The lymphatic system, as well as pathological changes of the lymphatic system, underlies the progress of an array of diseases and conditions, including cancer, inflammation and autoimmune disorders, infectious diseases and metabolic syndrome. A variety of biological targets in the lymphatic system can be employed to modulate these high-burden diseases, and the pharmacokinetics and drug delivery strategies in the context of lymphatics are of critical importance to optimise drug exposure to lymphatic-related targets. As such, research and drug development in this field has gained increasing attention in recent years. This article aims to provide an overview of pharmaceutical research with a focus on the lymphatic system and therapeutic targets within the lymphatics, followed by lymphatic drug delivery approaches, which may be of interest for researchers in academia, pharmaceutical industry and regulatory sciences.

Digital intraoral scanning is a hot topic in the field of oral digital technology.In recent years,digital intra-oral scanning has gradually become the mainstream technology in orthodontics,prosthodontics,and implant dentistry.The precision of digital intraoral scanning and the accuracy and stitching of data collection are the keys to the success of the impression.However,the operators are less familiar with the intraoral scanning characteristics,imaging process-ing,operator scanning method,oral tissue specificity of the scanned object,and restoration design.Thus far,no unified standard and consensus on digital intraoral scanning technology has been achieved at home or abroad.To deal with the problems encountered in oral scanning and improve the quality of digital scanning,we collected common expert opin-ions and sought to expound the causes of scanning errors and countermeasures by summarizing the existing evidence.We also describe the scanning strategies under different oral impression requirements.The expert consensus is that due to various factors affecting the accuracy of digital intraoral scanning and the reproducibility of scanned images,adopting the correct scanning trajectory can shorten clinical operation time and improve scanning accuracy.The scanning trajec-tories mainly include the E-shaped,segmented,and S-shaped methods.When performing fixed denture restoration,it is recommended to first scan the abutment and adjacent teeth.When performing fixed denture restoration,it is recommend-ed to scan the abutment and adjacent teeth first.Then the cavity in the abutment area is excavated.Lastly,the cavity gap was scanned after completing the abutment preparation.This method not only meets clinical needs but also achieves the most reliable accuracy.When performing full denture restoration in edentulous jaws,setting markers on the mucosal tissue at the bottom of the alveolar ridge,simultaneously capturing images of the vestibular area,using different types of scanning paths such as Z-shaped,S-shaped,buccal-palatal and palatal-buccal pathways,segmented scanning of dental arches,and other strategies can reduce scanning errors and improve image stitching and overlap.For implant restora-tion,when a single crown restoration is supported by implants and a small span upper structure restoration,it is recom-mended to first pre-scan the required dental arch.Then the cavity in the abutment area is excavated.Lastly,scanning the cavity gap after installing the implant scanning rod.When repairing a bone level implant crown,an improved indi-rect scanning method can be used.The scanning process includes three steps:First,the temporary restoration,adjacent teeth,and gingival tissue in the mouth are scanned;second,the entire dental arch is scanned after installing a standard scanning rod on the implant;and third,the temporary restoration outside the mouth is scanned to obtain the three-di-mensional shape of the gingival contour of the implant neck,thereby increasing the stability of soft tissue scanning around the implant and improving scanning restoration.For dental implant fixed bridge repair with missing teeth,the mobility of the mucosa increases the difficulty of scanning,making it difficult for scanners to distinguish scanning rods of the same shape and size,which can easily cause image stacking errors.Higher accuracy of digital implant impres-sions can be achieved by changing the geometric shape of the scanning rods to change the optical curvature radius.The consensus confirms that as the range of scanned dental arches and the number of data concatenations increases,the scanning accuracy decreases accordingly,especially when performing full mouth implant restoration impressions.The difficulty of image stitching processing can easily be increased by the presence of unstable and uneven mucosal mor-phology inside the mouth and the lack of relatively obvious and fixed reference objects,which results in insufficient ac-curacy.When designing restorations of this type,it is advisable to carefully choose digital intraoral scanning methods to obtain model data.It is not recommended to use digital impressions when there are more than five missing teeth.

Objective:To investigate the effect of estrogen-related receptor α (ESRRA)-mediated lipophagy on the proliferation and migration abilities of nasopharyngeal carcinoma cells.Methods:A total of 16 clinical samples diagnosed by pathology in the Affiliated Hospital of Nantong University from 2021 to 2023 were selected, including 8 normal nasopharyngeal mucosa tissues and 8 nasopharyngeal carcinoma tissues. Immortalized normal nasopharyngeal epithelial cell line NP69 and nasopharyngeal carcinoma cell lines C666-1, CNE2, TW03-EBV and TW03 were selected. The cell lines C666-1 and CNE2 were divided into the siR-NC group (transfected with small interfering RNA negative control sequence) and siR-ESRRA group (transfected with small interfering RNA against ESRRA gene). The relative expression levels of ESRRA were detected by Western blotting and immunohistochemical assay. EdU assay was used to detect the proliferation ability of C666-1 and CNE2 cells, and Transwell assay was used to detect the migration ability. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the relative expression levels of ESRRA and perilipin 3 (PLIN3) mRNA. The formation of lipophagy in C666-1 and CNE2 cells was observed by transmission electron microscopy. The co-localization of LC3, PLIN3 and LAMP2 with lipid droplets labeling with Bodipy was detected by immunofluorescence assay. Dual-luciferase reporter gene assay was used to verify the targeting relationship between ESRRA and PLIN3.Results:The relative expression level of ESRRA in nasopharyngeal carcinoma tissues was higher than that in normal nasopharyngeal mucosa tissues(1.15±0.75 vs. 0.32±0.21, t = 3.02, P = 0.009). The relative expression level of ESRRA in nasopharyngeal carcinoma cell lines C666-1 (1.539±0.044), CNE2 (1.420±0.030), TW03-EBV (2.867±0.044), and TW03 (1.323±0.022) were higher than that in normal nasopharyngeal epithelial cell line NP69 (0.094±0.002), and the difference was statistically significant ( F = 34.08, P < 0.001).The results of EdU assay showed that the proportions of EdU labeled positive cells in CNE2 cells of siR-NC group and siR-ESRRA group were (70.44±4.06)% and (51.51±0.92)% ( t = 7.88, P = 0.001), and the proportions in C666-1 cells were (62.25±3.89)% and (54.91±0.27)% ( t = 3.26, P = 0.031). The results of Transwell assay showed that the number of migrating cells in CNE2 and C666-1 cells was less than that in siR-NC group [CNE2 cells: (181±7) cells vs. (261±21) cells; C666-1 cells: (201±16) cells vs. (256±7) cells], and the differences were statistically significant ( t = 6.30, P = 0.003; t = 5.43, P = 0.006). According to qRT-PCR results, the relative expression level of PLIN3 mRNA in the siR-ESRRA group was higher than that in the siR-NC group (CNE2 cells: 1.58±0.16 vs. 0.83±0.17, t = 5.59, P = 0.005; C666-1 cells: 1.37±0.12 vs. 1.06±0.06, t = 3.86, P = 0.018). The dual-luciferase reporter gene assay results indicated a targeted binding interaction between PLIN3 and ESRRA. Transmission electron microscopy observation showed that the lipid droplets in nasopharyngeal carcinoma cells increased and the binding to autophagosomes decreased after knockdown of ESRRA. The results of immunofluorescence assay demonstrated that, in contrast to the siR-NC group, there was a decrease in the co-localization of LC3 and LAMP2 and an increase in the co-localization of lipid droplets with PLIN3. Conclusions:ESRRA is highly expressed in nasopharyngeal carcinoma tissues and cells. As a transcription repressor, ESRRA may work to prevent PLIN3 from being transcribed, decrease lipid droplet stability, mediate lipophagy, and promote proliferation and migration of nasopharyngeal carcinoma cells.

There is still a lack of experience in the perioperative strategy for esophageal cancer patients in China during the epidemic of COVID-19. In December 2022, a 59-year-old male patient with esophageal cancer was admitted to our department. He received 2 cycles of neoadjuvant therapy before surgery, and developed COVID-19 perioperatively. After treatment, the infection symptoms of the patient were improved, and the postoperative recovery was satisfactory.

Background: Lac color, a natural red dye derived from the larvae of laccifer lacca kerr, is one of the most commonly used substances in food. To date, no studies have reported on the antigenicity of lac color and the other biomarkers that can determine anaphylactic reactions. To address this, we evaluated the antigenicity of lac color through active systemic anaphylaxis (ASA) in addition to identifying potential biomarkers performing exploratory studies. For ASA test, Guinea pigs (n = 5) were sensitized with 0(negative control), 4 mg/kg of lac color, 4 mg/kg of lac color + FCA, and 5 mg/kg of ovalbumin + FCA (positive control) 3 times a week for three weeks. Fourteen days after the last sensi‑ tization, animals were challenged intravenously weekly for two weeks. Hematological and histopathological analyses were performed and compared to control groups. Results: In the ASA test, all lac color groups showed mild symptoms such as nose rubbing, urination, and evacuation, which are insufficient indicators of anaphylaxis. Exploratory studies identified several biomarkers: decreased platelet count, and increased basophil count; distention in the lung, and redness on the inner wall of trachea; mononuclear inflammatory cell infiltration (MICI) in the ear, and heart hemorrhage. When these biomarkers were applied to the ASA test of lac color, in comparison to the negative control group, the positive control group (ovalbumin + FCA) showed a significant over 60-fold reduction in platelet count and nearly threefold higher basophil count compared to other groups. Furthermore, only positive control group exhibited full lung distention and severe redness on the inner wall of the trachea. Mononuclear inflammatory cell infiltration (MICI) in the ear was about three times higher, and heart hemorrhage was only present in the positive control group compared to others. None of the lac color groups were different from the negative control group (p > 0.05), whereas the positive control group was significantly different (p < 0.05). Conclusions Our study concludes that lac color, at the tested concentrations, does not induce antigenicity in the guinea pig model, providing valuable safety data. Furthermore, the biomarkers identified in this study offer a supportive approach to evaluating the immunogenicity of substances in future research.

Background: Diabetic nephropathy (DN) is a progressive complication among patients with diabetes and the most common cause of end-stage kidney disease. Neutrophil extracellular traps (NETs) are known to play a role in kidney disease, thus this study aimed to determine their role in the development of diabetic kidney disease using diabetic murine models. Results: Protein and histological analyses revealed that db/db mice and streptozotocin DN models expressed no significant NET-related proteins, myeloperoxidase, citrullinated histone H3 (citH3), neutrophil elastase, and lymphocyte antigen 6 complex locus G6D (Ly6G). However, the inflamed individuals in the DN model showed that citH3 and Ly6G were highly deposited in the renal system based on immunohistochemistry images. In vitro, NET treatment did not induce apoptosis in glomerular endothelial and renal tubular epithelial cells. NET inhibition by DNase administration demonstrated no significant changes in cell apoptosis. Conclusions NET-related proteins were only expressed in the DN model with tubulointerstitial inflammation. Our study revealed that NETs are only induced in mice with hyperglycemia-induced inflammation.

Objective:To elucidate the cytopathological characteristics,molecular subtypes,and clinical prognoses of metastatic breast car-cinoma with serosal effusions.Methods:Seventeen cases that included effusion cytology and clinical data were retrospectively analyzed.Two patients were diagnosed between April 2016 and September 2023 at the Suzhou Ninth Hospital Affiliated to Soochow University,and 15 patients were diagnosed at The First Affiliated Hospital of Soochow University.Cytopathological characteristics,molecular subtypes,and prognoses were analyzed.Results:The cytopathological features of metastatic breast carcinoma in serosal effusions were as follows:1)In-vasive ductal carcinoma:one cell type was relatively densely arranged in nests or colored spheres,which displayed an elevated nuclear/cyto-plasmic ratio,irregular nuclear membrane,and cytoplasmic mucin vacuoles.The other cell type was tiled,single scattered,and varied in size and shape,with enlarged nuclei and elevated nuclear/cytoplasmic ratio.2)Invasive lobular carcinoma:cells were scattered and uniform in size and shape.The nuclei had a relatively regular shape,but displayed an elevated nuclear-to-cytoplasmic ratio.Among the 17 breast can-cer cases,6 had transitioned in molecular subtyping,including 1 case from Luminal A to triple-negative type,1 case from Luminal B to hu-man epidermal growth factor receptor 2(HER-2)-overexpressing type,and 4 cases from Luminal B to triple-negative type.Conclusions:The cytopathological characteristics of serous effusion cells combined with immunocytochemical staining and fluorescence in situ hybridization(FISH)suggest that it is important to determine the origin and molecular typing of tumor cells.This provides an important basis for precise clinical treatment and prognosis.

As a novel tumor treatment,photodynamic therapy(PDT)has been widely used in clinical treatment of a variety of tumors due to its advantages,such as fewer adverse reactions,precise targeting and repeatability of treatment.Unlike conventional treatments,such as surgery,chemotherapy and radiotherapy,PDT not only eliminates the primary tumor but also effectively inhibits metastatic tumors by activating the body's immune response.However,the PDT-activated immune response is influenced by multiple factors,including the localization and dose of photosensitizer in the cells,light parameters,oxygen concentration in the tumor,and the integrity of immune function.This review summarizes the mechanisms behind the PDT-activated anti-tumor immune response,systematically examines the key influencing factors on the immune effect of PDT,and discusses the future development direction of PDT in cancer treatment.

Aim To establish a gait analysis system based on DeepLabCut(DLC)algorithm for evaluating motor function in aged mice.Methods Based on DLC algorithm in deep learning technology,treadmill device and fully closed design were used in the system,including software and hardware.This system was applied to evaluate gait characteristics of mice due to aging un-der different movement modes.Correlation analysis was used to explore the effects of body weight and body length on gait indica-tors.Results This system realized the synchronous analysis of three-dimensional gait(lateral and ventral plane)of mice at specific gait speed,and automatically quantified 47 gait indica-tors.Using this system,it was found that during walking(15 cm·s-1),the standard deviation of body turning angle decreased,forelimb sway duration,standard deviation of knee angle,mean outward angles of left and right hind paw increased in 8 and 15 month-old mice,compared with 2-month-old mice.However,15-month-old mice showed decreased walking frequency,and in-creased stride width,total duration of double support,and knee extension and contraction distance.In addition,at trot(20 cm·s-1),15-month-old mice were unable to walk steadily,and 8-month-old mice had increased total duration of double support and mean outward angles of left hind paw,compared with 2-month-old mice.Correlation analysis revealed that indicators like walking frequency,stride width,forelimb sway duration,total duration of double support,standard deviation of knee an-gle,knee extension and contraction distance,were not affected by changes in body weight and body length.Conclusions The gait analysis system based on DLC algorithm can achieve a more sensitive,accurate and comprehensive evaluation of the gait of aged mice,distinguishing the gait characteristics of aged mice to maintain gait stability,and selecting behavioral indicators that better reflect the gait changes of aged mice.It provides a meth-odological basis for more effective assessment of efficacy and side effects of drugs for anti-aging and anti-decline of motor coordina-tion in the future.

Objective:To observe the effect of warming needle therapy combined with Tuina(Chinese therapeutic massage)on the clinical symptoms and anxiety state of patients with cervical vertigo accompanied by anxiety. Methods:Seventy patients with cervical vertigo accompanied by anxiety state were divided into an observation group and a control group using the random number table method,with 35 patients in each group.In addition to disease education,the observation group was treated with warming needle therapy and Tuina 3 times a week,and the control group was treated with betahistine mesylate tablets orally 3 times a day.Both groups were treated for 4 weeks.The changes in the scores of the evaluation scale for cervical vertigo(ESCV),self-rating anxiety scale(SAS),and Hamilton anxiety rating scale(HAMA)were compared between the two groups after treatment. Results:One case in the observation group dropped out due to failure to cooperate with the treatment during the study.In the treatment group,the total effective rate and the cured plus markedly effective rate were 94.1%and 50.0%,respectively,and 88.6%and 8.6%in the control group,respectively;the differences between the two groups were statistically significant(P<0.05).After treatment,the ESCV,SAS,and HAMA scores of both groups decreased significantly compared with those before treatment(P<0.01),and the scores of the observation group were lower than those of the control group(P<0.01 or P<0.05). Conclusion:Warming needle therapy combined with Tuina can significantly improve the clinical symptoms of patients with cervical vertigo accompanied by anxiety state.