Objective: To explore the clinical manifestations, diagnosis, differential diagnosis, and treatment of granulomatous cheilitis complications after treatment in patients with upper lip venous malformations, as well as to provide a reference for their clinical diagnosis and treatment. Methods: This report provides details on the clinical manifestations, diagnosis, differential diagnosis, and treatment of a case of granulomatous cheilitis after the treatment of upper lip venous malformation, and then analyzes granulomatous cheilitis alongside the related literature. The patient, a 30-year old male, was first seen in the dermatology department of another hospital with bright red spots on his lips, diagnosed with allergic dermatitis and received symptomatic treatment, and the erythema did not improve. He was diagnosed with ‘cavernous hemangioma’ and was treated with polydocanol and bleomycin injections. The bright red spots on his lips improved, but the swelling worsened for more than half a year. He then sought treatment at the oral mucosal department of our hospital. At the time of consultation, the swelling of the upper lip and perilabial skin was obvious, and there was a red patch on the right side of the upper lip, that was congested with blood. The upper lip was tough, with hard nodules, unclear borders, and poor mobility. Pathological examination showed epithelial hyperplasia of the upper lip mucosa, surface hyperkeratosis, subepithelial fibrous tissue hyperplasia, and chronic inflammation of the mucosa and minor salivary glands. Focal histiocyte, lymphocyte, and plasma cell infiltration was seen in the submucosal layer, with granulomatous inflammatory manifestations. Based on the patient's medical history, clinical manifestations, and histopathological manifestations, the diagnosis of granulomatous cheilitis was made. Tretinoin 0.3 mL (40 mg/mL, 1 mL/vial) was injected into the deep layer of the mucosa of the right and left upper lips for local block treatment. Prednisone acetate tablets (10 mg/Qd) were taken orally, and after 1 week of follow-up, the symptoms improved, so the original treatment was continued. After 2 weeks of follow-up, the swelling of the lips improved significantly, and the oral prednisone acetate tablets were adjusted to 5 mg/Qd. After 4 weeks of follow-up, the shape of the lips was largely back to normal, and the color and suppleness of the lips had improved significantly. The local block treatment and oral medication were stopped, and the patient was instructed to apply the topical tretinoin ointment Bid on the upper lip. Results: The patient had a follow-up visit 8 weeks later, at which their lip color, shape, and texture remained normal, and the patient was instructed to stop the medication and follow up. A review of the literature suggests that the etiology of granulomatous cheilitis is unknown and that it is associated with genetic predisposition, odontogenic infections, allergic factors, microbial infections, and immunological factors. It needs to be clinically differentiated from diseases such as lip venous malformations, lip angioneurotic oedema, Crohn's disease, and tuberculosis. At present, the clinical treatment of granulomatous cheilitis is still based on local glucocorticoid block therapy or a combination of oral glucocorticoid drugs. In this case, the area of erythema on the lips decreased in size, but swelling occurred and continued to worsen after polydocanol and bleomycin injection treatment. Pre-existing venous malformation should be considered as a complication associated with injectable drugs that can produce granulomatous cheilitis. Conclusion The injection-based treatment of lip venous malformation may be complicated by granulomatous cheilitis, and in the process of clinical diagnosis and treatment, it is necessary to be aware to the existence of drug-related factors in the occurrence and development of granulomatous diseases.

ObjectiveTo establish a quality evaluation method for Zhuye Shigao granules（Zhuye Shigaotang） based on fingerprint and determination of index components， and to investigate the therapeutic effect of Zhuye Shigao granules on mice with cold-dampness pestilence attacking lung syndrome. MethodsThe fingerprint of Zhuye Shigao granules was established by high performance liquid chromatography（HPLC）， and the methods for determination of total calcium， orientin， isoorientin， ginsenosides Rg₁， Re and Rb₁ and other 2 index components were established. Fifty ICR mice were randomly divided into the blank group， model group， Zhuye Shigao granules low， medium and high dose groups（9.3， 18.6， 37.2 g·kg^-1·d^-1）， with 10 mice in each group. In addition to the blank group， the model mice with cold-dampness pestilence attacking lung syndrome was prepared by nasal drip of lipopolysaccharide combined with cold-dampness environment. Each administration group was given the corresponding liquid by gavage according to the dose， while the blank group and model group were given the same volume of normal saline by gavage. Then， the body temperature and organ index of mice in each group were measured， hematoxylin-eosin（HE） staining was used to investigate the lung tissue injury of mice in each group， and enzyme-linked immunosorbent assay（ELISA） was used to detect the changes of tumor necrosis factor-α（TNF-α）， interleukin（IL）-lβ， IL-6， IL-10 levels in serum and lung tissue， as well as immunoglobulin（Ig）A and IgM levels in serum. ResultsThe fingerprint similarity of 10 batches of Zhuye Shigao granules was>0.950， and 20 common peaks were calibrated. Seven of them were identified， including peak 11（isoorientin）， peak 12（orientin）， peak 14（apioside liquiritin）， peak 15（liquiritin）， peak 17（apioside isoliquiritin）， peak 19（isoliquiritin） and peak 20（liquiritigenin）. The results of quantitative analysis showed that the content range of each index component in 10 batches of Zhuye Shigao granules was as follows：Total calcium of 9.978-11.294 mg·g^-1， isoorientin of 0.033-0.041 mg·g^-1， orientin of 0.046-0.055 mg·g^-1， ginsenoside Rg₁+ginsenoside Re of 0.748-0.762 mg·g^-1， ginsenoside Rb₁ of 0.151-0.197 mg·g^-1， liquiritin of 1.106-1.366 mg·g^-1， glycyrrhizic acid of 0.904-1.182 mg·g^-1_. Compared with the blank group， the body temperature of mice in the model group was significantly increased， the organ indexes of liver， lung and spleen were significantly decreased， the organ index of thymus was significantly increased， HE staining of lung tissue showed infiltration of inflammatory cells， a small amount of serous exudation was observed in the alveoli， and lung tissue was damaged. After the intervention of Zhuye Shigao granules， the pathological changes were improved compared with the model group. The expression levels of IL-1β， IL-6 and TNF-α were significantly increased， the expression level of IL-10 was significantly decreased in serum and lung tissue. The levels of IgA and IgM in serum were significantly decreased（P<0.01）. Compared with the model group， the body temperature， the organ indexes and immune factor levels in serum and lung tissue of mice in the Zhuye Shigao granules medium and high dose groups were significantly reduced（P<0.05， P<0.01）. ConclusionIn this study， the quality evaluation of Zhuye Shigao granules was carried out based on fingerprint combined with determination of index components， and the fingerprint of four herbs（Lophatheri Herba， Ophiopogonis Radix， Pinelliae Rhizoma and Glycyrrhizae Radix et Rhizoma） in this formula and the determination of 8 index components were established. The therapeutic effect of Zhuye Shigao granules on mice with cold-dampness pestilence attacking lung syndrome may be related to inhibiting inflammatory response and mediating immune regulation.

ObjectiveTo clarify the neuroprotective effect of black Panacis Quinquefolii Radix（PQR） and explore its active ingredients， with the aim of establishing an activity-oriented quality evaluation method. MethodsTransgenic Tg（HuC∶EGFP） zebrafish was used to establish a neuronal injury model by aluminum chloride immersion. Different doses（10， 20 mg·L^-1） of PQR and black PQR ethanol extracts were administered. The neuroprotective effects of PQR and black PQR were compared by analyzing the fluorescent area and intensity of zebrafish neurons. Based on ultra-performance liquid chromatography（UPLC）， a fingerprint profile of black PQR was established， followed by principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）. Differential components were screened using the criteria of variable importance in the projection（VIP） value>1 and P<0.05. The neuroprotective activity of 14 batches of black PQR was assessed， and Spearman correlation analysis was used to identify saponins related to neuroprotective activity， which were then validated. Based on the above results， active marker components were determined， and an UPLC method was established for their quantitation with clear content limits. ResultsPharmacological efficacy results showed that both PQR and black PQR at different doses could significantly improved neuronal damage in zebrafish. At a dose of 20 mg·L^-1， black PQR demonstrated superior efficacy（P<0.05）. The fingerprint similarities of 14 batches of black PQR were>0.94， with 26 common peaks identified. Through comparison with the reference standards， 8 components were confirmed， including peak 1（ginsenoside Rg₁）， peak 2（ginsenoside Re）， peak 5（ginsenoside Rb₁）， peak 9（ginsenoside Rd）， peak 16［ginsenoside 20（S）-Rg₃］， peak 17［ginsenoside 20（R）-Rg₃］， peak 18（ginsenoside Rk₁）， and peak 19（ginsenoside Rg₅）. The results of PCA and OPLS-DA indicated that there were differences in saponins among black PQR samples from different origins， and 12 differential components were screened. All 14 batches of black PQR exhibited good protective effects on zebrafish neurons， with Shaanxi-produced black PQR showing superior protective effects compared to the other three production regions. Spearman correlation analysis revealed that a total of 11 components， including ginsenosides 20（S）-Rg₃， 20（R）-Rg₃， Rk₁ and Rg₅， showed a significant positive correlation with the neuroprotective effect in zebrafish（P<0.05）. The activity validation results indicated that ginsenosides 20（S）-Rg₃， 20（R）-Rg₃， Rk₁ and Rg₅ were the primary components responsible for the neuroprotective effects of black PQR. Quantitative analysis showed that the content of ginsenoside 20（S）-Rg₃ in 14 batches of black PQR ranged from 0.17% to 0.52%， and the repair rate of neuronal damage ranged from 42.77% to 97.83%. ConclusionBased on the fingerprint and neuronal protective activity， the spectrum-effect related quality control model of black PQR was established， with ginsenoside 20（S）-Rg₃ as the quality control index， and the neuronal damage repair rate≥60% as the evaluation standard， the minimum limit of ginsenoside 20（S）-Rg₃ in black PQR should be≥0.20%.

Objective: To investigate the predictive value of EZH2 expression for malignant transformation in oral leukoplakia (OLK) and to provide a reference for clinical practice. Methods: This study was approved by the institutional ethics committee, and informed consent was obtained from all participants. A total of 114 patients diagnosed with OLK by pathological examination and treated at our hospital between November 2020 and July 2022 were initially enrolled. After excluding those with incomplete data or follow-up, 105 participants were included in the final analysis, comprising 14 in the high EZH2 expression group and 91 in the low EZH2 expression group. Histopathological examination of oral mucosa and immunohistochemical detection of EZH2 protein expression were performed. The follow-up period was 30 months; participants were followed until malignant transformation occurred or until the end of follow-up, at which point they were withdrawn from the study. The exposure factor was the level of EZH2 protein expression, and the outcome was the malignant transformation rate of OLK. Differences in EZH2 expression levels and transformation outcomes were analyzed. Results: There were no statistically significant differences between the high and low EZH2 expression groups in terms of age, sex, history of systemic disease, lifestyle habits, psychological status, diet, and sleep conditions (P > 0.05). Lesions in the high EZH2 expression group were mainly located on the ventral tongue, while in the low EZH2 expression group, they were more commonly found on the dorsal tongue and buccal mucosa. The malignant transformation rate was 28.6% (4/14) in the high expression group and 8.8% (8/91) in the low expression group; these differences were not statistically significant (P=0.053). In univariate Cox regression analysis, the risk of malignant transformation in the high EZH2 expression group was 3.647 times that of the low EZH2 expression group (HR = 3.647, 95% CI: 1.097-12.120, P<0.05). Kaplan-Meier survival analysis showed that over the 30-month follow-up period, the cancer-free survival rate in the high EZH2 expression group was 19.8% lower than in the low expression group, and the difference was statistically significant (P<0.05). In multivariate Cox regression analysis, only moderate and severe epithelial dysplasia were identified as independent risk factors for malignant transformation. The risk of malignant transformation in the moderate and severe dysplasia groups was 10.695 and 13.623 times higher, respectively, than in the mild dysplasia group (HR = 10.695, 95% CI: 2.270-50.396, P<0.05; HR=13.623, 95% CI: 1.918-96.774, P<0.05). EZH2 high expression was not an independent risk factor in the multivariate model (HR= 2.528, 95% CI: 0.752-8.500, P = 0.134). Conclusion High EZH2 protein expression is a risk factor for the malignant transformation of OLK but does not have independent predictive value.

Objective:To explore the impact of self-disclosure on demoralization syndrome in patients with permanent enterostomy for colorectal cancer, so as to provide reference for clinical nursing interventions for those patients.Methods:From January to May 2023, convenience sampling was used to select 207 patients with permanent enterostomy for colocrctal cancer of the Wound Ostomy Clinic of Laoshan Campus of the Affiliated Hospital of Qingdao University as the research subjects. A survey was conducted on patients using the General Information Questionnaire, Distress Disclosure Index, Social Support Rating Scale, and the Demoralization Scale Mandarin Version.Results:Among 207 patients with permanent enterostomy for colorectal cancer, the scores of self-disclosure, social support, and demoralization syndrome were 35.00 (26.00, 47.00) , 32.00 (26.00, 39.00) , and 35.00 (23.00, 47.00) , respectively. A total of 128 patients (61.8%) were in moderate demoralization, and 37 patients (17.9%) were in severe demoralization. Multiple linear regression analysis showed that place of residence, self-care of stoma, self-disclosure, and social support were the influencing factors for demoralization syndrome in patients with permanent enterostomy for colorectal cancer ( P<0.05) . Conclusions:Patients with permanent enterostomy for colorectal cancer have a high overall score of demoralization syndrome, and a high proportion of patients with moderate to severe demoralization. Medical and nursing staff should focus on patients in remote rural areas and those with poor self-care abilities to stomas, develop targeted intervention measures to improve patients' negative emotions, enhance their self-disclosure, and pay attention to strengthening social support to relieve their demoralization syndrome, thereby improving their quality of life.

Abstract Flexibleis an important classification of flat foot. Flatfoot occurs due to a variety of reasons and causes the medial longitudinal arch to collapse or disappear. However, many children still do not develop a normal foot arch as the grow, and a failure to intervene in a timely manner will greatly harm a child s normal mobility development. Timely detection and intervention are the key to improve the prognosis. There is a lack of uniform quantitative criteria for the diagnosis of flexible flatfoot. Currently, the commonly used diagnostic methods include physical examination, foot printing, plantar pressure test and imaging examination. This article reviews the risk factors, diagnosis, prevention and treatment of Flexible Flatfoot.

Articular cartilage (AC) injuries often lead to cartilage degeneration and may ultimately result in osteoarthritis (OA) due to the limited self-repair ability. To date, numerous intra-articular delivery systems carrying various therapeutic agents have been developed to improve therapeutic localization and retention, optimize controlled drug release profiles and target different pathological processes. Due to the complex and multifactorial characteristics of cartilage injury pathology and heterogeneity of the cartilage structure deposited within a dense matrix, delivery systems loaded with a single therapeutic agent are hindered from reaching multiple targets in a spatiotemporal matched manner and thus fail to mimic the natural processes of biosynthesis, compromising the goal of full cartilage regeneration. Emerging evidence highlights the importance of sequential delivery strategies targeting multiple pathological processes. In this review, we first summarize the current status and progress achieved in single-drug delivery strategies for the treatment of AC diseases. Subsequently, we focus mainly on advances in multiple drug delivery applications, including sequential release formulations targeting various pathological processes, synergistic targeting of the same pathological process, the spatial distribution in multiple tissues, and heterogeneous regeneration. We hope that this review will inspire the rational design of intra-articular drug delivery systems (DDSs) in the future.

Objective: To find any differentially expressed circRNAs in oral leukoplakia (OLK) and oral lichen planus (OLP), to investigate the possible role of circRNAs in the pathogenesis of these two diseases. Methods: This study obtained hospital ethical approval. High-throughput sequencing was used to detect differentially expressed circRNAs in OLK, OLP, oral squamous cell carcinoma and normal oral mucosal tissues. CircRNAs were verified by qRT-PCR, enzyme tolerance assays and Sanger sequencing. GO functional analysis and KEGG pathway analysis were performed to predict the functions of circRNAs in OLP. TargetScan and miRanda were applied to predict targeted miRNAs and mRNAs of circRNAs, and ceRNA networks were mapped. Results: A total of 49 circRNAs were differentially expressed in OLK and OLP together, including 30 upregulated and 19 downregulated circRNAs. The five circRNAs confirmed with RT-qPCR, including circHLA-C, circRNF13, circTTN, circSEPN2 and circALDH3A2, were all abnormally expressed in OLK and OLP, among which circHLA-C was a key circRNA with trans splice sites, which was validated by expanding the sample size. ROC curve analysis showed that the area under the circHLA-C curve for predicting OLK was 0.955, and the area under the circHLA-C curve for predicting OLP was 0.988. GO functional analysis showed enrichment of many biological processes related to the immune process. The KEGG pathway with the highest enrichment score was "Natural killer cell mediated cytotoxicity". HLA-C was significantly enriched in these processes/pathways. CeRNA network analysis showed that circHLA-C interacted with a variety of miRNAs, such as hsa-miR-26a-5p, hsa-miR-129-5p, and hsa-miR-29a-3p. Conclusion Many circRNAs were differentially expressed in both OLK and OLP, circHLA-C being the most elevated. CircHLA-C is valuable for the early diagnosis of OLK and OLP and may serve as a potential biomarker for the diagnosis and prognosis of OLK and OLP.

Objective:To investigate the clinical application value of enhanced recovery after surgery using the LEER model in patients subjected to laparoscopic cholecystectomy in basic hospitals of Yi nationality area.Methods:Twenty-six patients who underwent laparoscopic cholecystectomy based on the concept of enhancing recovery after surgery using the LEER model in People's Hospital of Jinkouhe District of Leshan from January to October 2021 were included in the observation group. An additional 20 patients who concurrently underwent laparoscopic cholecystectomy and conventional intervention were included in the control group. Clinical efficacy, postoperative complications and postoperative pain were compared between the two groups.Results:Postoperative fasting time, length of hospital stay, and total hospital days in the observation group were 6 (6, 6) hours, 2 (2, 3) days and 4 (4, 6) days respectively, which were significantly shorter than 24 (24, 36) hours, 5 (5, 6) days, 7 (7, 9) days in the control group ( H = 351.00, 407.50, 458.00, all P < 0.05). Hospitalization cost in the observation group was 5 454.58 (5 014.11, 6 016.58) yuan, which was significantly lower than 6 611.91 (6 192.68, 7 841.73) yuan in the control group ( H = 420.00, P < 0.05). There were no significant differences in operative time and postoperative complications between the two groups (both P > 0.05). At postoperative 6 hours, Visual Analogue Scale score in the observation group was 3 (3, 4) points, and patients with mild pain accounted for 73.07% (19/26). At postoperative 24 hours, Visual Analogue Scale score in the observation group was 2 (2, 3) points, and patients with mild pain accounted for 92.31% (24/26). Overall pain was well controlled after surgery. Patient satisfaction rate in the observation was 96.15% (25/26). All patients recovered and were discharged. Conclusion:Application of enhanced recovery after surgery using the LEER model in patients subjected to laparoscopic cholecystectomy in basic hospitals of Yi nationality area can promote postoperative recovery, contribute to changing the theory of diagnosis and treatment, and improve overall medical quality. The enhanced recovery after surgery protocol using the LEER model has a good application value.

Objective:To understand the status of self-transcendence, social support and stoma psychosocial adaptation in patients with enterostomy, and to analyze the correlation among the three.Methods:This study was a cross-sectional study. From July to November 2021, convenience sampling was used to select 210 patients with enterostomy who visited the Wound and Stoma Outpatient Clinic in Laoshan Campus, the Affiliated Hospital of Qingdao University as the research object. The General Information Questionnaire, Self-transcendence Scale (STS) , Social Support Rating Scale (SSRS) and Ostomy Adjustment Inventory-20 (OAI-20) were used to investigate the patients. Pearson correlation was used to test the correlation among variables, and multiple linear regression was used to explore the influencing factors of self-transcendence. A total of 210 questionnaires were distributed, and 196 effective questionnaires were recovered, with an effective recovery rate of 93.33% (196/210) .Results:Among 196 patients with enterostomy, the STS score was (36.48±11.84) . Pearson correlation analysis showed that the self-transcendence in colostomy patients was positively correlated with social support and stoma psychosocial adaptation ( r=0.712, 0.855; P<0.01) . Multiple linear regression analysis showed that educational level, stoma self-care, social support and stoma psychosocial adaptation were the main influencing factors of self-transcendence in patients with enterostomy ( P<0.05) . Conclusions:The self-transcendence of patients with enterostomy needs to be improved, and the self-transcendence is related to social support and stoma psychosocial adaptation. Medical and nursing staff should take targeted measures to improve the social support and social adaptation of patients with enterostomy, thereby improving the self-transcendence and the quality of life of patients.