OBJECTIVE To compare the efficacy and safety of dupilumab versus thalidomide in the treatment of refractory prurigo nodularis （PN） in adults. METHODS A retrospective analysis was conducted on the clinical data of 123 adult patients with refractory PN admitted to Wuhan First Hospital from May 2021 to June 2024. Among them， 63 patients who received dupilumab comprised the observation group and 60 patients who received thalidomide comprised the control group. Clinical efficacy indicators [Investigator Global Assessment （IGA） score， Pruritus Numerical Rating Scale （P-NRS） score， Patient-Oriented Eczema Measure （POEM） score， and Dermatology Life Quality Index （DLQI） score]， allergic biomarkers [eosinophil （EOS） count in peripheral blood and serum total immunoglobulin E （IgE） level]， psychological scores [Hospital Anxiety and Depression Scale （HADS）] before and after treatment， as well as the occurrence of adverse drug reaction during treatment， were compared between the two groups. RESULTS Before treatment， there were no statistically significant differences between the two groups in above clinical efficacy indicators， allergic biomarkers， or psychological scores （P＞0.05）. At 4， 8， 12 and 16 weeks after treatment， both groups showed significant decreases in IGA score （except for the control group 4 weeks after treatment）， IGA activity score （except for the control group 4 weeks after treatment）， P-NRS score， POEM score， DLQI score （except for the control group 4 weeks after treatment）， serum EOS count， and serum total IgE level compared with baseline （P＜0.05）； at 12 and 16 weeks after treatment， scores on both the HADS-anxiety subscale and HADS-depression subscale were also significantly lower than baseline in both groups （P＜0.05）； the observation group was significantly lower than the control group （P＜0.05）. The overall incidence of adverse events was 12.70% in the observation group， which was significantly lower than 28.33% in the control group （P＜0.05）. CONCLUSIONS Dupilumab treatment in adults with refractory PN demonstrates superior efficacy compared with thalidomide in improving skin lesions， relieving pruritus， reducing peripheral EOS counts and serum total IgE， and improving quality of life and psychological status， while showing a more favorable safety profile.

Photodynamic immunotherapy is a promising strategy for cancer treatment. However, the dysfunctional tumor vasculature results in tumor hypoxia and the low efficiency of drug delivery, which in turn restricts the anticancer effect of photodynamic immunotherapy. In this study, we designed photosensitive lipid nanoparticles. The synthesized PFBT@Rox Lip nanoparticles could produce type I/II reactive oxygen species (ROS) by electron or energy transfer through PFBT under light irradiation. Moreover, this nanosystem could alleviate tumor hypoxia and promote vascular normalization through Roxadustat. Upon irradiation with white light, the ROS produced by PFBT@Rox Lip nanoparticles in situ dysregulated calcium homeostasis and triggered endoplasmic reticulum stress, which further promoted the release of damage-associated molecular patterns, enhanced antigen presentation, and stimulated an effective adaptive immune response, ultimately priming the tumor microenvironment (TME) together with the hypoxia alleviation and vessel normalization by Roxadustat. Indeed, in vivo results indicated that PFBT@Rox Lip nanoparticles promoted M1 polarization of tumor-associated macrophages, recruited more natural killer cells, and augmented infiltration of T cells, thereby leading to efficient photodynamic immunotherapy and potentiating the anti-primary and metastatic tumor efficacy of PD-1 antibody. Collectively, photodynamic immunotherapy with PFBT@Rox Lip nanoparticles efficiently program TME through the induction of immunogenicity and oxygenation, and effectively suppress tumor growth through immunogenic cell death and enhanced anti-tumor immunity.

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

Objective To explore the optimal ratio of Baitong decoction based on efficacy,clarify its spectrum-effect relationship,and identify its potential quality markers.Methods An ulcerative colitis(UC)model in mice was established using dextran sulfate sodium.The efficacy of Baitong decoction with varying drug ratios was assessed by evaluating the apparent score,pathological score and inflammatory factor changes of UC in each group of experimental animals.The fingerprints of Baitong decoction with different ratios were established by high performance liquid chromatography(HPLC),and the relationship between the content of each substance and its efficacy was analyzed by partial least squares regression to determine the potential quality markers of Baitong decoction.Results Baitong decoction was most effective in relieving ulcerative colitis when the mass ratio of Fuzi,Ganjiang and Congbai was 1∶2∶2.The fingerprinting identified 14 common peaks across 7 ratios,with 9 peaks were found to be associated with the remission of ulcerative colitis by partial least squares regression analysis.Conclusion The optimal ratio of Fuzi,Ganjiang and Congbai for treating UC is 1∶2∶2.The spectrum-effect relationship analysis suggested that the quality markers of Baitong decoction may be the substances represented by peak 2(benzoylaconine),3,5,6,8(mesaconine),9(aconitine),10(hypaconitine),13(10-gingerol)and 14.

Orbital fracture often leads to facial collapse, diplopia, enophthalmos, and even blindness. Traditional surgery relies on the experiences of physicians to achieve fracture reduction and orbital wall reconstruction, but the repair effect is not satisfactory. In recent years, with the development of digital technology, technologies such as computer-assisted surgery, 3D printing, surgical navigation systems, and intraoperative CT imaging have become increasingly widespread in the field of orbital reconstruction. Such techniques can avoid dependence on physicians′ experiences and make it easy for estimating and positioning the implantation sites, which subsequently contributes to better surgery efficiency and precise reconstruction of the orbit, improving aesthetics and visual function of patients. To this end, the authors reviewed the recent progress in application of digital technology for orbital fracture reconstruction, so as to provide reference and theoretical basis for clinical practice.

Objective:To determine the optimal concentration of inhaled oxygen in pediatric patients undergoing laparoscopic choledochal cyst resection under general anesthesia.Methods:Seventy-five pediatric patients of both sexes, aged 1-3 yr, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, with body mass index of 15-18 kg/m 2, with expected operation time≥3 h, scheduled for elective laparoscopic choledochal cyst resection with general anesthesia, were divided into 3 groups ( n=25 each) using a random number table method: C 40 group (FiO 2=40%), C 30 group (FiO 2=30%) and C 21 group (FiO 2=21%). Blood samples were collected from the radial artery for blood gas analysis after operation for determination of oxygenation index (OI), respiratory index (RI), alveolar-arterial oxygen partial pressure difference (PA-aO 2) and arterial-alveolar oxygen partial pressure ratio (PaO 2/PAO 2). The occurrence of high risk events of hypoxia (SpO 2<94%), extubation time, and occurrence of pneumonia and atelectasis at day 7 after operation were recorded. Results:Compared with C 21 group, PaO 2, PAO 2, PA-aO 2 and RI were significantly increased, PaO 2/PAO 2 was decreased, and the incidence of high risk events of hypoxia was decreased in C 30 and C 40 groups, and the incidence of atelectasis in C 30 group and pneumonia and atelectasis in C 40 group was increased at day 7 after operation ( P<0.05). Compared with C 30 group, PaO 2, PAO 2, PA-aO 2 and RI were significantly increased, and PaO 2/PAO 2 was decreased in C 40 group ( P<0.05). Conclusions:The optimal concentration of inhaled oxygen recommended is 21%-30% in the pediatric patients undergoing laparoscopic choledochal cyst resection under general anesthesia.

Objective:To explore the application effect and evaluation of virtual reality technology in oral implant therapy training.Methods:In November 2018, one adult patient (female, 36 years old) with missing right mandibular first molar was treated in the Department of Implantology, School and Hospital of Stomatology, Fujian Medical University. The three-dimensional virtual models of mandible and implant surgery tools were established, and the virtual reality software (Unity 3D 5.5.1) was imported. Combined with the virtual reality head mounted display, a virtual reality training system simulating the dental implant treatment process was independently developed. Ten refresher doctors and 20 graduate students in Department of Implantology, School and Hospital of Stomatology, Fujian Medical University from September 2018 to December 2019 were recruited as the experimental objects (no clinical experience was found). According to the level and seniority of doctors, they were randomly divided into virtual training group and conventional training control group, which made the two groups comparable, with 15 in each group. Subjective scores (including anatomical structure, surgical field of vision, cavity preparation, implant placement and process mastery) were given after the corresponding training in the two groups, and the virtual reality training system was used to test. The mesial and distal direction, buccolingual direction, depth and angle deviation of implants before and after the training were analyzed, and the differences between the two groups were compared.Results:The subjective scores of five dimensions in the virtual training group were significantly higher than those in the conventional training control group ( P<0.05). In the virtual training group, the mesial and distal, buccolingual, depth and angle deviation of implants were (0.73±0.33), (0.78±0.41), (0.61±0.32) mm and 6.66°±3.87°. All of them were significantly lower than those in the control group [(0.85±0.32), (1.12±0.38), (0.89±0.24) mm and 9.68°±3.74°] ( P<0.05). Conclusions:The self-developed virtual reality system of oral implant has good application effect, good operability and predictability. It can be effectively carried out in implant education and training, and it can strengthen skills of doctors, and is conducive to the practical operation.

Objective:To explore the values of Z-scores of fetal heart circumference (HC) and heart area (HA) in prediction of homozygous α-thalassemia.Methods:From February 2014 to March 2019, 233 fetuses of 15 to 23 gestation weeks with risk of homozygous α-thalassemia were examined by prenatal ultrasound in the Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region. HC, HA and cardiothoracic ratio (CTR) were measured. HC and HA were converted into Z-scores, respectively. The ROC curves were established and analyzed based on HC Z-score, HA Z-score or CTR respectively to compare their predicting efficacies for fetal homozygous α-thalassemia. Finally, the sensitivity, specificity, positive predictive value and negative predictive value were obtained by the best cutoff values.Results:①Sixty-five fetuses were diagnosed as homozygous α-thalassemia and classified as α-thalassemia group. One hundred and sixty-eight fetuses were mild and normal and were classified as control group. ②HC Z-score, HA Z-score and CTR in the α-thalassemia group were significantly higher than those in the control group, and the differences between the two groups were statistically significant ( P<0.001). ③The area under ROC curve of HA Z-score was the largest compared with HC Z-score and CTR, and the prediction efficacy was the highest ( Z test=2.144 and 2.517 respectively, P<0.05). ④The best cutoff values were HC Z-score>1.67, HA Z-score>2.06 and CTR>0.53. Sensitivities of predicting homozygous α-thalassemia in 15 to 23 gestation weeks were 92.31%, 100% and 89.23%, respectively. Specificities were 94.05%, 95.83% and 93.45%, respectively. Positive predictive values were 84.43%, 89.00% and 84.05%, respectively. Negative predictive values were 96.91%, 100% and 95.57%, respectively. Conclusions:Fetal heart HC Z-score and HA Z-score are safe and effective novel ultrasonic indexes for predicting homozygous α-thalassemia. Especially compared with traditional CTR, HA Z-score has a significantly higher predicting efficacy, which can improve the detection rate of homozygous α-thalassemia and reduce the need for invasive examination.

Objective:To construct Z-score ranges for normal fetal middle cerebral artery peak systolic velocity(MCA-PSV).Methods:From May 2017 to October 2019, 865 normal singleton fetuses of 10th to 40th gestational weeks underwent prenatal ultrasound in the Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region. Using fetal biometric parameters as independent variables, and measurement of MCA-PSV on standard section as dependent variables, the regression analyses of the mean(M) and the standard deviation(SD) for each parameter were calculated separately and then the best fitting equation was selected. A group of diseases which might cause the abnormal MCA-PSV were assessed using these standards.Results:①Strong correlations were found between MCA-PSV and fetal biometric parameters ( r=0.935-0.939, P<0.001). ②Quadratic or cubic regression equations were fitted to the models of the means of the MCA-PSV, whereas linear equations were fitted to the SDs. ③In these case groups, intrauterine growth restriction, severe preeclampsia, intrauterine infection and homozygous α-thalassemia-1 demonstrated Z-score>2 reflective of increased MCA-PSV with varying degrees, especially with the homozygous α-thalassemia-1 fetus being the most significant (17/20, 85%). Conclusions:The calculation of Z-score for MCA-PSV as a function of fetal biometric parameters is intuitive and simple, it can be used as an important indicator especially for homozygous α-thalassemia-1.

Objective: To improve the clinical understanding of Castleman disease (CD) with different types of thoracic involvement, including their clinical features, radiological and pathological findings, diagnosis and current treatment strategies. Methods: Retrospective analysis of 30 patients diagnosed with CD with thoracic involvement and hospitalized between June 2009 and May 2019 in The First Affiliated Hospital of Guangzhou Medical University was performed. Patients were divided into three groups for subsequent analysis based on the clinical data: CD with bronchiolitis obliterans (BO) , unicentric Castleman disease (UCD) without BO, and multicentric Castleman disease (MCD) without BO. Results: Among the 30 patients, there were 5 (16.7%) patients diagnosed with BO, 18 (60.0%) patients had UCD without BO and 7 (23.3%) patients had MCD without BO. The average age of MCD without BO patients was significantly older than that of BO and UCD without BO patients[ (49.29±5.39) ys vs (27.20±3.76) ys and (37.17±2.87) ys; P=0.005 and 0.034, respectively) ]. Pulmonary symptoms were commonly seen in BO group (100%) and MCD without BO group (71.4%) . while no pulmonary symptoms were seen in UCD without BO group. Key abnormal laboratory findings were erythrocyte sedimentation rate (ESR) increase (40%in BO group and 57.1% in MCD without BO group) and hypoxia (60% in BO group and 28.6% in MCD without BO group) . Other abnormal laboratory findings seen in MCD without BO group included anemia and IgG increase (both 57.1%) . Notably, all patients in BO group had extremely severe mixed ventilation dysfunction in the lung function test. CT scan showed lung parenchyma involvement in BO group (100%) , in UCD without BO group (11.1%) featured by solitary pulmonary nodule and in MCD without BO group (57.1%) featured by diffuse lesions in bilateral lungs. The size of lymph nodes was significantly smaller in MCD without BO group comparing to that in BO group and UCD without BO group[short diameter (1.83±0.51) cm vs (4.73±1.63) cm and (3.62±0.26) cm; P=0.006 and 0.011, respectively]. All patients (100%) in the BO group had a pathological type of transparent vascular variant while the same pathological type accounts for 88.9% in UCD without BO patients. The predominantly pathological type (57.1%) was plasma cell variant in the MCD without BO group. Oral ulcers presented in all patients in BO group but were relieved after the mass resection and immunomodulatory therapy, but the pulmonary symptoms were still progressively aggravated. Thoracoscopic mass excision was the main treatment for UCD without BO patients while chemotherapy, immunomodulatory and targeted therapy were commonly used for MCD without BO treatment. Conclusion The age, clinical symptom, laboratory finding, lung function, imaging manifestation, pathology, treatment and prognosis were different among the three groups. This classification could improve clinical understanding of the disease.