Azvudine and nirmatrelvir/ritonavir (Paxlovid) are recommended for COVID-19 treatment in China, but their safety and efficacy in the elderly population are not fully known. In this multicenter, retrospective, cohort study, we identified 5131 elderly hospitalized COVID-19 patients from 32,864 COVID-19 patients admitted to nine hospitals in Henan Province, China, from December 5, 2022, to January 31, 2023. The primary outcome was all-cause death, and the secondary outcome was composite disease progression. Propensity score matching (PSM) was performed to control for confounding factors, including demographics, vaccination status, comorbidities, and laboratory tests. After 2:1 PSM, 1786 elderly patients receiving azvudine and 893 elderly patients receiving Paxlovid were included. Kaplan-Meier and Cox regression analyses revealed that compared with Paxlovid group, azvudine could significantly reduce the risk of all-cause death (log-rank P = 0.002; HR: 0.71, 95% CI: 0.573-0.883, P = 0.002), but there was no difference in composite disease progression (log-rank P = 0.52; HR: 1.05, 95% CI: 0.877-1.260, P = 0.588). Four sensitivity analyses verified the robustness of above results. Subgroup analysis suggested that a greater benefit of azvudine over Paxlovid was observed in elderly patients with primary malignant tumors (P for interaction = 0.005, HR: 0.32, 95% CI: 0.18-0.57) compared to patients without primary malignant tumors. Safety analysis revealed that azvudine treatment had a lower incidence of adverse events and higher lymphocyte levels than Paxlovid treatment. In conclusion, azvudine treatment is not inferior to Paxlovid treatment in terms of all-cause death, composite disease progression and adverse events in elderly hospitalized COVID-19 patients.

OBJECTIVE To study the anti-ulcerative colitis(UC) effect of Sargentodoxae Caulis and explore its mechanism. METHODS The UC mice model induced by dextran sodium sulfate was used to evaluate the anti-UC effect of Sargentodoxae Caulis. The ingredients of Sargentodoxae Caulis were obtained according to the CNKI and PubMed website, component targets were screened by SwissTargetPrediction database, GEO gene chip was used to extract UC differential genes, then a network of "ingredients-targets-disease" of the Sargentodoxae Caulis was constructed. After screening the core targets, protein interaction and cluster analysis, biological process and pathway enrichment analysis were performed, and the reliability of network analysis was preliminarily verified by molecular docking and literatures. RESULTS Sargentodoxae Caulis could significantly improve the disease activity index score, colon shortening and colonic histopathological changes of UC mice, and had a good anti-UC effect. The network analysis found that the core components of the anti-UC of Sargentodoxae Caulis include (+)-Dihydroxyurearetic acid, Isorhaponigenin and Pinosylvin, and 63 core targets, such as EGFR, STAT1 and LCK, regulating PI3K-Akt signal pathway and cancer proteoglycan and other related signal pathways of immune anti-inflammatory and anti-cancer, and it could affect the biological processes such as amino acid modification, kinase activity regulation, cell reaction and oxidative stress to treat UC. Molecular docking and literature showed that the constructed network had high reliability. CONCLUSION Sargentodoxae Caulis has a good anti-UC effect, and its mechanism may be closely related to the regulation of intestinal immune inflammation and cell proliferation, differentiation and migration. It has the characteristics of multi-component, multi-target and multi-way.

Pancreatic cancer induced by mutation KRAS exhibited a higher risk of incidence, recurrence and mortality. C-Myc is downstream of KRAS and can be involved in the regulation of multiple oncogenic pathways and signaling pathways in pancreatic cancer. Over expressing of C-Myc promotes glycolysis and glutamine uptake in pancreatic cancer cells, promotes cell metabolism and proliferation, is an important factor driving the progress and maintenance of pancreatic cancer, and is related to chemotherapy and immunotherapy drug resistance. C-Myc also interacts with cell cyclin-dependent kinase(CDK) and non-coding RNA to regulate the proliferation, development and metastasis of pancreatic cancer. Therefore, targeting C-Myc was regarded as an effective strategy for the treatment of pancreatic cancer. The activation of C-Myc depends on heterodimerization with its partner MAX and thereby paly a role through binding to the canonical E-Box sequence 5’-CACGTG-3’. Researches showed direct targeting of C-Myc can inhibit the growth of pancreatic carcinoma,such as promoting the degradation of C-Myc, inhibiting the binding of C-Myc/MAX and blocking the binding of C-Myc/MAX to E-box. However, direct targeting has been proved challenging because of its special protein structure. Indirect targeting of C-Myc provided a new strategy for the treatment of pancreatic cancer. C-Myc can be indirected targeting through inhibiting transcription and translation of C-Myc, C-Myc-MAX heterodimerization and promote the ubiquitination and degradation of C-Myc, thus affects the occurrence, development and metastasis of pancreatic cancer.

At present,the commonly used clinical protocols of oral comestic restoration are mostly based on the aes-thetic indicators proposed by Western developed countries(referred to as Western aesthetics).Mechanically copying the Western aesthetic scheme,ignoring the difference between it and the Chinese oral aesthetic indicators(referred to as Chinese aesthetics),is unable to effectively support personalized cosmetic restoration diagnosis and treatment.In addition,new technologies and new solutions for cosmetic restoration,which are developing rapidly in recent years,are emerging one after another,but many popular concepts are confusing and lack of proper hierarchical diagnosis and treatment norms,and there is indeed an urgent need for discussion and clarity.From the perspective of serving clinical application,this paper discusses the deficiencies of the Chinese translation of the word"aesthetics",the diffe-rence and connection between aesthetics and cosmetolo-gy,and the relationship between cosmetic restoration and fixed restoration.It also discusses the difference be-tween anterior teeth,esthetic zone and exposed zone,the diagnostic and therapeutic value of oral aesthetic analysis,as well as the application methods of desensitization,suggestion,and other therapies in difficult oral cosmetic restoration cases.We further introduce the decision tree and the clinical pathway for restoration and reconstruction of teeth in ex-posed zone guided by aesthetic analysis,and introduce the clinical process of aesthetic analysis and evaluation,the clinical triclassification of oral cosmetic restoration,and the corresponding clinical classification diagnosis and treat-ment points.

At present,the commonly used clinical protocols of oral cosmetic restoration are mostly based on the oral aesthetic indexes proposed by Western developed countries(referred to as Western aesthetics),which are different from the oral aesthetic indexes unique to Chinese people(referred to as Chinese aesthetics).In the design of restoration schemes and the evaluation of restoration effects,these differences have a large or small effect on the doctor-patient-tech-nology triad.Improper handling could directly weaken the cooperation efficiency of the three parties,reduce patient satis-faction,and even lead to medical disputes in serious cases.From doing a good job of oral cosmetic restoration in China,the connotative characteristics of Chinese oral aesthetics are introduced in this paper,and the value of oral aesthetic anal-ysis in diagnosis and treatment is discussed.The process and method of aesthetic analysis and assessment through the modified Chinese psychosocial impact of dental aesthetics questionnaire and the evaluation ruler of the expected value of oral cosmetic restoration are further introduced in detail.

Objective:To investigate the clinical effects of combined tissue flap transplantation in repairing giant chest wall defects.Methods:This study was a retrospective observational study. From August 2013 to December 2020, 31 patients with chest wall tumor or radiation ulcer after radical resection of chest wall tumor and conformed to the inclusion criteria were admitted to the Department of Breast Oncoplastic Surgery of Hunan Cancer Hospital, including 12 males and 19 females, aged 25-71 years. After resection of tumor or ulcer and wound debridement, the area of secondary chest wall defect was 300-600 cm 2 with length of 16-35 cm and width of 16-32 cm. According to the actual situation of the patients and the preoperative design, the chest wall defects were repaired with the flexible combination of perforator flaps and myocutaneous flaps from different donor sites, and the area of the combined tissue flap was 260-540 cm 2 with length of 20-30 cm and width of 13-20 cm. Free posteromedial thigh perforator flap+free anterolateral thigh myocutaneous flap were used in 2 patients, free deep inferior epigastric artery perforator flap+free anterolateral thigh myocutaneous flap were used in 5 patients, free deep inferior epigastric artery perforator flap+pedicled rectus abdominis myocutaneous flap+free anterolateral thigh myocutaneous flap were used in 7 patients, free deep inferior epigastric artery perforator flap+pedicled rectus abdominis myocutaneous flap+pedicled latissimus dorsi myocutaneous flap were used in 2 patients, and bilateral free anterolateral thigh myocutaneous flaps were used in 15 patients. For the remaining small area of superficial tissue defect after being repaired by combined tissue flaps, skin graft was used to repair or delayed local flap transfering was performed after the tissue flaps survived and edema subsided. The appropriate blood vessels in the donor and recipient sites were selected for anastomosis to reconstruct the blood supply of tissue flaps. The wounds in the donor sites of tissue flaps that can be directly sutured were sutured directly; for those that cannot be sutured directly, the skin grafting or delayed suture was performed. The anastomosis of blood vessels in the recipient sites, operation length, and postoperative hospital stay were recorded. The survivals of tissue flaps and skin grafts, the shape and texture of reconstructed chest wall, the wound healing, scar formation, and function of donor sites of tissue flaps, and the scar formation of the donor sites of skin grafts were observed after operation. Tumor recurrence and death of recurrent patients were followed up after operation. Results:The blood vessels in the recipient sites were anastomosed as follows: proximal internal thoracic vessels for 24 times, distal internal thoracic vessels for 12 times, trunk of thoracodorsal vessels for 4 times, anterior serratus branches of thoracodorsal vessels for 8 times, and thoracoacromial vessels for 12 times. The operation length was 6.0 to 8.5 hours, and the postoperative hospital stay was 9 to 21 days. Necrosis at the edge of partial tissue flaps occurred in 4 patients after operation, which healed after dressing change, and the tissue flaps and skin grafts of the other patients survived completely. The shape and texture of the reconstructed chest wall were good. Four patients had poor wound healing in the donor sites of abdominal tissue flaps, which healed after dressing change and local drainage. Only linear scar was left in the donor sites of all tissue flaps, and there was no obvious dysfunction in the donor sites of tissue flaps. Mild hypertrophic scar was left in the donor sites of skin grafts. During follow-up of 9 to 36 months after operation, 6 patients had tumor recurrence, and the recurrence time was 5 to 20 months after operation. After comprehensive treatment for patients with tumor recurrence, 3 patients died.Conclusions:Transplantation of combined tissue flaps in repairing the giant chest wall defects can shorten the time of total operation and hospital stay, and avoid multiple operations. After operation, patients had good chest wall appearance, with reduced tumor recurrence in patients with chest wall tumor.

Purpose/Significance To bridge the digital service gap of the digital wellness consortium in Zhejiang province.Method/Process The study systematically reviews the evolution and development of digital elderly care theories and practices,using the digital wellness consortium in Zhejiang province as a case study,and examines it from theoretical,modeling,and practical dimensions.Result/Conclusion The digital wellness consortium has made rapid progress in recent years,however,it still faces numerous challenges in provi-ding digital elderly care services.From the perspective of digital adaptation for the elderly,the development strategies for the consortium are proposed at the government,corporate,and community levels.

P21-activated kinase 5 (PAK5) belongs to the PAK-II subfamily, which is an important regulator of cell survival, adhesion, and motility. However, the functions of PAK5 in endometriosis remain unclear. Here, PAK5 is strikingly upregulated in endometriosis. Furthermore, the knockdown of PAK5 or its inhibitor GNE 2861 blocks the development of endometriosis, which is equally demonstrated in PAK5-knockout mice. In addition, PAK5 promotes glycolysis by enhancing the protein stability of pyruvate kinase 2 (PKM2) in endometriotic cells, which is a key enzyme for glucose metabolism. Moreover, the phosphorylation of PKM2 at Ser519 by PAK5 mediates endometriosis cell proliferation and metastasis. Collectively, PAK5 plays an indispensable role in endometriosis. Our findings demonstrate that PAK5 is an important target for the treatment of endometriosis.
Endometriosis/genetics* ; Female ; Animals ; p21-Activated Kinases/genetics* ; Mice ; Phosphorylation ; Glycolysis ; Humans ; Thyroid Hormone-Binding Proteins ; Membrane Proteins/genetics* ; Carrier Proteins/genetics* ; Cell Proliferation ; Mice, Knockout ; Thyroid Hormones/metabolism* ; Pyruvate Kinase/genetics*