BACKGROUND:At present,the use of a locking bone plate combined with steel wire or steel cable for the treatment of periprosthetic femoral fracture often adopts monocortical fixation,which is not stable and the proximal end of the bone cannot be achieved anatomically fitted by plate.The customized anatomical plate system can effectively solve this problem. OBJECTIVE:To explore the biomechanical strength of a customized anatomical plate system in fixation of Vancouver BI periprosthetic femoral fracture. METHODS:CT thin layer scanning data of normal femurs of 1 006 cases were selected and input into the MIMICS 21.0 software to establish the three-dimensional reconstruction model of the femur,which was set as the three-dimensional reconstruction group.56 complete human femoral specimens were selected as the femoral specimen group.The measured results of the two groups for femoral anatomical appearance were compared.If there was no significant difference between the two groups,the approximate appearance of a customized anatomical plate system was designed based on the measurement results in MIMICS 21.0 software and NX11.0 software.The customized anatomical plate system was designed and prepared according to the above measurement results.Eight pairs of frozen human femurs were selected to make Vancouver BI periprosthetic femoral fracture,which of the left were thin layer scanned by dual-source CT to obtain data.The data were transferred to determine the customized anatomical plate system model by the above design software.Eight sets of customized anatomical plate systems were ultimately produced,relying on the instrument company.The eight pairs of models were numbered 1-8.The left side was fixed with the customized anatomical plate system(customized anatomical plate system group);the right side was fixed with a metal locking plate system-large locking plate(claw plate group).L1-L4 and R1-R4 were subjected to vertical short-cycle loading test and vertical loading test.L5-L8 and R5-R8 were subjected to horizontal short-cycle loading test and four-point bending test.The vertical loading test and four-point bending test were used to collect bending load,bending displacement,and bending strain.Two short cycle loading tests were used to collect strain displacement to compare the maximum load,maximum displacement,bending stiffness,and short-period displacement resistance of the two kinds of bone plates. RESULTS AND CONCLUSION:(1)There were no significant differences in all indexes between the three-dimensional reconstruction group and the femoral specimen group(P>0.05).Individual customized anatomical plate system was designed based on the measurement results combined with digital software.(2)In the vertical loading test,the maximum load was higher(P=0.015),the maximum bending displacement was smaller(P=0.014),and the bending stiffness was higher(P=0.005)in the customized anatomical plate system group compared with the claw plate group.(3)In the four-point bending test,the maximum load was higher(P=0.023),the bending stiffness was higher(P=0.005),and the maximum bending displacement was not significant(P=0.216>0.05)in the customized anatomical plate system group compared with the claw plate group.(4)In the vertical short-cycle loading test,the average level of bending displacement in the customized anatomical plate system group(0.23±0.10 mm)was significantly lower than that in the claw plate group(0.44±0.02 mm)(P<0.05).(5)There was no significant difference in the average level of bending displacement between the two groups in the horizontal short cycle loading test(P>0.05).(6)It is concluded that the customized anatomical plate system has personalized anatomical characteristics,and the fixation of Vancouver BI periprosthetic femoral fracture is more stable,which has certain significance for clinical treatment.

Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory therapy.However,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified.Deoxynyboquinone(DNQ)is a natural small molecule discovered from marine actinomycetes.The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1.DNQ exhibited signif-icant anti-inflammatory properties both in vitro and in vivo.The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α,β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine.DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway.Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation.The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry.DNQ triggered the ubiquitination and subsequent degra-dation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of Nrf2.Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

Cornus officinalis,a medicinal and edible plant known for its liver-nourishing properties,has shown promise in inhibiting the activation of hepatic stellate cells(HSCs),crucial indicators of hepatic fibrosis,especially when processed by high pressure wine steaming(HPWS).Herein,this study aims to investigate the regulatory effects of cornus officinalis,both in its raw and HPWS forms,on inflammation and apoptosis in liver fibrosis and their underlying mechanisms.In vivo liver fibrosis models were established by subcutaneous injection of CCl4,while in vitro HSCs were exposed to transforming growth factor-β(TGF-β).These findings demonstrated that cornus officinalis with HPWS conspicuously ameliorated his-topathological injury,reduced the release of proinflammatory factors,and decreased collagen deposition in CCl4-induced rats compared to its raw form.Utilizing ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer(UHPLC-QTOF-MS)combined with network analysis,we identified that the pharmacological effects of the changed components of cornus officinalis before and after HPWS,primarily centered on the adenosine phosphate(AMP)-activated protein kinase(AMPK)pathway.Of note,cornus officinalis activated AMPK and sirtuin 3(SIRT3),promoting the apoptosis of activated HSCs through the caspase cascade by regulating caspase3,caspase6 and caspase9.small interfering RNA(siRNA)experiments showed that cornus officinalis could regulate AMPK activity and its mediated-apoptosis through SIRT3.In conclusion,cornus officinalis exhibited the ability to reduce inflammation and apoptosis,with the SIRT3-AMPK signaling pathway identified as a potential mecha-nism underlying the synergistic effect of cornus officinalis with HPWS on anti-liver fibrosis.

Objective:To investigate the clinical risk factors of large volume lymph node metastasis (LV-LNM) in the central region of papillary thyroid cancer (PTC) .Methods:The clinical data of 1367 PTC patients admitted to the Department of Oncological Surgery, Hangzhou First People’s Hospital, Affiliated to Zhejiang University School of Medicine from Jan. 2016 to Jan. 2019 were retrospectively analyzed. There were 310 males and 1057 females. A total of 1644 cases of central region were included in the study.According to the number of lymph node metastasis in the central area, they were classified into small-volume lymph node metastasis (SV-LNM) group and LV-LNM group.71 cases of LV-LNM, 1573 cases of SV-LNM.The correlation between CLNM and LV-LNM and various clinicopathological features such as the sex, age, tumor size and so on of PTC patients was analyzed by chi-square test and Logistic regression analysis.Results:The proportion of CLNM in the affected side was 35.28% (580/1 644) , and the incidence of LV-LNM in the central area of the affected side was 4.32% (71/1644) . Univariate analysis showed that the LV-LNM in the central region of the affected side was closely correlated with gender, age, bilateral lesions, multiple lesions, size of lesions, membranous invasion and lateral cervical lymph node metastasis on the affected side were closely related ( P<0.05) . Multivariate regression analysis showed that male (OR=2.115, P=0.006) , age < 38 years old (OR=0.586, P=0.004) , multiple lesions on the affected side (OR=2.837, P=0.004) , lesions >7mm on the affected side (OR=1.762, P=0.002) and cervical lymph node metastasis on the affected side (OR=7.023, P<0.001) were independent predictors of LV-LNM in the central region of the affected side ( P<0.001) . The receiver operating characteristic curve (ROC) , sensitivity and specificity of LV-LNM predicted by the model were 0.839, 81.69% and 78.39%. The incidence of ipsilateral cervical lymph node metastasis in the affected central region of LV-LNM was 11.57 times higher than that of SV-LNM. Conclusion:PTC with male, age < 38 years old, multiple lesions on the affected side, lesion >7 mm and lateral cervical lymph node metastasis are prone to LV-LNM in the affected central region.

OBJECTIVE To analyze the risks of prescription drugs sold online by drug retail enterprises， and to provide countermeasures and suggestions for risk prevention and control of prescription drugs sold online. METHODS The risk hierarchy structure model of prescription drugs sold online by drug retail enterprises was constructed by using analytic hierarchy process. Multiple rounds of risk research and judgment were carried out on 123 pairs of evaluation indicators by using Delphi expert survey method. The normalized weight calculation and consistency test of risk judgment matrix were carried out to perform fuzzy quantitative research. RESULTS The risk of prescription dispensing and review （6.48%）， the risk of drug first and prescription later （5.48%）， the risk of rational drug use guidance （4.99%）， the risk of buying drugs by abnormal channel （4.97%）， the risk of “first diagnosis， non-chronic disease and non-common disease” （4.43%）， and the quality and safety risk of returned drugs （4.34%） and the application risk of regulatory technology （4.06%） were high risks； the overall risk of drug retail enterprises （chain） selling prescription drugs online was 38.67%， and the overall risk of drug retail enterprises （individual） selling prescription drugs online was 61.33%， with a difference of 22.66% between them. CONCLUSIONS There were 7 high-risk indicators for prescription drugs sold online by drug retail enterprises. Among them， the risk of prescription dispensing and review， the risk of drug first and prescription later， and the risk of rational drug use guidance are the top three high-risk points. The risk of prescription drugs sold online by drug retail enterprises （individual） is higher than that of drug retail enterprises （chain）. It is recommended that regulatory authorities focus on and regulate the prescription drugs sold online by drug retail enterprises （individual）， and encourage drug retail enterprises （chain） to establish a systematic online sales process for prescription drugs； for high-risk points of prescription drugs sold online， it is recommended that regulatory authorities and drug retail enterprises focus on it and take effective risk prevention and control measures to ensure the safe use of prescription drugs by the general public.

Objective: To investigate the prognostic factors of children with congenital heart disease (CHD) who had undergone cardiopulmonary resuscitation (CPR) in pediatric intensive care unit (PICU) in China. Methods: From November 2017 to October 2018, this retrospective multi-center study was conducted in 11 hospitals in China. It contained data from 281 cases who had undergone CPR and all of the subjects were divided into CHD group and non-CHD group. The general condition, duration of CPR, epinephrine doses during resuscitation, recovery of spontaneous circulation (ROSC), discharge survival rate and pediatric cerebral performance category in viable children at discharge were compared. According to whether malignant arrhythmia is the direct cause of cardiopulmonary arrest or not, children in CHD and non-CHD groups were divided into 2 subgroups: arrhythmia and non-arrhythmia, and the ROSC and survival rate to discharge were compared. Data in both groups were analyzed by t-test, chi-square analysis or ANOVA, and logistic regression were used to analyze the prognostic factors for ROSC and survival to discharge after cardiac arrest (CA). Results: The incidence of CA in PICU was 3.2% (372/11 588), and the implementation rate of CPR was 75.5% (281/372). There were 144 males and 137 females with median age of 32.8 (5.6, 42.7) months in all 281 CPA cases who received CPR. CHD group had 56 cases while non-CHD had 225 cases, with the percentage of 19.9% (56/281) and 80.1% (225/281) respectively. The proportion of female in CHD group was 60.7% (34/56) which was higher than that in non-CHD group (45.8%, 103/225) (χ²=4.00, P=0.045). There were no differences in ROSC and rate of survival to discharge between the two groups (P>0.05). The ROSC rate of children with arthythmid in CHD group was 70.0% (28/40), higher than 6/16 for non-arrhythmic children (χ²=5.06, P=0.024). At discharge, the pediatric cerebral performance category scores (1-3 scores) of CHD and non-CHD child were 50.9% (26/51) and 44.9% (92/205) respectively. Logistic regression analysis indicated that the independent prognostic factors of ROSC and survival to discharge in children with CHD were CPR duration (odds ratio (OR)=0.95, 0.97; 95%CI: 0.92~0.97, 0.95~0.99; both P<0.05) and epinephrine dosage (OR=0.87 and 0.79, 95%CI: 0.76-1.00 and 0.69-0.89, respectively; both P<0.05). Conclusions: There is no difference between CHD and non-CHD children in ROSC and survival rate of survival to discharge was low. The epinephrine dosage and the duration of CPR are related to the ROSC and survival to discharge of children with CHD.
Cardiopulmonary Resuscitation ; Child ; Child, Preschool ; Female ; Heart Arrest/therapy* ; Heart Defects, Congenital/therapy* ; Humans ; Intensive Care Units, Pediatric ; Male ; Retrospective Studies

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

Objective Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are major public health and social issues worldwide. The long-term follow-up of COVID-19 with pulmonary TB (PTB) survivors after discharge is unclear. This study aimed to comprehensively describe clinical outcomes, including sequela and recurrence at 3, 12, and 24 months after discharge, among COVID-19 with PTB survivors. Methods From January 22, 2020 to May 6, 2022, with a follow-up by August 26, 2022, a prospective, multicenter follow-up study was conducted on COVID-19 with PTB survivors after discharge in 13hospitals from four provinces in China. Clinical outcomes, including sequela, recurrence of COVID-19, and PTB survivors, were collected via telephone and face-to-face interviews at 3, 12, and 24 months after discharge. Results Thirty-two COVID-19 with PTB survivors were included. The median age was 52 (45, 59) years, and 23 (71.9％) were men. Among them, nearly two-thirds (62.5％) of the survivors were moderate, three (9.4％) were severe, and more than half (59.4％) had at least one comorbidity (PTB excluded). The proportion of COVID-19 survivors with at least one sequela symptom decreased from 40.6％ at 3 months to 15.8％ at 24 months, with anxiety having a higher proportion over a follow-up. Cough and amnesia recovered at the 12-month follow-up, while anxiety, fatigue, and trouble sleeping remained after 24 months. Additionally, one (3.1％) case presented two recurrences of PTB and no re-positive COVID-19 during the follow-up period. Conclusion The proportion of long symptoms in COVID-19 with PTB survivors decreased over time, while nearly one in six still experience persistent symptoms with a higher proportion of anxiety. The recurrence of PTB and the psychological support of COVID-19 with PTB after discharge require more attention.

Background::The calcineurin inhibitor (CNI)-based immune maintenance regimen that is commonly used after renal transplantation has greatly improved early graft survival after transplantation; however, the long-term prognosis of grafts has not been significantly improved. The nephrotoxicity of CNI drugs is one of the main risk factors for the poor long-term prognosis of grafts. Sirolimus (SRL) has been employed as an immunosuppressant in clinical practice for over 20 years and has been found to have no nephrotoxic effects on grafts. Presently, the regimen and timing of SRL application after renal transplantation vary, and clinical data are scarce. Multicenter prospective randomized controlled studies are particularly rare. This study aims to investigate the effects of early conversion to a low-dose CNI combined with SRL on the long-term prognosis of renal transplantation.Methods::Patients who receive four weeks of a standard regimen with CNI + mycophenolic acid (MPA) + glucocorticoid after renal transplantation in multiple transplant centers across China will be included in this study. At week 5, after the operation, patients in the experimental group will receive an additional administration of SRL, a reduction in the CNI drug doses, withdrawal of MPA medication, and maintenance of glucocorticoids. In addition, patients in the control group will receive the maintained standard of care. The patients’ vital signs, routine blood tests, routine urine tests, blood biochemistry, serum creatinine, BK virus (BKV)/cytomegalovirus (CMV), and trough concentrations of CNI drugs and SRL at the baseline and weeks 12, 24, 36, 48, 72, and 104 after conversion will be recorded. Patient survival, graft survival, and estimated glomerular filtration rate will be calculated, and concomitant medications and adverse events will also be recorded.Conclusion::The study data will be utilized to evaluate the efficacy and safety of early conversion to low-dose CNIs combined with SRL in renal transplant patients.Trial registration::Chinese Clinical Trial Registry, ChiCTR1800017277.

OBJECTIVE: To investigate the endoscopic and pathological characteristics of gastric adenomatous polyps and to assess the potential risk factors for canceration of gastric adenomatous polyps. METHODS: The endoscopic and pathological characteristics of the patients with gastric adenomatous polyps from January 1, 2005 to December 31, 2019 were summarized retrospectively, and the risk factors of canceration were analyzed. RESULTS: A total of 125 patients with gastric adenomatous polyps were included, 51.20% of whom were females. The average age was (66.7±12.3) years. 64.80% of patients with gastric adenomatous polyps equal or more than 65 years old, and only 5.60% of the patients less than 45 years old. Adenomatous polyps were mostly distributed in the corpus and antrum with 40.80% and 32.80%, respectively. The majority of them were single (90.40%) and sessile (76.81%). 65.4% of adenomatous polyps were no more than 1.0 cm in diameter, and 23.20% of patients with adenomatous polyps were combined with hyperplastic polyps and/or fundus glandular polyps, and 1.60% had both pathological types of polyps. 58.62% (17/29) patients with hyperplastic polyps and/or fundus glandular polyps had multiple polyps. 1.60% (2/125) of the patients had gastric neuroendocrine tumor of G1 stage. Synchronous gastric cancer was detected in 13.60% (17/125) of the patients with adenomatous polyps, and the proportion of low-grade intraepithelial neoplasia was 18.40% (23/125). The main types of synchronous gastric cancer were progressive (70.59%) and undifferentiated (66.67%). Chronic atrophic gastritis with intestinal metaplasia was found in 52.80% of the patients, and autoimmune gastritis accounted for 11.20%. The positive rate of Helicobacter pylori was 21.60%. The canceration rate of gastric adenomatous polyps was 20.80%. The cancer was mainly differentiated, but there was sigmoid ring cell carcinoma as well. Diameter of >1.0 cm (OR=5.092, 95%CI: 1.447-17.923, P=0.011), uneven surface morphology and erosion (OR=13.749, 95%CI: 1.072-176.339, P=0.044) were independent risk factors of adenomatous polyps. CONCLUSION The synchronous gastric cancer is common and the canceration of gastric adenomatous polyps is high with diameter and surface morphology as independent risk factors. We should pay attention to the identification of the pathological types of polyps and the evaluation of the whole gastric mucosa during the endoscopic examination.
Adenomatous Polyps/epidemiology* ; Aged ; Female ; Gastric Mucosa ; Humans ; Middle Aged ; Retrospective Studies ; Risk Factors ; Stomach Neoplasms/epidemiology*