A major challenge facing photodynamic therapy (PDT) is that the activity of the immune-induced infiltrating CD8⁺ T cells is subject to the regulatory T lymphocytes (Tregs), leaving the tumor at risk of recurrence and metastasis after the initial ablation. To augment the antitumor response and reprogram the immunosuppressive tumor microenvironment (TME), a supramolecular photodynamic nanoparticle (DACss) is constructed by the host-guest interaction between demethylcantharidin-conjugated β-cyclodextrin (DMC-CD) and amantadine-terminated disulfide-conjugated FFVLGGGC peptide with chlorin e6 decoration (Ad-ss-pep-Ce6) to achieve intelligent delivery of photosensitizer and immunomodulator for breast cancer treatment. The acid-labile β-carboxamide bond of DMC-CD is hydrolyzed in response to the acidic TME, resulting in the localized release of DMC and subsequent inhibition of Tregs. The guest molecule Ad-ss-pep-Ce6 can be cleaved by a high level of intracellular GSH, reducing photosensitizer toxicity and increasing photosensitizer retention in the tumor. With a significant increase in the CTL/Treg ratio, the combination of Ce6-based PDT and DMC-mediated immunomodulation adequately achieved spatiotemporal regulation and remodeling of the TME, as well as improved primary tumor and in situ lung metastasis suppression with the aid of PD-1 antibody.

OBJECTIVE To establish an HPLC fingerprint of Xiao’er resuqing oral liquid， and to determine the contents of twelve index components. METHODS HPLC method was adopted. The determination was performed on Venusil MP C18 column with mobile phase consisting of acetonitrile-0.1% phosphate aqueous solution （gradient elution） at a flow rate of 1.0 mL/min. The detection wavelength was set at 210 nm， the column temperature was 30 ℃， the injection volume was 10 μL. HPLC fingerprint of Xiao’er resuqing oral liquid was established by using the Similarity Evaluation System of Chromatographic Fingerprint of TCM （2012 edition） to evaluate the similarity. The contents of 12 components were determined， including （R， S）-goitrin， 3，5-O-dicaffeoyl quinic acid， puerarin， forsythin， forsythoside A， chlorogenic acid， baicalin， saikosaponins d， wogonoside， baicalein， emodin and chrysophanol. RESULTS The similarity of HPLC fingerprints of 13 batches of Xiao’er resuqing oral liquid was greater than 0.97， and 14 common peaks were confirmed. The contents of the above 12 index components in 13 batches of Xiao’er resuqing oral liquid were as follows： 0.078-0.172， 1.564-2.736， 1.338-2.578， 0.426-0.872， 1.477-2.628， 1.396-2.447， 4.052-9.146， 0.367- 0.692， 1.974-4.674， 1.274-2.969， 0.085-0.167 and 0.155-0.307 mg/mL. CONCLUSIONS The established HPLC fingerprint and content determination methods have high accuracy and high specificity， which can be used for the quality evaluation of Xiao’er resuqing oral liquid.

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.

Hepatocellular carcinoma(HCC)is one of the most common malignancies with high morbidity and mortality rates worldwide.With the advances in molecular biology and tumor immunology,molecular-targeted agents represented by tyrosine kinase inhibitors(such as sorafenib and lenvatinib)and immunotherapy represented by PD-1/PD-L1 monoclonal antibodies have brought hope for patients with advanced HCC.The combination of immunotherapy and anti-angiogenic therapy can further improve the treatment outcome of patients.In addition,the optimization and integration of stereotactic body radiotherapy,local treatment,and systemic treatment may maximize the benefits of patients.In the future,through a deep understanding of the heterogeneity of HCC,the development of precision molecular subtyping and individualized treatment,and the establishment of a multidisciplinary collaborative diagnosis and treatment system,systemic therapy is expected to achieve long-term management of advanced HCC.This article reviews the current status and advances in systemic therapy for advanced HCC.

Objective To investigate the relationship between the expression levels of serum microRNA-181a(miR-181a)and sphingosine 1-phosphate receptor 1(S1PR1)messenger RNA(mRNA)and the occur-rence of acute exacerbation in patients with bronchial asthma.Methods From January 2021 to May 2023,a to-tal of 132 patients with bronchial asthma in acute exacerbation stage from Shijiazhuang Emergency Center were selected as the acute stage group,89 patients with bronchial asthma in remission stage were selected as the remission stage group and 90 healthy personnel for physical examination were selected as the control group.The acute stage group was divided into mild group(50 cases),moderate group(45 cases)and severe group(37 cases).Clinical data were collected and pulmonary function[ratio of forced expiratory volume to forced vital capacity in the first second(FEV1/FVC)and percentage of peak expiratory flow rate to expected value(PEF％pred)]was examined.Real-time fluorescence quantitative PCR was used to detect the serum miR-181a and S1PR1 mRNA expression.Pearson method was used to analyze the correlation between serum miR-181a and S1PR1 mRNA and lung function indicators in patients with acute exacerbation of bronchial asthma.Multivariate Logistic regression analysis was used to identify factors affecting the occurrence of acute exacerbation in patients with bronchial asthma.Receiver operating characteristic(ROC)curve was used to e-valuate the value of serum miR-181a and S1PR1 mRNA in predicting the occurrence of acute exacerbation in patients with bronchial asthma.Results The FEV1/FVC,PEF％pred and relative expression level of serum miR-181a in control group,remission stage group and acute stage group were decreased successively,while the relative expression level of S1PR1 mRNA were increased successively(P＜0.05).The relative expression lev-el of serum miR-181a in mild group,moderate group and severe group was decreased successively,and the rel-ative expression level of S1PR1 mRNA was increased successively(P＜0.05).In patients with acute exacer-bation of bronchial asthma,serum miR-181a and S1PR1 mRNA were negatively correlated(P＜0.05),serum miR-181a was positively correlated with FEV1/FVC,PEF％pred(P＜0.05),and serum S1PR1 mRNA was negatively correlated with FEV1/FVC,PEF％pred(P＜0.05).Low level of FEV1/FVC,low level of PEF％pred,low relative expression level of miR-181a and high relative expression level of S1PR1 mRNA were inde-pendent risk factors affecting the occurrence of acute exacerbation in patients with bronchial asthma(P＜0.05).The area under the curve(AUC)of the combination of serum miR-181a and S1PR1 mRNA for predic-ting the acute exacerbation in patients with bronchial asthma was 0.890,which was higher than the AUC of the two predicted alone(P＜0.05).Conclusion The serum miR-181a in patients with bronchial asthma is lowly expressed,while S1PR1 mRNA is highly expressed.Both are related to the occurrence and severity of acute exacerba-tion as well as lung function,and have high predictive efficacy for the occurrence of acute exacerbation.

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.

A 14-year-old boy presented with coma and convulsion following a 3-day high fever of unknown origin was initially diagnosed with a central nervous system infection with uncertain pathogen. Direct microscopic examination of wet slides of cerebrospinal fluid cytology revealed active amoeboid trophozoites with different shapes. The amoeba trophozoite could be seen at high magnification after Wright′s-Giemsa staining. A diagnosis of primary amoebic meningoencephalitis was made according to the cellular morphology results of the cerebrospinal fluid, imaging data, and clinical symptoms. After high-throughput gene detection targeting the infection pathogen and specific PCR verification of amoeba species, it was confirmed that the infection was caused by Naegleria fowleri. Timely antiamoebic treatment and other related treatments were implemented, but the patient progressed to brain death after 50 days, leading to the discontinuation of treatment by the family.

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 review relevant research on the application of self-help intervention model in adult depression patients, analyze the main characteristics and application effects of self-help intervention model, in order to provide reference for related research in this field.Methods:According to the methodological framework of the scope review, searched 12 Chinese and English databases including CNKI, Wanfang, PubMed, Web of Science, etc. from the establishment of the database until April 20, 2021, and sorted and analyzed the obtained documents according to the inclusion and exclusion standards.Results:A total of 45 documents were included, of which only 5 were from China; the included studies were mainly based on the Internet platform, using cognitive behavioral therapy, reading therapy, acceptance and commitment therapy, and problem-solving therapy for intervention; the duration of the intervention was 3 weeks to 4 months, participants complete an intervention module or read a specified number of chapters every 3 to 7 days on average, and receive regular guidance and supervision from the intervention facilitator every 1-2 weeks. The total contact time with the facilitator was 80-160 minutes. Various modes of self-help intervention based on the Internet could effectively improve the negative emotions of patients with depression.Conclusions:The self-help intervention model has shown good results in the treatment of patients with depression, but there is a lack of local intervention research in China, and there is no clear standard for the number of interventions and the length of the intervention guide. Under the general trend of "Internet + medical health", it is necessary to actively construct a self-help intervention model for depression with Chinese cultural characteristics, and form a systematic and standardized intervention strategy to address the many obstacles in time, location, resources and cost of people with depression, and finally achieve the purpose of improving the patients′ depressive symptoms and helping them to restore their social functions.

Objective:To explore the diagnostic efficacy difference and clinical diagnostic value of chronic lymphocytic leukemia flow (CLLflow) score and Moreau score (MS) in the diagnosis of chronic lymphocytic leukemia (CLL).Methods:According to the latest international and national diagnosis criteria for CLL, 133 patients with B-cell chronic lymphoproliferative diseases and uncertain immunophenotypes (B-CLPD), diagnosed by Zhengzhou Jinyu Comprehensive Haematological Pathology Diagnosis Centre from March 2020 to May 2021, were included in this study. Above patients were divided into the CLL group ( n=83) and non-CLL group ( n=50). The expression of clusters of differentiation (CD)5, CD10, CD20, CD19, κ light chain, λ light chain, FMC7, CD23, CD22, surface immunoglobulin M, CD200 and CD79 were detected by flow cytometry, and CLLflow score and MS score were calculated respectively according to the scoring rules. A fourfold table was used to compare the diagnostic efficacy of the two scoring systems, and the Kappa test and McNemar test were used to compare the consistency and superiority of the systems. Results:The rate of negative and positive CLLflow score were 4.8% (4/83) and 95.2% (79/83) in the CLL group and were 80.0% (40/50) and 20.0% (10/50) in the non-CLL group, and respectively (both P<0.001). The MS score (≤2, =3 and≥4) was 1.2% (1/83), 10.8% (9/83) and 88.0% (73/83) in the CLL group and was 86.0% (43/50), 14.0% (7/50) and 0 in the non-CLL group, there were significant statistical difference between the two groups ( P<0.001). The sensitivity, specificity, positive predictive value and negative predictive value of the CLLflow score were 95.2% (79/83), 80.0% (40/50), 88.8% (79/89) and 90.9% (40/44), respectively and those of MS score were 98.8% (82/83), 86.0% (43/50), 92.1% (82/89) and 97.7% (43/44) respectively. The overall coincidence rate, positive and negative coincidence rate between the CLLflow score and MS score were 91.0% (121/133), 93.3% (83/89) and 86.4% (38/44) respectively. Besides, the McNeamr dominance test presented no significant difference ( P>0.05) and high consistency (Kappa=0.796) between the two scoring systems. With MS≤2 and MS≥4, the sensitivity and the specificity of the MS score were 100% (73/73) and 97.7% (43/44) respectively, and for the CLLflow score, the sensitivity and the specificity were 97.3% (71/73) and 86.4% (38/44) in this MS range. With MS = 3, the sensitivity and specificity of the MS score were 100% (9/9) and 0 (0/7), and CLLflow was 88.9% (8/9) and 57.1% (4/7). Conclusions:The diagnostic efficacy is similar and presents high consistency between the CLLflow score and MS score in CLL diagnosis. For CLL patients with MS = 3, the specificity of MS is relatively low, combined assessment with CLLflow score could improve the diagnosis efficacy for CLL in these patients.