD), and comparing the predictive power of laboratory inflammatory indicators with CEUS on Crohn's disease (CD), the significance of CEUS was evaluated. Methods: A case-control study. From October 2019 to December 2021, the clinical data of 67 patients with CD who were diagnosed by endoscopy and underwent contrast-enhanced ultrasonography were retrospectively analyzed in the First Affiliated Hospital with Nanjing Medical University, and their routine ultrasound and CEUS parameters, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fecal calprotectin (FC), Crohn's disease activity index (CDAI) and simplified endoscopic score for Crohn's disease (SES-CD) were collected. Using SES-CD as the standard, the patients were divided into a remission group and an active group, and the correlation of laboratory inflammatory indexes and contrast-enhanced ultrasound parameters with CDAI and SES-CD were evaluated. Besides, the ROC curve was used to analyze the predictive efficacy of each index on CD endoscopic activity. Results: A total of 67 patients were included in this study. According to the SES-CD score, there were 17 patients in the remission group and 50 patients in the active group. Except for the coefficient of the enhancement wash in slope and time to peak (TTP), the peak intensity (PI), area under the angiography curve, and laboratory inflammatory indexes were significantly different between the two groups (P<0.05), which also showed a moderate positive correlation with CDAI and SES-CD (P<0.05). ROC analysis showed that among the non-invasive indicators, PI and area under the angiography curve had the highest AUCs for predicting CD endoscopic activity, which were 0.912 and 0.891, respectively; with SES-CD taking >3 as the cut-off value, the corresponding sensitivities were 78.0% and 72.0%, with specificities of 100.0% and 94.1%, respectively. Conclusion: CEUS can objectively and repeatedly evaluate the disease activity of CD patients, and has great clinical application value, which can be used as a reliable imaging method for diagnosis and follow-up of patients with Crohn's disease.

Risk factors of in-hospital death in severe pneumonia patients receiving enteral nutrition support / 中华临床营养杂志

Objective:The decline in nutritional status in patients with severe pneumonia may contribute to an increase in in-hospital mortality. Enteral nutrition support can improve the nutritional status of patients, and is relatively easy to manage, with low cost and fewer serious complications. On the other hand, adverse reactions such as gastric retention and gastric microbiota translocation may increase the incidence of nosocomial pneumonia and increase the uncertainty of patient prognosis. There is no predictive model for in-hospital death in severe pneumonia patients receiving enteral nutrition support. The objective of this study was to investigate the risk factors of in-hospital death in patients with severe pneumonia receiving enteral nutrition support and to establish a prognostic model for such patients.Methods:This was a single-center retrospective study. Patients with severe pneumonia who were hospitalized in Peking Union Medical College Hospital and received enteral nutrition support were included from January 1, 2015 to December 31, 2020. The primary endpoints were in-hospital mortality rate and unordered discharge rate. The independent risk factors were determined using univariate and multifactorial logistic regression analysis, the nomogram scoring model was constructed, and the decision curve analysis (DCA) was performed.Results:A total of 632 severe pneumonia patients who received enteral nutrition support were included. Patients were divided into death and survival groups according to the presence or absence of in-hospital death, and 24 parameters were found with significant differences between groups. Nine parameters were independent predictors of mortality, namely the duration of ventilator use, the presence of malignant hyperplasia diseases, the maximal levels of platelet and prothrombin during hospitalization, and the nadir levels of alanine aminotransferase, serum albumin, sodium, potassium, and blood glucose. Based on these variables, a risk prediction scoring model was established (ROC = 0.782; 95% CI: 0.744 to 0.819, concordance index: 0.772). Calibration curves, DCA, and clinical impact curve were plotted to evaluate the goodness of function, accuracy, and applicability of the predictive nomogram, using the training and test sets. Conclusion:This study summarized the clinical characteristics of patients with severe pneumonia receiving enteral nutrition support and developed a scoring model to identify risk factors and establish prognostic models.

Analysis of clinical and pathological features of 54 adult inpatients with erythema nodosum / 中华皮肤科杂志

Objective:To investigate clinical and histopathological features of adult erythema nodosum (EN) .Methods:Clinical data were collected from 54 adult inpatients with histopathologically confirmed EN in Department of Dermatology and Venereology, the First Affiliated Hospital of Wannan Medical College from November 2019 to July 2022, and analyzed retrospectively.Results:Among the 54 EN patients, there were 6 males and 48 females, their ages were 42.50 ± 11.68 years (range, 18 - 73 years), and their disease course ranged from 1 day to 10 years; 30 patients (55.56%) were diagnosed with idiopathic EN, and 24 (44.44%) with secondary EN. The most common etiological factor in secondary EN was infection (17 cases), including respiratory tract infection (9 cases), tuberculosis infection (6 cases), upper respiratory tract infection comorbid with active hepatitis B virus infection (2 cases) ; the following common etiological factor was connective tissue disease (7 cases), including Behcet′s syndrome (4 cases), Sj?gren′s syndrome (1 case), and undifferentiated connective tissue diseases (2 cases). The patients′ ages were significantly younger in the secondary EN group (38.33 ± 12.15 years) than in the idiopathic EN group (46.17 ± 10.20 years, t = 2.58, P = 0.013). All patients had skin lesions on their lower limbs, lesions were limited to both lower limbs in 24 patients with idiopathic EN and 12 with secondary EN, and the proportion of patients with lesions limited to both lower limbs was significantly lower in the secondary EN group than in the idiopathic EN group ( χ2 = 5.44, P = 0.020). Compared with the idiopathic EN group, the secondary EN group showed significantly increased white blood cell counts ([7.56 ± 2.46] × 10 9/L vs. [6.04 ± 1.60] × 10 9/L, t = 2.62, P < 0.05) and C-reaction protein levels (34.34 ± 46.48 mg/L vs. 11.45 ± 18.13 mg/L, t = 2.28, P < 0.05). In the idiopathic EN group, 23 patients mainly showed histopathological features of septal panniculitis, while 17 patients in the secondary EN group mainly showed histopathological features of mixed panniculitis or lobular panniculitis, and the proportion of patients with histopathological features of mixed panniculitis or lobular panniculitis was significantly higher in the secondary EN group than in the idiopathic EN group ( χ2 = 12.18, P < 0.001) . Conclusion:EN was more common in female adults; idiopathic EN was the most common type, and secondary EN may be a cutaneous sign of systemic diseases; for EN patients at a relatively young age, with lesions involving both lower limbs or more sites, higher white blood cell counts and C-reaction protein levels, and histopathological manifestations of lobular panniculitis, systemic examinations were required to rule out underlying causes.

Three new cucurbitane-type triterpenoid glycosides from Citrullus colocynthis and their anti-inflammatory activity / 中国中药杂志

Three new cucurbitane-type triterpenoid glycosides were separated from the ethyl acetate extract of Citrullus colocynthis by a variety of chromatographic techniques. According to the data of NMR, HR-ESI-MS, and/or comparison with the reported data, the three novel cucurbitane-type triterpenoid glycosides were identified as colocynthenin E(1), colocynthenin G(2), and colocynthenin H(3). The cell inflammation model was established with RAW264.7 macrophages exposed to lipopolysaccharide and then used to determine the anti-inflammatory activities of the three compounds. Compounds 2 and 3 showed mild anti-inflammatory activities with the IC_(50) of 48.21 and 40.11 μmol·L~(-1), respectively, compared with that(IC_(50)=7.57 μmol·L~(-1)) of the positive control dexamethasone.

Deubiquitinating enzyme JOSD2 affects susceptibility of non-small cell lung carcinoma cells to anti-cancer drugs through DNA damage repair / 浙江大学学报·医学版

OBJECTIVES@#To investigate the effects and mechanisms of deubiquitinating enzyme Josephin domain containing 2 (JOSD2) on susceptibility of non-small cell lung carcinoma (NSCLC) cells to anti-cancer drugs.@*METHODS@#The transcriptome expression and clinical data of NSCLC were downloaded from the Gene Expression Omnibus. Principal component analysis and limma analysis were used to investigate the deubiquitinating enzymes up-regulated in NSCLC tissues. Kaplan-Meier analysis was used to investigate the relationship between the expression of deubiquitinating enzymes and overall survival of NSCLC patients. Gene ontology enrichment and gene set enrichment analysis (GSEA) were used to analyze the activation of signaling pathways in NSCLC patients with high expression of JOSD2. Gene set variation analysis and Pearson correlation were used to investigate the correlation between JOSD2 expression levels and DNA damage response (DDR) pathway. Western blotting was performed to examine the expression levels of JOSD2 and proteins associated with the DDR pathway. Immunofluorescence was used to detect the localization of JOSD2. Sulforhodamine B staining was used to examine the sensitivity of JOSD2-knock-down NSCLC cells to DNA damaging drugs.@*RESULTS@#Compared with adjacent tissues, the expression level of JOSD2 was significantly up-regulated in NSCLC tissues (P<0.05), and was significantly correlated with the prognosis in NSCLC patients (P<0.05). Compared with the tissues with low expression of JOSD2, the DDR-related pathways were significantly upregulated in NSCLC tissues with high expression of JOSD2 (all P<0.05). In addition, the expression of JOSD2 was positively correlated with the activation of DDR-related pathways (all P<0.01). Compared with the control group, overexpression of JOSD2 significantly promoted the DDR in NSCLC cells. In addition, DNA damaging agents significantly increase the nuclear localization of JOSD2, whereas depletion of JOSD2 significantly enhanced the sensitivity of NSCLC cells to DNA damaging agents (all P<0.05).@*CONCLUSIONS@#Deubiquitinating enzyme JOSD2 may regulate the malignant progression of NSCLC by promoting DNA damage repair pathway, and depletion of JOSD2 significantly enhances the sensitivity of NSCLC cells to DNA damaging agents.

Application of preoperative serum CYFRA 21-1 level in the prognosis of colorectal cancer / 中华预防医学杂志

To explore the predictive value of preoperative serum CYFRA 21-1 in colorectal cancer (CRC) resection patients. In this retrospective study, 456 patients with CRC who received surgical treatment in the Department of General Surgery, Affiliated Hospital of Nantong University from January 2016 to February 2018 were analyzed. Preoperative CYFRA 21-1, CEA, CA19-9 and pathological data of the study subjects were collected. Determine the cut-off value of CYFRA 21-1 based on the X-tile. Chi-square test or Fisher exact probability test were used to compare clinicopathological features in different CYFRA 21-1 level groups. Univariate and multivariate regression analysis of factors affecting 5-year overall survival (OS) and disease-free survival (DFS). Kaplan-Meier survival curves were used to analyze 5-year differences in OS and DFS in CRC patients with different levels of CYFRA 21-1, CEA and CA19-9. Receiver operating characteristic(ROC) was adopted. ROC curves were used to analyze the prognostic efficacy of CYFRA21-1 for CRC, and nomogram maps were used to predict 1, 3, and 5-year survival rates. The results showed that the optimal cut-off values of serum CYFRA 21-1, CEA and CA19-9 were 4.9 ng/ml, 29.2 ng/ml and 72.8 U/ml, respectively. Different gender, tumor size, location, degree of differentiation, depth of invasion, lymph node metastasis and tumor node metastasis (TNM) classification stage were significantly different between the two groups with high and low CYFRA 21-1, the P-values were 0.018,<0.001,<0.001,<0.001, 0.002, 0.001, 0.003, respectively. CYFRA 21-1 (≥4.9 ng/ml) was an independent risk factor for 5-year OS (HR: 4.008, 95%CI: 2.309-6.958, P<0.001) and DFS (HR: 3.75, 95%CI: 2.227-6.314, P<0.001) in CRC patients. CYFRA 21-1 predicts a 5-year AUC of 0.725 and 0.720 for OS and DFS, respectively, and 0.804 and 0.827 for the combination of CEA and CA19-9. Based on the results of multivariate Cox regression analysis, nomogram graphs of OS and DFS were established, the C-indexes were 0.799 and 0.803, respectively. In conclusion, preoperative serum CYFRA 21-1 level may be an independent risk factor affecting the prognosis of patients with colorectal cancer. The prognostic model established by CYFRA 21-1 combined with CEA, CA19-9 and TNM stages may provide references for the prevention of CRC recurrence and clinical decision-making.

Application of preoperative serum CYFRA 21-1 level in the prognosis of colorectal cancer / 中华预防医学杂志

To explore the predictive value of preoperative serum CYFRA 21-1 in colorectal cancer (CRC) resection patients. In this retrospective study, 456 patients with CRC who received surgical treatment in the Department of General Surgery, Affiliated Hospital of Nantong University from January 2016 to February 2018 were analyzed. Preoperative CYFRA 21-1, CEA, CA19-9 and pathological data of the study subjects were collected. Determine the cut-off value of CYFRA 21-1 based on the X-tile. Chi-square test or Fisher exact probability test were used to compare clinicopathological features in different CYFRA 21-1 level groups. Univariate and multivariate regression analysis of factors affecting 5-year overall survival (OS) and disease-free survival (DFS). Kaplan-Meier survival curves were used to analyze 5-year differences in OS and DFS in CRC patients with different levels of CYFRA 21-1, CEA and CA19-9. Receiver operating characteristic(ROC) was adopted. ROC curves were used to analyze the prognostic efficacy of CYFRA21-1 for CRC, and nomogram maps were used to predict 1, 3, and 5-year survival rates. The results showed that the optimal cut-off values of serum CYFRA 21-1, CEA and CA19-9 were 4.9 ng/ml, 29.2 ng/ml and 72.8 U/ml, respectively. Different gender, tumor size, location, degree of differentiation, depth of invasion, lymph node metastasis and tumor node metastasis (TNM) classification stage were significantly different between the two groups with high and low CYFRA 21-1, the P-values were 0.018,<0.001,<0.001,<0.001, 0.002, 0.001, 0.003, respectively. CYFRA 21-1 (≥4.9 ng/ml) was an independent risk factor for 5-year OS (HR: 4.008, 95%CI: 2.309-6.958, P<0.001) and DFS (HR: 3.75, 95%CI: 2.227-6.314, P<0.001) in CRC patients. CYFRA 21-1 predicts a 5-year AUC of 0.725 and 0.720 for OS and DFS, respectively, and 0.804 and 0.827 for the combination of CEA and CA19-9. Based on the results of multivariate Cox regression analysis, nomogram graphs of OS and DFS were established, the C-indexes were 0.799 and 0.803, respectively. In conclusion, preoperative serum CYFRA 21-1 level may be an independent risk factor affecting the prognosis of patients with colorectal cancer. The prognostic model established by CYFRA 21-1 combined with CEA, CA19-9 and TNM stages may provide references for the prevention of CRC recurrence and clinical decision-making.

Comparison of platelet-rich plasma and sodium hyaluronate in treatment of rotator cuff injury / 中华创伤骨科杂志

Objective:To compare the clinical effects of platelet-rich plasma (PRP) and sodium hyaluronate on rotator cuff injury.Methods:From February 2022 to December 2022, 226 patients with rotator cuff injury caused by military training were treated at Department of Orthopaedics, Jinling Hospital, School of Medicine, Nanjing University. They were all male, aged (24.5±3.7) years, and their time from injury to treatment was (4.6±2.2) months. They were divided into 2 even groups according to different treatments: an observation group of 113 cases into whose subacromial space PRP was injected, and a control group of 113 cases into whose subacromial space sodium hyaluronate was injected. In both groups, the injection was performed once a week for consecutive 3 weeks. The 2 groups were compared in terms of visual analogue scale (VAS) and Constant-Murley shoulder function scale (CMS) before treatment and 4 and 8 weeks after treatment, and the levels of TNF- α and IL-6 in the shoulder synovial fluid before treatment and 8 weeks after treatment. Results:There was no statistical difference between the 2 groups in general clinical data before treatment, indicating comparability ( P>0.05). At 4 and 8 weeks after treatment, compared with the pre-treatment values, the VAS scores were significantly decreased and the Constant-Murley scores significantly increased in both groups ( P<0.001). At 4 and 8 weeks after treatment, the VAS scores in the observation group (3.1±0.9 and 1.5±0.5) were significantly lower than those in the control group (3.7±0.8 and 2.3±0.6) while the Constant-Murley scores in the observation group (58.6±4.5 and 72.2±4.1) significantly higher than those in the control group (55.2±5.3 and 67.8±5.0) ( P<0.001). At 8 weeks after treatment, the levels of TNF- α and IL-6 in the 2 groups were significantly lower than the levels before treatment ( P<0.001). At 8 weeks after treatment, the levels of TNF- α and IL-6 in the observation group [(2.9±0.9) μg/L and (0.8±0.2) μg/L] were significantly lower than those in the control group [(4.0±0.4) μg/L and (1.1±0.4) μg/L] ( P<0.001). Conclusion:Injection of PRP or sodium hyaluronate can relieve pain and improve shoulder function obviously in patients with rotator cuff injury, but PRP is superior to sodium hyaluronate in the treatment of rotator cuff injury.

Comparison of short-term curative effects between three fixations of the tibial end in reconstruction of the anterior cruciate ligament / 中华创伤骨科杂志

Objective:To compare the short-term curative effects between 3 fixations of the tibial end with an interface screw, an interface screw + a portal nail and an interface screw + a knotless rivet in reconstruction of the anterior cruciate ligament (ACL).Methods:A retrospective study was conducted to analyze the data of 150 patients who had undergone reconstruction surgery for ACL injury at Department of Orthopaedics, Jinling Clinical Medical College, Nanjing Medical University from January 2019 to December 2021. The patients were divided into 3 groups according to their different fixations of the tibial end. In group A of 51 cases subjected to fixation of the tibial end with an interface screw, there were 40 males and 11 females with a mean age of (29.8±10.6) years. In group B of 55 cases whose tibial end was fixated with an interface screw + a portal nail, there were 47 males and 8 females with a mean age of (28.6±6.9) years. In group C of 44 cases whose tibial end was fixated with an interface screw + a knotless rivet, there were 39 males and 5 females with a mean age of (28.6±8.1) years. The 3 groups were compared in terms of International Knee Documentation Committee (IKDC) scoring and Lysholm knee function scoring at 12 and 48 weeks after operation, incidence of local pain at 4 weeks after operation, and stability of the knee at 48 weeks after operation.Results:There was no significant difference in the preoperative general data or follow-up time between the 3 groups, indicating comparability ( P>0.05). At 12 weeks after surgery, in Group B and Group C, the IKDC scores [(74.27±3.32) and (76.48±3.83) points] and Lysholm knee joint scores [(77.65±3.14) and (79.75±5.39) points] were significantly better than those in Group A [(69.73±6.04) and (71.63±3.36) points] ( P<0.05). However, there was no statistically significant difference in the above scores among the 3 groups at 48 weeks after surgery ( P>0.05). The incidence of local pain at the tibial end in group B (9.1%, 5/55) was significantly higher than that in group A (0, 0/51) and group C (2.3%, 1/44) at 4 weeks after surgery, and the results of the anterior drawer test in group A (36 negative cases, 14 cases of grade Ⅰ, and 1 case of grade Ⅱ) were significantly worse than those in group B (50 negative cases, and 5 cases of grade Ⅰ) and group C (40 negative cases, and 4 cases of grade Ⅰ) at 48 weeks after surgery ( P<0.05). Conclusions:In ACL reconstruction, all the 3 fixations of the tibial end can achieve fine short-term curative effects. Fixation with an interface screw + a knotless rivet may lead to a lower rate of ligament relaxation and a higher score of early knee function than fixation with an interface screw, and a lower incidence of local pain at the tibial end than fixation with an interface screw + a portal nail.

Butyrate facilitates immune clearance of colorectal cancer cells by suppressing STAT1-mediated PD-L1 expression

Abstract Objective Immunotherapy has been proven to improve the prognosis of patients with advanced malignancy but has shown limited efficacy in patients with Colorectal Cancer (CRC). Increasing evidence suggests that butyrate, a bacterial metabolite, enhances the efficacy of cancer therapies by modulating immune responses. Here, the effect and the mechanism of butyrate on anti-PD-L1 therapy were investigated in CRC. Methods The expression of PD-L1 and STAT1, and the lysine acetylation of STAT1 in CRC cells were observed after treatment with butyrate (2, 5, and 10 mM) for 24h or butyrate (5 mM) for 8, 16, and 24h. Site-directed mutations of STAT1 (K410R or K413R) were introduced to determine the role of STAT1 acetylation in modulating PD-L1 expression. The effect of butyrate on the cytotoxicity of CD8+ T-cells against CRC cells with or without PD-L1 overexpression was explored in vitro and in vivo. Results Butyrate could suppress IFN-γ-induced PD-L1 up-regulation in CRC cells in a dose- and time-dependent way. Butyrate promoted the lysine acetylation of STAT1 to reduce STAT1 expression. Non-acetylated mutant STAT1 not only ameliorated butyrate-induced suppression of lysine acetylation and nuclear translocation of STAT1 but also blocked the effect of butyrate on PD-L1. Butyrate attenuated the IFN-γ-induced impairment of CD8+ T-cell cytotoxicity against CRC cells. Meanwhile, butyrate suppressed CRC tumor growth by enhancing CD8+ T-cell infiltration. However, directly overexpressing PD-L1 in CRC cells could abolish the effect of butyrate. Conclusion Butyrate strengthens the immune response to CRC cells by suppressing PD-L1 expression via acetylation of STAT1.

A new type of extreme insulin resistance—type C insulin resistance syndrome and its clinical characteristics / 中华内分泌代谢杂志

We report on two cases of type C insulin resistance syndrome(TCIRS) admitted to the Department of Endocrinology, Peking Union Medical College Hospital from January 2000 to December 2020. Both patients presented with persistent hyperglycemia, low immunoreactive insulin, extreme insulin resistance, high insulin autoantibodies, high total insulin, and large insulin antibody pool. TCIRS is marked by extreme insulin resistance with ketoacidosis and respond to medium to high doses glucocorticoids rather than plasmapheresis.

Recent advances in mechanisms of KRASG12C inhibitors anti-tumor resistance and relevant overcoming strategies / 药学学报

KRAS is one of the most frequently mutated human oncogenes. In spite of mounting efforts on the development of direct or indirect inhibition targeting KRAS, little has been achieved because of insurmountable difficulties, titling KRAS "undruggable". Recently, subtype-specific inhibitors have shown great hope. Some KRASG12C inhibitors have entered clinical trials, including adagrasib and sotorasib, and have shown preliminary clinical effectiveness. Experiences from the inhibitors targeting the downstream factors of RAS pathways show that the anticancer activity of these drugs will be limited due to the development of drug resistance. Preclinical studies of KRASG12C inhibitors have revealed that the application of these agents might be hampered by the drug resistance issue. The current review aims to describe the current status of KRASG12C inhibitors, and discuss the mechanisms underlying KRASG12C inhibitor resistance, so as to provide the clues for the combat of drug resistance.

A Young Hemophilia Patient with Advanced Hemophilic Arthritis and HIV Infection / 罕见病研究

A young male diagnosed with severe hemophilia A since childhood, was presented with recurrent joint and urinary bleeding. Annualized bleed rates dropped below five with low dose prophylactic medication.Bleeding in the right knee joint recently aggravated. Due to coexisting HIV infection and advanced hemophilic arthritis, the patient was managed by a multi-disciplinary team(MDT).Total knee arthroplasty was performed by an experienced surgeon using modern prosthesis design and intraoperative navigation technologies.Physical and rehabilitation therapy was provided during the postoperative period, and joint function improved. The MDT managed the young patient with HIV infection and advanced hemophilic arthritis. The patient was diagnosed with osteoporosis thought to have been caused by hemophilia, HIV infection and antiviral drugs; and he received treatment. The treatment of this patient reflects the importance of multidisciplinary cooperation in the management of difficult and rare diseases.

Progress in the treatment of mucosal pemphigoid / 中国临床药理学与治疗学

Mucosal pemphigoid is a rare subepidermal immune bullous disease, mainly involving the oral cavity, eyes and other mucous membranes, with the risk of scarring, which can be life-threatening in severe cases. For patients with mucosal pemphigoid, early diagnosis and early treatment can avoid serious complications. For mild patients, dapsone or topical glucocorticoids can be used; for severe patients, combination of immunosup-pressants helps to improve clinical efficacy and reduce the dosage of glucocorticoid, including cyclophosphamide, azathioprine, methotrexate, and mycophenolic acid esters. For some refractory cases without any response to the treatments of dapsone, glucocorticoids and immunosuppressants, biological agents (including rituximab, etanercept, infliximab, and braziltinib), intravenous immune globulin and other therapies can be selected. For some patients with mucosal scarring, surgery or laser therapy can be considered to improve symptoms. However, it is necessary to further demonstrate the clinical efficacy of some immunosuppressants and biologic agents on mucosal pemphigoid in a lot of larger clinical trials.

Three patients with ectopic corticotropin-releasing hormone(CRH)syndrome due to medullary thyroid carcinoma and literature review / 中华内分泌代谢杂志

Objective:To investigate the pathogenesis of Cushing′s syndrome induced by medullary thyroid carcinoma.Methods:Started from April 2011 to present, three medullary thyroid carcinoma patients with Cushing′s syndrome were enrolled in this study. All patients were 40 to 50 years old, one female and two males. The blood pressure, blood glucose, thyroid function and antibodies, calcitonin, and carcinoembryonic antigen(CEA)were detected. The qualitative and localized diagnosis of Cushing′s syndrome was performed by high- and low-dose dexamethasone suppression tests as well as imaging examinations. The biopsies of all patients were taken to test the immunostaining of calcitonin, adrenocorticotropin(ACTH), and corticotropin-releasing hormone(CRH).Results:According to the clinical manifestation and function tests, three patients were diagnosed as medullary thyroid carcinoma accompanied by ACTH-dependent Cushing′s syndrome. All patients showed positive immunohistochemical staining of calcitonin and CRH, with negative immunostaining of ACTH in one and positive immunostaining of ACTH in two patients. Therefore, the diagnosis of ectopic CRH syndrome caused by medullary thyroid carcinoma was definite.Conclusions:Medullary thyroid carcinoma is a rare cause of Cushing′s syndrome. Tumor cells secrete ACTH and CRH, which in turn cause hypercorticoremia. Ectopic CRH syndrome is very rare. Early diagnosis can be made by immunohistochemical staining of biopsy tissues to guide early targeted treatment and improve the prognosis.