A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in SLCO2A1, c.1658T > A and c.96+4A > C.Through multidisciplinary consultation, we confirmed the diagnosis of pachydermoperiostosis.

Objective To explore the development and validation of a prediction model for severe communi-ty-acquired pneumonia in adults based on peripheral blood inflammatory indicators.Methods Venous blood samples of 204 community-acquired pneumonia in adults patients admitted to 7 hospitals in Chongqing area from April 2021 to August 2022 were collected to detect C-reactive protein(CRP),peripheral white blood cell count(WBC),neutrophil to lymphocyte ratio(NLR),cytokines,lymphocyte subgroups and neutrophil CD64 index.All of patients were divided into a training group and a validation group according to the time of admis-sion.Univariate and multivariate Logistic regression were used to analyze the data of the training group,the characteristic factors of severe progression for pneumonia were selected to construct the nomogram model,and the data of the validation group was used to verify the model.The receiver operating characteristic(ROC)curve,calibration curve and decision curve analysis(DCA)were used to evaluate the prediction ability of the model for severe community-acquired pneumonia in adults.Results Logistic regression analysis showed that age,CRP,WBC,interleukin(IL)-4/interferon gamma ratio and IL-6/IL-10 ratio were independent risk factors for severe community-acquired pneumonia in adults.The area under the ROC curve of the nomogram model in the training group and the validation group was 0.893 and 0.880,respectively.The calibration curve and DCA results shown that the model had a good prediction effect for severe community-acquired pneumonia in adults.Conclusion The inflammatory indicators included in this model are simple and easy to obtain clinically.This model with good differentiation and accuracy,it can be used as a practical tool to predict severe community-ac-quired pneumonia in adults,and has certain clinical application value.

Objective:To investigate the application value of dual-energy CT in the differential diagnosis of lung metastases and benign nodules in breast cancer.Methods:The data of 96 patients with pathology-confirmed breast cancer at the Fifth Affiliated Hospital of Wenzhou Medical University from March 2017 to June 2021 were analyzed retrospectively. All patients received dual-energy chest CT scans within 2 weeks before surgery. All 96 patients were female, aged 31-84 (56±12) years. A total of 207 pulmonary nodules from 96 patients were classified into 81 lung metastases and 126 benign nodules according to pathological findings. Conventional CT features [longest diameter, boundary, location and CT value difference between arterial and venous phases (ΔCT) of nodules] and dual-energy CT parameters [standardized iodine concentration (NIC), slope of energy spectrum (λ HU) and normalized effective atomic number (nZ eff) in arterial and venous phases] were analyzed and measured. The χ 2 test, independent samples t test and Kruskal-Wallis rank-sum test were used to analyze the differences of conventional CT features and dual-energy CT parameters between lung metastases and benign nodules. First, the least shrinkage and selection operator (LASSO) regression method was used to screen conventional CT features and dual-energy CT parameters, and then logistic regression analysis was performed to screen out independent risk factors for lung metastases. Receiver operating characteristic (ROC) curves were used to evaluate the efficacy of CT parameters alone and logistic model in differentiating lung metastases from benign lung nodules. Results:There were statistically significant differences between lung metastases and benign nodules in longest diameter, ?CT, NIC, λ HU and nZ eff in arterial and venous phases (all P<0.05). LASSO regression and binary logistic regression analysis showed that the venous phase λ HU (OR=59.413, 95%CI 14.233-248.002, P<0.001) and the venous phase nZ eff (OR=4.508, 95%CI 2.787-7.290, P<0.001) were independent risk factors for predicting lung metastases. Among them, the venous phase λ HU had the highest diagnostic efficiency, with an area under curve (AUC) of 0.794 and an accuracy of 74.88%. The AUC of the logistic model constructed by combining the venous phase λ HU and the venous phase nZ eff could reach 0.958, and the accuracy was improved to 92.27%, which was significantly higher than the efficacy of the two alone ( Z=6.02, 9.54, all P<0.001). Conclusion:Dual-energy CT has great application value in the identification of lung metastases and benign nodules in patients with breast cancer, especially when combined with venous phase λ HU and venous phase nZ eff, the diagnostic efficiency is further improved.

OBJECTIVE: To detect the genetic variant of a child with cleidocranial dysplasia (CCD) and to find out the causation of the illness. METHODS: Gene variant was identified by the second generation targeted sequencing and Sanger sequencing. RESULTS: The gene sequencing revealed that the RUNX2 gene had c.196C>T(p.Glu66*) nonsense variant, which was predicted to be a pathogenic variant according to the ACMG guidelines(PVS1+PS2). CONCLUSION The variant of c.196C > T in the RUNX2 gene may be the cause of the child with CCD, and the novel variant enriches the RUNX2 gene variant spectrum.
Asians/genetics* ; Child ; China ; Cleidocranial Dysplasia/genetics* ; Core Binding Factor Alpha 1 Subunit/genetics* ; Humans ; Mutation

Objective:To provide more options for preoperative localization diagnosis in patients with primary hyperparathyroidism (PHPT), the diagnostic efficacy of parathyroid 4-dimensional computed tomography (4D-CT) in patients with PHPT was evaluated.Methods:This was a single-center retrospective study including 57 patients with surgical proved PHPT. All of the patients underwent 4D-CT, 99Tc m -sestamibi parathyroid imaging (MIBI), and ultrasonography (US) preoperatively. The reference standard for correct localization was based on operation reports and pathology confirmation. The patients were grouped according to the preoperative serum calcium levels, tumor diameter, or ectopic lesions (yes/no), respectively. The sensitivity, specificity, positive predictive value, negative predictive value and area under the curve (AUC) of 4D-CT, MIBI and US, alone or in combination, were analyzed in total and each subgroup patients. Results:Fifty-seven patients (39 women, 18 men; mean age of 56.5 years) were evaluated, including four cases with multi-gland disease and thirteen cases with ectopic parathyroid lesions. In all the patients, similar diagnostic efficacy was found in 4D-CT (AUC: 0.943) and MIBI (AUC: 0.927), both of which were higher than that of US (AUC: 0.847) ( P = 0.01 for 4D-CT vs. US; P = 0.04 for MIBI vs. US). In a subset analysis for ectopic quadrants, the diagnostic efficacy of 4D-CT was significantly higher than that of MIBI ( P = 0.04) or US ( P = 0.01), with the sensitivity of 100%, 69.2%, and 61.5%, and AUC of 0.989, 0.846, and 0.808 for 4D-CT, MIBI and US, respectively. Conclusions:4D-CT has similar diagnostic efficacy for preoperative localization to MIBI in patients with PHPT, and it is superior to MIBI and US in identifying the ectopic parathyroid gland. 4D-CT can be recommended as an alternative preoperative localization method, especially when parathyroid lesions could not be precisely located by US and MIBI.

Objective:To investigate the effect of pulmonary vascular dysfunction in the prognosis of patients with acute lung injury (ALI).Methods:Patients with ALI who underwent pulmonary artery catheterization in the department of critical care medicine of Wuhan NO.1 Hospital from June 2017 to June 2019 were enrolled. The general information, clinical and hemodynamic indexes [central venous pressure (CVP), pulmonary artery wedge pressure (PAWP), pulmonary artery systolic pressure (sPAP), pulmonary artery diastolic pressure (dPAP), mean pulmonary artery pressure (mPAP), cardiac index (CI)], acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, arterial blood gas parameters [pH, partial pressure of oxygen (PO 2), partial pressure of carbon dioxide (PCO 2), oxygenation index (PaO 2/FiO 2)], whether there was shock or not; ventilator parameters [platform pressure (Plat), positive end-expiratory pressure (PEEP)], etc. were recorded. Pulmonary artery oxygen saturation, pulmonary vascular function indexes [transpulmonary potential gradient (TPG) and pulmonary vascular resistance index (PVRi)] were calculated. The relationship between TPG, PVRi and mechanical ventilation time, the length of intensive care unit (ICU) stay, cardiovascular days and 60-day mortality were analyzed in patients with different prognosis of 60-day and whether the TPG increased (≥12 mmHg was defined as elevated TPG, 1 mmHg = 0.133 kPa). Results:A total of 65 patients were included in the study, including 30 males and 35 females; aged (48.9±15.2) years old. Forty-eight cases survived in 60-days, 17 died, and the 60-day mortality was 26.2%. At the baseline, there were no significant differences in cardiopulmonary function measurements, such as CVP, sPAP, dPAP, PAWP, CI, etc. between the two groups of patients with different prognosis. The APACHEⅡ score, shock ratio, TPG and PVRi of the death group were significant higher than those of the survival group [APACHEⅡ: 34±9 vs. 28±11, shock: 52.9% vs. 25.0%, TPG (mmHg): 16.2±1.9 vs. 14.6±2.1, PVRi (kPa·s·L -1): 31.8±4.2 vs. 29.7±3.5, all P < 0.05]. The 60-day mortality of 47 patients with TPG ≥ 12 mmHg was significantly higher than that of 18 patients with TPG < 12 mmHg (34.0% vs. 5.6%), and the mechanical ventilation time and the length of ICU stay were also significantly longer (days: 17±9 vs. 11±8, 16±5 vs. 12±5), and the cardiovascular days also increased significantly (days: 23±7 vs. 18±6), and the differences were statistically significant (all P < 0.05). Pearson correlation analysis showed that PVRi was significantly correlated with mechanical ventilation time, the length of ICU stay and cardiovascular days ( r1 = 0.317, P1 = 0.030; r2 = 0.277, P2 = 0.005; r3 = 0.285, P3 = 0.002). In the individual multivariate Logistic regression model, the highest PVRi was an independent risk factor for the 60-day mortality [odds ratio ( OR) = 30.5, 95% confidence interval was 20.4-43.1, P = 0.023]. Conclusion:Pulmonary vascular dysfunction is common in ALI patients and is independently associated with adverse outcomes.

Objective:To explore the feasibility and optimization effect of modifying the Henry Ford Hospital (HFHS) RapidPlan model for stereotactic body radiation therapy planning based on local requirements.Methods:The following changes were made based on Henry Ford Health System(HFHS) Rapid Plan Lung SBRT model, taking the latest clinical guideline evidence and local clinical practice into account: Internal gross target volume(IGTV) and organ at risk(OAR) structure, lung, were added and set corresponding parameters.The upper value of planning target volume (PTV) was adjusted from 109% to 125%. The original training library was replaced with 73 local historical simultaneous integrated boosting plans, and statistical verification and outlier cleaning of the initial trained model were performed using Model Analytics software. Totally 10 cases not included in the model library were selected for independent verification, and automatic optimization result of the models before and after modifying were compared under the same beam condition. The following dosimetric parameters were compared after target dose normalization: conformal index (CI) of target volume, the mean doses, maximum doses and dose-volume parameters of OARs.Results:The " tail" of the PTV′s DVH and the " shoulder" and " tail" of the IGTV′s DVH of model M (local) validation plan (M (local)_P) performs higher than the original model HFHS (HFHS_P). The PTV_CI (1.07±0.13) of M local_P were significantly smaller than HFHS_P (1.25±0.24) ( Z=-2.497, P<0.05). Except for Heart_ D15 cm 3 and Heart_ Dmax, most of the M local_P dosimetric parameters of OARs were lower than HFHS_P, and the standard deviation was smaller. However, the difference of between two plans was no more than 3.06%. 10 HFHS_P plans don′t satisfy dose parameters requirement, two of which PTV_CI values are 1.52 and 1.74, far beyond the clinically acceptable range. Conclusions:Commercial model HFHS could be localized by replacing training library and adjusting parameters. Moreover, plans optimized by the modified model are local clinical acceptable in the aspects of target volume conformity and hotspots, and have a better performance in terms of OAR sparing and plan consistency.

Objective To observe the effects of enhanced exercise and combined vitamin D and calcium supplementation on muscular strength and fracture occurrence in postmenopausal women with a high risk of osteoporosis.Methods Totally 614 postmenopausal women at high risk factors of osteoporosis were enrolled in Dongcheng district of Beijing and randomized into four groups:group A(control group,n=173),group B(regular Tai Chi exercise,n=171),group C(calcium 600 mg/d+VitD800 U/d,n=139),and group D[calcium 600 mg/d+25 hydroxyl vitamin D(25OHD) 0.25 μg/d,n=131].Muscular strength was measured at baseline and one and two years after intervention.Bone turnover markers were measured at baseline and during the two-year follow-up.Falls and fractures were recorded.Results The incidence of 25OHD<50 nmol/L was approximately 92.6%.During the follow-up,the left grip strength decreased significantly two years after intervention(t=-3.252,P=0.001)in group A.Right grip strength decreased significantly in group B(t=2.460,P=0.015)while left grip strength improved significantly in group C(t=-2.051,P=0.043)one year after intervention.In group D,muscular strength in both 12-month and 24-month did not change compared with baseline(both P>0.05).Furthermore,serum procollagen type I N-terminal propeptide elevated significantly in group A(t=-2.962,P=0.004),group B(t=-2.888,P=0.005),and group C(t=-2.441,P=0.016),whereas β-C-terminal telopeptide of type I collagen decreased significantly in group B(t=2.285,P=0.024)and group D(t=2.596,P=0.011)two years after intervention.Conclusion Enhanced exercise and combined calcium vitamin D supplementation may help sustain muscle strength in postmenopausal women,while calcium and vitamin D supplementation may improve muscular strength within a short period of time.

Objective: To evaluate the efficacy and safety of maintenance therapy with reduced dose of rhTPO in the patients with primary immune thrombocytopenia (ITP) who attained stable platelet (PLT) counts after daily administration of rhTPO. Methods: Treatment was started with a daily administration of rhTPO (300 U/kg) for 2 consecutive weeks. Patients who attained stable PLT≥50×10⁹/L were enrolled to maintenance therapy starting with every other day administration of rhTPO, then adjusted dose interval to maintain platelet count (30-100) ×10⁹/L. Results: A total of 91 eligible patients were enrolled. Fourteen patients discontinued the study due to noncompliance (12/14) and investigator decision (2/14) . Among 77 patients who completed the study, 38 patients with the administration of rhTPO at every other day or less could maintain PLT≥30×10⁹/L for 12 weeks. The percentage of patients with a platelet response (PLT≥30×10⁹/L) at 4^th week, 8^th week and 12^th week of maintain therapy was 92.6% (63/68) , 82.7% (43/52) and 85.0% (34/40) , respectively. Median platelet counts remained in the range of (70-124) ×10⁹/L. The overall incidence of rhTPO-related adverse events was 7.7%. All the adverse events were generally mild. Conclusion Extending the dose interval of rhTPO is feasible to maintain stable platelet count in the patients with ITP, but the optimal dose interval is uncertain and might vary with individuals.

AIM:Early calcification of atherosclerotic plaques are colocalized with macrophage and high mobility group box 1 (HMGB1), a cytokine associated with biomineralizing process under physiological and pathological conditions .Our study aims to evaluate whether HMGB1 induces ectopic mineralization via promoting the secretion of matrix vesicles ( MVs) from macrophages .METHODS:HMGB1 was added to the medium of macrophages , the secretion of MVs in the supernatant was tested by flow cytometry analysis .The mineral deposition in calcifying medium was detected by Alizarin Red staining and von Kossa staining .Transmission electron microscopy showed the formation of hydroxyapatite crystals in MVs .Then we subcutaneous injection into mice with MVs to induce regional minera-lization.RESULTS:HMGB1 significantly promoted secretion of MVs from macrophages as raveled by flow cytometry analysis .TNAP activity, considered as a marker of MVs maturation , was higher in HMGB1-induced MVs compared to the control-MVs.HMGB1-MVs also led to mineral deposition in an in vitro MVs-collagen mineralization model .Subcutaneous injection into mice with MVs derived from HMGB1-treated cells showed a greater potential to initiate regional mineralization .Mechanistic experiments revealed that HMGB 1 activated neutral sphingomyelinase 2 ( nSMase2 ) that involved the receptor for advanced glycation end products ( RAGE ) and p38 MAPK (upstream of nSMase2).Inhibition of nSMase2 with GW4869 or p38 MAPK with SB-239063 prevented MVs secretion and min-eral deposition .CONCLUSIONS: HMGB1 induces MVs secretion from macrophages at least in part , via the RAGE/p38 MAPK/nSMase2 signaling pathway .Our findings thus reveal a novel mechanism by which HMGB 1 may participated in the early calcification of atherosclerotic plaques .