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: This study aims to explore the influencing factors, formation mechanisms, and treatment methods of labial protuberance in the anterior maxilla during orthodontic treatment, providing a reference for clinical practice. Method: This study reports a case where the absence of upper anterior teeth 11 and 21, and the retraction tilting movement of teeth 12 and 22, resulted in labial protuberance and gingival hyperplasia. Alveolar osteoplasty and gingivoplasty were performed. The specific changes in the alveolar bone during the retraction of the anterior teeth and the characteristics of its remodeling were analyzed. Combined with relevant literature, the factors influencing the formation of labial protuberance in orthodontic patients, mechanisms, and methods for prevention and treatment were summarized. Results: After periodental surgery follow-up for 6 months, the gingival color and shape of teeth 12 and 22 were good, the labial alveolar bone was normal, and the overall condition was stable. A review of the literature showed that labial protuberance is more common in adult orthodontic patients, and the distance (>4 mm) and speed of retraction of anterior teeth are related to its formation, with the main mechanism likely being differential remodeling of the alveolar bone. In adult patients, the number of active osteoblasts and osteoclasts in the alveolar bone decreases, along with a reduction in metabolic activity and overall cellular activity, which diminishes the reactivity of the alveolar bone. After treatment of anterior teeth retraction, there is insufficient labial bone resorption. Moreover, the lack of mechanical stress-mediated periodontal ligament in the interdental space leads to reduced bone remodeling stimulation in this area, resulting in thickening of the labial alveolar bone of the upper anterior teeth. The remodeling rates of cortical and trabecular bone differ, with active trabecular bone proliferation near the tooth root surface and slow cortical bone resorption near the outer surface, which ultimately results in increased bone thickness at the labial cervical region. Specific case analysis indicates that the retraction distance of the upper anterior teeth in this case was about 6 mm. The alveolar bone at the missing sites of teeth 11 and 21, lacking periodontal ligament stimulation, showed less remodeling and absorption, likely appearing as hyperplasia. The prevention of labial bone protrusion mainly involves controlling the speed and distance of retraction of anterior teeth. Smaller labial protuberances generally do not require treatment, but those affecting function and aesthetics can be addressed with periodontal alveolar osteoplasty. Conclusion After the retraction of anterior teeth in orthodontics, a prominent, hard bone protuberance on the labial side can sometimes occur, which may be due to differential remodeling efficiency in different regions of the alveolar bone. For bone protuberance that influences aesthetics or function, periodontal alveolar osteoplasty can be a reliable option.

Objective: To investigate the trends in disease burden due to childhood asthma in China from 1990 to 2021 and to project the disease burden from 2022 to 2035, so as to provide insights into formulation of the control interventions for childhood asthma in China. Methods: The prevalent case, agestandard prevalence, disability-adjusted life years (DALYs) and agestandard DALYs rate of children with asthma at ages of 0 to 14 years and their 95% uncertainty interval (UI) in China from 1990 to 2021 were extracted from the Global Burden of Disease (GBD) database. The temporal trends in the disease burden of childhood asthma were evaluated with estimated annual percentage change (EAPC) and its 95% confidence interval (CI), and the disease burden due to asthma was projected among children at ages of 0 to 14 years in China using a Bayesian age-period-cohort (BAPC) model from 2022 to 2035. Results: There were 9.368 3 million (95%UI=6.410 7 million to 14.026 1 million) prevalent cases of asthma among children at ages of 0 to 14 years in China in 2021, contributing to 0.387 9 million (95%UI=0.216 1 million to 0.668 8 million) DALYs loss. The prevalent cases and DALYs of asthma decreased by 37.28% and 52.55% among children at ages of 0 to 14 years in China in 2021 compared with 1990, and the agestandardized prevalence [EAPC=-0.70%, 95%CI=-1.26% to -0.13%)] and DALY rates [EAPC=-1.71%, 95%CI=-2.32% to -1.10%)] also appeared a tendency towards a decline. From 1990 to 2021, the prevalent cases, prevalence, DALYs and DALYs rate of asthma were all higher among male children than among female children, and the disease burden of asthma was higher among children at ages of 5 to 9 years than at other age groups. BAPC model predicted a decline in both prevalent cases and DALYs of asthma among children at ages of 0 to 14 years in China from 2022 to 2035, with 6.759 6 million prevalent cases and DALYs of 0.228 4 million personyears in 2035, while the prevalence and DALYs rates were projected to rise to 5 143.35/105 and 173.75/105 in 2035. Conclusions Despite a reduction in the disease burden of asthma among children at ages of 0 to 14 years in China from 1990 to 2021, the prevalence remained high. The disease burden due to asthma is projected to appear a decline among children at ages of 0 to 14 years in China from 2022 to 2035; however, the prevalence and DALYs rates still rise. Intensified control measures and targeted interventions are required to reduce the disease burden of childhood asthma.

Objective:To investigate the feasibility and clinical effects of the application of augmented reality (AR) navigation on assisted design of the chimeric twin-paddled anterolateral thigh perforator flap (ALTPF) in reconstruction of soft tissue defects in extremities.Methods:From June 2017 to June 2023, 8 patients with soft tissue defects in extremities received reconstruction of chimeric twin-paddled ALTPF designed with the assistance of AR navigation in Department of Hand & Foot Microsurgery Orthopaedics, Guigang City People’s Hospital. All of them were traffic accidents or machine injuries, with 3 cases of calf, 2 cases of ankle, 1 case of foot, and 2 cases of hand defects. All the wounds were wide or irregular (defect sized 14 cm×14 cm-25 cm×13 cm). The images of bilateral thighs were acquired by CT angiography preoperatively. The dominant side and dominant perforators were selected. Three dimensional reconstruction was performed by Mimics software. AR technology was applied to guide the design and harvest of the chimeric twin-paddled ALTPF. Flap area was 15 cm × 16 cm to 26 cm × 14 cm. The donor site was sutured directly. Follow-up with outpatient visits or WeChat images and videos at 1, 3, 6 and 12 months postoperatively to record the appearance, colour, texture, recurrence of infection, and knee extension function of the flap donor site.Results:According to the preoperative design, the perforator flaps were harvested and transferred in all the 8 patients. All flaps survived and the recipient and donor sites healed in one stage. All patients entered postoperative follow-up for 3 to 12 (mean, 8.6)months. The colour and texture of the flaps were excellent, and the appearance of donor and recipient sites was satisfactory. Two patients with hand injuries were evaluated using the brief Michigan Hand Outcomes Questionnaire (MHQ), with scores of 43.74 and 81.25, respectively. Six patients with lower limb injuries were evaluated using the Maryland foot score, with scores of 2 excellent, 3 good and 1 fair.Conclusion:The application of AR navigation can effectively assist the design of a chimeric twin-paddled ALTPF. It also provides an effective basis for clinical personalised flap design.

Objective To analyze the detection efficiency of p16INK4a protein combined with human papillomavirus and liquid-based cytology(LCT)in the screening of cervical precancerous lesions,and to provide a basis for cervical cancer preven-tion and treatment.Methods The results of p16INK4a staining of cervical epithelial cells,human papillomavirus testing and cer-vical cytology were analyzed in 139 inpatients at Guangzhou Women's and Children's Medical Center between January 2019 and December 2020.Of them,there were 111 patients with cervical intraepithelial neoplasia(CIN)and 28 cases of cervical inflam-matory disease.The efficacy of the three methods alone and in combination to screen for CIN lesions was compared.Results In the detection of CIN patients,the sensitivity of p16INK4a,microfluidic microarray and cervical cytology for detecting CIN and a-bove lesions was 91.89% ,94.59% and82.88% ,with specificity of 57.14% ,17.86% and46.43% ,and AUC of 0.75,0.56 and 0.65,respectively;while the sensitivity of"p16INK4a+LCT","p16INK4a+hrHPV","LCT+hrHPV"and their sen-sitivity were 96.40% ,97.30% ,94.59% and 99.10% ,their specificity was 85.71% ,92.86% ,89.29% and 92.86% ,and the AUC was 0.91,0.95,0.92 and 0.96,respectively.Conclusion The combined p16INK4a and hrHPV test helps to improve diagnostic accuracy and early detection,thus allowing for earlier intervention or treatment.This combined application allows for more accurate identification of low-grade and high-grade cervical intraepithelial neoplasia,providing more information for indi-vidualized patient management.

Objective This study aimed to clarify the intervention effect of salidroside(SAL)on lung injury caused by PM2.5 in mice and illuminate the function of SIRT1-PGC-1ɑ axis. Methods Specific pathogen-free(SPF)grade male C57BL/6 mice were randomly assigned to the following groups:control group,SAL group,PM2.5 group,SAL+PM2.5 group.On the first day,SAL was given by gavage,and on the second day,PM2.5 suspension was given by intratracheal instillation.The whole experiment consist of a total of 10 cycles,lasting 20 days.At the end of treatment,blood samples and lung tissues were collected and analyzed.Observation of pathological changes in lung tissue using inverted microscopy and transmission electron microscopy.The expression of inflammatory,antioxidants,apoptosis,and SIRT1-PGC-1ɑ proteins were detected by Western blotting. Results Exposure to PM2.5 leads to obvious morphological and pathologica changes in the lung of mice.PM2.5 caused a decline in levels of antioxidant-related enzymes and protein expressions of HO-1,Nrf2,SOD2,SIRT1 and PGC-1ɑ,and an increase in the protein expressions of IL-6,IL-1β,Bax,caspase-9 and cleaved caspase-3.However,SAL reversed the aforementioned changes caused by PM2.5 by activating the SIRT1-PGC-1α pathway. Conclusion SAL can activate SIRT1-PGC-1ɑ to ameliorate PM2.5-induced lung injury.

Objective To explore the value of T2*mapping in quantitatively evaluate changes in knee joint cartilage and subchon-dral bone of new recruits before and after intensive training.Methods MRI scans of the right knee joint were performed three times on 20 new recruits:before intensive training,after one week of intensive training,and after one month of rest.The knee joint cartilage was divided into six regions:lateral femur(LF),medial femur(MF),lateral tibia(LT),medial tibia(MT),patella cartilage(PC),and trochlea cartilage(TC).Using the posterior angle of the meniscus as a boundary,LF and MF were divided into the cLF/cMF and pLF/pMF.Divid-ed into superficial zone(SZ)cartilage and deep zone(DZ)cartilage based on a thickness of 1/2 of the cartilage.The subchondral bone was divided into superficial bone(SB)within 5 mm of the joint cartilage,and deep bone(DB)within 6-10 mm of the joint cartilage.The T2*values of each region of cartilage and subchondral bone were evaluated through region of interest(ROI)analysis.Single fac-tor analysis of variance was used to compare the changes in T2*values.The LSD test method was used for inter-group comparison.Results After one week of intensive training,MT-SZ,cMF-SZ,PC-SZ,TC-SZ were significantly higher than before intensive training(P＜0.05).After one month of rest,there was no statistically significant difference in the T2*value of the cartilage area compared with before intensive training(P＞0.05).There was a trend of"rising first and then falling".There was no statistically signifi-cant difference in the T2*value of subchondral bone of the knee joint before intensive training and after one week of intensive training(P＞0.05).Compared with after one month of rest,except for cLF-DB,pLF-DB,trochlea cartilage-deep bone(TC-DB),the T2*value of the subchondral bone of the remaining knee joint increased before intensive training and after one week of intensive training,with sta-tistically significant differences(P＜0.05).Conclusion T2*mapping can display the changes in the ultrastructure and biochemical components of joint cartilage and subchondral bone after the new recruits intensive training,detect early injuries and conduct non-invasive quantitative evaluation.

Objective To explore clinical effect of distal tibial tubercle-high tibial osteotomy(DTT-HTO)in treating knee osteoarthritis(KO A)with medial meniscus posterior root tear(MMPRT).Methods A retrospective analysis was performed on 21 patients with varus KOA with MMPRT from May 2020 to December 2021,including 3 males and 18 females,aged from 49 to 75 years old with an average of(63.81±6.56)years old,the courses of disease ranged from 0.5 to 18.0 years with an average of(5.9±4.2)years,and 4 patients with grade Ⅱ,14 patients with grade Ⅲ,and 3 patients with grade Ⅳ according to Kellgren-Lawrence;14 patients with type 1 and 7 patients with type 2 according to MMPRT damage classification.The distance of medi-al meniscusextrusion(MME)and weight-bearing line ratio(WBLR)of lower extremity were compared before and 12 months after operation.Visual analogue scale(V AS),Western Ontarioand and McMaster Universities(WOMAC)osteoarthritis index,and Lysholm knee score were used to evaluate knee pain and functional improvement before operation,1,6 and 12 months after operation,respectively.Results Twenty-one patients were followed up for 12 to 18 months with an average of(13.52±1.72)months.MME distance was improved from(4.99±1.05)mm before operation to(1.87±0.76)mm at 12 months after operation(P＜0.05).WBLR was increased from(15.49±7.04)％before operation to(62.71±2.27)％at 12 months after operation(P＜0.05).VAS was decreased from(7.00±1.14)before operation to(2.04±0.80),(0.90±0.62)and(0.61±0.50)at 1,6 and 12 months after operation.WOMAC were decreased from preoperative(147.90±9.88)to postoperative(103.43±8.52),(74.00±9.54)and(47.62±9.53)at 1,6 and 12 months,and the difference were statistically significant(P＜0.05).Lysholm scores were increased from(46.04±7.34)before oepration to(63.19±8.93),(81.10±6.41)and(89.29±3.04)at 1,6 and 12 months after operation(P＜0.05).Conclusion For the treatment of varus KOA with MMPRT,DTT-HTO could reduce medial meniscus pro-trusion distance,improve the ratio of lower limb force line,and effectively reduce knee pain and improve knee joint function.

Objective To observe the changes of expression of lysyl oxidase family(LOXs)on the retina in acute ocular hypertension(AOH)rats.Methods The SD adult male rats were randomly divided into the control group(CON group)and the AOH group.The rats in the CON group were fed normally without any treatment,and the rats in the AOH group were established AOH model by anterior chamber perfusion.All rats were sacrificed after 2 weeks and retinal tissues were collected.The expression of LOXs[including lysyl oxidase(LOX)and lysyl oxidase-like proteins of LOXL1,LOXL2,LOXL3,LOXL4],and the expression of extracellular matrix(ECM)proteins of Collagen 1/3/4 a1(Col1/3/4 a1),Elastin(Eln),and Fibulin1/4(Fbn 1/4)in the retinal tissues were detected by qRT-PCR.The localiza-tion of LOXs in rat retina was detected by immunohistochemistry.The expression of LOX in retina was detected by Western blot.Results LOXs were expressed to varying degrees in all layers of the rat retina,LOX was mainly expressed in the retinal ganglion cell layer,nerve fiber layer,inner plexiform layer and outer plexiform layer;LOXL1 was mainly expressed in the inner plexiform layer,outer plexiform layer and vascular wall;LOXL2 was mainly expressed in retinal ganglion cell layer,inner plexiform layer and inner nuclear layer;LOXL4 was mainly expressed in the inner plexiform layer and inner nuclear layer;while LOXL3 was only expressed in the vascular wall.Compared with the CON group,the expression of LOX,Col1a1 and Eln in the retina of rats in the AOH group were significantly increased(P<0.05),and there was no significantly significant difference in the expression of LOXL1,LOXL2,LOXL3,LOXL4,Col3a1,Col4a1,Fbn1,Fbn4 mRNAs in the retina of rats between the two groups(P>0.05).Conclusion LOX is highly expressed in the retina of AOH rats,which may be involved in the pathological process of retinal injury caused by high intraocular pressure through ECM remodeling.

Objective:To explore the effect of TP53 mutation variant allele frequency(VAF)on the prognosis of diffuse large B-cell lymphoma(DLBCL)patients.Methods:This study included 155 patients with DLBCL who were first diagnosed in the People's Hospital of Xinjiang Uygur Autonomous Region from March 2009 to March 2022. Complete clinical data and paraffin-embedded tumor tissue samples were obtained,and DNA was extracted from tumor tissues.The gene mutation profile of DLBCL patients was detected and analyzed by second-generation sequencing technology.Kaplan-Meier method was used to analyze the mutation status of TP53 gene and the relationship between mutation VAF and OS.Cox regression univariate and multivariate analysis was use to analyze the independent factors affecting OS.A nornogram model for predicting 1,3,and 5 years OS in DLBCL patients were established to evaluated the performance of the model based on C-index and calibration curves.Results:The average value of TP53 mutation VAF in male DLBCL patients was significantly higher than that in female patients (P<0.05 ).Patients with TP53 mutantion had shorter OS than those with wild-type patients (P=0.030).The optimal VAF threshold for TP53 mutation based on OS stratification was 33.61％(P<0.001),and patients with TP53 mutation VAF≥34％had shorter OS than those with TP53 mutation VAF<34％and wild-type patients (P<0.001).Multivariate Cox analysis showed that TP53 mutation VAF≥34％ was an independent poor predictor of OS (HR=4.05,P<0.001),and IPI score ≥3 was an independent predictor of OS poor (HR=2.27,P=0.008).In combination with factors with independent prognostic significance obtained from multi-factor analysis,we constructed a nomogram model for predicting 1-year,3-year,5-year OS in DLBCL patients.The results showed that the C index of TP53-mutated VAF combined with IPI model was 0.743,which predicted the value of 1-year,3-year,and 5-year OS in DLBCL patients.Calibration curves show that the model has good agreement between predicted and actual survival of DLBCL patients at 1-year,3-year,and 5-year. Conclusion:TP53 mutant VAF has prognostic value in DLBCL patients,and TP53 mutant VAF≥34％ is an independent risk factor for OS in DLBCL patients.The prognosis model of TP53 mutation VAF combined with IPI nomogram constructed in this study has good predictive performance for DLBCL patients.