Objective To assess the potential role of disulfidptosis-related genes (DRGs) in pan-cancer on prognosis and immunity on the basis of bioinformatics approaches. Methods Pan-cancer RNA-seq data, mutation profiles, clinical information, TMB, MSI, stemness scores, and tumor and immune microenvironment data contained in TCGA and various open-source online databases, and multi-group R-language algorithms were used for comprehensive analysis. The expression levels of DRGs at the cellular level were experimentally validated using qPCR. Results LRPPRC, NCKAP1, NDUFS1, and NUBPL had a better prognosis in renal clear cell carcinoma (P<0.001), whereas SLC7A11, NCKAP1, and SLC3A2 had a worse prognosis in hepatocellular carcinoma (P<0.001). TME analysis showed that LRPPRC was negatively correlated with immune cells, stromal cells, and estimated scores in all tumor types. TMB analysis revealed the potential research value of DRGs for PD-1/PD-L1 therapy in pan-cancer. Drug sensitivity analysis showed that SLC7A11 (r=0.454), SLC3A2 (r=0.366), and NCKAP1 (r=0.455) were significantly associated with Kahalide F (P<0.01). Experimental validation demonstrated the overall higher expression levels of GYS1 and NCKAP1 than normal cells in lung adenocarcinoma, colon adenocarcinoma, esophageal squamous carcinoma, and hepatocellular carcinoma (P<0.05). Conclusion Pan-cancer analysis of DRGs indicates that DRGs may serve as important biomarkers for the diagnosis and prognosis of renal clear-cell carcinoma, lung adenocarcinoma, and hepatocellular carcinoma.

This article explored the strategies of promoting access to medicines for rare diseases with digital and intelligent transformation technology in China. It summarized the mature, global-oriented, digital and intelligent transformation supported platforms for promoting rare disease research, technology and product development, as well as diagnosis and treatment information sharing in typical countries and region. This was followed with analyses of the challenges of access to medicines for rare diseases in China. It also systematically reviewed a range of policies implemented in China intended to promote access to medicines for rare diseases, and the digital and intelligent solutions to promote access to medicines for rare diseases at national and regional levels. The authors proposed that the central government agencies and their technical support institutions take a lead to construct a patient-centered dynamic and decentralized national big data sharing platform for rare diseases registry and research, medicines development, production and supply, access to care and medicines, payment and security, utilization surveillance in China. With the support of digital and intelligent technologies, this national platform would be able to link multiple stakeholders to achieve integrated analysis of big data, as well as international sharing and exchange, which will help to effectively and efficiently promote access to medicines for rare diseases in China.

ObjectiveTo screen key genes associated with neuroblastoma （NB） diagnosis and prognosis using the Gene Expression Omnibus （GEO） database， and to investigate the expression and clinical significance of nucleoporin 93 （NUP93） in NB tissues. MethodsNB gene chip data （GSE73517， GSE49710， GSE19274） were retrieved from the GEO database. Differentially expressed genes （DEGs） commonly upregulated in high-risk groups were screened. The R2 database was then used to assess the prognostic value of DEGs that were commonly upregulated in the MYCN amplification group. Finally， NUP93 expression levels in the tissues from 60 NB， 25 ganglioneuroblastoma （GNB）， and 26 ganglioneuroma （GN） cases were measured by immunohistochemistry . ResultsTwenty-five DEGs were identified as commonly upregulated in high-risk groups. Among these， 10 genes （SIVA1， NUP93， STIP1， LSM4， RAI14， MYOZ3， KNTC1， TNFRSF10B， TACC3 and CEP152） showed significantly higher expression in MYCN-amplified subgroups （P＜0.05）. Survival analysis revealed that high NUP93 expression was associated with shorter overall survival （HR = 4.0， 95% CI： 3.0，5.3， P = 1.80 × 10⁻³⁴）. Immunohistochemistry results revealed that NUP93 expression in NB tissues was significantly higher than in GNB and GN tissues （P＜0.001）. NUP93 expression was positively correlated with high mitosis-karyorrhexis index （MKI； P=0.040）， poor differentiation （P＜0.001）， and MYCN expression （r_s = 0.793， P ＜0.001）. ConclusionsHigh expression of NUP93 is associated with high MKI and poor differentiation， and predicts unfavorable prognosis in patients with NB， suggesting it may promote tumor progression by regulating MYCN. NUP93 has the potential to be a novel diagnostic biomarker and therapeutic target for NB.

Tumorigenesis， invasion， and metastasis occur in the context of a persistent inflammatory microenvironment， and a variety of inflammatory factors can lead to the development of various tumors. Guided by the thought of "preventive treatment of disease" in TCM and the concept of tertiary prevention in modern medicine， it is of great significance to effectively intervene in the inflammatory stage of the disease， interrupt disease progression， prevent the occurrence of malignant tumors， and reverse the process of "inflammation-to-cancer transformation". Sinisan， a commonly used prescription in the Treatise on Febrile Diseases， has been widely applied in the treatment of precancerous lesions of the digestive system， demonstrating considerable advantages. This article reviewed literature from the past 20 years， summarizing the application of Sinisan in precancerous lesions of the digestive system from three aspects： the exploration of its prescription-syndrome relationship， clinical application， and mechanistic study. It is found that basic syndrome indications of Sinisan include harmonizing the Earth element to promote spleen-stomach transportation and transformation， soothing the liver and nourishing the Wood element to restore the smooth flow of Qi， and regulating Yin and Yang to relieve stagnation within the system. In clinical application， Sinisan has shown significant efficacy in atrophic gastritis and precancerous conditions such as intestinal metaplasia， gastric ulcer， ulcerative colitis， esophagitis， and pancreatitis. Mechanistic studies have revealed that Sinisan can inhibit inflammatory factors and improve the inflammatory microenvironment， inhibit cell proliferation and regulate apoptosis， exhibit anti-angiogenic and antitumorigenic effects， modulate immune function， and exert antioxidant effects. These mechanisms can be achieved by regulating pathways such as nuclear factor erythroid 2-related factor 2/heme oxygenase-1 （Nrf2/HO-1）， farnesoid X receptor （FXR）/Nrf2， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， Takeda G protein-coupled receptor 5/cyclic adenosine monophosphate/protein kinase A （TGR5/cAMP/PKA）， interleukin-4/signal transducer and activator of transcription 6 （IL-4/STAT6）， Janus kinase/signal transducer and activator of transcription （JAK/STAT）， RhoA/Rho-associated protein kinase （RhoA/ROCK）， and transforming growth factor-β/Smad proteins （TGF-β/Smads）， confirming Sinisan's role in reversing the inflammation-to-cancer transformation. The current research status of Sinisan in precancerous lesions of the digestive system was thoroughly examined through the above three aspects， along with the identification of limitations and areas for improvement in current research. The aim is to provide a basis and support for future in-depth research on Sinisan， promote the development of new integrated treatment models combining TCM and Western medicine for precancerous lesions， and aid in the research and development of drugs related to precancerous lesions.

Zhigancao Tang （also known as Fumaitang） is a classic formula for treating "intermittent pulse and palpitations" and is widely used in clinical practice. Sanjia Fumaitang， included in the Catalogue of Ancient Classical Formulas （First Batch） published by the National Administration of Traditional Chinese Medicine of China in 2018， is derived from this formula. This paper employed bibliometric methods to comprehensively investigate and summarize the historical evolution， drug composition， herb origins and preparation， prescription meanings， and ancient and modern applications of Zhigancao Tang， analyzed the composition and usage of Zhigancao Tang， and discussed the reasons and applications of the "Fumaitang" variants created by Wu Jutong. A total of 47 valid pieces of data from 38 ancient texts were included. Results showe that Zhigancao Tang originates from the Treatise on Cold Damage （Shang Han Lun）， and the name "Fumaitang" is also recorded in the formula's description. Converted to modern measurements from the Han dynasty system， the recommended preparation for Zhigancao Tang includes 55.2 g of fried Glycyrrhizae Radix et Rhizoma， 41.4 g of Cinnamomi Ramulus， 27.6 g of Ginseng Radix et Rhizoma， 220 g of fresh Rehmannia glutinosa， 27.6 g of Asini Corii Colla， 53 g of Ophiopogonis Radix， 45 g of Cannabis Fructus， and 90 g of Jujubae Fructus. All herbs should be decocted with 1 400 mL of yellow rice wine and 1 600 mL of water until 600 mL. Once the Asini Corii Colla is fully dissolved， the decoction should be taken warm at a dosage of 200 mL， three times a day. Zhigancao Tang is effective for replenishing Qi， warming Yang， nourishing Yin， and nourishing blood and is primarily used to treat “intermittent pulse and palpitations” caused by deficiencies in heart Yin and Yang， as well as malnutrition of the heart meridian and conditions like lung atrophy. Modern applications mainly focus on cardiovascular and cerebrovascular diseases， including arrhythmias， coronary heart disease， and premature ventricular contractions. The findings from this research provide a reference for the further development of Zhigancao Tang.

Objective To analyze the occurrence characteristics of adverse events following immunization (AEFI) of 23-valent pneumococcal polysaccharide vaccine (PPSV-23) in Hebei Province and to evaluate the safety of the vaccine. Methods AEFI cases related to vaccination of PPSV-23 in Hebei Province from January 1, 2020 to December 31, 2022 were collected through the AEFI surveillance module of Chinese Center for Disease Control and Prevention Information System. The incidence of reported AEFI cases were then analyzed and compared. Results The reported incidence rate of AEFI of PPSV-23 was 56.12 /100,000 doses, and the incidence rate of adverse reactions was 55.50 /100 000 doses. The incidence rate of common adverse reactions was 53.94/100 000 doses, and the incidence rate of rare adverse reactions was 1.56/100 000 doses. Most of the reported AEFI cases caused by PPSV-23 were common adverse reactions, which occurred mainly within one day after vaccination, and the overall regression was positive. Conclusion The 23-valent pneumococcal polysaccharide vaccine used in Hebei Province is safe，but its safety monitoring still needs to be strengthened.

Objective:To identify the development trajectories of self-neglect behavior in older adults and explore the associated influencing factors.Methods:A fixed cohort was constructed based on the data from three surveys of Chinese longitudinal healthy longevity survey (CLHLS) from 2011 to 2018. A total of eight variables from 4 dimensions including living environment, lifestyle, social interaction, and health care were selected to evaluate self-neglect. Group-based trajectory model was used to identify the development trajectory of self-neglect behavior in the older adults, and polynomial Logistic regression model was used to explore its influencing factors by Stata 16.1.Results:Finally, 2 754 older adults aged 60 and above were included.The development trajectory of self-neglect behavior in older adults, based on the group-based trajectory model, can be classified into stable-low group ( n=268, 9.7%), descending-moderate group ( n=2 224, 80.8%), and decreasing-high group ( n=262, 9.5%). Polynomial Logistic regression showed that, compared with stable-low group, living in rural areas ( B=1.116, OR=3.053, 95% CI= 2.278-4.091) and higher activities of daily living scores( B=0.137, OR=1.147, 95% CI=1.046-1.258) were the risk factors of descending-moderate group. Education levels with 1-6 years( B=-0.398, OR=0.672, 95% CI=0.469-0.963), >6 years( B=-1.072, OR=0.342, 95% CI=0.229-0.513), being married( B=-0.476, OR=0.621, 95% CI=0.444-0.870), self-reported good health( B=-0.808, OR=0.446, 95% CI= 0.213-0.932), improved health status( B=-0.704, OR=0.495, 95% CI=0.320-0.766), self-reported average economic status( B=-1.065, OR=0.345, 95% CI=0.148-0.802), self-reported good economic status( B=-1.634, OR=0.195, 95% CI=0.082-0.467), and a higher cognition score( B=-0.142, OR=0.867, 95% CI=0.798-0.942) served as protective factors of descending-moderate group. In addition to the above factors, being in the age group of 75-89 years( B=0.481, OR=1.617, 95% CI=1.057-2.473) was a risk factor for decreasing-high group compared to stable-low group. Conclusions:Three types of self-neglect behavior trajectories among older adults were identified in this study, suggesting that physical health and economy are the influencing factors of the development trajectory of self-neglect of the elderly.

Background and objective Isoliquiritigenin(ISL)is an important pharmacological constituent of Glycyrrhiza glabra,which possesses a range of physiological and pharmacological activities,as well as significant antitumor ac-tivity,and can be used as a potential drug for targeted cancer therapy.LINC01503 is an oncogene,which has been closely asso-ciated with the malignant biological processes of many cancers.The aim of this study was to investigate the effects of ISL on the proliferation,apoptosis,invasion and migration oflung squamous carcinoma cells by regulating LINC01503.Methods Plasma was collected from lung squamous carcinoma patients and healthy individuals treated at Tangshan People's Hospital from Janu-ary 2021 to December 2022.The expression of LINC01503 in lung squamous carcinoma plasma,tissues and cells was detected by real-time quantitative fluorescence polymerase chain reaction(qRT-PCR).Lung squamous carcinoma cells were treated with different concentrations of ISL for 24 h,and LINC01503 expression was detected by qRT-PCR.The cells were treated in groups:si-NC group,si-LINC01503 group,DMSO(0.1％dimethyl sulfone)group,ISL group,pc DNA3.1(+)-NC group,pc DNA3.1(+)-LINC01503 group,ISL+pc DNA3.1(+)-NC group and ISL+pc DNA3.1(+)-LINC01503 groups.CCK-8 assay,clone formation assay,flow cytometry,Transwell assay and scratch assay were used to explore the effect of LINC01503 on the functional phenotype of lung squamous carcinoma cells.Results Fluorescence in situ hybridization results showed that the average fluorescence intensity of LINC01503 in tissue microarrays of lung squamous carcinoma patients was higher than that in paracancerous tissues(P＜0.05).The expression of LINC01503 in the plasma of patients with lung squamous carcinoma was higher than that in the plasma of healthy individuals(P＜0.05).Knockdown of LINC01503 inhibited the proliferation,invasion and migration of lung squamous carcinoma cells and promoted apoptosis(P＜0.05).ISL inhibited the proliferation,invasion,migration and promoted apoptosis of lung squamous carcinoma cells(P＜0.05).Overexpression of LINC01503 followed by intervention with ISL reversed the promotional effect of overexpression of LINC01503 on the proliferation,invasion and migration of lung squamous carcinoma cells as well as the inhibitory effect on apoptosis(P＜0.05).Conclusion LINC01503 was highly expressed in lung squamous carcinoma,and LINC01503 could promote the proliferation,invasion and migra-tion of lung squamous carcinoma cells and inhibit the apoptosis,ISL could inhibit the proliferation,invasion and migration of lung squamous carcinoma cells and promote apoptosis of lung squamous carcinoma cells by regulating the expression of LINC01503.

Objective:To explore the clinical effectiveness of high-frequency color Doppler ultrasound (HFCDU) assisted harvest of radial artery perforator-pedicled lateral forearm neurocutaneous vascular flap to repair soft tissue defect below the elbow.Methods:A retrospective study was conducted on the clinical data of patients who underwent repair of soft tissue defects below the elbow using the radial artery perforator-pedicled lateral forearm neurocutaneous vascular flap at the Second Hospital of Tangshan from January 2016 to June 2021. Prior to the surgery, HFCDU was utilized to identify and measure the course of the lateral forearm cutaneous nerve and the perforating branch of the radial artery surrounding the wound. Subsequently, the flap rotation point, axis, and area were meticulously designed. During the surgical procedure, the skin flap was harvested either through a subcutaneous tunnel or by direct transfer, while the nerve stump at the defect site was anastomosed end-to-end with the lateral cutaneous nerve of the forearm contained in the skin flap. After reducing the wound at the donor site, it was either directly sutured or repaired using a medium-thick skin graft harvested from the thigh. After surgery, the survival of the skin flap, wound healing at the donor site, and the survival of the skin graft were observed. At the last follow-up, the static two-point discrimination of the flap was measured, and patient satisfaction with the appearance of the flap was assessed using the Michigan hand outcomes questionnaire(MHQ). This questionnaire categorized satisfaction into five levels: very dissatisfied (1 point), dissatisfied (2 points), fair (3 points), satisfied (4 points), and very satisfied (5 points). The scar condition of the donor site was evaluated according to the Vancouver scar scale (VSS), which scored from 0 to 15 points, with higher scores indicating more severe scarring. Descriptive analysis of the data was performed using SPSS 27.0 software.Results:A total of 33 patients were included in the study, comprising 20 males and 13 females, with an average age of (41.0±11.7) years (range, 23-65 years). The defect locations included 6 forearms, 9 wrists, and 18 hands, with all patients having exposed bones and (or) tendons. The defect area ranged from 3.0 cm × 2.5 cm to 12.0 cm × 5.0 cm. The detection result of cutaneous nerves and perforating blood vessels using HFCDU were consistent with the actual findings during surgery, showing no discrepancies. The area of the skin flaps ranged from 3.5 cm × 3.0 cm to 13.0 cm × 6.0 cm. All 33 skin flaps survived postoperatively, with good blood supply and no infections reported; the wounds at the donor site healed primarily, and all grafted skin survived. The duration of postoperative follow-up was (15.6±2.9) months (range, 10-24 months), and the patients’ static two-point discrimination of the flap was measured at (12.5±3.3) mm (range, 8-20 mm). The result of the MHQ indicated that 23 patients were very satisfied with the appearance of the flap (5 points), while 10 patients were satisfied (4 points). The VSS score for the donor site was (4.3±0.9) points (range, 3-6 points), indicating that the scar at the donor site was mild.Conclusion:HFCDU can accurately identify the lateral forearm cutaneous nerve and the perforating branch of the radial artery.The radial artery perforator-pedicled lateral forearm neurocutaneous vascular flap can provide a reliable blood supply, good appearance, sense and patient satisfaction, which is suitable for repairing soft tissue defects below the elbow.

Objective:To explore the clinical effectiveness of high-frequency color Doppler ultrasound (HFCDU) assisted harvest of radial artery perforator-pedicled lateral forearm neurocutaneous vascular flap to repair soft tissue defect below the elbow.Methods:A retrospective study was conducted on the clinical data of patients who underwent repair of soft tissue defects below the elbow using the radial artery perforator-pedicled lateral forearm neurocutaneous vascular flap at the Second Hospital of Tangshan from January 2016 to June 2021. Prior to the surgery, HFCDU was utilized to identify and measure the course of the lateral forearm cutaneous nerve and the perforating branch of the radial artery surrounding the wound. Subsequently, the flap rotation point, axis, and area were meticulously designed. During the surgical procedure, the skin flap was harvested either through a subcutaneous tunnel or by direct transfer, while the nerve stump at the defect site was anastomosed end-to-end with the lateral cutaneous nerve of the forearm contained in the skin flap. After reducing the wound at the donor site, it was either directly sutured or repaired using a medium-thick skin graft harvested from the thigh. After surgery, the survival of the skin flap, wound healing at the donor site, and the survival of the skin graft were observed. At the last follow-up, the static two-point discrimination of the flap was measured, and patient satisfaction with the appearance of the flap was assessed using the Michigan hand outcomes questionnaire(MHQ). This questionnaire categorized satisfaction into five levels: very dissatisfied (1 point), dissatisfied (2 points), fair (3 points), satisfied (4 points), and very satisfied (5 points). The scar condition of the donor site was evaluated according to the Vancouver scar scale (VSS), which scored from 0 to 15 points, with higher scores indicating more severe scarring. Descriptive analysis of the data was performed using SPSS 27.0 software.Results:A total of 33 patients were included in the study, comprising 20 males and 13 females, with an average age of (41.0±11.7) years (range, 23-65 years). The defect locations included 6 forearms, 9 wrists, and 18 hands, with all patients having exposed bones and (or) tendons. The defect area ranged from 3.0 cm × 2.5 cm to 12.0 cm × 5.0 cm. The detection result of cutaneous nerves and perforating blood vessels using HFCDU were consistent with the actual findings during surgery, showing no discrepancies. The area of the skin flaps ranged from 3.5 cm × 3.0 cm to 13.0 cm × 6.0 cm. All 33 skin flaps survived postoperatively, with good blood supply and no infections reported; the wounds at the donor site healed primarily, and all grafted skin survived. The duration of postoperative follow-up was (15.6±2.9) months (range, 10-24 months), and the patients’ static two-point discrimination of the flap was measured at (12.5±3.3) mm (range, 8-20 mm). The result of the MHQ indicated that 23 patients were very satisfied with the appearance of the flap (5 points), while 10 patients were satisfied (4 points). The VSS score for the donor site was (4.3±0.9) points (range, 3-6 points), indicating that the scar at the donor site was mild.Conclusion:HFCDU can accurately identify the lateral forearm cutaneous nerve and the perforating branch of the radial artery.The radial artery perforator-pedicled lateral forearm neurocutaneous vascular flap can provide a reliable blood supply, good appearance, sense and patient satisfaction, which is suitable for repairing soft tissue defects below the elbow.