Osteosarcopenia (OS) is a multifactorial, multiaetiologic degenerative metabolic syndrome in which sarcopenia coexists with osteoporosis, and its influences are related to aging-induced mechanics, genetics, inflammatory factors, endocrine disorders, and irregular lifestyles. With the accelerated aging process in our country, osteosarcopenia has become a public health problem that cannot be ignored, with a higher risk of falls, fractures, impaired mobility and death. In recent years, scholars at home and abroad have conducted a lot of research on osteosarcopenia, but their pathogenesis is still unclear. Understanding the signaling pathways associated with osteosarcopenia is of great significance for further research on the pathogenesis of these disorders and for finding new targets for treatment. Studies have shown that activation of the PI3K/Akt signaling pathway promotes osteoblast differentiation as well as skeletal muscle regeneration, indicating that inhibition of thePI3K/Akt signaling pathway is closely related to the development of osteosarcopenia. Muscle factor-mechanical stress interactions can maintain osteoblast viability by activating the Wnt/β-catenin signaling pathway, suggesting that Wnt signaling is important in muscle and bone crosstalk. The Notch signaling pathway also plays an important role in improving bone and muscle mass and function, but different researchers hold different views, which need to be further validated and refined in subsequent studies. Exercise, as an existing non-pharmacological treatment with strong and sustained effects on physical function and muscle strength, also significantly increases bone density in osteoporosis patients, which may be mainly due to the fact that exercise induces changes in the form and function of bones, in the form of muscular pulling and indirectly improves the bone mass, and changes in the bone strength can also change the number, shape as well as the function of the muscles. At the same time, the mechanism of different exercise modalities focuses on different aspects, and there are differences in exercise time, exercise intensity, and therapeutic effects in the implementation of interventions. Aerobic exercise can improve the quality of skeletal muscle and increase the expression of osteogenesis-related genes by stimulating mitochondrial biosynthesis, as well as improve the quality and strength of bones and muscles through the Wnt/β- catenin and PI3K/Akt signaling pathways, effectively preventing and controlling the occurrence of musculoskeletal disorders. High-intensity resistance exercise has a significant effect on improving the quality of muscles and bone mineral density, but older people with osteosarcopenia suffer from a decline in muscle quality and strength, and a decline in bone mineral density, which makes them very susceptible to fracture, so they should select the intensity of the training in a gradual and orderly manner, from small to large. What kind of exercise intensity and exercise modalities are most effective in improving the occurrence and development of osteosarcopenia needs to be further investigated. Therefore, this paper mainly reviews the epidemiology of osteosarcopenia, diagnostic criteria, the related signaling pathways (PI3K/Akt pathway, Wnt/β-catenin pathway, Notch pathway, NF-κB pathway) that jointly regulate the metabolic process of myocytes and skeletal cells, as well as the interventional effects of different exercise modes on osteosarcopenia, with the aim of providing theoretical bases for the clinical treatment of osteosarcopenia, as well as enhancing the preventive capacity of the disease in old age.

Osteoporosis leads to an imbalance in bone remodelling, where bone resorption is greater than bone formation and osteoclast degradation increases, resulting in severe bone loss. Autophagy is a lysosomal degradation pathway that regulates the proliferation, differentiation, and apoptosis of various bone cells (including osteoblasts, osteoclasts, and osteoclasts), and is deeply involved in the bone remodelling process. In recent years, the role of autophagy in the progression of osteoporosis and related bone metabolic diseases has received more and more attention, and it has become a research hotspot in this field. Summarising the existing studies, it is found that senile osteoporosis is the result of a combination of factors. On the one hand, it is the imbalance of bone remodelling and the increase of bone resorption/bone formation ratio with ageing, which causes progressive bone loss. On the other hand, aging leads to a general decrease in the level of autophagy, a decrease in the activity of osteoblasts and osteoclasts, and an inhibition of osteogenic differentiation. The lack of oestrogen leads to the immune system being in a low activation state, and the antioxidant capacity is weakened and inflammatory response is increased, inducing autophagy-related proteins to participate in the transmission of inflammatory signals, excessive accumulation of reactive oxygen species (ROS) in the skeleton, and negatively regulating bone formation. In addition, with aging and the occurrence of related diseases, glucocorticoid treatments also mediate autophagy in bone tissue cells, contributing to the decline in bone strength. Exercise, as an effective means of combating osteoporosis, improves bone biomechanical properties and increases bone density. It has been found that exercise induces oxidative stress, energy imbalance, protein defolding and increased intracellular calcium ions in the organism, which in turn activates autophagy. In bone, exercise of different intensities activates messengers such as ROS, PI3K, and AMP. These messengers signal downstream cascades, which in turn induce autophagy to restore dynamic homeostasis in vivo. During exercise, increased production of AMP, PI3K, and ROS activate their downstream effectors, AMPK, Akt, and p38MAPK, respectively, and these molecules in turn lead to activation of the autophagy pathway. Activation of AMPK inhibits mTOR activity and phosphorylates ULK1 at different sites, inducing autophagy. AMPK and p38 up-regulate per-PGC-1α activity and activate transcription factors in the nucleus, resulting in increased autophagy and lysosomal genes. Together, they activate FoxOs, whose transcriptional activity controls cellular processes including autophagy and can act on autophagy key proteins, while FoxOs proteins are expressed in osteoblasts. Exercise also regulates the expression of mTORC1, FoxO1, and PGC-1 through the PI3K/Akt signalling pathway, which ultimately plays a role in the differentiation and proliferation of osteoblasts and regulates bone metabolism. In addition, BMPs signaling pathway and long chain non-coding RNAs also play a role in the proliferation and differentiation of osteoblasts and autophagy process under exercise stimulation. Therefore, exercise may become a new molecular regulatory mechanism to improve osteoporosis through the bone autophagy pathway, but the specific mechanism needs to be further investigated. How exercise affects bone autophagy and thus prevents and treats bone-related diseases will become a future research hotspot in the fields of biology, sports medicine and sports science, and it is believed that future studies will further reveal its mechanism and provide new theoretical basis and ideas.

Objective    To investigate the clinical efficacy of minimally invasive Ivor-Lewis esophagectomy (MIILE) with reverse-puncture anastomosis. Methods    Clinical data of the patients with lower esophageal carcinoma who underwent MIILE with reverse-puncture anastomosis in our department from May 2015 to December 2020 were collected. Modified MIILE consisted of several key steps: (1) pylorus fully dissociated; (2) making gastric tube under laparoscope; (3) dissection of esophagus and thoracic lymph nodes under artificial pneumothorax with single-lumen endotracheal tube intubation in semi-prone position; (4) left lung ventilation with bronchial blocker; (5) intrathoracic anastomosis with reverse-puncture anastomosis technique. Results     Finally 248 patients were collected, including 206 males and 42 females, with a mean age of 63.3±7.4 years. All 248 patients underwent MIILE with reverse-puncture anastomosis successfully. The mean operation time was 176±35 min and estimated blood loss was 110±70 mL. The mean number of lymph nodes harvested from each patient was 24±8. The rate of lymph node metastasis was 43.1% (107/248). The pulmonary complication rate was 13.7% (34/248), including 6 patients of acute respiratory distress syndrome. Among the 6 patients, 2 patients needed endotracheal intubation-assisted respiration. Postoperative hemorrhage was observed in 5 patients and 2 of them needed hemostasis under thoracoscopy. Thoracoscopic thoracic duct ligation was performed in 1 patient due to the type Ⅲ chylothorax. TypeⅡ anastomotic leakage was found in 3 patients and 1 of them died of acute respiratory distress syndrome. One patient of delayed broncho-gastric fistula was cured after secondary operation. Ten patients with type Ⅰ recurrent laryngeal nerve injury were cured after conservative treatment. All patients were followe up for at least 16 months. The median follow-up time was 44 months. The 3-year survival rate was 71.8%, and the 5-year survival rate was 57.8%. Conclusion    The optimized MIILE with reverse-puncture anastomosis for the treatment of lower esophageal cancer is safe and feasible, and the long-term survival is satisfactory.

Lipopolysaccharides (LPS) are major outer membrane components of Gram-negative bacteria. Unlike most Gram-negative bacteria, Acinetobacter baumannii can still survive and acquire polymyxin resistance after complete loss of LPS. Previous studies of LPS-deficient Acinetobacter baumannii mostly focused on LPS-deficient strains induced by polymyxin, whose background was complex and unstable. To investigate LPS loss-mediated polymyxin resistant-Acinetobacter baumannii, this study constructed a stable and clear background LPS-deficient strain by knocking out lpxC gene in Acinetobacter baumannii ATCC 19606 with CIRSPR/Cas9, and then studied the phenotypic changes of the lpxC-deficient strain including morphology, growth rate, antibiotic susceptibility, virulence, membrane permeability, and membrane potential. Animal experiments were approved by the Animal Care and Welfare Committee Institute of Medicinal Biotechnology, CAMS and PUMC (approval number: IMB-20240119D₉). The results indicated that the lpxC gene of Acinetobacter baumannii ATCC 19606 was successfully knocked out. After losing the lpxC, the strain underwent the morphological change from rod-shaped to spherical. Furthermore, it leads to reduced growth rate, enhanced membrane permeability, decreased membrane potential, lower virulence, and increased antibiotic susceptibility to β-lactams, quinolones, aminoglycosides, macrolides, glycopeptides. The lpxC deletion results in significant changes in membrane homeostasis and adaptability of Acinetobacter baumannii. Understanding the phenotypic changes of colistin-resistant Acinetobacter baumannii mediated by LPS loss is useful for exploring the resistance mechanism of Acinetobacter baumannii and developing new therapeutic strategies.

Objective To study the bioequivalence of test and reference olmesartan tablet in Chinese healthy subjects after single dose under fasting and fed conditions.Methods A single-center,random,open,single-dose,two-preparations,double-period,crossover study was adopted.A total of 48 healthy adult male and female subjects(24 cases of fasting test and 24 cases of fed test)were included in the random crossover administration.Single oral dose 20 mg of test and reference were taken under fasting and postprandial conditions,respectively.Plasma concentration of olmesartan in plasma were determined by liquid chromatography tandem mass spectrometry.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin 8.0 software.Results The main pharmacokinetic parameters of the test and reference preparations of olmesartan tablets in the fasting group were as follows:Cmax were(653.06±133.53)and(617.37±151.16)ng·mL-1,AUC0-t were(4 201.18±1 035.21)and(4 087.38±889.99)ng·mL-1·h,AUC0-∞ were(4 254.30±1 058.90)and(4 135.69±905.29)ng·mL-1·h.The main pharmacokinetic parameters of the test and reference preparations of olmesartan tablets in the postprandial group were as follows:Cmax were(574.78±177.05)and(579.98±107.74)ng·mL-1,AUC0-t were(3 288.37±866.06)and(3 181.51±801.06)ng·mL-1·h,AUC0-∞ were(3 326.11±874.26)and(3 242.01±823.09)ng·mL-1·h.Under fasting and postprandial conditions,the 90％confidence intervals of the main pharmacokinetic parameters of the test and reference preparations are both 80.00％-125.00％.Conclusion Under fasting and postprandial conditions,a single oral dose of test and reference preparations olmesartan tablets in Chinese healthy adult volunteers showed bioequivalence.

Objective To observe the improvement of motor dysfunction and serum levels of C-reactive protein(CRP),blood glucose and blood lipid in post-stroke patients treated with scalp acupuncture at different needle retention time.Methods A total of 120 patients with motor dysfunction after stroke were randomly divided into control group,observation group 1 and observation group 2,with 40 cases in each group.The patients in the 3 groups were treated with scalp acupuncture,body acupuncture and routine rehabilitation exercise,once a day and 6 times a week,lasting for 2 weeks.The control group was given scalp acupuncture with retaining of needles for 30 minutes,the observation group 1 was given scalp acupuncture with retaining of needles for one hour,and the observation group 2 was given scalp acupuncture with retaining of needles for 2 hours.Before and after treatment,the 3 groups were observed in the changes of the scale scores of National Institutes of Health Stroke Scale(NIHSS),Fugl-Meyer Assessment(FM A),Berg Balance Scale(BBS)and modified Barthel Index(MBI),and the levels of laboratory indicators of peripheral blood CRP,fasting plasma glucose(FPG),total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C).After treatment,the clinical safety of the three groups was evaluated.Results(1)After treatment,the scale scores of NIHSS in the three groups were lower(P＜0.01)and the scale scores FMA,BBS and MBI were higher than those before treatment(P＜0.05 or P＜0.01).The comparison of post-treatment scale scores showed that the differences among the three groups were statistically significant(P＜0.01).The intergroup comparison showed that the decrease of NIHSS score and the increase of FMA,BBS and MBI scores in the observation group 2 were significantly superior to those in the control group and the observation group 1(P＜0.01);the improvement of FMA score in the observation group 1 was significantly superior to that in the control group(P＜0.01),while the improvement of NIHSS,BBS and MBI scores tended to be superior to that in the control group without statistically significant differences(P＞0.05).The results indicated that the curative effect of scalp acupuncture plus exercise regimen was positively correlated with the duration of needle retention for scalp acupuncture.(2)After treatment,the laboratory indicator levels of CRP and FPG in the peripheral blood of the three groups,the levels of TG and LDL-C in the two observation groups and the level of HDL-C in the observation group 2 were improved compared with those before treatment(P＜0.05 or P＜0.01).Statistically significant differences were presented in the post-treatment levels of CRP and TG in peripheral blood among the three groups(P＜0.05 or P＜0.01).The intergroup comparison showed that the improvement of CRP and TG levels in the observation group 2 was significantly superior to that in the control group,and the improvement of CRP level in the observation group 2 was significantly superior to that in the observation group 1,the differences being statistically significant(P＜0.05 or P＜0.01).The TC level in the three groups after treatment did not differ from that before treatment,and there was no significant difference in TC level after treatment among the three groups either(P＞0.05).(3)During the treatment,no adverse reactions such as fainting,needle breaking and hematoma occurred in the three groups,the vital signs of the patients were stable,and there were no obvious abnormal changes in pulse,blood pressure and respiratory rate.Conclusion Scalp acupuncture can effectively improve the motor function of post-stroke patients in a pasitive time-effect relationship with the needle retention,and better the curative effect can be achieved by retaining of the needle for 2 h.

Objective To design and evaluate a dilation incision device capable of facilitating stable support and flexible adjustment during neurosurgical procedures.Methods The dilation incision device was composed of a support plate,an adjustment assembly,a brain support ring,a rotation assembly,an electric motor,an expansion assembly and a neck support ring.The support plate was made of high-strength stainless steel;the adjustment assembly was made up of a first screw,a lifting groove,a slide bar and a nut;the brain support ring was fixed to the adjustment assembly through a support rod,with an outer layer of medical-grade silicone and an inner layer of stainless steel skeleton;the rotation assembly connected the brain support ring with the expansion assembly and consisted of a rotating shaft,a connecting rod and a rotating lug;a high-precision direct current servo motor was selected for the device;the expansion assembly included a spring,an expansion plate and a moving plate,which realized auto expansion or contraction through spring pressure;the neck support ring had its outer layer made of flexible polyurethane foam and inner layer being a stainless steel skeleton.The device had its stability and safety evaluated by static and dynamic tests at different heights(50,100,150 mm)and angles(0°,30°,60°),which was compared with the traditional fixation device to verify its application effect.Results Static and dynamic tests indicated the device showed high stability and safety in different heights and angles,and gained advantages over the traditional device in stability,convenient operation and surgical field visualization.Conclusion The device developed meets the requirements of neurosurgical procedures,and enhances the safety and portability of neurosurgical procedures.[Chinese Medical Equipment Journal,2024,45(10):37-40]

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective To investigate the expression of CD123 in children with acute lymphoblastic leukemia(ALL)and its effect on the clinical characteristics and prognosis of children with B-lineage acute lymphoblastic leukemia(B-ALL).Methods A retrospective analysis was conducted on the clinical data of 251 children with ALL who were admitted to the Department of Hematology and Oncology,Children's Hospital of Kunming Medical University,from December 2019 to June 2022.According to the expression of CD123 at initial diagnosis,the children were divided into CD123+group and CD123-group,and the two groups were compared in terms of clinical characteristics and treatment outcome.The factors influencing the prognosis were analyzed.Results Among the 251 children with ALL,there were 146 children(58.2%)in the CD123+group.The B-ALL group had a significantly higher positive expression rate of CD123 than the acute T lymphocyte leukemia group(P<0.05).Compared with the CD123-group,the CD123+group had significantly lower peripheral blood leukocyte count and percentage of juvenile cells and a significantly higher proportion of children with high hyperdiploid karyotype or an age of 1-10 years,with a relatively low proportion of children with E2A-PBX1 fusion gene(P<0.05).The multivariate Cox proportional-hazards regression model analysis showed that compared with the>10 years group,the 1-10 years group had a significantly higher overall survival rate(P<0.05),and compared with the high risk group,the moderate risk group had a significantly higher event-free survival rate in children with B-ALL(P<0.05).Conclusions CD123 is widely expressed in children with B-ALL,and positive expression of CD123 might be an indicator for good prognosis in children with B-ALL,which is of great significance for evaluating the efficacy of remission induction therapy and survival prognosis of children with B-ALL.

Aberration of the right coronary artery from the left anterior descending is a very rare congenital anomaly.The anomalous the right coronary artery,as a branch of the septal branch,has not been reported clinically.This article reports such rare case.A 52-year-old female was admitted due to"sudden chest pain and confusion for 4 hours".The ECG showed that the ST-segment of leads(V1-V4,V3R,V4R and V5R)were elevated about 0.1-0.3 mVThe blood pressure was 63/53 mmHg.She was diagnosed as cardiogenic shock second to acute anterior and right ventricular ST-segment elevation myocardial infarction.Emergency coronary angiography was performed after intra-aortic ballon pump was implanted to assist circulation.During the treatment of the culprit vessel,it was accidentally found that the right coronary artery,as a branch vessel,originated from the ostium of the second septal branch of the anterior descending artery.