Background Metals and metalloids in fine particulate matter (PM_2.5) may cause damage to the respiratory and circulatory systems of the human body, and long-term exposure is prone to causing chronic poisoning, cancer, and other adverse effects. Objective To assess the distribution characteristics of metals and metalloids in outdoor PM_2.5 in a southern city of China, conduct source apportionment, and evaluate the associated health risks, thereby providing theoretical support for further pollution control measures. Methods PM_2.5 samples were collected in districts A, B, and C of a southern China city, and the concentrations of 17 metals and metalloids were detected by inductively coupled plasma-mass spectrometry (ICP-MS). Pollution sources were assessed through enrichment factor and principal components analysis, and the main pollution sources were quantified using absolute principal component scores-multivariate linear regression (APCS-MLR). Health risks were evaluated based on the Technical guide for environmental health risk assessment of chemical exposure (WS/T777—2021). Results The ambient air PM_2.5 concentrations in the city were higher in winter and spring, and lower in summer and autumn. The annual average concentrations of ambient PM_2.5 in districts A, B, and C were 36.7, 31.9, and 24.4 μg·m⁻³, respectively. The ambient PM_2.5 levels in districts B and C were below the second-grade limit set by the Ambient air quality standards (GB 3095—2012). The enrichment factors of cadmium (Cd), aluminum (Al), and antimony (Sb) were greater than 10, those of copper (Cu), lead (Pb), arsenic (As), nickel (Ni), mercury (Hg), and molybdenum (Mo) fell between 1 and 10, and those of manganese (Mn), vanadium (V), chromium (Cr), cobalt (Co), barium (Ba), beryllium (Be), and uranium (U) were below or equal to 1. The comprehensive evaluation of source analysis showed that the main pollution sources in districts A and C and the whole city were coal-burning. In district B, the main pollution source was also coal combustion, followed by industrial process sources and dust sources. The carcinogenic risks of As and Cr were between 1×10⁻⁶ and 1×10⁻⁴. However, the hazard quotients for 15 metals and metalloids in terms of non-carcinogenic risk were below 1. Conclusion Cr and As in the atmospheric PM_2.5 of the city present a certain risk of cancer and should be paid attention to. In addition, preventive control measures should be taken against relevant pollution sources such as industrial emission, dust, and coal burning.

Osteoarthritis(OA),a common age-related chronic disease,is characterized by degenerative changes in the joints and surrounding tissues.Traditionally,research on OA has primarily focused on the pathological changes in articular cartilage and its repair.However,with the advancements in animal disease modeling in recent years,especially the widespread use of spatiotemporally specific transgenic mouse models,scholars have gradually come to realize that the subchondral bone also plays an important role in the occurrence and development of OA.That is,the pathological changes in articular cartilage and bone mutually affect and promote each other,jointly driving the progression of OA,involving such pathological processes as vascular invasion,ectopic calcification,nerve growth,and the occurrence of pain.Given the complexity of cartilage-bone pathological relationship,it is difficult to conduct in-depth research on subchondral bone pathology using clinical human samples,or to simulate the pathological processes of OA through in vitro cell experiments.Therefore,animal models play an irreplaceable role in investigating the pathological mechanisms of OA and developing clinical drugs.This review,in addition to providing an overview of OA animal models,synthesizes the latest progress in animal experimental research on OA,highlighting the active role of the cartilage-bone pathological relationship in OA progression.These new findings provide references for future in-depth investigations and also provide a theoretical basis for developing fundamental strategies for OA prevention and treatment.

Osteoporosis and cardiovascular calcification,two major age-related chronic diseases that China is confronting today,pose serious threats to public health.Previous studies have reported overlapping connections in the pathological processes and molecular mechanisms of these two diseases,particularly concerning inflammation,oxidative stress,and dysregulation of mineral metabolism,and that these two diseases tend to share common pathogenic factors.However,research exploring the comorbidity mechanisms of the two diseases remains limited in both depth and scope,largely due to the lack of widely accepted comorbidity animal models.Herein,we analyzed the latest research findings on the comorbidity mechanisms of vascular calcification and osteoporosis,focusing on summarizing the animal disease models currently in extensive use and the relevant evaluation criteria.We aim to provide new references for comorbidity research models and offer scientific evidence for future studies on pathological mechanisms and the development of new therapeutic strategies.

Objective To evaluate the efficacy of vitamin AD combined with step-up therapy in children with asthma and its impact on humoral immunity,pulmonary function and recurrence.Meth-ods A total of 94 children with asthma were enrolled,and randomly divided into study group(n=47)and control group(n=47)using random number table method.The control group adopted the step-up treatment plan on the basis of conventional treatment,while the study group was treated with vitamin AD on the basis of the control group.The clinical efficacy,pulmonary function indicators[forced vital capacity(FVC),forced expiratory volume in one second(FEV,),FEV1/FVC and peak expiratory flow rate(PEF)]and humoral immunefunction[immunoglobulin G(IgG),immuno-globulin A(IgA),immunoglobulin M(IgM)and immunoglobulin E(IgE)]after treatment were compared between the two groups.The recurrence rateand safety of the two groups after treatment were compared.Results The total effective rate of clinical efficacy in the study group was 93.62％,which was significantly higher than 78.72％in the control group(P＜0.05).After treatment,FVC,FEV1,FEV1/FVC and PEF levels were significantly higher in both groups compared to pre-treatment values,and the study group showed significantly better improvement than the control group(P＜0.05).After treatment,serum IgG and IgA levels in the study group were significantly higher than those in the control group,whereas IgM and IgE levels were significantly lower(P＜0.05).At 12 months after treatment,the recurrence rate in the study group was 4.26％(2/47),which was sig-nificantly lower than 19.15％(9/47)in the control group(P＜0.05).There was no statistically significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion Vitamin AD combined with step-up therapy effectively alleviates clinical symptoms,modulates humoral immune balance,improves pulmonary function,and reduces recurrence rates in children with asthma,and has high safety.

ObjectiveTo understand the characteristics of PM_2.5 pollution in the air of Pearl River Delta city in Guangdong Province under the COVID-19 epidemic and the health risks of inhaling elements in PM_2.5. MethodsIn 2022， 10 PM_2.5 monitoring points were set up in 10 districts in Guangzhou， Shenzhen， Foshan and Zhuhai， and air samples were collected for 7 consecutive days every month to analyze the concentration of PM_2.5 and the 12 elements in PM_2.5. The classic "four-step" method was used to evaluate the carcinogenic risk and chronic non-carcinogenic risk of the elements in air PM_2.5 on health. The age-sensitive characteristics of metal elements were combined in the carcinogenic risk assessment， and age-sensitive factors were introduced to analyze the impact of air pollution on population health. ResultsA total of818 samples were collected. and the average annual PM_2.5 concentration in the four cities of the Pearl River Delta was 30.17 （1.00-166.00， s=21.06） μg·m^-3， which was lower than the concentration limit of the secondary standard of the Ambient Air Quality Standard （GB 3095-2012）. The difference of PM_2.5 concentration in the four cities was statistically significant. The PM_2.5 concentrations in Zhuhai and Shenzhen， which were located near the sea， were lower than those in Guangzhou and Foshan. The monthly mean concentration of PM_2.5 in the four cities was the lowest at 13.70 （4.00-34.00， s=5.93） μg·m^-3 in July and the highest at 57.73 （14.00-146.00， s=27.96） μg·m^-3 in January， showing a low concentration from May to October and a high concentration from November to April of the following year. The average daily PM_2.5 concentration exceeded the secondary standard for 29 days， mainly distributed in January and November. The average annual mass concentration of elements in PM_2.5 in the four cities was Al>Mn>Pb>As>Ni>Cr>Se>Sb>Cd>Tl>Be>Hg. AS and Mn have chronic non-carcinogenic risk in population， while Cr， AS， Cd， Be and Ni have carcinogenic risk in population. ConclusionThe PM_2.5 pollution levels of the four cities in the Pearl River Delta are low and variable. Coastal cities are lower than non-coastal cities， which shows the characteristics of first decreasing and then increasing throughout the year. The order of mass concentration of metal elements of PM_2.5 in four cities is basically the same except Be and Ni. As and Mn in PM_2.5 show a certain degree of chronic non-carcinogenic risk， and As， Cr， Cd， Ni and Be have a certain degree of carcinogenic risk. The four cities need to take effective intervention measures to continue to strengthen the pollution control and health protection of Cr， As， Cd and Mn in the air， and control the health burden caused by air pollution.

Replantation of traumatic amputation in children has its own characteristics. This consensus primarily focuses on the issues related to the treatment of traumatically amputated limb injuries in children. Organised along a timeline, the consensus summarises domestic and international clinical experiences in emergency care and injury assessment of traumatic limb amputation limbs, indications and contraindications for replantation surgery, principles and procedures of replantation surgery, postoperative medication and management, as well as rehabilitation in children. The aim of this consensus is to propose standardise the treatment protocols for limb replantation for children therefore to serve as a reference for clinical practitioners in medical practices, and further improve the treatment and care for the traumatic limb amputations in children.

Hepatocellular carcinoma(HCC)is one of the leading causes of cancer-related deaths in the world.Due to the insidious onset and rapid progression and a lack of effective treatments,the prognosis of patients with HCC is extremely poor,with the average 5-year survival rate being less than 10%.The tumor microenvironment(TME),the internal environment in which HCC develops,can regulate the oncogenesis,development,invasion,and metastasis of HCC.During the process of cancer progression,HCC cells can regulate the biological behaviors of tumor cells,cancer-associated fibroblasts,cancer-associated immune cells,and other cells in the TME by releasing exosomes containing specific signals,thereby promoting cancer progression.However,the exact molecular mechanisms and the roles of exosomes in the specific cellular regulation of these processes are not fully understood.Herein,we summarized the TME components of HCC,the sources and the biological traits of exosomes in the TME,and the impact of mechanical factors on exosomes.In addition,special attention was given to the discussion of the effects of HCC-exosomes on different types of cells in the microenvironment.There are still many difficulties to be overcome before exosomes can be applied as carriers in clinical cancer treatment.First of all,the homogeneity of exosomes is difficult to ensure.Secondly,exosomes are mainly administered through subcutaneous injection.Although this method is simple and easy to implement,the absorption efficiency is not ideal.Thirdly,exosome extraction methods are limited in number and inefficient,making it difficult to prepare exosomes in large quantities.It is important to ensure that exosomes are used in sufficient quantities to trigger an effective tumor immune response,especially for exosome-mediated tumor immunotherapy.With the improvement in identification,isolation,and purification technology,exosomes are expected to be successfully used in the clinical diagnosis of early-stage HCC and the clinical treatment of liver cancer.

Objective To investigate the mechanical responses of mitochondrial morphology to extracellular matrix stiffness in human mesenchymal stem cells(hMSCs)and the role of AMP-activated protein kinase(AMPK)in the regulation of mitochondrial mechanoresponses.Methods Two polyacrylamide(PAAm)hydrogels,a soft one with a Young's modulus of 1 kPa and a stiff one of 20 kPa,were prepared by changing the monomer concentrations of acrylamide and bis-acrylamide.Then,hMSCs were cultured on the soft and stiff PAAm hydrogels and changes in mitochondrial morphology were observed using a laser confocal microscope.Western blot was performed to determine the expression and activation of AMPK,a protein associated with mitochondrial homeostasis.Furthermore,the activation of AMPK was regulated on the soft and stiff matrixes by AMPK activator A-769662 and the inhibitor Compound C,respectively,to observe the morphological changes of mitochondria.Results The morphology of the mitochondria in hMSCs showed heterogeneity when there was a change in gel stiffness.On the 1 kPa soft matrix,74%mitochondria exhibited a dense,elongated filamentous network structure,while on the 20 kPa stiff matrix,up to 63.3%mitochondria were fragmented or punctate and were sparsely distributed.Western blot results revealed that the phosphorylated AMPK(p-AMPK)/AMPK ratio on the stiff matrix was 1.6 times as high as that on the soft one.Immunofluorescence assay results revealed that the expression of p-AMPK was elevated on the hard matrix and showed nuclear localization,which indicated that the activation of intracellular AMPK increased continuously along with the increase in extracellular matrix stiffness.When the hMSCs on the soft matrix were treated with A-769662,an AMPK activator,the mitochondria transitioned from a filamentous network morphology to a fragmented morphology,with the ratio of filamentous network decreasing from 74%to 9.5%.Additionally,AMPK inhibition with Compound C promoted mitochondrial fusion on the stiff matrix and significantly reduced the generation of punctate mitochondria.Conclusion Extracellular matrix stiffness regulates mitochondrial morphology in hMSCs through the activation of AMPK.Stiff matrix promotes the AMPK activation,resulting in mitochondrial fission and the subsequent fragmentation of mitochondria.The impact of matrix stiffness on mitochondrial morphology can be reversed by altering the level of AMPK phosphorylation.

Objective:To explore the surgical procedure and effect of reconstruction of soft tissue defects in the distal segment of dorsal finger with a perforator(joint branch) flap of proper palmar digital artery combined with a dorsal metacarpal artery flap.Methods:From January 2019 to June 2022, 9 patients with soft tissue defects in distal dorsal finger, mostly with avulsion at the extensor tendon insertion point, were treated in Department of Hand and Foot Microsurgery, the Affiliated Hospital of Qingdao University. The defect areas were 1.0 cm×1.0 cm-2.5 cm×2.0 cm. Steel wires were used to reconstruct the extensor tendon insertion point. The defects were reconstructed by a perforator(joint) flap of proximal phalanx artery and a dorsal metacarpal artery flap was used to repair the donor site for proximal flap. Postoperative follow-up and evaluation included flap survival, flap appearance, scars and function of interphalangeal and metacarpophalangeal joints, through outpatient clinical, WeChat and so on.Results:The flap of digital artery perforator (joint branch) and the fasciocutaneous flap of dorsal metacarpal artery all survived. One flap of the digital artery perforator(joint branch) appeared purple and tension blisters after surgery. The stitches of the pedicle of the flap were partially dismantled at 36-48 hours after surgery. The flap was then turned to ruddy in colour 7 days after surgery. The wounds of the distal finger joint and nail bed healed well without redness and infection. The postoperative follow-up lasted for 5 to 12 months, 9 months in average. The appearance, colour and texture of the skin at distal finger were similar to those at the dorsal proximal finger and dorsal palm. Sensation recovered well, all flaps exceeding S 3. The two-point resolution (TPD) was 8-10 mm, with an average of 9.5 mm. According to the Evaluation Standard of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association, 5 cases were in excellent and 4 in good. Conclusion:The perforator(joint branch) flap of proper palmar digital artery combined with a dorsal metacarpal artery flap is simple and safe treatment. It has a fast functional recovery with an aesthetic appearance in reconstruction of the soft tissue defect in distal segment of dorsal finger.

Objective:To investigate the clinical effect of bilateral anteriolateral thigh perforator flaps (ALTPF) pedicled with descending branch of lateral circumflex femoral artery in series on reconstruction of large soft tissue defects in lower limbs.Methods:A total of 9 patients with large soft tissue defects in lower limbs were selected in the study. The patients were 6 males and 3 females aged between 18 and 57 years old. They were treated in the Department of Hand and Foot Microsurgery, the Affiliated Hospital of Qingdao University from June 2018 to January 2023. Causes of injury: 4 of traffic accident, 2 of crushing, 2 of falling from height and 1 of explosion. Five patients had combined defects in dorsal feet and 4 with tibia fractures and anterior-and-posterior-tibial soft tissue defects. All affected limbs had tissue necroses and infections in various degrees. Deep tissue defects such as tendons, nerves, bones and joints or orthopaedic implants were exposed. The areas of soft tissue defects were 30 cm×14 cm-42 cm×14 cm. All the defects were reconstructed by the bilateral ALTPF pedicled with descending branch of lateral circumflex femoral artery in series. The size of proximal flaps was 25 cm×8 cm-33 cm×13 cm and 20 cm×7 cm-29 cm×13 cm for the distal flaps. Scheduled postoperative follow-ups were conducted to observe the survival of the transferred flaps and functional recovery of calfs and feet. Sensory recovery was assessed against British Medical Research Council (BMRC) criteria. Puno scoring was used to assess the functional recovery and the effectiveness of treatment.Results:All flaps survived and the donor sites healed well. One patient developed vascular compromise within 24 hours after surgery, but it was rectified after timely surgical exploration, however it left with a small area of necrosis at distal end of the flap. The necrosis and wound healed after skin grafting in stage-two surgery. Postoperative follow-up lasted for 8.3 months in average. Two patients underwent flap thinning in stage-two surgery due to bloating appearance, 2 patients had slightly bloated flaps at the calfs, and the rest of 5 patients had satisfactory flap appearance. Two patients received nerve reconstruction by anastomosis of the lateral femoral cutaneous nerves. At the final follow-up, the sensory recovery in 9 patients achieved S 2-S 3+ according to BMRC. The average Puno score achieved 88.36 point±5.36 point, of which 4 patients in excellent, 3 in good and 2 in fair. Conclusion:The use of bilateral ALTPF pedicled with descending branch of lateral circumflex femoral artery in series to reconstruct a large soft tissue defect in lower extremity has a good clinical value, and it has become one of the effective methods.