[Incidence of postoperative complications in Chinese patients with gastric or colorectal cancer based on a national, multicenter, prospective, cohort study].

Objective: To investigate the incidence of postoperative complications in Chinese patients with gastric or colorectal cancer, and to evaluate the risk factors for postoperative complications. Methods: This was a national, multicenter, prospective, registry-based, cohort study of data obtained from the database of the Prevalence of Abdominal Complications After Gastro- enterological Surgery (PACAGE) study sponsored by the China Gastrointestinal Cancer Surgical Union. The PACAGE database prospectively collected general demographic characteristics, protocols for perioperative treatment, and variables associated with postoperative complications in patients treated for gastric or colorectal cancer in 20 medical centers from December 2018 to December 2020. The patients were grouped according to the presence or absence of postoperative complications. Postoperative complications were categorized and graded in accordance with the expert consensus on postoperative complications in gastrointestinal oncology surgery and Clavien-Dindo grading criteria. The incidence of postoperative complications of different grades are presented as bar charts. Independent risk factors for occurrence of postoperative complications were identified by multifactorial unconditional logistic regression. Results: The study cohort comprised 3926 patients with gastric or colorectal cancer, 657 (16.7%) of whom had a total of 876 postoperative complications. Serious complications (Grade III and above) occurred in 4.0% of patients (156/3926). The rate of Grade V complications was 0.2% (7/3926). The cohort included 2271 patients with gastric cancer with a postoperative complication rate of 18.1% (412/2271) and serious complication rate of 4.7% (106/2271); and 1655 with colorectal cancer, with a postoperative complication rate of 14.8% (245/1655) and serious complication rate of 3.0% (50/1655). The incidences of anastomotic leakage in patients with gastric and colorectal cancer were 3.3% (74/2271) and 3.4% (56/1655), respectively. Abdominal infection was the most frequently occurring complication, accounting for 28.7% (164/572) and 39.5% (120/304) of postoperative complications in patients with gastric and colorectal cancer, respectively. The most frequently occurring grade of postoperative complication was Grade II, accounting for 65.4% (374/572) and 56.6% (172/304) of complications in patients with gastric and colorectal cancers, respectively. Multifactorial analysis identified (1) the following independent risk factors for postoperative complications in patients in the gastric cancer group: preoperative comorbidities (OR=2.54, 95%CI: 1.51-4.28, P<0.001), neoadjuvant therapy (OR=1.42, 95%CI:1.06-1.89, P=0.020), high American Society of Anesthesiologists (ASA) scores (ASA score 2 points:OR=1.60, 95% CI: 1.23-2.07, P<0.001, ASA score ≥3 points:OR=0.43, 95% CI: 0.25-0.73, P=0.002), operative time >180 minutes (OR=1.81, 95% CI: 1.42-2.31, P<0.001), intraoperative bleeding >50 mL (OR=1.29,95%CI: 1.01-1.63, P=0.038), and distal gastrectomy compared with total gastrectomy (OR=0.65,95%CI: 0.51-0.83, P<0.001); and (2) the following independent risk factors for postoperative complications in patients in the colorectal cancer group: female (OR=0.60, 95%CI: 0.44-0.80, P<0.001), preoperative comorbidities (OR=2.73, 95%CI: 1.25-5.99, P=0.030), neoadjuvant therapy (OR=1.83, 95%CI:1.23-2.72, P=0.008), laparoscopic surgery (OR=0.47, 95%CI: 0.30-0.72, P=0.022), and abdominoperineal resection compared with low anterior resection (OR=2.74, 95%CI: 1.71-4.41, P<0.001). Conclusion: Postoperative complications associated with various types of infection were the most frequent complications in patients with gastric or colorectal cancer. Although the risk factors for postoperative complications differed between patients with gastric cancer and those with colorectal cancer, the presence of preoperative comorbidities, administration of neoadjuvant therapy, and extent of surgical resection, were the commonest factors associated with postoperative complications in patients of both categories.

The Essential Role of Proteoglycans and Glycosaminoglycans in Odontogenesis.

Tooth development and regeneration are regulated through a complex signaling network. Previous studies have focused on the exploration of intracellular signaling regulatory networks, but the regulatory roles of extracellular networks have only been revealed recently. Proteoglycans, which are essential components of the extracellular matrix (ECM) and pivotal signaling molecules, are extensively involved in the process of odontogenesis. Proteoglycans are composed of core proteins and covalently attached glycosaminoglycan chains (GAGs). The core proteins exhibit spatiotemporal expression patterns during odontogenesis and are pivotal for dental tissue formation and periodontium development. Knockout of core protein genes Biglycan, Decorin, Perlecan, and Fibromodulin has been shown to result in structural defects in enamel and dentin mineralization. They are also closely involved in the development and homeostasis of periodontium by regulating signaling transduction. As the functional component of proteoglycans, GAGs are negatively charged unbranched polysaccharides that consist of repeating disaccharides with various sulfation groups; they provide binding sites for cytokines and growth factors in regulating various cellular processes. In mice, GAG deficiency in dental epithelium leads to the reinitiation of tooth germ development and the formation of supernumerary incisors. Furthermore, GAGs are critical for the differentiation of dental stem cells. Inhibition of GAGs assembly hinders the differentiation of ameloblasts and odontoblasts. In summary, core proteins and GAGs are expressed distinctly and exert different functions at various stages of odontogenesis. Given their unique contributions in odontogenesis, this review summarizes the roles of proteoglycans and GAGs throughout the process of odontogenesis to provide a comprehensive understanding of tooth development.

[Association of urinary cadmium level with body mass index and body circumferences among older adults over 65 years old in 9 longevity areas of China].

Objective: To investigate the association of urinary cadmium level with body mass index (BMI) and body circumferences among the older adults over 65 years old in 9 longevity areas of China. Methods: Subjects were older adults over 65 years old from the Healthy Aging and Biomarkers Cohort Study (HABCS) between 2017 and 2018 conducted in 9 longevity areas in China. A total of 1 968 older adults were included in this study. Information including socio-demographic characteristics, lifestyles, diet intake, and health status was collected by using questionnaires and physical examinations. Urine samples were collected to detect urinary cadmium and creatinine levels. Body circumferences included waist circumference, hip circumference and calf circumference. Subjects were divided into three groups (low:<0.77 µg/g·creatinine, middle:0.77-1.69 µg/g·creatinine, high:≥1.69 µg/g·creatinine) by tertiles of creatinine-adjusted urinary cadmium concentration. Multiple linear regression models were used to analyze the association of creatinine-adjusted urinary cadmium level with BMI and body circumferences. The dose-response relationship of creatinine-adjusted urinary cadmium concentration with BMI and body circumferences was analyzed by using restrictive cubic splines fitting multiple linear regression model. Results: The mean age of subjects was (83.34±11.14) years old. The median (Q1, Q3) concentration of creatinine-adjusted urinary cadmium was 1.13 (0.63, 2.09) µg/g·creatinine, and the BMI was (22.70±3.82) kg/m2. The mean values of waist circumference, hip circumference, and calf circumference were (85.42±10.68) cm, (92.67±8.90) cm, and (31.08±4.76) cm, respectively. After controlling confounding factors, the results of the multiple linear regression model showed that for each increment of 1 µg/g·creatinine in creatinine-adjusted urinary cadmium, the change of BMI, waist circumference, hip circumference, and calf circumference in the high-level group was -0.28 (-0.37, -0.19) kg/m2, -0.74 (-0.96, -0.52) cm, -0.78 (-0.96, -0.61) cm, and -0.20 (-0.30, -0.11) cm, respectively. The restrictive cubic splines curve showed a negative nonlinear association of creatinine-adjusted urinary cadmium with BMI (Pnonlinear<0.001) and negative linear associations of creatinine-adjusted urinary cadmium with waist circumference (Plinear<0.001), hip circumference (Plinear<0.001), and calf circumference (Plinear<0.001). Conclusion: Urinary cadmium level is significantly associated with decreased BMI, waist circumference, hip circumference and calf circumference among older adults over 65 years old in 9 longevity areas of China.

AI's Role in Improving Social Connection and Oral Health for Older Adults: A Synergistic Approach.

KNOWLEDGE TRANSFER STATEMENT: This study explored how artificial intelligence (AI) can revolutionize geriatric care by improving oral health and alleviating social disconnection among isolated older adults. The findings can guide clinicians in integrating AI tools into practices, assist policymakers in developing AI-inclusive health policies, and inform patients about the potential benefits of AI in enhancing their health outcomes and social connection.

[Association of sleep duration and physical exercise with dyslipidemia in older adults aged 80 years and over in China].

Objective: To explore the impact of sleep duration, physical exercise, and their interactions on the risk of dyslipidemia in older adults aged ≥80 (the oldest old) in China. Methods: The study subjects were the oldest old from four rounds of Healthy Aging and Biomarkers Cohort Study (2008-2009, 2011-2012, 2014 and 2017-2018). The information about their demographic characteristics, lifestyles, physical examination results and others were collected, and fasting venous blood samples were collected from them for blood lipid testing. Competing risk model was used to analyze the causal associations of sleep duration and physical exercise with the risk for dyslipidemia. Restricted cubic spline (RCS) function was used to explore the dose-response relationship between sleep duration and the risk for dyslipidemia. Additive and multiplicative interaction model were used to explore the interaction of sleep duration and physical exercise on the risk for dyslipidemia. Results: The average age of 1 809 subjects was (93.1±7.7) years, 65.1% of them were women. The average sleep duration of the subjects was (8.0±2.5) hours/day, 28.1% of them had sleep duration for less than 7 hours/day, and 27.2% had sleep for duration more than 9 hours/day at baseline survey. During the 9-year cumulative follow-up of 6 150.6 person years (follow-up of average 3.4 years for one person), there were 304 new cases of dyslipidemia, with an incidence density of 4 942.6/100 000 person years. The results of competitive risk model analysis showed that compared with those who slept for 7-9 hours/day, the risk for dyslipidemia in oldest old with sleep duration >9 hours/day increased by 22% (HR=1.22, 95%CI: 1.07-1.39). Compared with the oldest old having no physical exercise, the risk for dyslipidemia in the oldest old having physical exercise decreased by 33% (HR=0.67, 95%CI: 0.57-0.78). The RCS function showed a linear positive dose-response relationship between sleep duration and the risk for hyperlipidemia. The interaction analysis showed that physical exercise and sleep duration had an antagonistic effect on the risk for hyperlipidemia. Conclusion: Physical exercise could reduce the adverse effects of prolonged sleep on blood lipids in the oldest old.

Toripalimab plus axitinib versus sunitinib as first-line treatment for advanced renal cell carcinoma: RENOTORCH, a randomized, open-label, phase III study.

BACKGROUND: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC. PATIENTS AND METHODS: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety. RESULTS: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group. CONCLUSION: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975.

Response-guided neoadjuvant sacituzumab govitecan for localized triple-negative breast cancer: results from the NeoSTAR trial.

BACKGROUND: Sacituzumab govitecan (SG), a novel antibody-drug conjugate (ADC) targeting TROP2, is approved for pre-treated metastatic triple-negative breast cancer (mTNBC). We conducted an investigator-initiated clinical trial evaluating neoadjuvant (NA) SG (NCT04230109), and report primary results. PATIENTS AND METHODS: Participants with early-stage TNBC received NA SG for four cycles. The primary objective was to assess pathological complete response (pCR) rate in breast and lymph nodes (ypT0/isN0) to SG. Secondary objectives included overall response rate (ORR), safety, event-free survival (EFS), and predictive biomarkers. A response-guided approach was utilized, and subsequent systemic therapy decisions were at the discretion of the treating physician. RESULTS: From July 2020 to August 2021, 50 participants were enrolled (median age = 48.5 years; 13 clinical stage I disease, 26 stage II, 11 stage III). Forty-nine (98%) completed four cycles of SG. Overall, the pCR rate with SG alone was 30% [n = 15, 95% confidence interval (CI) 18% to 45%]. The ORR per RECIST V1.1 after SG alone was 64% (n = 32/50, 95% CI 77% to 98%). Higher Ki-67 and tumor-infiltrating lymphocytes (TILs) were predictive of pCR to SG (P = 0.007 for Ki-67 and 0.002 for TILs), while baseline TROP2 expression was not (P = 0.440). Common adverse events were nausea (82%), fatigue (76%), alopecia (76%), neutropenia (44%), and rash (48%). With a median follow-up time of 18.9 months (95% CI 16.3-21.9 months), the 2-year EFS for all participants was 95%. Among participants with a pCR with SG (n = 15), the 2-year EFS was 100%. CONCLUSIONS: In the first NA trial with an ADC in localized TNBC, SG demonstrated single-agent efficacy and feasibility of response-guided escalation/de-escalation. Further research on optimal duration of SG as well as NA combination strategies, including immunotherapy, are needed.

Effect of modified gastrointestinal decompression under abdominal CT in patients with intestinal obstruction.

INTRODUCTION: We aimed to evaluate the effect of continuous quality improvement on modified gastrointestinal decompression under abdominal computed tomography (CT) in patients with intestinal obstruction. METHODS: The CT images of 74 patients with intestinal obstruction who underwent gastrointestinal decompression in our hospital from 1 January 2018 to 31 December 2019 were analysed retrospectively (Control group). Factors influencing unsatisfactory decompression effects were analysed, and corresponding improvement measures were formulated and implemented. A total of 77 patients from 1 January 2020 to 31 March 2022 were enrolled prospectively (Study group). The position of the nasogastric tube end, the amount of gastric drainage within 24h and the degree of abdominal distension relief were compared before and after the improvement. RESULTS: After implementation of continuous quality improvement, the proportion of the end of the nasogastric tube reaching the antrum, the amount of gastric fluid drainage within 24h and the degree of abdominal distension relief were better than those before improvement (p<0.001, respectively). The execution rate and accuracy rate of CT interpretations by nurses reached 100% and 82%, respectively. CONCLUSIONS: Modified gastrointestinal decompression based on abdominal CT scans can increase the success of gastrointestinal decompression and effectively reduce the discomfort of patients.

Geroscience: Aging and Oral Health Research.

Research in aging has significantly advanced; scientists are now able to identify interventions that slow the biologic aging processes (i.e., the "hallmarks of aging"), thus delaying the onset and progression of multiple diseases, including oral conditions. Presentations given during the 3-part session "Geroscience: Aging and Oral Health Research," held during the 2023 American Association for Dental, Oral, and Craniofacial Research meeting, are summarized in this publication. Speakers' topics spanned the translational research spectrum. Session 1 provided an overview of the geroscience and health span (disease-free and functional health throughout life) concepts. The common molecular mechanisms between oral cancer and aging were discussed, and research was presented that showed periodontal microflora as a potential factor in Alzheimer's disease progression. Session 2 focused on behavioral and social science aspects of aging and their oral health significance. The keynote provided evidence that loneliness and isolation can have major health effects. These social conditions, along with poor oral health, tooth loss, and cognitive decline, could potentially affect healthy eating ability and systemic health in older adults. Research could help elucidate the directions and pathways connecting these seemingly disparate conditions. Session 3 focused on the delivery of oral care in different settings and the many barriers to access care faced by older adults. Research is needed to identify and implement effective technology and strategies to improve access to dental care, including new delivery and financing mechanisms, workforce models, interprofessional provider education and practice, and use of big data from medical-dental integration of electronic health records. Research to improve the "oral health span," reduce oral health disparities, and increase health equity must be tackled at all levels from biologic pathways to social determinants of health and health policies.

Turbulent burning velocity and thermodiffusive instability of premixed flames.

Reported in the paper are results of unsteady three-dimensional direct numerical simulations of laminar and turbulent, lean hydrogen-air, complex-chemistry flames propagating in forced turbulence in a box. To explore the eventual influence of thermodiffusive instability of laminar flames on turbulent burning velocity, (i) a critical length scale Λ_{n} that bounds regimes of unstable and stable laminar combustion is numerically determined by gradually decreasing the width Λ of computational domain until a stable laminar flame is obtained, and (ii) simulations of turbulent flames are performed by varying the width from Λ<Λ_{n} (in this case, the instability is suppressed) to Λ>Λ_{n} (in this case, the instability may grow). Moreover, simulations are performed either using mixture-averaged transport properties (low Lewis number flames) or setting diffusivities of all species equal to heat diffusivity of the mixture (equidiffusive flames), with all other things being equal. Obtained results show a significant increase in turbulent burning velocity U_{T} when the boundary Λ=Λ_{n} is crossed in weak turbulence, but almost equal values of U_{T} are computed at Λ<Λ_{n} and Λ>Λ_{n} in moderately turbulent flames characterized by a Karlovitz number equal to 3.4 or larger. These results imply that thermodiffusive instability of laminar premixed flames substantially affects burning velocity in weak turbulence only, in line with a simple criterion proposed by Chomiak and Lipatnikov (Phys. Rev. E 107, 015102, (2023)10.1103/PhysRevE.107.015102).

[Further understanding and paying attention to normoalbuminuric diabetic kidney disease].

Diabetes mellitus (DM) has grown up to be an important issue of global public health because of its high incidence rate. Diabetic kidney disease (DKD) is the main cause of end-stage kidney disease (ESKD). Therefore, early diagnosis and timely prevention and treatment of DKD are essential for the progress of DM. The clinical diagnosis and staging of DKD are mostly based on the urinary albumin excretion rate (UAER) and estimated glomerular filtration rate (eGFR). However, clinically, DKD patients show normoalbuminuric diabetic kidney disease (NADKD) instead of clinical proteinuria. The old NADKD concept is no longer suitable and should be updated accordingly with the redefinition of normal proteinuria by NKF/FDA (National Kidney Foundation/Food and Drug Administration). Based on the relevant guidelines of DM and chronic kidney disease (CKD) and combined with the current situation of clinical research, the review described NADKD from the aspects of epidemiology, pathological mechanism, disease diagnosis, clinical characteristics and biomarkers, to arouse the new understanding of NADKD in the medical profession and pay attention to it.

[Association between sarcopenia and abdominal aortic calcification in maintenance hemodialysis patients].

Objective: To investigate the relationship between sarcopenia and abdominal aortic calcification (AAC) in maintenance hemodialysis (MHD) patients. Methods: A cross-sectional study was conducted. MHD patients who underwent regular dialysis between January 2021 and January 2022 at hemodialysis center in Jiangdu People's Hospital Affiliated to Yangzhou University were enrolled. The incidence of sarcopenia in these patients was examined by measuring handgrip strength, gait speed and appendicular skeletal muscle mass index (ASMI) using bioelectrical impedance analysis. AAC score was measured by a lateral lumbar spinal radiograph. The general information of the patients was collected and the blood biochemical indexes were detected. These patients were divided into non-calcification group (n=104) and calcification group (n=127) according to the score of AAC. Multivariate logistic regression was used to analyze the related factors of AAC. Results: A total of 231 MHD patients (134 males and 97 females) were enrolled in the study, with the mean age of (57.1±11.4) years. Among 231 hemodialysis patients, the incidence of sarcopenia and AAC were 46.3% (107 cases) and 55.0% (127 cases), respectively. The age [(60.2±11.1) vs (53.4±12.2) years, P<0.001] and dialysis vintage [86 (46, 135) vs 57 (27, 109) months, P=0.005] in calcification group were longer than these in the non-calcification group. The level of 25(OH)D3 [17.7 (13.5, 24.3) vs 20.5 (15.1, 28.1) µg/L, P=0.008] and gait speed [(0.88±0.23) vs (1.01±0.20) m/s, P=0.024], handgrip strength [(17.9±9.1) vs (20.7±9.9) kg, P=0.013], ASMI [(6.65±2.24) vs (7.83±2.46) kg/m2, P<0.001] were lower. While, AAC score [12 (9, 19) vs 0 (0, 3), P<0.001] and the incidence of sarcopenia [58.3% (74/127) vs 31.7% (33/104), P<0.001] were higher in the calcification group than these in the non-calcification group. Multivariate logistic regression analysis indicated that sarcopenia (OR=1.928, 95%CI: 1.302-2.855, P=0.001), decrease of 25(OH)D3 level (OR=0.969, 95%CI: 0.940-1.000, P=0.047), age (OR=1.043, 95%CI: 1.015-1.072, P=0.002), and dialysis vintage (OR=1.009, 95%CI: 1.004-1.015, P=0.001) were related factors of AAC. Conclusions: Sarcopenia is associated with AAC in MHD patients. In clinical practice, attention should be paid to sarcopenia in MHD patients.

[Clinical application of combination of different types of free perforator flaps in the repair of complex wounds in extremities].

Objective: To investigate the clinical application effects of combination of different types of free perforator flaps in the repair of complex wounds in extremities. Methods: A retrospective observational study was conducted. From January 2018 to June 2022, 11 patients with complex wounds in extremities who met the inclusion criteria was admitted to the Affiliated Hospital of Zunyi Medical University, including 8 males and 3 females, aged 28 to 55 years. The wounds in the upper extremities in 4 cases and in the lower extremities in 7 cases were repaired with different combination of free perforator flaps. After debridement, the wound area was 7.0 cm×6.0 cm-28.0 cm×12.0 cm. A combination of different types of perforator flaps were applied, including the perforator tri-leaf flap of the descending branch of the lateral femoral circumflex artery in 6 cases, the descending branch of lateral femoral circumflex artery combined with oblique branch perforating branch flap in 2 cases, the lobulated flap of the descending branch of the lateral femoral circumflex artery combined with the contralateral medial plantar artery perforator flap in 2 cases, and the bilateral perforator flap of the descending branch of lateral femoral circumflex artery combined with great toe nail flap in 1 case, with the size of a single flap ranged from 2.0 cm×2.0 cm-25.0 cm×6.0 cm. The donor site was repaired by direct suture, skin grafting, or flap transplantation. During free flap transplantation, the flap was cut and split according to the distribution of perforators, and end-to-end or end-to-side anastomosis was performed between the donor area and the recipient area. After surgery, the survival of transplanted flap in the primary recipient site, the occurrence of vascular crisis, the wound healing in the flap donor site, and the survival of transplanted skin or flap in the flap donor site were observed. During follow-up, the blood supply, appearance and texture of the transplanted flap in the primary recipient site were observed; and at the same time, the weight bearing of the plantar receiving area, the presence of sliding, ulcers, and sinus tracts of the flap, and the appearance and function of the hand were observed; the complications in the donor area were observed. Results: After surgery, one patient's transplanted flap in the primary recipient site had vascular crisis but survived after exploration+vein graft bridging; partial necrosis occurred in one lobe of anterolateral thigh lobulated flap transplanted to the primary recipient site in one patient and recovered after dressing change+skin grafting, and the different types of perforator flap transplanted to the primary recipient site in the other 9 patients all survived. After surgery, the wound with direct suture at the donor site healed well, and the skin or flap transplanted to the donor area survived well. During 3-24 months of follow-up, the blood supply, appearance, and texture of the transplanted flap at the primary recipient site were good. In two patients, the anterolateral thigh flap combined with the medial plantar flap were used to repair plantar defects. The plantar receiving area was able to bear weight, and the texture of the flaps in the recipient area was close to the normal plantar skin, without flap sliding, ulcer, or sinus tract formation. In one patient, bilateral anterolateral thigh flap combined with great toe nail flap were used to repair hand combined with soft forearm defect, and the appearance and function of hand, especially thumb were good. Only linear scar was left in the donor site without other obvious complications. Conclusions: The combination of different types of perforator flaps is a reliable clinical method to repair complex wounds in extremities with high safety, good efficacy, and less complications.

[A clinical cohort study of split and whole liver transplantations].

Objective: To investigate the surgical efficacy of split liver transplantation. Methods: Patients who underwent liver transplantation at the Affiliated Hospital of Qingdao University between January 2015 and December 2022 were retrospectively analyzed. They were divided into split liver transplantation group (n=60) and whole liver transplantation group (n=765)according to graft types.In the split liver transplantation group, there were 23 males and 37 females, aged (52.5±10.2) years, and the body mass index was (22.4±3.3) kg/m2. In the whole liver transplantation group, there were 630 males and 135 females, aged (51.2±9.6) years, and body mass index was (24.5±3.7) kg/m2.The basic data of the two groups were matched 1∶1 using the propensity score matching method. The independent sample t test and χ2 test were used to compare the intraoperative and postoperative recovery of the two groups of donors and recipients. The overall survival rate and the graft survival rate of the two groups were analyzed by Kaplan-Meier method and the cumulative survival rate was compared by the Log-rank test. Results: Fifty-one well-matched pairs of data with similar baseline characteristics were obtained. The ratio of graft mass to recipient body weight in the matched split liver transplantation group was (1.78±0.55)%. Operation time(M(IQR))(10.8(1.5)hours vs. 8.0(1.9)hours,U=6.608,P<0.01) and cold ischaemia time(5.4(1.3)hours vs. 4.6(2.2)hours,U=2.825,P=0.005) were significantly longer in the split liver transplantation group than those in the whole liver transplantation group. Intra-operative anhepatic phase(53.0(15.0)minutes vs. 57.0(24.0)minutes,U=1.048,P=0.295),bleeding volume(1 000(1 400)ml vs. 1 200(1 200)ml,U=0.966,P=0.334) and intraoperative instillation of red blood cells(9.0(6.5)U vs. 11.0(11.0)U,U=1.732,P=0.083) were not significantly different between the two groups. However,the split liver transplantation group showed significantly longer postoperative intensive care unit stay(5.0(3.0)days vs. 4.0(4.0)days,U=2.677,P=0.007) and postoperative hospital stay(30.0(15.0)days vs. 26.0(15.0)days,U=2.237,P=0.025) and significantly higher incidence of postoperative complications(56.8%(29/51) vs. 36.6%(19/51),χ2=3.935,P=0.047) than the whole liver transplantation group. Furthermore,levels of alanine transaminase and aspartate aminotransferase were significantly higher on postoperative days 1,4 and 7 in the split liver transplantation group(all P<0.05) than in the whole liver transplantation group;however,there were no significant differences in these levels on postoperative days 14 and 28. The time to restoration of normal liver function in both groups(12.5(13.7)days vs. 9.0(12.5)days,U=1.607,P=0.108) was not statistically significant. Furthermore,the median follow-up time after surgery was 25.6 months in both groups. In postoperative years 1,2,3 and 5, the graft survival rates were 88.1%,80.8%,77.8% and 66.7% in the whole liver transplantation group and 80.3%,70.3%,67.3% and 60.5% in the split liver transplantation group(P=0.171),respectively. The patient survival rates in post-operative years 1,2,3 and 5 were 88.1%,80.8%,77.8% and 66.7% in the whole liver transplantation group and 80.3%,75.9%,70.3% and 63.3% in the split liver transplantation group,respectively(P=0.252). However,the differences of graft survival rates and patient survival rates between the two groups were not significant. Conclusion: Although it affects the early recovery of patients after liver transplantation,split liver transplantation has no effect on long-term survival rates and demonstrates surgical efficacy similar to that of whole liver transplantation.

[Application of target trail emulation in real world: a case study of effect of statins on mortality in diabetes patients].

Target trail emulation is an observational research method, which can use real-world data (such as observational data and historical data) to carry out research design according to the design principles of randomized controlled trials (RCT) when RCT cannot be carried out. The intervention group and the control group were classified by simulating random grouping. Finally a high-reliable conclusion similar to RCT can be obtained. This paper summarizes the basic concepts and application process of target trail emulation based on the effect of statins on the prognosis of myocardial infarction in diabetic patients to provide reference for the application of this method in real world.

[Fungal peritoneal dialysis catheter-related exit-site infection combined with tunnel infection: A case report].

Peritoneal dialysis (PD) catheter-related infection (i.e. exit-site infection and tunnel infection) is one of the main causes of PD-related peritonitis. If it cannot be controlled effectively, it could lead to PD technique failure. Therefore, timely and effective diagnosis and treatment and active prevention so as to reduce PD catheter-related infection is an important treatment goal in PD patients. PD catheter exit-site infection (ESI) and tunnel infection can be caused by a variety of microorganisms, mainly bacteria, while fungi are very rare. Few public data can be used to guide treatment of PD catheter-related fungal infection, and there is no related report in China till now. Once fungal peritonitis occurred, the patient can only withdraw from PD treatment. Here, we report a case of fungal PD catheter ESI combined with tunnel infection which was successfully diagnosed and treated in our PD center. A 71-year-old woman came to clinic because of "PD for 5 years, secretions from exit site for 8 days and aggravation for 1 day". The patient suffered from peritonitis, ESI and tunnel infection for many times in the past 5 years, involving a variety of pathogens. Eight days before, she found white viscous discharge from exit site. The subcutaneous cuff completely came out of it and rubbed its skin. The Schaefer exit-site score was 3 points. Due to the suspected ESI 2 months before, the discharge swab for bacterial culture was positive for Pseudomonas aeruginosa, so the exit site swab for bacterial culture was done again, and gentamicin injection was applied topically once a day for empirical treatment. The exit site was evaluated one day before: The subcutaneous tunnel was significantly swollen and slightly tender at 2.5 cm away from the exit site, and with white medium amount of viscous secretions. The exit-site score increased to 4 points. Routine test of dialysis effluent was (-). The bacterial culture of the exit-site discharge was rechecked twice, and Candida parapsilosis was positive for two times, so the diagnosis of fungal PD catheter ESI combined with tunnel infection was clear. Immediately we searched for the causes of ESI and tunnel infection. We found that the patient had a suspicious history of gray toenail on the foot. The toenail smear was positive for fungi and visible hyphae. She washed feet with hands every day, and washed clothes on a low bench every day, which made the exit-site and tunnel squeezed for a long time. Based on the above causes, we gave her comprehensive treatment as follows: For ESI and tunnel fungal infections, fluco-nazole was used systemically according to the drug sensitivity results, and miconazole cream was applied to the exit-site locally. For the subcutaneous cuff that came out completely, daily iodophor disinfection was given locally. At the same time, local antifungal treatment was given to the foot. We followed up closely during treatment, evaluated the exit-site every 2-3 days, and took photos of the exit-site to dynamically observe the effect. After 14 days of treatment, the exit-site score continued to be 0-1, the bacterial culture of the exit-site was negative, the cuff culture was negative, and the tunnel B-ultrasound was normal. The patient had been followed up regularly once a month for 60 months, no ESI and tunnel infection occurred. Fungal PD catheter ESI and tunnel infection are rare complications of PD. When the standard anti-infection treatment is ineffective, the possibility of fungal infection should be considered, so as to avoid prolonged use of antibiotics, aggravating fungal infection, and even progressing to fungal peritonitis, leading to withdrawal from PD. Accurate exit-site evaluation is helpful for timely diagnosis and early treatment of ESI and tunnel infection. The exit-site discharge culture and drug sensitivity test before treatment are helpful to identify the pathogen and adjust subsequent treatment. At the same time, repeated discharge culture is required in order to exclude positive fungal culture results caused by contamination. Once fungal catheter-related infection is diagnosed, we should search for possible causes actively, subsequent targeted and comprehensive treatment plays a decisive role for the prognosis of patients.

[Development and validation of a prognostic prediction model for patients with stage â to â ¢ colon cancer incorporating high-risk pathological features].

Objective: To examine a predictive model that incorporating high risk pathological factors for the prognosis of stage Ⅰ to Ⅲ colon cancer. Methods: This study retrospectively collected clinicopathological information and survival outcomes of stage Ⅰ~Ⅲ colon cancer patients who underwent curative surgery in 7 tertiary hospitals in China from January 1, 2016 to December 31, 2017. A total of 1 650 patients were enrolled, aged (M(IQR)) 62 (18) years (range: 14 to 100). There were 963 males and 687 females. The median follow-up period was 51 months. The Cox proportional hazardous regression model was utilized to select high-risk pathological factors, establish the nomogram and scoring system. The Bootstrap resampling method was utilized for internal validation of the model, the concordance index (C-index) was used to assess discrimination and calibration curves were presented to assess model calibration. The Kaplan-Meier method was used to plot survival curves after risk grouping, and Cox regression was used to compare disease-free survival between subgroups. Results: Age (HR=1.020, 95%CI: 1.008 to 1.033, P=0.001), T stage (T3:HR=1.995,95%CI:1.062 to 3.750,P=0.032;T4:HR=4.196, 95%CI: 2.188 to 8.045, P<0.01), N stage (N1: HR=1.834, 95%CI: 1.307 to 2.574, P<0.01; N2: HR=3.970, 95%CI: 2.724 to 5.787, P<0.01) and number of lymph nodes examined (≥36: HR=0.438, 95%CI: 0.242 to 0.790, P=0.006) were independently associated with disease-free survival. The C-index of the scoring model (model 1) based on age, T stage, N stage, and dichotomous variables of the lymph nodes examined (<12 and ≥12) was 0.723, and the C-index of the scoring model (model 2) based on age, T stage, N stage, and multi-categorical variables of the lymph nodes examined (<12, 12 to <24, 24 to <36, and ≥36) was 0.726. A scoring system was established based on age, T stage, N stage, and multi-categorical variables of lymph nodes examined, the 3-year DFS of the low-risk (≤1), middle-risk (2 to 4) and high-risk (≥5) group were 96.3% (n=711), 89.0% (n=626) and 71.4% (n=313), respectively. Statistically significant difference was observed among groups (P<0.01). Conclusions: The number of lymph nodes examined was an independent prognostic factor for disease-free survival after curative surgery in patients with stage Ⅰ to Ⅲ colon cancer. Incorporating the number of lymph nodes examined as a multi-categorical variable into the T and N staging system could improve prognostic predictive validity.

[Analysis of influencing factors and clinical value of anterior peritoneal reflection for patients with rectal cancer].

Objectives: To investigate the factors influencing the height of anterior peritoneal reflection (APR) for patients with rectal cancer, and to analyze the relationship between the APR and the lateral lymph node metastasis. Methods: Clinical data of 432 patients with tumor located within and below APR were retrospectively collected from the rectal cancer database at the Department of General Surgery, Peking Union Medical College Hospital from August 2020 to September 2022. Ninty-eight non-rectal cancer patients were also enrolled as a control group. There were 308 males and 124 females in the tumor group, aged (M(IQR)) 62 (16) years (range: 24 to 85 years) and 53 males and 45 females in the control group, aged 60 (22) years (range: 27 to 87 years). The APR height, pelvis, and tumor-related parameters were measured by MRI. A multifactor linear regression model was established to analyze the dependent correlation factors of APR height. These factors of the two groups were matched by propensity score matching and their APR heights were compared after matching. An ordinal Logistic regression model was established to explore the relationship between APR-related parameters and radiographic lateral lymph node metastasis. Results: The APR height of the tumor group was (98.7±14.4) mm (range: 43.3 to 154.0 mm) and the control group was (95.1±12.7) mm (range: 68.0 to 137.9 mm). Multivariable linear regression revealed that the greater the weight (B=0.519, 95%CI: 0.399 to 0.640, P<0.01), the anterior pelvic depth (B=0.109, 95%CI: 0.005 to 0.213, P=0.039) and the smaller the bi-ischial diameter (B=-0.172, 95%CI:-0.294 to -0.049, P=0.006), the higher the APR height. The tumor group had a higher APR height than the control group after propensity score matching ((98.3±14.2) mm vs. (95.1±12.7) mm, t=-1.992, P=0.047). Ordinal Logistic regression indicated that the longer segment of the tumor invade the nonperitoneal rectum was an independent influencing factor of radiographic lateral lymph node metastasis (OR=1.016, 95%CI: 1.002 to 1.030, P=0.021), while the distance between the anal verge and the tumor was not (OR=0.986, 95%CI: 0.972 to 1.000, P=0.058). Conclusions: The higher the weight, the deeper and narrower the pelvis, the higher the APR height. There is a certain relationship between APR and lateral lymph node metastasis on imaging.

[Notch signaling pathway inhibitor DAPT improves alcohol-induced neuronal differentiation impairment in zebrafish].

OBJECTIVE: To explore the role of the Notch signaling pathway in regulating neuronal differentiation and sensorimotor ability in a zebrafish model of fetal alcohol spectrum disorder. METHODS: Zebrafish embryos treated with DMSO or 50 µmol/L DAPT (a Notch signaling pathway inhibitor) were examined for mortality rate, hatching rate, malformation rate, and body length at 15 days post fertilization (dpf). The mRNA expression levels of sox2, neurogenin1 and huc in the treated zebrafish embryos were detected using in situ hybridization and qRT-PCR, and their behavioral responses to strong light and vibration stimulation were observed. The zebrafish embryos were then exposed to DMSO, 1.5% ethanol, DAPT, or both ethanol and DAPT, and the changes in mRNA expression levels of sox2, neurogenin1, huc, and the Notch signaling pathway genes as well as behavioral responses were evaluated. RESULTS: Exposure to 50 µmol/L DAPT significantly increased the mortality rate of 1 dpf zebrafish embryos (P < 0.01), decreased the hatching rate of 2 dpf embryos (P < 0.01), increased the malformation rate of 3 dpf embryos (P < 0.001), and reduced the body length of 15 dpf embryos (P < 0.05). DAPT treatment significantly downregulated sox2 mRNA expression (P < 0.01) and increased neurogenin1 (P < 0.05) and huc (P < 0.01) mRNA expressions in zebrafish embryos. The zebrafish with DAPT treatment exhibited significantly shortened movement distance (P < 0.001) and lowered movement speed (P < 0.05) in response to all the stimulation conditions. Compared with treatment with 1.5% ethanol alone, which obviously upregulated notch1a, her8a and NICD mRNA expressions in zebrafish embryos (P < 0.05), the combined treatment with ethanol and DAPT significantly increased neurogenin1 and huc mRNA expression, decreased sox2 mRNA expression (P < 0.01), and increased the moving distance and moving speed of zebrafish embryos in response to strong light stimulation (P < 0.05). CONCLUSION: Ethanol exposure causes upregulation of the Notch signaling pathway and impairs neuronal differentiation and sensorimotor ability of zebrafish embryos, and these detrimental effects can be lessened by inhibiting the Notch signaling pathway.