Targeted protein degradation via nanoparticle-based universal strategy modifies nanoparticles with antibodies and ingeniously utilizes its cellular transport characteristics. This strategy achieved targeted degradation of extracellular proteins without complex design.Image 1.

Tongue squamous cell carcinoma (TSCC) is a prevalent malignancy that afflicts the head and neck area and presents a high incidence of metastasis and invasion. Accurate diagnosis and effective treatment are essential for enhancing the quality of life and the survival rates of TSCC patients. The current treatment modalities for TSCC frequently suffer from a lack of specificity and efficacy. Nanoparticles with diagnostic and photothermal therapeutic properties may offer a new approach for the targeted therapy of TSCC. However, inadequate accumulation of photosensitizers at the tumor site diminishes the efficacy of photothermal therapy (PTT). This study modified gold nanodots (AuNDs) with the TSCC-targeting peptide HN-1 to improve the selectivity and therapeutic effects of PTT. The Au-HN-1 nanosystem effectively targeted the TSCC cells and was rapidly delivered to the tumor tissues compared to the AuNDs. The enhanced accumulation of photosensitizing agents at tumor sites achieved significant PTT effects in a mouse model of TSCC. Moreover, owing to its stable long-term fluorescence and high X-ray attenuation coefficient, the Au-HN-1 nanosystem can be used for fluorescence and computed tomography imaging of TSCC, rendering it useful for early tumor detection and accurate delineation of surgical margins. In conclusion, Au-HN-1 represents a promising nanomedicine for imaging-based diagnosis and targeted PTT of TSCC.
Tongue Neoplasms/diagnostic imaging* ; Carcinoma, Squamous Cell/diagnostic imaging* ; Animals ; Gold/chemistry* ; Mice ; Photothermal Therapy/methods* ; Tomography, X-Ray Computed ; Photosensitizing Agents ; Metal Nanoparticles ; Humans ; Cell Line, Tumor

Objective:To understand the loss to follow-up of children born to pregnant women with HIV infection (HIV-exposed children) and analyze its influencing factors in China in 2019.Methods:The data were collected from the follow-up records of pregnant women with HIV infection and their children reported by the national "Management Information System for the Prevention of HIV, syphilis and Hepatitis B Mother-to-Child Transmission" in 2019. HIV-exposed children were defined as those who were not followed up after birth or who were not followed up at 18 months of age and who were not followed up at 21 months of age. The univariate and multivariate influencing factors of loss to follow-up of children born to HIV-infected pregnant women were analyzed by χ2 test and logistic regression model. SPSS 25.0 software was used for statistical analysis. Results:The number of HIV-infected pregnant women was 5 039, the number of live-born children was 5 035, the number of loss to follow-up children within 18 months of age was 283, and the loss to follow-up rate children was 5.62%(283/5 035). The results of multivariate logistic regression analysis showed that the rate of loss to follow-up of exposed children born to pregnant women who worked as farmers (animal husbandry and fishery) (a OR=0.34, 95% CI: 0.22-0.53), unmarried (a OR=0.47, 95% CI: 0.24-0.93), first marriage (a OR=0.38, 95% CI: 0.22-0.67), remarriage (a OR=0.36, 95% CI: 0.20-0.67) and cohabiting (a OR=0.47, 95% CI: 0.23-0.97), and knew they had HIV infection before this pregnancy (a OR=0.53, 95% CI: 0.40-0.70) was lower. Han nationality (a OR=1.52, 95% CI: 1.09-2.13), primary school (a OR=2.06, 95% CI: 1.10-3.89) and junior middle school (a OR=1.81, 95% CI: 1.03-3.17) educational level, non-use of antiviral drugs (a OR=6.21, 95% CI: 4.32-8.93) and delivery in township (street) level midwifery institutions (a OR=5.72, 95% CI: 1.61-20.27) had higher rates of loss to follow-up among infants born to HIV-infected pregnant women. Conclusions:HIV-exposed children still have a specific rate of loss to follow-up in China in 2019. In order to further reduce the rate of loss to follow-up, it is of great significance to improve the detection rate of HIV before pregnancy and the rate of antiviral drugs used in pregnant women with HIV infection, which is of great significance for the effective implementation of comprehensive intervention measures of prevention of mother-to-child transmission of HIV.

Objective:To explore whether tryptophan metabolism is related to bone growth by comparing the differences in tryptophan metabolism after rotator cuff tear (RCT) repair between rats with normal bone remodeling capability and those with defective bone remodeling capability.Methods:Of the 50 adult female Sprague Dawley (SD) rats used for this study, 18 were randomly selected to undergo bilateral ovariectomy (OVX) (OVX group), and the remaining 32 underwent bilateral OVX sham surgery (sham surgery group). All rats were maintained in standard conditions. Three months after surgery, 4 rats were randomly selected from OVX group and the sham surgery group, respectively, for Micro CT identification of bone loss at the rat humeral head. The remaining rats in OVX group underwent RCT modeling and surgical repair of acute supraspinatus muscle transection (OVX+RCT group) ( n=14); the remaining rats in the sham surgery group were subjected to either surgical repair of acute supraspinatus muscle transection (RCT group, n=14) or RCT sham surgery (SO group, n=14). The grip power of the rats was tested 2 weeks after surgery. The supraspinatus tendon-bone complex was harvested for evaluation of new bone formation and growth through real-time fluorescence quantitative polymerase chain reaction (qPCR), hematoxylin eosin (HE) staining, and immunohistochemistry (IHC) staining. The tryptophan metabolism was analyzed using ultra high performance liquid chromatography (UPLC). Results:The grip power test showed that SO group had the greatest grip power, followed by RCT group and OVX+RCT group, with statistically significant differences between the 3 groups ( P<0.05). The qPCR showed that the relative expression of osteosclerosis in the tendon-bone complex in SO group was significantly higher than that in OVX+RCT group and RCT group; IHC staining showed that the relative expression of osteocalcin in RCT group was significantly higher than that in SO group and OVX+RCT group ( P<0.05). The UPLC showed that the content of tryptophan in the rotator cuff tendon-bone complex was similar among SO, RCT, and OVX+RCT groups, showing no significant difference ( P>0.05). The qPCR showed that the expression of indoleamine 2, 3-dioxygenase 2 in the Kynurenic acid metabolism pathway showed an increasing trend from SO group to RCT group to OVX+RCT group, with OVX+RCT group significantly higher than SO group ( P<0.05). The expression of 3-hydroxybenzoate 3, 4-dioxygenase in OVX+RCT group was significantly higher than that in RCT group and in SO group ( P<0.001). The subtypes A and B of monoamine oxidase in the 5-hydroxytryptamine metabolism pathway increased from SO group to RCT group to OVX+RCT group. The subtypes A and B of monoamine oxidase in the 5-hydroxytryptamine metabolism pathway increased among SO, RCT, and OVX+RCT groups( P<0.001). The expression of dopamine decarboxylase in the indole metabolism pathway in OVX+RCT group was significantly higher than that in SO group ( P<0.01). The expression of cytochrome P450 oxidoreductase increased from SO group to RCT group to OVX+RCT group ( P<0.001). Conclusions:The tryptophan metabolism in the supraspinatus tendon-bone complex after RCT in rats is mainly dominated by kynurenic acid metabolism, followed by 5-hydroxytryptamine metabolism. In RCT bone remodeling, the 5-hydroxytryptamine metabolic pathway changes the most, followed by the indole pathway. The contents of niacin and xanthurenic acid in the kynurenic acid metabolism pathway are related to bone growth; the 5-hydroxytryptamine, hydroxyindoleacetic acid, and melatonin in the 5-hydroxytryptophan metabolic pathway are related to bone growth; the tryptophan and indole lactate in the indole metabolism pathway are related to bone growth. Therefore, tryptophan metabolism is related to bone growth, providing potential therapeutic targets for RCT repair.

With the growing demand for facial aesthetics,facial asymmetry has emerged as a prominent clinical concern.Skeletal Class Ⅲ malocclusion could not only affect facial aesthetics,but also have an adverse effect on oral function.Facial asymmetry is caused by complex factors and can manifest in various ways,including morphological asymmetry of the maxillofacial unit,positional asymmetry of maxillofacial units,and transverse dentition compensation.Therefore,comprehensive classification based on maxillofacial features of facial asymmetry is crucial for diagnosis,treatment,and surgical planning.This article aims to review recent progress of re-search on the maxillofacial features,classification,and treatment of skeletal Class Ⅲ malocclusion with facial asymmetry,in order to provide reference for clinical diagnosis and treatment.

Objective:To analyze the clinical features of adrenal metastases and summarize the experience of diagnosis and treatment.Methods:The clinicopathological data of 210 patients with adrenal metastases admitted to Peking Union Medical College Hospital from Jan. 1990 to Jun. 2021 were retrospectively analyzed, and the relevant literature was reviewed. The clinical characteristics, primary tumor types, imaging examination methods and diagnosis and treatment methods of adrenal metastases were summarized.Results:Among 210 patients, 153 were males and 57 were females, with an average age of (60±12) years. The average maximum diameter of the tumor was (4.7±2.6) cm, the maximum was 14.5 cm, and the minimum was 0.5 cm. Tumor occurred in 84 cases on the left, 81 cases on the right, and 44 cases bilateral. The primary tumors of 210 patients were 72 cases of lung cancer, 48 cases of renal cancer, 29 cases of hepatobiliary cancer, 18 cases of colorectal cancer, 11 cases of gastric esophageal cancer, 6 cases of pancreatic cancer, 5 cases of breast cancer, 3 cases of melanoma, and 18 cases of other tumors. 108 patients had no obvious clinical symptoms of discomfort, only found in the review of primary tumor or routine physical examination. 102 were primary disease-related symptoms, and 210 patients had no abnormal endocrine signs such as moon face and buffalo back. The median time from diagnosis of primary tumor to adrenal metastasis was 3 months. 95 cases were diagnosed with primary tumor at the same time. The longest time was 228 months. Of the 210 patients, 203 underwent CT, 99 PET-CT, 74 B-ultrasound and 25 MRI. A total of 122 patients were clinically diagnosed as adrenal metastasis by history and imaging examination. One patient was treated with adrenal photon knife, one patient was treated with adrenal artery embolization chemotherapy, and 21 patients were treated with adrenal radiotherapy or CT-guided adrenal radiofrequency ablation. A total of 88 patients were diagnosed as adrenal metastasis by histopathology. Among them, 12 patients were diagnosed by adrenal puncture under CT guidance, 74 patients were diagnosed by adrenal surgery, and 2 patients were further treated with metastatic tumor resection after adrenal metastasis was diagnosed by puncture. Finally, all patients were diagnosed as adrenal metastasis of malignant tumor by pathology, and they continued to be treated with primary tumor.Conclusions:Lung cancer is the most common type of primary adrenal metastases in our hospital. Most of the elderly men have no obvious endocrine-related symptoms and signs. CT is an effective means of examination, supplemented by B ultrasound or MRI diagnostic accuracy will be further improved, but the diagnosis still depends on histopathological examination. For patients with isolated adrenal metastasis, surgical treatment can significantly improve the prognosis. However, comprehensive treatment should be carried out according to the general situation of patients, the type and biological behavior of primary tumors, and the characteristics of metastatic tumors, so as to achieve the best curative effect.

Objective To explore the solvent effect on the chromatographic retention performance by RP-HPLC in traditional Chinese medicine analysis.Methods Five traditional Chinese medicines were selected to determin by HPLC according to the requirements of each medicinal content determination item in Chinese pharmacopoeia(Vol.Ⅰ,2020),they were gentiopicroside-Radix gentianae,syringin-Acanthopanax enticosus,rosin diglucoside-Eucommia ulmoides,aesculin-Fraxinus Cortex,and adenosine-Cordyceps sinensis respectively.The effect of sample solvent in RP-HPLC was explored preliminarily on the chromatographic peak abnormalities and some solutions were proposed.Results The abnormal chromatographic retention behavior of the five traditional Chinese medicine components were characterized by retention time drift,peak broadening,extending and splitting,the fundamental reason for the above abnormal phenomenons was that there was a certain mismatch between the sample solvent and the mobile phase,leading to different existing forms of the sample between the sample solvent and the mobile phase(Solvent Effect).The results showed that the mobile phase or similar to mobile phase solution was a preferred method to reduce and eliminate solvent effect.In addition,reducing the injection volume or using the solvent effect eliminator can also be used as auxiliary means.Conclusion Solvent effect can cause abnormal peak shape,and had an influence on the accuracy of qualitative and quantitative results,it should be taken seriously in daily Chinese medicine analysis work.

Purpose: To intelligently diagnose whether there is bladder outlet obstruction (BOO) in female with decent detrusor contraction ability by focusing on urodynamic study (UDS) data. Materials and Methods: We retrospectively reviewed the UDS data of female patients during urination. Eleven easily accessible urinary flow indicators were calculated according to the UDS data of each patient during voiding period. Eight diagnosis models based on back propagation neural network with different input feature combination were constructed by analyzing the correlations between indicators and lower urinary tract dysfunction labels. Subsequently, the stability of diagnostic models was evaluated by five-fold cross-validation based on training data, while the performance was compared on test dataset. Results: UDS data from 134 female patients with a median age of 51 years (range, 27–78 years) were selected for our study.Among them, 66 patients suffered BOO and the remaining were normal. Applying the 5-fold cross-validation method, the model with the best performance achieved an area under the receiver operating characteristic curve (AUC) value of 0.949±0.060 using 9 UDS input features. The accuracy, sensitivity, and specificity for BOO diagnosis model in the testing process are 94.4%, 100%, and 89.3%, respectively. Conclusions The 9 significant indicators in UDS were employed to construct a diagnostic model of female BOO based on machine learning algorithm, which performs preferable classification accuracy and stability.

Objective:To investigate the driving effect of prostate cancer associated transcript 4 (PCAT4) on the up-regulation of upregulator of cell proliferation (URGCP) expression in breast cancer progression through sponging miR-508-5p.Methods:The microarray data of lncRNA and miRNA with differential expression in breast cancer tissue were analyzed by Cancer Genome Atlas. The expression of PCAT4 in breast cancer was evaluated by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation was measured by MTT and colony formation, cell apoptosis was analyzed by TUNEL, and cell migration and invasion were analyzed by Transwell. The correlation between PCAT4 and miR-508-5p, and miR-508-5p and URGCP was analyzed by RNA pull-down and double luciferase assay. Tumor xenograft studies were performed to analyze the correlation between PCAT4/miR-508-5p/URGCP axis and breast cancer cell growth in vivo. Measurement data were expressed as mean ± standard deviation ( ± s). T-test was used for comparison between two groups, and one-way analysis of variance was used for comparison between multiple groups. The correlation between PCAT4 and URGCP and miR-508-5p expression was evaluated by Pearson correlation analysis. Results:The expression level of PCAT4 was up-regulated in breast cancer tissues and cells. Knockout of PCAT4 inhibited cell proliferation and metastasis and promoted cell apoptosis. miR-508-5p was the target of PCAT4 and was negatively correlated with PCAT4. Overexpression of miR-508-5p in breast cancer can inhibit cell growth, migration and invasion, and promote cell apoptosis. URGCP is the target of miR-508-5p and induces progression of breast cancer. Tumor xenograft studies showed that PCAT4 drives breast cancer progression by affecting miR-508-5p/URGCP.Conclusion:The expression of PCAT4 is up-regulated in breast cancer tissues and cells, and PCAT4 can act as a molecular sponge of miR-508-5p, and significantly promote breast cancer progression by activating URGCP protein expression.