Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.

AIM:This study investigates the effect of fibroblast growth factor 21(FGF21)long-acting ana-logue PF-05231023 on promoting the"browning"of white adipose tissue(WAT)by inhibiting mitophagy in WAT and the molecular mechanisms involved.METHODS:Using a high-fat diet(HFD)to replicate an obesity model in mice,18 C57BL/6J mice were divided into three groups:normal control(NC)group,HFD group,and PF-05231023 intervention(PF+HFD)group,each consisting of 6 mice.After 12 weeks of feeding,the mice were anaesthetized,their eyeballs were removed to collect blood samples,and serum was separated to measure levels of total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C)、alanine aminotransferase(ALT),and aspartate aminotransferase(AST)in mouse serum.The inguinal WAT(iWAT),epididymal WAT(eWAT)and liver were collected.Part of the tis-sues were used for Western blot experiments to measure the protein levels of"browning"related markers uncoupling pro-tein-1(Ucp-1)and peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α),as well as mitophagy-related markers PTEN-induced kinase 1(Pink1),parkin,beclin-1 and microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ).Another part of the tissues was fixed in paraformaldehyde for subsequent HE and immunohistochemical staining.3T3-L1 cells were induced to mature adipocytes using the classic"cocktail"method.The CCK-8 assay was used to assess the impact of different concentrations of PF-05231023 intervention on cell viability.After 48 h of PF-05231023 intervention,the 3T3-L1 cell clumps were collected for Western blot experiments to measure the expression levels of"browning"related markers Ucp-1 and PGC-1α,as well as mitochondrial autophagy-related markers Pink1,parkin,beclin-1,and LC3-Ⅱ proteins.Oil red O staining was performed to detect cell accumulation,and immunofluorescence staining was used to mea-sure Ucp-1 protein content.Subsequently,3T3-L1 cells were divided into the normal group,PF-05231023 intervention group,Pink1 agonist MTK458 intervention group,and MTK458+PF-05231023 intervention group.Cell clumps were col-lected for Western blot experiments to measure the markers as mentioned above.RESULTS:The key findings of our study indicate that the PF-05231023 intervention did not affect energy intake in mice but significantly reduced the weight,liver weight,and fat weight of mice induced by a high-fat diet(P<0.05).The intervention also decreased lipid accumula-tion(TC,TG、LDL-C)and liver damage(ALT,AST)and alleviated hepatocyte vacuolization and adipocyte size(P<0.05).Compared with the HFD group,the PF-05231023 intervention increased the levels of Ucp-1 and PGC-1α protein expression in iWAT and eWAT(P<0.01).Immunohistochemical staining showed higher Ucp-1 protein content in the PF-05231023 intervention group than in the HFD group.The PF-05231023 intervention dose-dependently increased Ucp-1 and PGC-1α protein expression levels in mature 3T3-L1 cells(P<0.01),reduced cellular lipid accumulation,and immu-nofluorescence staining showed increased Ucp-1 protein content in mature 3T3-L1 cells after PF-05231023 intervention.The PF-05231023 intervention inhibited mitochondrial autophagy-related indicators Pink1,parkin,beclin-1,and LC3-Ⅱ protein expression levels in iWAT,eWAT,and induced mature 3T3-L1 cells(P<0.05).The MTK intervention increased Pink1,parkin,beclin-1,and LC3-Ⅱ protein expression levels,increased Ucp-1 protein expression level,compared with the MTK intervention group,after MTK and PF-05231023 co-intervention,partially decreased Pink1,parkin,beclin-1,and LC3-Ⅱ protein expression levels,and partially restored Ucp-1 protein expression level(P<0.01).CONCLUSION:(1)Intervention with PF-05231023 can improve obesity and related metabolic disorders induced by a high-fat diet in mice;(2)PF-05231023 intervention can inhibit white adipose tissue(WAT)and induce mature 3T3-L1 cell mitochondria autophagy,promoting"browning"by inhibiting mitochondrial autophagy;(3)Its mechanism may be related to the inhibi-tion of the Pink1-parkin signalling pathway.

Objective:To analyze regional differences in MMACHC gene variations among patients with cblC-type methylmalonic acidemia (MMA) in China and to explore the relationship between these variations and neonatal screening, biochemical markers and prognosis.Methods:Retrospective case summary. Clinical and laboratory data, including general condition, biochemical markers and genetic analysis, were collected from 1 859 cblC MMA patients from 2005 to 2023. Patients were divided into 7 groups according to their regions: north China, northeast China, east China, central China, south China, southwest China and northwest China. They were also classified into neonatal screening and non-neonatal screening groups. Mann-Whitney U and Kruskal-Wallis tests were used to compare biochemical marker levels. In contrast, the Chi-square test was applied to compare MMACHC gene variant frequencies, neonatal screening proportion, onset age and prognosis between groups. Results:Among 1 859 cases of cblC MMA, 1 019 were male and 840 were female, with a consultation age of 1.0 (0.1, 5.0) month. A total of 1 787 cases carried compound heterozygous or homozygous variants and only 1 variant site was identified in 72 cases. The 10 most frequent variants were c.609G>A (1 238 cases), c.658_660delAAG (343 cases), c.80A>G (284 cases), c.482G>A (239 cases), c.567dupT (191 cases), c.656_658delAGA (131 cases), c.217C>T (109 cases), c.394C>T (105 cases), c.445_446delTG (51 cases) and c.1A>G (50 cases). The frequency of the c.609G>A was the lowest in northwest China (28.8% (44/154), χ2=-18.42, P<0.05). The frequency of the c.567dupT was the most common in southwest China (25.0% (20/80), χ2=71.70, P<0.001) and c.656_658delAGA had the highest frequency in northeast China (9.3% (19/205), χ2=32.08, P<0.001). Non-missense variants (91.2% (62/68), 88.5% (46/52)) and early-onset patients (90.0% (36/40), 94.4% (34/36)) were both more prevalent in southwest and south China ( χ2=14.95, 31.69, both P<0.05). The proportion of neonatal screening was the lowest in south China (22.2% (8/36), χ2=98.48, P<0.05), where the mortality rate was the highest (19.1% (4/21), χ2=38.98, P<0.001). East China exhibited the highest frequency of missense variants (21.5% (339/1 579)), the highest proportion of patients identified through neonatal screening (54.5% (465/853)), and a more significant proportion of patients with good prognosis (36.6% (227/621), χ2=14.57, 93.49, 38.98, all P<0.05). In addition, the c.482G>A variant was more frequent in patients diagnosed by neonatal screening compared to those diagnosed by other methods (8.3% (132/1 586) vs. 5.9% (122/2 060), χ2=7.97, P<0.05). Conclusions:The frequency of MMACHC gene variation varies across different regions. The c.609G>A was least frequent in northwest China, c.567dupT was most common in southwest China, and c.656_658delAGA was most prevalent in northeast China. South China had the lowest neonatal screening rate and the highest mortality. At the same time, east China exhibited the highest frequency of missense variants, the highest proportion of patients identified through neonatal screening and the best prognosis. The c.482G>A variant was more frequent in patients diagnosed by neonatal screening compared to those diagnosed by other methods.

Objective    To compare and investigate the efficacy and differences of modified B-T shunt, central shunt and right ventricle-pulmonary artery (RV-PA) connection in the treatment of pulmonary atresia with ventricular septal defect (PA/VSD). Methods    A total of 124 children with PA/VSD underwent initial palliative repair in Shanghai Children's Medical Center from September 2014 to August 2019, including 63 males and 61 females, aged 7 days to 15 years. They were divided into in a modified B-T shunt group (55 patients), a central shunt group (22 patients) and a RV-PA connection group (47 patients). The clinical data of these children were retrospectively analyzed. Results    There were 9 early deaths after palliation, with an early mortality rate of 7.3%. The mean follow-up time was 26.5±20.3 months, with 5 patients lost to follow-up, 5 deaths during the follow-up period, and 105 survivors. The 1-year and 5-year survival rates were both 89.7%. The monthly increased Nakata index was 5.2 (–0.2, 12.3) mm2/m2, 9.2 (0.1, 23.6) mm2/m2, 6.3 (1.8, 23.3) mm2/m2 in the modified B-T shunt group, the central shunt group, and the RV-PA connection group, respectively, with no statistical difference among the three groups. The 1-year survival rate was 85.3%, 78.4%, 95.2%, and the 5-year (4-year in the central shunt group) survival rate was 85.3%, 58.8%, 95.2% in the three groups, respectively, with a statistical difference among them (P<0.05). The complete repair rate was 36.5%, 19.0% and 67.4% in the three groups, respectively, with a statistical difference among the three groups (P<0.001). Conclusion    All these three palliative surgical approaches can effectively promote pulmonary vascular development. But compared with systemic-pulmonary shunt, RV-PA connection has a lower perioperative mortality rate and can achieve a higher complete repair rate at a later stage, which is beneficial for long-term prognosis.

OBJECTIVE To establish a method for the determination of plasma protein binding rate of imatinib and its metabolite（N-desmethyl imatinib ）and apply it to patients with gastrointestinal stromal tumor （GIST）.METHODS Using imatinib - d8 as the internal standard ，after being deproteinized methanol ，the sample was determined by equilibrium dialysis combined with liquid chromatography -tandem mass spectrometry . The free concentrations of imatinib and its metabolites in plasma of GIST patients were detected by the same method . RESULTS The protein binding rates of imatinib with albumin ，α1-acid glycoprotein and globulin at 120 ng/mL and 4 000 ng/mL were （92.5±1.0）% and（91.7±0.4）%，（56.6±2.0）% and（62.6±2.6）%，（56.3±3.1）% and （68.0±8.6）% ，respectively. The protein binding rates of N-desmethyl imatinib with albumin ，α1-acid glycoprotein and globulin at 60 ng/mL and 2 000 ng/mL were （90.6±3.5）% and（91.3±1.5）%，（54.1±5.1）% and（63.7±1.3）%，（56.2±7.6）% and（67.5±7.3）%，respectively. Compared with the low concentration group of imatinib （120 ng/mL）and its metabolite （60 ng/mL），the plasma protein binding rate of high concentration of imatinib （4 000 ng/mL）and its metabolite （2 000 ng/mL）with α1-acid glycoprotein and globulin was significantly increased （P＜ Δ基金项目 国家自然科学基金资助项目（No.81503160）；江苏省 0.05），but there was no signifi -cant difference with albumin 卫生健康发展研究中心 2021年度开放课题（No.JSHD2021004）；江苏 （P＞0.05）. In blank plasma ，the protein binding rates of imatinib（4 000 ng/mL）at high concentration and its metabolites（2 000 ng/mL）were significantly lower than those of low （120， 60 ng/mL） and medium （750， 375 ng/mL）concentration （P＜0.01）. Average protein binding rates of imatinib and its metabolite in plasma of GIST patients were （99.0±0.3）% and（99.2±0.3）%，respectively；the correlation coefficients between the concentrations of imatinib and its metabolites and the protein binding rates were －0.298 5 and －3.332 3，respectively（all P＜0.05）. CONCLUSIONS The method for determining the plasma protein binding rates of imatinib and its metabolites is successfully established . The plasma protein binding rates of imatinib and its metabolites in patients with GIST are negatively correlated with drug concentration .

Objective    To analyze the outcomes of surgical repair for mixed total anomalous pulmonary venous connection (TAPVC). Methods    Between 2006 and 2018, a total of 51 patients with mixed TAPVC underwent surgery in our hospital. Patients with such associated anomalies as single ventricle and tetralogy of Fallot were excluded. There were 35 males and 16 females with a median age of 102.0 (59.0, 181.0) days and a median weight of 5.0 (4.1, 6.4) kg. Patients were divided into three categories based on the anatomy: "3+1" pattern (n=38, three pulmonary veins drained at one site, and the other drained at the opposite site); "2+2" pattern (n=9, the pulmonary veins from each lung joined to form a confluence and drained at separate sites); bizarre pattern (n=4, the anatomy could not be classified into the above two patterns). Results    There was no in-hospital death. The median follow-up was 41.0 (18.0, 86.5) months. Postoperative pulmonary venous obstruction occurred in 10 patients. Kaplan-Meier survival curves showed no statistically significant difference in postoperative pulmonary venous obstruction among the three groups (P=0.239). Cox risk regression showed that preoperative pulmonary venous obstruction was significantly associated with postoperative pulmonary venous obstruction (P=0.024). Conclusion    Mixed TAPVC has various anatomic morphologies and requires individualized surgery.

Objective    To compare the outcomes of sutureless technique and conventional technique in the surgical repair for infracardiac total anomalous pulmonary venous connection (TAPVC). Methods    The clinical data of 46 consecutive patients with infracardiac TAPVC undergoing surgical repair in our hospital between June 2014 and April 2019 were retrospectively analyzed. Patients with combined congenital cardiac anomalies such as single ventricle and tetralogy of Fallot were excluded. Patients were divided into a conventional technique group and a sutureless technique group according to the surgical techniques. There were 35 patients in the conventional technique group, including 28 males (80.0%) and 7 females (20.0%) with a median age of 21 (8, 42) d and a median weight of 3.6 (3.0, 4.0) kg. There were 11 patients in the sutureless technique group, including 8 males (72.7%) and 3 females (27.3%) with a median age of 14 (6, 22) d and a median weight of 3.5 (2.9, 3.6) kg. The curative effect of the two groups was compared. Results    There were 5 deaths (10.9%) in the conventional technique group, including 4 in-hospital deaths (8.7%) and 1 late death (2.2%). Overall mortality of the conventional technique group (14.3%, 5/35) was higher than that of the sutureless technique group (0.0%, 0/11), although the difference was not statistically significant (P=0.317). Cox regression analysis showed that sex (P=0.042), age at repair (P=0.028), cardiopulmonary bypass time (P=0.007), aortic cross-clamping time (P=0.018) and duration of ventilation (P=0.042) were risk factors for postoperative mortality. The median follow-up was 18.00 (5.00, 37.75) months. Postoperative pulmonary venous obstruction occurred in 22 patients of the conventional technique group, which was significantly more than that of the sutureless technique group (P=0.000). Conclusion    For infracardiac TAPVC, sutureless technique can reduce the incidence of postoperative pulmonary venous obstruction compared with conventional technique.

Objective:To summarized the experience of 149 cases of critical pediatric cardiac surgery in a single-center during the epidemic period, for providing a safe and feasible management strategy.Methods:Based on the epidemiological characteristics of COVID-19, a strategy consisting of 14 days of isolation was established for the arrangement of cardiac surgery in children during the epidemic period. Retrospective analysis of clinical data of 149 cases of critical cardiac surgery performed from January 23, 2020 to March 20, 2020 under the guidance of this strategy. The primary composite endpoint was death and suspected or confirmed COVID-19.Results:The median age of the children undergoing surgery was 136 days; 73(49.0%) cases were male. Twenty-one cases (14.1%) came from Shanghai, one case (0.7%) came from Hubei Province, and 127 cases (85.2%) came from areas other than Hubei and Shanghai. One patient (0.7%) outside Shanghai who had been isolated for less than 14 days carried emergency surgery under special protection; other 148 patients (99.3%) underwent elective early repair procedure. One patient (0.7%) died, and no COVID-19 was confirmed or suspected.Conclusion:During the COVID-19 epidemic, pediatric cardiac surgery can be safely performed using a specific management strategy, which can be used as a reference when major public health events occur.

To establish a novel colloidal gold immunochromatography assay (GICA) for rapid, sensitive and accurate detection of Haemophilus influenzae infection by using the outer membrane protein P6 as detection target. First, the linear antigen epitope located in the extracellular domain of the P6 protein (GenBank accession number: AGH02799) was predicted by bioinformatics analysis. The region (62-75 aa of the protein) with strong antigen specificity was chosen and synthesized. Two rabbits were then immunized by the polypeptides (14 aa) for production of polyclonal antibodies. Then, the recombinant P6 proteins were also obtained to produce polyclonal antibodies. Finally, based on the two antibodies, a novel colloidal GICA for detection of Haemophilus influenzae infection was established and the specificity, sensitivity, repeatability and stability of this method were evaluated. At the same time, the method was tested in clinical simulation, and the plate culture method was used to verify its accuracy. The test strip for Haemophilus influenzae infection was successfully prepared. The detection limit of the test strip was as low as 1×105 CFU/mL and the whole process can be completed within 15 minutes. The strip specifically recognized Haemophilus influenzae and did not react with nine of other common respiratory pathogens such as Streptococcus pneumoniae, Moraxella catarrhalis, Mycoplasma pneumonia, and Legionella pneumophila. And the strips could be stored at 25 °C for at least 6 months without losing sensitivity or specificity. The coincidence rate between the results of 200 clinical samples and the plate culture method was 90.5%. Haemophilus influenzae protein P6, which possessed a high degree of surface antigen accessibility and antigencity, could be used as a marker for Haemophilus influenzae detection. The immunochromatographic colloidal gold test strip which bears the features of rapidity, convenience and sensitivity provides a unique tool for the on-site surveillance and diagnosis of Haemophilus influenzae infection in clinical test.
Animals ; Chromatography, Affinity ; instrumentation ; Diagnostic Tests, Routine ; standards ; Gold Colloid ; chemistry ; Haemophilus Infections ; diagnosis ; Haemophilus influenzae ; Humans ; Limit of Detection ; Rabbits ; Sensitivity and Specificity

OBJECTIVE3-Methylcrotonyl-coenzyme A carboxylase deficiency (MCCD) is an autosomal recessive inborn error of leucine catabolism. The cases suspected as MCCD detected by neonatal screening are not rare. The aim of the study was to investigate the clinical outcomes in cases suspected as MCCD by neonatal screening. The second aim was to investigate the mutation spectrum of MCC gene in Chinese population and hotspot mutation.

METHODForty-two cases (male 33, female 9) , who had higher blood 3-hydroxy-isovalerylcarnitine (C5-OH) levels(cut-off <0.6 µmol/L) detected by neonatal screening using MS/MS, were recruited to this study during Sept.2011 to Mar.2013. The C5-OH concentrations were [0.84 (0.61-20.15) µmol/L] in 42 cases at the screening recall. Five cases were firstly diagnosed as maternal MCCD, 6 cases as benign MCCD and 31 cases were suspected as MCCD. To follow up the height, weight, mental development, blood C5-OH concentrations and urinary 3-methylcrotonyl-glycine (3-MCG) and 3-hydroxy isovalerate (3-HIVA) in order to investigate the clinical outcome. The MCCC1 and MCCC2 gene mutation were analyzed for some cases. The novel gene variants were evaluated, and the influence of novel missense variants on the protein structure and function were predicted by PolyPhen-2, SIFT, UniProt and PDB software.

RESULT(1) Forty-two cases had no symptoms, their physical and mental development were normal in the last visit at the median ages of 29 months, the oldest age of follow up was nearly 9 years. (2) Gene mutation analysis was performed for 29 cases with informed consent signed by parents.Fourteen different mutations were identified in 19 cases. The mutations in MCCC1 gene accounted for 86%, the most common mutation was c.ins1680A, (accounted for 40%). Nine kinds of novel variant were detected including 211AG>CC/p.Q74P, c.295G>A/p.G99S, c.764A>C/p.H255P, c.964G>A/p. E322K, c.1331G>A/p.R444H, c.1124delT, c.39_58del20, c.1518delG, c.639+2T>A.Other 3 kinds of mutation in MCCC1 gene and 2 kinds of mutation in MCCC2 gene have been reported previously; the amino acid of mutant positions of five kinds of novel missense variant are almost highly conserved. These missense variants were predicted to cause change of human MCC protein side chain structure by changing hydrogen bonding, size of amino acid residue and electric charge, and predicted to damage the protein function possibly according to PolyPhen-2 and PDB analysis. So these novel variants may be disease-causing mutations. No mutation were detected in 10 cases. (3) Blood concentrations of C5-OH when screening, recall and end of follow-up in maternal MCCD was 3.50 (1.63-11.43), 1.84 (1.00-9.30), 0.27 (0.26-5.81) µmol/L. There was a significant downward trend.In contrast, benign MCCD group was 8.20 (3.60-9.60), 9.67 (3.88-20.15), 23.0 (5.87-49.10) µmol/L.It showed a rising trend. Children's urinary 3-MCG of benign MCCD group was found abnormally elevated in 4 cases (100%) when they were recalled.

CONCLUSIONA certain number of cases with MCCD or suspected as MCCD in this study had no symptoms and normal physical and mental development after follow-up to oldest age of nearly 9 years. The mutation in MCCC1 gene is common, nine novel mutations were found, c.ins1680A may be a hotspot mutation in Chinese population. The urinary GC/MS analysis and blood MS/MS analysis for mother should be routinely performed for all cases with high blood C5-OH level detected by neonatal screening.

Amino Acid Sequence ; Asian Continental Ancestry Group ; genetics ; Carbon-Carbon Ligases ; blood ; deficiency ; genetics ; Carnitine ; analogs & derivatives ; blood ; Child ; Child, Preschool ; DNA Mutational Analysis ; Female ; Follow-Up Studies ; Humans ; Infant ; Infant, Newborn ; Male ; Mutation ; Neonatal Screening ; Tandem Mass Spectrometry ; Urea Cycle Disorders, Inborn ; blood ; diagnosis ; enzymology ; genetics