Objective: To understand the status and influencing factors of loss to follow-up among HIV/AIDS cases in Gulou District, Nanjing City, so as to provide evidence for optimizing the follow-up management of HIV/AIDS cases. Methods: Reporting information and follow-up data of HIV/AIDS cases in Gulou District from January 1, 1994, to July 31, 2025, were collected through the HIV/AIDS Comprehensive Control System of Chinese Disease Prevention and Control Information System. The confirmed date of HIV/AIDS diagnosis was defined as the start of follow-up observation, and July 31, 2025, as the end of observation , with loss to follow-up as the outcome event. Factors affecting loss to follow-up among HIV/AIDS cases were analyzed using a multivariable Cox proportional risk regression model. Results: A total of 1 279 HIV/AIDS cases were observed from January 1, 1994, to July 31, 2025, with a total observation period of 8 834.23 person-years. There were 1 198 males (93.67%) and 81 females (6.33%). The median age was 32.00 (interquartile range, 20.00) years. There were 848 HIV-infected individuals (66.30%) and 431 AIDS patients (33.70%). As of July 31, 2025, 152 cases were lost to follow-up, with a loss to follow-up density of 17.21 thousand person-years and a cumulative loss to follow-up rate of 11.88%. Multivariable Cox proportional risk regression analysis showed that HIV/AIDS cases with non-Jiangsu household registration (HR=1.721, 95%CI: 1.212-2.444), passive testing (HR=2.031, 95%CI: 1.346-3.065), and heterosexual transmission (HR=2.542, 95%CI: 1.669-3.872) had a higher risk of loss to follow-up, whereas those who were married/with a spouse (HR=0.432, 95%CI: 0.283-0.661), AIDS patients (HR=0.152, 95%CI: 0.085-0.271), reported by general hospitals (HR=0.382, 95%CI: 0.226-0.645) or Centers for Disease Control and Prevention (HR=0.505, 95%CI: 0.323-0.790) had a lower risk of loss to follow-up. Conclusions The risk of loss to follow-up among HIV/AIDS cases was mainly associated with residence, marital status, HIV/AIDS stage, reporting institution, case detection method, and route of infection. Cases at high risk of loss to follow-up should be prioritized, and follow-up mana gement should be strengthened to reduce the occurrence of loss to follow-up.

Serine protease inhibitor Kazal-type (SPINK) is a skin keratinizing protease inhibitor, which was initially found in animal serum and is widely present in plants, animals, bacteria, and viruses, and they act as key regulators of skin keratinizing proteases and are involved in the regulation of keratinocyte proliferation and inflammation, primarily through the inhibition of deregulated tissue kinin-releasing enzymes (KLKs) in skin response. This process plays a crucial role in alleviating various skin problems caused by hyperkeratinization and inflammation, and can greatly improve the overall condition of the skin. Specifically, the different members of the SPINK family, such as SPINK5, SPINK6, SPINK7, and SPINK9, each have unique biological functions and mechanisms of action. The existence of these members demonstrates the diversity and complexity of skin health and disease. First, SPINK5 mutations are closely associated with the development of various skin diseases, such as Netherton’s syndrome and atopic dermatitis, and SPINK5 is able to inhibit the activation of the STAT3 signaling pathway, thereby effectively preventing the metastasis of melanoma cells, which is important in preventing the invasion and migration of malignant tumors. Secondly, SPINK6 is mainly distributed in the epidermis and contains lysine and glutamate residues, which can act as a substrate for epidermal transglutaminase to maintain the normal structure and function of the skin. In addition, SPINK6 can activate the intracellular ERK1/2 and AKT signaling pathways through the activation of epidermal growth factor receptor and protease receptor-2 (EphA2), which can promote the migration of melanoma cells, and SPINK6 further deepens its role in stimulating the migration of malignant tumor cells by inhibiting the activation of STAT3 signaling pathway. This process further deepens its potential impact in stimulating tumor invasive migration. Furthermore, SPINK7 plays a role in the pathology of some inflammatory skin diseases, and is likely to be an important factor contributing to the exacerbation of skin diseases by promoting aberrant proliferation of keratinocytes and local inflammatory responses. Finally, SPINK9 can induce cell migration and promote skin wound healing by activating purinergic receptor 2 (P2R) to induce phosphorylation of epidermal growth factor and further activating the downstream ERK1/2 signaling pathway. In addition, SPINK9 also plays an antimicrobial role, preventing the interference of some pathogenic microorganisms. Taken as a whole, some members of the SPINK family may be potential targets for the treatment of dermatological disorders by regulating multiple biological processes such as keratinization metabolism and immuno-inflammatory processes in the skin. The development of drugs such as small molecule inhibitors and monoclonal antibodies has great potential for the treatment of dermatologic diseases, and future research on SPINK will help to gain a deeper understanding of the physiopathologic processes of the skin. Through its functions and regulatory mechanisms, the formation and maintenance of the skin barrier and the occurrence and development of inflammatory responses can be better understood, which will provide novel ideas and methods for the prevention and treatment of skin diseases.

Objective To investigate the potential mechanism of action of polygonatum odoratum in treating Alzheimer's disease through the utilization of network pharmacology and molecular docking techniques.Methods The methods employed include target screening,Gene Ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,and molecular docking simulations to assess the binding interactions between the active compounds in polygonatum odoratum(POD)and the key target proteins associated with Alzheimer's disease.Subsequently,lipopolysaccharide(LPS)was used to induce an inflammatory cell model in BV2 microglial cells.After treating the cell model with POD extract for 24 hours,the cells were collected,and the expression of the target genes were detected by Real-time PCR.Results Eight active ingredients and 172 targets of POD were screened.The biological processes such as protein phosphorylation and signal transduction,protein binding and ATP binding were obtained by GO functional analysis.KEGG enrichment yielded PI3K/Akt,cAMP and other signaling pathways.The molecular docking result showed that the active ingredient of POD had well binding activity with epidermal growth factor receptor(EGFR),proto-oncogene tyrosine-protein kinase Src(SRC),tumor necrosis factor(TNF),STAT3.Through Real-time PCR experiments,the gene expressions of inducible nitric oxide synthase(iNOS),prostaglandin G/H synthase 2(PTGS2),interleukin(IL)-6,and IL-1β in the LPS-induced inflammatory cell model were significantly upregulated.After treating the inflammatory model with POD extract for 24 hours,the expression of TNF-α was significantly reduced,the expression of STAT3 was upregulated,there were no significant changes in the expressions of SRC and EGFR.Conclusion Network pharmacology suggests polygonatum odoratum's potential anti-Alzheimer's effects may be mediated through its interaction with targets such as EGFR,TNF,SRC,and STAT3.The experimental results suggest that polygonatum odoratum exerts an anti-inflammatory effect by acting on TNF-α,which may further alleviate the symptoms of Alzheimer's disease.

In this experiment, self-assembled nanoparticles(SANs) were prepared by the pH-driven method, and Her-HCP SAN was constructed by using herpetrione(Her) and Herpetospermum caudigerum polysaccharides(HCPs). The average particle size and polydispersity index(PDI) were used as evaluation indexes for process optimization, and the quality of the final formulation was evaluated in terms of particle size, PDI, Zeta potential, and microstructure. The proposed Her-HCP SAN showed a spheroid structure and uniform morphology, with an average particle size of(244.58±16.84) nm, a PDI of 0.147 1±0.014 8, and a Zeta potential of(-38.52±2.11) mV. Her-HCP SAN significantly increased the saturation solubility of Her by 2.69 times, with a cumulative release of 90.18% within eight hours. The results of in vivo unidirectional intestinal perfusion reveal that Her active pharmaceutical ingredient(API) is most effectively absorbed in the jejunum, where both K_a and P_(app) are significantly higher compared to the ileum(P<0.001). However, the addition of HCP leads to a significant reduction in the P_(app) of Her in the jejunum(P<0.05). Furthermore, the formation of the Her-HCP SAN results in a notably lower P_(app) in the jejunum compared to Her API alone(P<0.001), while both K_a and P_(app) in the ileum are significantly increased(P<0.001, P<0.05). The absorption of Her-HCP SAN at different concentrations in the ileum shows no significant differences, and the pH has no significant effect on the absorption of Her-HCP SAN in the ileum. The addition of the transporter protein inhibitors(indomethacin and rifampicin) significantly increases the absorption parameters K_a and P_(app) of Her-HCP SAN in the ileum(P<0.05,P<0.01), whereas the addition of verapamil has no significant effect on the intestinal absorption parameters of Her-HCP SAN, suggesting that Her may be a substrate for multidrug resistance-associated protein 2 and breast cancer resistance proteins but not a substrate of P-glycoprotein.
Nanoparticles/metabolism* ; Polysaccharides/pharmacokinetics* ; Intestinal Absorption/drug effects* ; Animals ; Rats ; Particle Size ; Drugs, Chinese Herbal/pharmacokinetics* ; Male ; Rats, Sprague-Dawley ; Drug Carriers/chemistry* ; Drug Compounding ; Cucurbitaceae/chemistry*

Eight butyl-phthalides, senkyunolide K(1), senkyunolide N(2), butylphthalide(3), senkyunolide I(4), senkyunolide H(5),(Z)-butylidenephthalide(6),(Z)-ligustilide(7), and 3-butylidene-7-hydroxyphthalide(8) were isolated from the aerial part of Ligusticum sinense by column chromatography on silica gel column, ODS, Sephadex LH-20 and semi-preparative HPLC. Their structures were elucidated on the basis of spectroscopic and chemical data, especially NMR and MS. Compound 1 was a new butyl-phthalide and compounds 2-8 were isolated from the aerial part of L. sinense for the first time. Furthermore, the inhibitory activities of compounds 1-8 against the nitric oxide(NO) production induced by lipopolysaccharide(LPS) in mouse RAW264.7 macrophages in vitro were evaluated. The results showed that compounds 1-8 exerted inhibitory activities on NO production with IC_(50) of 19.34-42.16 μmol·L~(-1).
Animals ; Mice ; Nitric Oxide/biosynthesis* ; Ligusticum/chemistry* ; Benzofurans/isolation & purification* ; Drugs, Chinese Herbal/isolation & purification* ; Macrophages/immunology* ; RAW 264.7 Cells ; Molecular Structure

This study aimed to explore the pharmacological mechanism of Yourenji Capsules(YRJ) in improving osteoporosis by combining network pharmacology and proteomics technologies. The SD rats were randomly divided into a blank control group and a 700 mg·kg~(-1) YRJ group. The rats were subjected to gavage administration with the corresponding drugs, and the blank serum, drug-containing serum, and YRJ samples were compared using ultra performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS) to analyze the main components absorbed into blood. Network pharmacology analysis was conducted based on the YRJ components absorbed into blood to obtain related targets of the components and target genes involved in osteoporosis, and Venn diagrams were used to identify the intersection of drug action targets and disease targets. The STRING database was used for protein-protein interaction(PPI) network analysis of potential target proteins to construct a PPI network. Gene Ontology(GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment were performed using Enrichr to investigate the potential mechanism of action of YRJ. Ovariectomy(OVX) was performed to establish a rat model of osteoporosis, and the rats were divided into a sham group, a model group, and a 700 mg·kg~(-1) YRJ group. The rats were given the corresponding drugs by gavage. The femurs of the rats were subjected to label-free proteomics analysis to detect differentially expressed proteins, and GO functional enrichment and KEGG pathway enrichment analyses were performed on the differentially expressed proteins. With the help of network pharmacology and proteomics results, the mechanism by which YRJ improves osteoporosis was predicted. The analysis of the YRJ components absorbed into blood revealed 23 bioactive components of YRJ, and network pharmacology results indicated that key targets involved include tumor necrosis factor(TNF), tumor protein p53(TP53), protein kinase(AKT1), and matrix metalloproteinase 9(MMP9). These targets are mainly involved in osteoclast differentiation, estrogen signaling pathways, and nuclear factor-kappa B(NF-κB) signaling pathways. Additionally, the proteomics analysis highlighted important pathways such as peroxisome proliferator-activated receptor(PPAR) signaling pathways, mitogen-activated protein kinase(MAPK) signaling pathways, and β-alanine metabolism. The combined approaches of network pharmacology and proteomics have revealed that the mechanism by which YRJ improves osteoporosis may be closely related to the regulation of inflammation, osteoblast, and osteoclast metabolic pathways. The main pathways involved include the NF-κB signaling pathways, MAPK signaling pathways, and PPAR signaling pathways, among others.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Osteoporosis/metabolism* ; Proteomics ; Rats ; Rats, Sprague-Dawley ; Network Pharmacology ; Female ; Protein Interaction Maps/drug effects* ; Capsules ; Humans ; Signal Transduction/drug effects*

By reconstructing the integrated Chinese and western medicine diagnostic and treatment system， the "Two Reconstructions" theoretical framework establishes a standardized pathway of "classification-staging-syndrome differentiation"， which improves the accuracy of disease identification and strengthens the capacity for full-course intervention； in addition， by reconstructing the modern materia medica system， it innovatively integrates the traditional properties and efficacy of Chinese herbal medicinals with modern pharmacological mechanisms， forming a "state-target co-regulation" precise medication model， and builds a dose-effect theoretical system for prescriptions and medicinals， thereby enhancing both the targeting accuracy and dosage precision of therapeutic interventions. The "Two Reconstructions" theorecitcal framework is a key strategy for enhancing clinical efficacy. It can precisely identify "states" and "targets" for directed intervention， shift the focus of prevention and treatment earlier to enable full-cycle management， establish standardized paradigms for reproducible and evaluable efficacy， and expand the scope of clinical practice to address conditions without typical syndromes and critical illnesses. As a systematic pathway for innovation in TCM， this theoretical framework provides valuable insights and references for promoting the high-quality development of integrative Chinese and western medicine.

Objective:To analyze the incidence of pregnancy complications and maternal-neonatal outcomes in women with a history of preconception metabolic and bariatric surgery (MBS).Methods:This study was a retrospective cohort study. Pregnant women with singleton pregnancy who delivered in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, from September 2019 to December 2024 were selected as the observation subjects. After propensity score matching, 42 women in the MBS group and 157 women in the control group were finally included. The general clinical characteristics, pregnancy status and maternal-neonatal outcomes of the two groups were compared and analyzed.Results:(1) There were no statistically significant differences in the age, proportion of preconception obesity, chronic hypertension, preconception diabetes and primipara between the MBS group and the control group (all P>0.05). The median interval between surgery and pregnancy of pregnant women in the MBS group was 14.0 months (6.0, 27.5 months). Twenty-nine pregnant women (69%, 29/42) were pregnant after 1 year of surgery, and 13 pregnant women (31%, 13/42) were pregnant within 1 year. (2) The levels of hemoglobin, serum iron and triglyceride in the MBS group were significantly lower than those in the control group in the second and third trimester (all P<0.05), but there were no statistically significant differences in the levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total cholesterol and albumin between the two groups (all P>0.05). (3) Compared with the control group, the incidence of gestational diabetes mellitus in MBS group [21.7% (34/157) vs 7.1% (3/42)] and the proportion of large for gestational age [23.6% (37/157) vs 2.4% (1/42)] were lower; the incidence of anemia [6.4% (10/157) vs 33.3% (14/42)], fetal growth restriction [7.0% (11/157) vs 23.8% (10/42)] and small for gestational age [3.8% (6/157) vs 19.0% (8/42)] were higher; the differences were statistically significant (all P<0.05). There were no significant differences in the cesarean section rate, premature rupture of membranes rate, postpartum hemorrhage ≥1 000 ml rate, gestational age at delivery and preterm birth rate between the two groups (all P>0.05). The neonatal birth weight of the MBS group was significantly lower than that of the control group [(3 044±523) vs (3 256±491) g, P=0.016], but the proportion of neonates with 1-minute Apgar score<7 and the rate of neonatal intensive care unit admission were not statistically significant (all P>0.05). Conclusions:Women who got pregnant after MBS had lower neonatal weight, decreased incidence of gestational diabetes mellitus and large for gestational age, but higher incidence of small for gestational age and anemia in late pregnancy. It is necessary to focus on the nutritional management of pregnant women with MBS before pregnancy, improve anemia, and strengthen the ultrasound follow-up of fetal growth to optimize the perinatal outcome.

Hepatocellular carcinoma (HCC) is a prevalent malignant tumor that poses a significant threat to public health. Advances in medical science and increased screening awareness have improved early-stage diagnosis rates, allowing more patients to undergo radical treatment at initial diagnosis. Concurrently, ongoing developments in treatment modalities have expanded the options available for both patients and clinicians. The challenge now lies in making informed decisions to achieve individualized precision medicine, which merits thorough exploration. This article aims to review the latest research on personalized treatment strategies for early-stage HCC, providing a reasonable reference and valuable insights for clinicians.

The liver is the most common anatomical site for hematogenous metastases of colorectal cancer. Hepatic resection is the preferred treatment for colorectal cancer liver metastasis (CRLM). However, a disappointingly small proportion of patients are deemed suitable for surgical resection upon initial consultation. Failure to adequately address these metastatic tumors results in a dire 5-year survival rate of less than 5%. In recent times, thermal ablation, a minimally invasive procedure aimed at controlling local tumor progression, has undergone rigorous validation and garnered recognition for its effectiveness and safety in managing CRLM. This article endeavors to review the advancements in research concerning thermal ablation in the treatment of CRLM, exploring its efficacy, safety profile, and the promising avenues for its clinical application.