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 understand the epidemiology of rubella and the genetic characteristics of the virus circulating during the period 2021-2022, providing basic scientific data for rubella prevention and control in China.Methods:National rubella incidence data for the period 2021-2022 were obtained from the Infectious Disease Surveillance System module and the Surveillance Report Management module of the China′s Disease Prevention and Control Information System. Positive rubella virus(RuV)isolates were obtained from the National Measles/Rubella Laboratory Network. Two nucleotide (nt) fragments [F1-480 (8 633-9 112 nt) and F2-633 (8 945-9 577 nt)] located in the E1 gene were amplified and determined by reverse transcription polymerase chain reaction (RT-PCR), and the target gene (E1-739) was obtained after collating and splicing. The sequences obtained in this study were used to construct a phylogenetic tree with the reported reference strains for genotype and lineage identification. Additionally, the phylogenetic analysis was performed to assess their genetic relatedness of RuV strains prevalent in China during 2018-2020 from GenBank database.Results:In 2021-2022, the rubella incidence in China was 0.06/100, 000 (2021: 840 cases; 2022: 784 cases), with cases primarily concentrated in the western and southern provinces. Age distribution analysis showed that rubella cases in 2021-2022 was mainly in children under 5 years of age (2021: 34.17%, 287/840; 2022: 42.09%, 330/784), with the highest proportion in children aged 0-2 years. Further analysis of the immunization history of cases revealed that in the 8-23 months age group, a significant proportion of cases had received only one dose of rubella containing vaccine (RCV); cases in the 2-14 years age group were mainly among children who had received two or more doses of RCV; however, cases over 15 years of age were primarily found in individuals who had not received RCV or had unknown immunization history. National virological surveillance data showed that totally 22 RuV virus isolates were obtained, from 6 provinces in China during 2021-2022, which belonged to lineage 1E-L2 (11 strains) and 2B-L2c (11 strains). And these viruses displayed high genetic homology with RuV prevalent from 2018 to 2020.Conclusions:The incidence of rubella in China was maintained at a low level during 2021-2022, and the prevalent RuV strains were lineage 1E-L2 and 2B-L2c.

Objective:To analyze the epidemiological characteristics of respiratory virus infections in Sichuan from 2017 to 2023, and investigate the changes in detection rates of various viruses in different periods and age groups.Methods:The study included 41 516 patients with acute respiratory infections. Clinical laboratory results of these patients were retrospectively collected to calculate the detection rates of various viruses. The epidemiological characteristics of respiratory virus infections before, during, and after the COVID-19 pandemic, the prevalence of mixed infections, and the detection rates in different seasons and age groups were analyzed.Results:The overall detection rate of respiratory viruses was 23.35% (9 696/41 516), with influenza A virus (8.47%, 3 515/41 516), rhinovirus (7.13%, 2 961/41 516), and influenza B virus (2.04%, 846/41 516) being the most prevalent. The highest detection rate was observed in children aged 0-14 years (48.62%, 1 429/2 939), while the detection rates in young, middle-aged, and elderly individuals were similar [21.00% (1 482/7 057), 22.06% (3 828/17 350), 20.33% (2 685/13 205)]. The detection rate of influenza A virus dropped to 1.35% (253/18 717) during the COVID-19 pandemic, and rebounded to 13.05% (1 560/11 953) after the pandemic. A similar pattern was observed in other viruses such as human metapneumovirus, influenza B virus, coronavirus, and respiratory syncytial virus, with significant reductions during the COVID-19 pandemic and subsequent increases that even exceeded pre-pandemic levels. The detection rates of adenovirus, bocavirus, and rhinovirus gradually decreased over time, while the prevalence of parainfluenza virus remained stable, indicating a less significant impact of COVID-19 on these viruses. Higher detection rates were observed in autumn (28.90%, 2 324/8 041) and winter (26.52%, 4 093/15 433) as compared to that in spring (17.61%, 1 848/10 494) and summer (18.96%, 1 431/7 548), suggesting significant seasonal impacts on virus detection rates ( P<0.001). This study identified 8 666 cases of single-virus infections, 948 double infections, 77 triple infections, and five quadruple infections. Co-infection of bocavirus and rhinovirus was the most common type of double infections (17.41%, 165/948), and 59.60% (565/948) of double infections involved rhinovirus. Conclusions:The overall detection rate of respiratory viruses is higher in autumn and winter than in spring and summer. The prevalence of some respiratory viruses such as influenza viruses decreases during the COVID-19 pandemic. People of different ages can develop multiple infections with rhinovirus being the most common in double infections.

Objective To discuss the application of mind map in self-management of elderly patients after receiving mitral valve transcatheter edge-to-edge repair(M-TEER).Methods A total of 66 patients,who underwent M-TEER at Nanjing Hospital of Nanjing Medical University from August 2021 to October 2022,were enrolled in this study.Using the envelope concealment method,a total of 66 data analysis samples were included in the analysis.There were 33 patients each in the study group and control group.Routine health education was adopted for the patients of the control group,while the responsible nurse conducted health education for the patients of the study group under the guidance of the mind map that was designed by a multidisciplinary specialized nurses.Results There was a significant difference in postoperative medication compliance between the study group and the control group(P＜0.05),i.e.the degree of compliance,including taking medicine on time,insisting on taking medicine and taking medicine as prescribed,in the study group was obviously higher than that in the control group.The postoperative 6-min walking test,which was regarded as one of the indicators of cardiac functions,in the study group was remarkably better than that in the control group,the difference was statistically significant(P＜0.05).The postoperative quality of life(including daily activity ability,frailty degree,social support,and incidence of hospitalization for heart failure within one year after treatment)in the study group was strikingly better than that in the control group(P＜0.05).Conclusion The use of mind map in self-management of elderly patients after receiving M-TEER can effectively improve the medication compliance of the patients after discharge,improve the quality of life of patients,and reduce the incidence of hospitalization due to heart failure.

Objective　To analyze the epidemiological characteristics, trends, risk factors, and pathogenic spectrum of adult diarrheal diseases in Xuhui District, Shanghai from 2017 to 2023, so as to provide scientific reference for pathogen monitoring and disease prevention and control of diarrheal diseases. Methods Samples of adult patients with diarrhea in sentinel hospitals of Xuhui District from 2017 to 2023 were collected, and nucleic acid detection of intestinal pathogens was conducted using real-time quantitative PCR. Thirty specimens were subjected to shotgun metagenomic next-generation sequencing (mNGS), with species identified as metagenomic positive pathogens at the level of genus or species by a threshold that at least one read per million of total reads identified by METAMIC. Pathogenic spectrum detected by qPCR and mNGS was listed and compared. Results A total of 1 265 adult diarrheal specimens were collected, showing a significant upward trend in pathogen positivity rates (χ2=23.493, P<0.05), peaking in 2023 at 64.9% (100/154). A higher incidence was found among males (52.9%, 669/1 265), with the primary affected age group being 26-45 years (51.8%, 655/1 265), and summer and autumn being peak seasons for infection (67.7%, 857/1 265). Most patients (72.3%, 914/1 265) sought medical attention within one day of onset. Before onset, 67.8% (858/1 265) of patients had eaten suspicious meat, eggs, dairy, or seafood products. qPCR results revealed the top three dominant pathogens as Norovirus GII (22.6%, 132/584), Campylobacter jejuni (20.0%, 117/584 ), and enterotoxigenic Escherichia coli (13.0%, 76/584). There were significant differences in pathogenic spectrum across different years (χ2=79.578, P<0.05), with enteroaggregative E. coli, Campylobacter jejuni, and Norovirus GII showing the most variation in prevalence. The difference in pathogenic spectrum detected by mNGS and qPCR was also significant (P<0.05), with the top three most abundant pathogens being Rotavirus (93.3%, 28/30), Vesiculovirus (83.3%, 25/30), and Herpesvirus (80.0%, 24/30). Factor analysis indicated that age, suspicious food, and fever were statistically significant related factors to the detection rates (P<0.05). Conclusions From 2017 to 2023, the overall positive rate of adults with diarrhea in Xuhui District exhibited an increasing trend. Summer and autumn were the peak infection seasons, with viruses predominantly detected in summer and bacteria in both summer and autumn. In addition, mNGS could be used as a complementary technology for conventional detection techniques to provide a scientific basis for the effective prevention and control of diarrhea.

Objective To prepare and identify rabbit anti-cyclin dependent kinase 6 (CDK6) antibody. Methods The recombinant pET21a (+)/CDK6 was successfully constructed, then the recombinant plasmid was transformed into E.coli BL21 (DE3) competent cells and was induced by isopropyl-β-D-thiogalactopyranoside (IPTG) for protein expression, which was detected by SDS-PAGE and Western blot analysis. The expressed protein was purified by nickel-chelating nitrilotriacetic acid (Ni-NTA) agarose and then analyzed by SDS-PAGE. Japanese white rabbits were immunized with purified CDK6 protein for many times every two weeks. The blood was collected at 0, 2, 4 and 6 weeks after immunization, and serum was separated from blood. The titer was detected by indirect ELISA. Western blot analysis, immunofluorescence assay and immunohistochemistry were employed to determine the specificity. Results High purity CDK6 protein and high specificity of rabbit anti-CDK6 antibody were successfully prepared. The titer of CDK6 rabbit serum antibody reached 1:30 000 after immunization, which could specifically recognize the CDK6 protein expressed in cervical cancer cell line and cervical cancer tissues. Conclusion The high titer and specificity of rabbit anti-CDK6 antibody is successfully prepared.
Animals ; Female ; Humans ; Rabbits ; Antibodies ; Antibody Specificity ; Blotting, Western ; Cyclin-Dependent Kinase 6 ; Enzyme-Linked Immunosorbent Assay ; Uterine Cervical Neoplasms

In the context of non-alcoholic fatty liver disease (NAFLD), characterized by dysregulated lipid metabolism in hepatocytes, the quest for safe and effective therapeutics targeting lipid metabolism has gained paramount importance. Sanhuang Xiexin Tang (SXT) and Baihu Tang (BHT) have emerged as prominent candidates for treating metabolic disorders. SXT combined with BHT plus Cangzhu (SBC) has been used clinically for Weihuochisheng obese patients. This retrospective analysis focused on assessing the anti-obesity effects of SBC in Weihuochisheng obese patients. We observed significant reductions in body weight and hepatic lipid content among obese patients following SBC treatment. To gain further insights, we investigated the effects and underlying mechanisms of SBC in HFD-fed mice. The results demonstrated that SBC treatment mitigated body weight gain and hepatic lipid accumulation in HFD-fed mice. Pharmacological network analysis suggested that SBC may affect lipid metabolism, mitochondria, inflammation, and apoptosis-a hypothesis supported by the hepatic transcriptomic analysis in HFD-fed mice treated with SBC. Notably, SBC treatment was associated with enhanced hepatic mitochondrial biogenesis and the inhibition of the c-Jun N-terminal kinase (JNK)/nuclear factor-kappa B (NF-κB) and extracellular signal-regulated kinase (ERK)/NF-κB pathways. In conclusion, SBC treatment alleviates NAFLD in both obese patients and mouse models by improving lipid metabolism, potentially through enhancing mitochondrial biogenesis. These effects, in turn, ameliorate inflammation in hepatocytes.
Humans ; Mice ; Animals ; Non-alcoholic Fatty Liver Disease/metabolism* ; NF-kappa B/metabolism* ; Organelle Biogenesis ; Retrospective Studies ; Mice, Inbred C57BL ; Obesity/metabolism* ; Liver ; Inflammation/metabolism* ; Body Weight ; Lipid Metabolism ; Lipids ; Diet, High-Fat/adverse effects*

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 analyze the evolutionary characteristics and variation of etiological agent in an acute hemorrhagic conjunctivitis (AHC) outbreak in a city of Guangdong province in May, so as to provide scientific basis for formulating a new round of measures for prevention and control of AHC epidemic.Methods:In this study, 20 conjunctival swabs were collected from AHC patients, and enterovirus, human enterovirus 70 (HEV70) and coxsackievirus A 24 variant (CVA24v) nucleic acids were detected by real-time fluorescence quantitative PCR. In addition, the VP1 and 3Cpro regions of the CVA24v positive samples were sequenced to analyze their evolutionary relationship with the CVA24v strains circulating in China and abroad.Results:All the 20 eye swab samples were EV-positive, and CVA24v-positive, with a positive rate of 100.00%, and all were HEV70-negative.The genomes of CVA24v in VP1 and 3Cpro regions of CVA24v in 5 and 7 samples were successfully sequenced. Based on molecular characterization analysis of VP1 and 3Cpro regions, it was found that the CVA24v isolated in this outbreak had the greatest nucleotide similarity with the CVA24v strains isolated in Thailand in 2014 and French Reunion Islands in 2015. The phylogenetic analysis of 3Cpro and VP1 regions showed that the CVA24v isolated in this outbreak is clustered together with the CVA24v that was prevalent in Thailand in 2014 and the French Reunion Islands in 2015, and have high affinity. Compared with CVA24v isolated in Guangdong in 2010, Thailand in 2014, and French Reunion Islands in 2015, CVA24v isolated in this outbreak was replaced at 4 amino acid sites in 3Cpro region and 1 amino acid site in VP1 region.Conclusions:The cause of this outbreak is enterovirus CVA24v, which has the highest similarity to CVA24v isolated in Thailand in 2014 and in the French Reunion Islands in 2015. There were new amino acid mutations in both 3Cpro and VP1 regions.