Tuberous sclerosis complex(TSC)is a rare genetic disease that can lead to benign dysplasia in multiple organs such as the skin, brain, eyes, oral cavity, heart, lungs, kidneys, liver, and bones. Its main symptoms include epilepsy, intellectual disabilities, skin depigmentation, and facial angiofibromas, whilst incidence is approximately 1 in 10 000 to 1 in 6000 newborns. This case presents a middle-aged woman who initially manifested with epilepsy and nodular depigmentation. Later, she developed a lower abdominal mass, elevated creatinine, and severe anemia. Based on clinical features and whole exome sequencing, the primary diagnosis was confirmed as TSC. Laboratory and imaging examinations revealed that the lower abdominal mass originated from the uterus. CT-guided biopsy pathology and surgical pathology suggested a combination of leiomyoma and abscess. With the involvement of multiple organs and various complications beyond the main diagnosis, the diagnostic and therapeutic process for this patient highlights the importance of rigorous clinical thinking and multidisciplinary collaboration in the diagnosis and treatment of rare and challenging diseases.

Objective To construct hepatocyte-specific silence information regulator 3(Sirt3)gene knockout(Sirt3 Δhep)mice by Cre-loxP technique,and to provide an important animal model for further studying the biological function of the hepatocyte Sirt3 gene in diseases.Methods LoxP-labeled Sirt3flox/flox mice were mated with Alb-Cre homozygous(Alb-Cre+/+)mice,and the F1 generation Sirt3flox/-/Alb-Cre+/-mice were then mated with Sirt3flox/flox mice,and the F2 genotype of Sirt3flox/flox/Alb-Cre+/-mice were the Sirt3 Δhep mice constructed in this ex-periment.Sirt3flox/flox/Alb-Cre-/-(Sirt3flox/flox)mice were the control mice.Mouse tail genome DNA was extracted and PCR was used to identify the genotypes of the offspring mice.Immunofluorescence was used to detect Sirt3 ex-pression in mouse hepatocytes.Primary hepatocytes and tissue proteins of Sirt3 Δhep mice were extracted,and the ex-pression of Sirt3 in mouse hepatocytes and other tissues was verified by Western blot.HE staining was used to ob-serve mice's liver,heart,spleen,and lung tissue structure.Results Sirt3 Δhep mice were successfully identified.Immunofluorescence and Western blot results demonstrated a significant decrease in the expression of Sirt3 in the hepatocytes of these mice compared to the control group(P<0.01).At the same time,there was no significant difference in the expression of Sirt3 in the heart,spleen,kidney,and lung tissues of Sirt3 Δhep mice compared with the control group(P>0.05).The results of HE staining showed that the histological characteristics of the liver,heart,spleen,lungs,kidneys,and other major organs of Sirt3 Δhep mice were not significantly different from those of the control group mice.Conclusion Hepatocyte-specific Sirt3 gene knockout mice are successfully constructed,which provides an animal model to explore further the role and molecular mechanism of the hepatocyte Sirt3 gene in diseases.

Background::The Global Leadership Initiative on Malnutrition (GLIM) criteria were published to build a global consensus on nutritional diagnosis. Reduced muscle mass is a phenotypic criterion with strong evidence to support its inclusion in the GLIM consensus criteria. However, there is no consensus regarding how to accurately measure and define reduced muscle mass in clinical settings. This study aimed to investigate the optimal reference values of skeletal muscle mass index for diagnosing sarcopenia and GLIM-defined malnutrition, as well as the prevalence of GLIM-defined malnutrition in hospitalized cirrhotic patients.Methods::This retrospective study was conducted on 1002 adult patients with liver cirrhosis between January 1, 2018, and February 28, 2022, at Beijing You-An Hospital, Capital Medical University. Adult patients with a clinical diagnosis of liver cirrhosis and who underwent an abdominal computed tomography (CT) examination during hospitalization were included in the study. These patients were randomly divided into a modeling group (cohort 1, 667 patients) and a validation group (cohort 2, 335 patients). In cohort 1, optimal cut-off values of skeletal muscle index at the third lumbar skeletal muscle index (L3-SMI) were determined using receiver operating characteristic analyses against in-hospital mortality in different gender groups. Next, patients in cohort 2 were screened for nutritional risk using the Nutritional Risk Screening 2002 (NRS-2002), and malnutrition was diagnosed by GLIM criteria. Additionally, the reference values of reduced muscle mass in GLIM criteria were derived from the L3-SMI values from cohort 1. Multivariate logistic regression analysis was used to analyze the association between GLIM-defined malnutrition and clinical outcomes.Results::The optimal cut-off values of L3-SMI were 39.50 cm 2/m 2 for male patients and 33.06 cm 2/m 2 for female patients. Based on the cut-off values, 31.63% (68/215) of the male patients and 23.3% (28/120) of the female patients had CT-determined sarcopenia in cohort 2. The prevalence of GLIM-defined malnutrition in cirrhotic patients was 34.3% (115/335) and GLIM-defined malnutrition was an independent risk factor for in-hospital mortality in patients with liver cirrhosis ( Wald = 6.347, P = 0.012). Conclusions::This study provided reference values for skeletal muscle mass index and the prevalence of GLIM-defined malnutrition in hospitalized patients with liver cirrhosis. These reference values will contribute to applying the GLIM criteria in cirrhotic patients.

Hip fracture in the elderly is characterized by high incidence, high disability rate, and high mortality and has been recognized as a public health issue threatening their health. Surgery is the preferred choice for the treatment of elderly patients with hip fracture. However, lower extremity deep venous thrombosis (DVT) has an extremely high incidence rate during the perioperative period, and may significantly increase the risk of patients′ death once it progresses to pulmonary embolism. In response to this issue, the clinical guidelines and expert consensuses all emphasize active application of comprehensive preventive measures, including basic prevention, physical prevention, and pharmacological prevention. In this prevention system, basic prevention is the basis of physical and pharmacological prevention. However,there is a lack of unified and definite recommendations for basic preventive measures in clinical practice. To this end, the Orthopedic Nursing Professional Committee of the Chinese Nursing Association and Nursing Department of the Orthopedic Branch of the China International Exchange and Promotive Association for Medical and Health Care organized relevant nursing experts to formulate Expert consensus on perioperative basic prevention for lower extremity deep venous thrombosis in elderly patients with hip fracture ( version 2024) . A total of 10 recommendations were proposed, aiming to standardize the basic preventive measures for lower extremity DVT in elderly patients with hip fractures during the perioperative period and promote their subsequent rehabilitation.

Objective:To investigate the feasibility, clinical efficacy and donor site impact of the deep inferior epigastric artery perforator flap (DIEPF) with transverse symmetrical design in reconstruction of soft tissue defects in limbs.Methods:From September 2020 to August 2023, 12 patients with soft tissue defects of limbs who agreed to flap donor site in the lower abdominal wall were treated in the Department of Hand Surgery and Microsurgery, Sichuan Modern Hospital. There were 10 females and 2 males with an average age of 58.42 years old. Defect sites: 3 in upper limbs and 9 in lower limbs. Sizes of the soft tissue defect were 8.0 cm×15.0 cm-13.0 cm×40.0 cm. CTA or CDU was used to detect the perforators of deep inferior epigastric artery and appropriate perforators were selected. The width and length of redundant skin and subcutaneous tissues in the lower abdomen were evaluated according to the "pinch and lift test". Taking into account the requirements of abdominoplasty, symmetrical bilateral DIEPFs were designed in the transverse direction on the lower abdominal wall. The sizes of the flaps were 7.5 cm×24.0 cm-13.0 cm ×42.0 cm. The harvested flaps were firstly thinned under the microscope, trimmed and shaped properly to match the profile of the wounds. Blood circulation was reconstructed with various forms of vascular anastomoses, such as internal pressurisation, connection in series and Flow-through, etc. Lower abdominal wall wound should be gradually reduced in tension according to the requirements of abdominal wall plastic surgery, and cosmetic suturing should be performed.Results:All 12 DIEPFs survived. The lower abdominal donor site healed primarily. All patients were included in postoperative follow-up for 6 to 42 (average 18.31) months. All flaps were normal in colour and soft in texture. The appearance of abdominal walls were improved, and the function was not affected, except 1 patient who underwent debulking procedure 3 months after the surgery.Conclusion:The transverse symmetrical design of a DIEPF is an ideal method for reconstruction of soft tissue defects in limbs after appropriate flap modification. It is a win-win solution for an aesthetic appearance of donor and recipient sites of the flap.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).

Objective To observe the expression of tyrosine kinase 2(JAK2)and signal transducer and activator of transcription 3(STAT3)in myocardial tissue of rats with myocardial ischemia-reperfusion injury(MIRI)by electroacupuncture at"Neiguan"point,and explore the mechanism of electroacupuncture in up regulating JAK2/STAT3 signal pathway,promoting the expression of anti-inflammatory factors,and reducing MIRI injury.Methods Thirty male SD rats with normal echocardiography were randomly divided into sham operation group,model group and electroacupuncture group,with 10 rats in each group.MIRI models were prepared by ligation of left anterior descending coronary artery(LAD)in model group and electroacupuncture group,while in sham operation group,only threading was performed without ligation.In the electroacupuncture group,electroacupuncture(density wave,2 Hz/100 Hz,2 mA)at bilateral"Neiguan"points was performed on the 1st,3rd and 5th days after the modeling operation,once a day,20 minutes each time.The left ventricular ejection fraction(LVEF)of rats on the 1st,3rd and 5th day after operation was observed by echocardiography to evaluate cardiac function;HE staining was used to observe the pathological changes of rat myocardium;The myocardial fibrosis was observed by Masson staining;The expression of IL-4 and IL-6 in myocardium was detected by ELISA;The expressions of IL-1β and IL-10 in myocardial tissue were detected by immunohistochemistry;The expression of JAK2,p-JAK2,STAT3,p-STAT3 protein in myocardial infarction area was measured by Western blot.Results Compared with sham operation group,EF in model group decreased significantly(P<0.05),fibrosis area increased(P<0.05),IL-4,IL-6,IL-10,IL-1β The content of JAK2,p-JAK2,STAT3,p-STAT3 protein increased(P<0.05);Compared with the model group,the EF of rats in the electroacupuncture group increased(P<0.05),the fibrotic area of rats in the electroacupuncture group decreased(P<0.05),the content of IL-4 and IL-10 increased,and IL-6 and IL-1β The expression of JAK2,p-JAK2,STAT3,p-STAT3 protein increased(P<0.05).Conclusion Electroacupuncture at Neiguan point can significantly up regulate JAK2/STAT3 signal pathway,reduce the secretion of proinflammatory factors,increase the expression of anti-inflammatory factors,and alleviate myocardial ischemia reperfusion injury in rats.

Hip fracture is considered as the most severe osteoporotic fracture characterized by high disability and mortality in the elderly. Improved surgical techniques and multidisciplinary team play an active role in alleviating prognosis, which places higher demands on perioperative nursing. Dysfunction, complications, and secondary impact of anaesthesia and surgery add more difficulties to clinical nursing. Besides, there still lack clinical practices in perioperative nursing for elderly patients with hip fracture in China. In this context, led by the Orthopedic Nursing Committee of Chinese Nursing Association, the Expert consensus on clinical practice in perioperative nursing for elderly patients with hip fracture ( version 2023) is developed based on the evidence-based medicine. This consensus provides 11 recommendations on elderly patients with hip fracture from aspects of perioperative health education, condition monitoring and inspection, complication risk assessment and prevention, and rehabilitation, in order to provide guiding advices for clinical practice, improve the quality of nursing and ameliorate the prognosis of elderly patients with hip fracture.

Objective: To observe the effects of electroacupuncture (EA) at Neiguan (PC6) on arrhythmia during acute myocardial ischemia-reperfusion and the expression of connexin 43 (Cx43) in rats. Methods: A total of 40 Sprague-Dawley male rats were used. Ten rats were randomly selected as the blank group, and the remaining 30 rats were randomly divided into a model group and an EA group, with 15 rats in each group. Before modeling, rats in the EA group received one session of EA intervention at bilateral Neiguan (PC6) for 30 min; the other groups were treated with the same grasping and anesthesia for 30 min without intervention. PowerLab physiological recorder was used to record electrocardiograph within 30 min of infarction. After the experiment, cardiac tissue and serum were collected from rats. Hematoxylin-eosin (HE) staining was used to observe the morphological changes of myocardial tissue in the ventricular infarction area of rats in each group. The expression of Cx43 protein in the myocardium of each group was detected by Western blotting (WB). Enzyme-linked immunosorbent assay (ELISA) was used to determine the activity of Na+-K+-ATPase in myocardial tissue and the serum content of endogenous digitalis-like factor (EDLF) in rats. Results: There was no statistical difference in arrhythmia score between the EA group and the model group, but the total duration and average duration of arrhythmia in the EA group were decreased (P<0.01). HE staining showed that compared with the blank group, myocardial cells in the model group were disorganized and seriously damaged. The pathological changes in the EA group were similar to those in the model group, but the damage was relatively minor. The results of WB showed that compared with the blank group, the Cx43 expression in myocardial tissue of the model group was decreased (P<0.01); compared with the model group, the Cx43 expression in the EA group was increased (P<0.01); compared with the blank group, the Na+-K+-ATPase activity in myocardial tissue of the model group was significantly decreased (P<0.01); compared with the model group, the Na+-K+-ATPase activity in the EA group was increased (P<0.01). ELISA results showed that compared with the blank group, the serum EDLF content in the model group was significantly increased (P<0.01); compared with the model group, the EDLF content in the EA group was decreased (P<0.01). Conclusion: EA at Neiguan (PC6) can delay and reduce the onset of arrhythmia during myocardial infarction in the rat model of myocardial ischemia-reperfusion. Its mechanism of action may be related to the regulation of the Cx43 expression in myocardial tissue, improvement of the activity of Na+-K+-ATPase in myocardial tissue, and increase in the content of serum EDLF.

Objective:To establish a disease risk prediction model for the newborn screening system of inherited metabolic diseases by artificial intelligence technology.Methods:This was a retrospectively study. Newborn screening data ( n=5 907 547) from February 2010 to May 2019 from 31 hospitals in China and verified data ( n=3 028) from 34 hospitals of the same period were collected to establish the artificial intelligence model for the prediction of inherited metabolic diseases in neonates. The validity of the artificial intelligence disease risk prediction model was verified by 360 814 newborns ' screening data from January 2018 to September 2018 through a single-blind experiment. The effectiveness of the artificial intelligence disease risk prediction model was verified by comparing the detection rate of clinically confirmed cases, the positive rate of initial screening and the positive predictive value between the clinicians and the artificial intelligence prediction model of inherited metabolic diseases. Results:A total of 3 665 697 newborns ' screening data were collected including 3 019 cases ' positive data to establish the 16 artificial intelligence models for 32 inherited metabolic diseases. The single-blind experiment ( n=360 814) showed that 45 clinically diagnosed infants were detected by both artificial intelligence model and clinicians. A total of 2 684 cases were positive in tandem mass spectrometry screening and 1 694 cases were with high risk in artificial intelligence prediction model of inherited metabolic diseases, with the positive rates of tandem 0.74% (2 684/360 814)and 0.46% (1 694/360 814), respectively. Compared to clinicians, the positive rate of newborns was reduced by 36.89% (990/2 684) after the application of the artificial intelligence model, and the positive predictive values of clinicians and artificial intelligence prediction model of inherited metabolic diseases were 1.68% (45/2 684) and 2.66% (45/1 694) respectively. Conclusion:An accurate, fast, and the lower false positive rate auxiliary diagnosis system for neonatal inherited metabolic diseases by artificial intelligence technology has been established, which may have an important clinical value.