Patients with skeletal ClassⅡ often show symptoms such as protrusion of maxillary anterior teeth,mandibular retraction,open lips and teeth,deep overbite,and deep overjet,which seriously affect the facial appearance.This article reports a case of an ado-lescent male patient with skeletal Class Ⅱ combined with impacted teeth treated by one-stage early correction and two-stage fixation.After treatment,the patient's skeletal Class Ⅱ symptoms improved significantly,including the improvement of mandibular retraction.The problem of open lips and teeth was solved;the facial appearance tended to be straight,and there was no obvious abnormality of the temporomandibular joint.This case shows that early correction can achieve good therapeutic effects on this kind of patients and can avoid or reduce the possibility of orthognathic surgery for these patients in adulthood.

IL-34 can promote osteoclast differentiation and activation, which may contribute to steroidinduced osteonecrosis of the femoral head (ONFH). Animal model was constructed in both BALB/c and IL-34 deficient mice to detect the relative expression of inflammation cytokines. Micro-CT was utilized to reveal the internal structure. In vitro differentiated osteoclast was induced by culturing bone marrow-derived macrophages with IL-34 conditioned medium or M-CSF. The relative expression of pro-inflammation cytokines, osteoclast marker genes, and relevant pathways molecules was detected with quantitative real-time RT-PCR, ELISA, and Western blot. Up-regulated IL-34 expression could be detected in the serum of ONFH patients and femoral heads of ONFH mice. IL-34 deficient mice showed the resistance to ONFH induction with the up-regulated trabecular number, trabecular thickness, bone value fraction, and down-regulated trabecular separation. On the other hand, inflammatory cytokines, such as TNF-α, IFN-γ, IL-6, IL-12, IL-2, and IL-17A, showed diminished expression in IL-34 deficient ONFH induced mice. IL-34 alone or works in coordination with M-CSF to promote osteoclastogenesis and activate ERK, STAT3, and non-canonical NF-κB pathways. These data demonstrate that IL-34 can promote the differentiation of osteoclast through ERK, STAT3, and non-canonical NF-κB pathways to aggravate steroid-induced ONFH, and IL-34 can be considered as a treatment target.

Natural products, and especially the active ingredients found in traditional Chinese medicine (TCM), have a thousand-year-long history of clinical use and a strong theoretical basis in TCM. As such, traditional remedies provide shortcuts for the development of original new drugs in China, and increasing numbers of natural products are showing great therapeutic potential in various diseases. This paper reviews the molecular mechanisms of action of natural products from different sources used in the treatment of inflammatory diseases and cancer, introduces the methods and newly emerging technologies used to identify and validate the targets of natural active ingredients, enumerates the expansive list of TCM used to treat inflammatory diseases and cancer, and summarizes the patterns of action of emerging technologies such as single-cell multiomics, network pharmacology, and artificial intelligence in the pharmacological studies of natural products to provide insights for the development of innovative natural product-based drugs. Our hope is that we can make use of advances in target identification and single-cell multiomics to obtain a deeper understanding of actions of mechanisms of natural products that will allow innovation and revitalization of TCM and its swift industrialization and internationalization.

Objective:To investigate the safety and efficacy of short-segment fixation covering the fractured vertebrae via posterior intermuscular approach plus percutaneous kyphoplasty (PKP) through the outer upper edge of the base of the fractured vertebral pedicle in the treatment of osteoporotic thoracolumbar burst fracture.Methods:A retrospective case series study was used to analyze the clinical data of 56 patients with osteoporotic thoracolumbar burst fracture admitted to Ningbo No.6 Hospital from January 2018 to February 2021, including 24 males and 32 females; aged 56-72 years [(63.5±4.6)years]. All patients underwent short-segment fixation covering the fractured vertebrae via posterior intermuscular approach combined with PKP through the outer upper edge of the base of the fractured vertebral pedicle. The operation time, intraoperative blood loss, hospitalization day and surgery-related complications were recorded. The visual analogue score (VAS) of back pain, ratios of the anterior, middle and posterior height of the fractured vertebrae and kyphotic Cobb angle were compared before operation, at postoperative 2 days and at the final follow-up.Results:All patients were followed up for 12-28 months [(14.5±2.2)months]. The operation time was 55-85 minutes [(62.0±12.1)minutes], intraoperative blood loss was 80-150 ml [(94.0±18.5)ml], and hospitalization day was 5-9 days [(7.4±1.1)days]. Based on CT examination at postoperative 2 days, there were 2 patients with paravertebral cement leakage, 2 with intervertebral space leakage and 1 with intracanal leakage, but none reported associated clinical symptoms. No implant failure or fractures of adjacent segments was detected during the follow-up period. The VAS was significantly decreased from preoperative (7.5±1.2)points to (3.2±0.8)points at postoperative 2 days ( P<0.01), and the score was further lowered to (2.2±0.8)points at the final follow-up when compared with that at postoperative 2 days ( P<0.01). The ratios of the anterior, middle and posterior height of the fractured vertebrae and kyphotic Cobb angle were significantly improved at postoperative 2 days [(89.5±13.2)%, (85.8±7.9)%, (89.5±9.0)% and (5.6±3.2)°] when compared with those before operation [(48.9±11.8)%, (61.9±11.9)%, (79.9±9.8)% and (26.3±5.6)°] (all P<0.01). Slight losses were observed in the ratios of the anterior, middle and posterior height of the fractured vertebrae and kyphotic Cobb angle at the final follow-up [(87.0±12.7)%, (82.1±7.8)%, (88.6±10.0)% and (5.4±3.2)°], but not significantly different from those at postoperative 2 days (all P>0.05). Conclusion:Short-segment fixation covering the fractured vertebrae via posterior intermuscular approach plus PKP through the outer upper edge of the base of the fractured vertebral pedicle can safely and effectively treat osteoporotic thoracolumbar burst fracture, for it can significantly improve back pain, restore the height of the fractured vertebrae and correct the kyphotic deformity.

Objective:To identify the molecular mechanisms of the effects of the Buyin Qianzheng formula (BYQZF)on the mitochondrial dynamics in a Parkin overexpression Parkinson's disease (PD) cell model.Methods:First,a stable Parkin overexpression cell model was constructed using plasmid transfection.Then,we examined the protective effect of BYQZF on the mitochondrial dysfunction of the Parkin overexpression PD cell model induced by neurotoxin 1-methyl-4-phenylpyridinium ion (MPP+).The mRNA expression level of Parkin was evaluated using real-time quantitative PCR.The cell survival rate was detected using the Cell Counting Kit-8 assay.We evaluated the cellular adenosine triphosphate (ATP)levels using luciferase assays.A laser scanning confocal microscope was used to observe the mito-chondrial morphology,activity,and mitochondrial membrane potential (ΔΨm).Western blot was con-ducted to evaluate the levels of the fusion proteins mitofusin1,mitofusin2,optic atrophy 1,dynamin-related protein 1,and mitochondrial fission protein 1.Results:Parkin overexpression attenuated MPP+-induced mitochondrial damage,increased mitochon-drial activity and AΨm.BYQZF increased the survival of MPP+-induced cells that overexpressed Parkin and upregulated the mitochondrial form factor and activity.It also inhibited a decrease in the ΔΨm and ATP levels.These findings suggested that BYQZF protected against MPP+-induced mitochondrial dysfunction and enhanced the protective effect of Parkin overexpression.Furthermore,the formula upregulated the expression of the fusion proteins mitofusin1,mitofusin2,and optic atrophy 1 (closely related to mitochondrial quality remodeling),and reduced the expression of the fission protein dynamic-related protein 1,as well as mitochondrial fission protein 1.Conclusion:The mechanism by which BYQZF increased the mitochondrial protective effect of Parkin gene overexpression in MPP+-induced cells may be related to improving mitochondrial function and regulating the balance of mitochondrial division and fusion proteins.

Objective:To explore the feasibility of emergency video call system in remote guidance of non-medical volunteers to implement single person cardiopulmonary resuscitation (CPR).Methods:A scenario of sudden cardiac arrest with a bystander in a public place was created at Clinical Skill Training Center. 60 non-medical volunteers were randomly (ramdom number) divided into video group ( n = 40) and audio group ( n = 20). Volunteers in video group were remote instructed with the smart phone application software (APP) of Emergency Video Call System to implement CPR; the audio group receives remote voice guidance for CPR with a smart phone. The pressing depth, pressing frequency, volume of ventilation and the time of the first compression were compared between the two groups. The video group was divided into 5 subgroups to compare the cardiopulmonary resuscitation effect of 5 different models of smart phones. Ten CPR cycles were observed in each group. Results:the accuracy rate of pressing position in the video group was significantly higher than that in the audio group (91.5% vs 71.35%, P < 0.05); the proportion of pressing depth in the range of 5-6 cm was significantly higher than that in the audio group (62.79% vs. 44.73%, P < 0.05); the average pressing frequency was 100-120 times / min (70% vs. 52%, P < 0.05); the ventilation volume was 500-600 mL / time (18.25% vs. 10.75%, P < 0.05); The proportion of ventilation volume greater than 500ml / min was higher than that of audio group (64.88% vs. 43%, P < 0.05). The first pressing time was longer in the video group than in the audio group (131 s vs. 106 s, P < 0.05). There was no significant difference in the first ventilation time between the two groups (148 s vs. 144 s, P > 0.05). The total pressing pause time in video group was less than that in audio group (122.4 s vs. 164.2 s, P < 0.05). There was no significant difference in the above indicators among the five different models of smart phones in the video group ( P > 0.05). Conclusions:compared with audio remote guidance, video emergency system has obvious advantages in the accuracy of pressing position, pressing depth, pressing frequency, ventilation volume and pressing pause time, but the first pressing time is slightly longer than that of audio group. The popularization and application of the video system is supposed to improve the CPR quality and recovery success rate of non-medical personnel, and facilitated to encourage the first witness to implement CPR.

Objective:To investigate the anatomical safety and feasibility ofposterior occipitocervical fixation with atlan-tooccipital-clivus screw.Methods:Data of 60 patients who treated in the spinal department of our hospital with upper cervical computed tomographic scans from February 2017 to November 2019 were retrospectively collected. Occipitocervical infection, injury, tumor and deformity were excluded. The Mimics software was used to reconstruct the occiput, atlas and measure the anatomical parameters, including the height and width of the anterior edge of the clivus, the height and width of the middle part of the clivus, the thinnest distance of the soft tissue in front of the clivus, the anteroposterior diameter, transverse diameter, the angle of inside tilting in coronary plane of the occipital condyle, the distance from the hypoglossal canal to the atlantooccipital articular surface, the anteroposterior diameter and transverse diameter of the superior joint of atlas, the height of the lateral mass, and the height and transverse diameter of the inferior articular process of the superior atlas joint. The three-dimensional digital modeling was performed and the screw diameter of 3.5mm was simulated. 3-Matic software were used to measure the screw placement parameters, including the inside tilting angle in coronary plane of screw, and the angle of upper tilting in sagittal plane and length of screw. The atlanto-occipital junction was exposed at the rear of 8 cadavers. According to the above parameters, the titanium alloy screws with a diameter of 3.5 mm were transferred from the inferior articular process and posterior arch of the atlas to the clivus through the atlantooccipital. Finally, the screw path was cut along the nail path with a pendulum saw, and the track of the screw was observed to confirm the safety and effectiveness of the screw.Results:The leading edge height and width of male clivus was 16.8±2.5 mm and 20.1±3.1 mm. The middle part of the clivus was 9.7±2.3 mm and 22.4±3.7 mm. The thinnest soft tissue in front of the clivus was 5.8±1.48 mm. The anteroposterior diameter of the occipital condyle was 19.1±1.9 mm, the transverse diameter was 12.6±2.0 mm, the inside tilting angle was 33.7°±4.5°, and the vertical distance from the lowest point of the neural tube to the articular surface of the occipital condyle was 9.6±1.1 mm. The height of the lateral mass of atlas was 12.9±2.4 mm, the anteroposterior diameter of the upper joint of atlas was 21.7±1.9 mm, and the transverse diameter was 11.7±1.4 mm. The width of the inferior facet was 14.9±1.4 mm and the height of the inferior facet was 5.7±0.85 mm. The distance from the screw entry point to the vertical line of the lateral mass migration midpoint was 2.5±0.6 mm; The distance from the screw entry point to the horizontal line of the midpoint was 2.3±0.7 mm.The inside titling angle of screw was 18.4°±1.6°, the upper tilting angle was 55.6°±3.1°, the length of the screw track was 53.0±2.8 mm, the adjustment range of upper tilting angle was 15.0±2.8 mm, the adjustment range of inside tilting angle was 10.4±2.4 mm. The anatomical parameters of females were slightly smaller than those of males, and the difference was statistically significant, but there was no significant difference between left and right parameters. The screws of 8 specimens could be inserted safely and effectively.Conclusion:Atlan-tooccipital-clivus screw can be implanted without damaging the nerve and vascular structure, and it can be used as a choice for occipitocervical fixation.

Objective:To explore the difference in properties of anterior occipital condyle plate screws compared with common anterior occipitalcervical fusion internal fixation.Methods:A 28-year-old healthy adult male volunteer's CT data of the occiput and neck was selected to establish finite element models：including the normal model，simple artificial vertebral fixation model（special-shaped titanium cage+clival screws），anterior occipital condyle plate and screw fixation model，and clival plate and screw fixation model，then a 50 N gravity and a torque of 1.5 N m were exerted upon the upper surface of the occipital bone to make the model produce flexion and extension，lateral bending and rotation. The motion range，internal fixation stress distribution and occipital bone stress distribution of each model under varying conditions were compared.Results:Under the conditions of flexion，extension，lateral bending and rotation，the range of motion of the normal model was 18.65°，15.35°，9.82° and 34.68°，respectively；that of the simple artificial vertebral fixation model was 3.20°，3.63°，2.94° and 3.92°，respectively；that of the clival plate and screw fixation model was 0.40°，0.50°，0.35° and 0.89°，respectively；that of the anterior occipital condylar plate and screw fixation model was 0.27°，0.33°，0.13° and 0.30°，respectively. Compared with the simple artificial vertebral fixation model，the range of motion of the clival plate and screw fixation model decreased by 87.5%，86.2%，88.1% and 77.3% in flexion，extension，lateral bending and rotation. The range of motion of the anterior occipital condylar plate and screw fixation model decreased by 91.5%，90.1%，95.6% and 92.3%，respectively. Under the conditions of flexion and extension，lateral bending and rotation，the stress peak of the simple artificial vertebral fixation model was 52.3 MPa，51.9 MPa，52.6 MPa，respectively；that of the clival plate and screw fixation was 100.1 MPa，158.1 MPa，170.6 MPa，respectively；that of the anterior occipital condylar plate and screw fixation was 114.2 MPa，62.9 MPa，132.9 MPa，respectively. Under the condition of flexion and extension，lateral bending and rotation，the stress peak of the occipital bone in the simple artificial vertebral body internal fixation model was 52.9 MPa，50.9 MPa and 62.3 MPa，respectively；that of the clival plate and screw fixation model was 19.7 MPa，55.9 MPa and 38.3 MPa，respectively；that of the anterior occipital condylar plate and screw fixation model was 37.8 MPa，15.0 MPa and 16.3 MPa，respectively. The stress in bone near the hypoglossal canal was close to 0 MPa，much smaller than the stress peak in occipital bone.Conclusion:Anterior occipital condylar plate and screw fixation in front of the special-shaped titanium cage can improve the stability of occipitocervical fusion with little effect on the occipital bone and hypoglossal canal or without obvious stress concentration，and hence is a safe and reliable anterior fixation method for upper cervical spine instability.

Objective:To provide a theoretical basis for the clinical application of the posterior route through atlas occipital articular slope screw internal fixation system through the biomechanical study.Methods:Eight cadavers of healthy adults aged 35-60 years and 155-180 cm in height were selected. The specimens with complete anatomical structure and without surgical operation were established as normal models. The model of occipito-atlantoaxial complex was established by breaking the articular capsule, ligament and other connecting structures and cutting the dentate process. The device was established as an internal fixation model through the specimen of atlantooccipital joint slope screw internal fixation system. Given normal model and internal fixation of 1.5 N·m in the moment of flexion, lateral bending and axial rotation and to measure the specimen C 0-C 1 and C 0-C 2 segment of the range (range of motion, ROM), comparative analysis of pillow neck area within the normal model and fixed model changes the range of movement, after the evaluation through the slope between atlas and the occipital screw internal fixation system of mechanical properties. Results:In the normal model, the flexion, flexion and extension, lateral bend and axial rotation ranges of C 0-C 1 segments were 23.85°±2.43°, 4.74°±0.55°, 5.77°±0.75°, respectively; the corresponding activity ranges of C 0-C 2 segments were 30.66°±3.05°, 9.09°±1.37°, 70.97°±9.48°, respectively; in the internal fixation model, the flexion and extension, lateral bend and axial rotation ranges of C 0-C 1 segments were 0.71°±0.24°, 0.24°±0.06°, 0.34°±0.09°, respectively. The corresponding activity range of C 0-C 2 segment was 3.09°±0.82°, 0.74°±0.07°, 1.22°±0.10°, respectively. Compared with the normal model, the range of activity of the internal fixation model in all directions was significantly reduced (<3°), and the reduction ratio of activity was more than 90%. Conclusion:The posterior route through pillow slope screw internal fixation system can effectively reduce the range of motion of the occipital neck in flexion, extension, lateral bending and rotation, and has safe and reliable biomechanical stability.

Objective To assess the imported risk of COVID-19 in Guangdong province and its cities, and conduct early warning. Methods Data of reported COVID-19 cases and Baidu Migration Index of 21 cities in Guangdong province and other provinces of China as of February 25, 2020 were collected. The imported risk index of each city in Guangdong province were calculated, and then correlation analysis was performed between reported cases and the imported risk index to identify lag time. Finally, we classified the early warming levels of epidemic by imported risk index. Results A total of 1 347 confirmed cases were reported in Guangdong province, and 90.0% of the cases were clustered in the Pearl River Delta region. The average daily imported risk index of Guangdong was 44.03. Among the imported risk sources of each city, the highest risk of almost all cities came from Hubei province, except for Zhanjiang from Hainan province. In addition, the neighboring provinces of Guangdong province also had a greater impact. The correlation between the imported risk index with a lag of 4 days and the daily reported cases was the strongest (correlation coefficient: 0.73). The early warning base on cumulative 4-day risk of each city showed that Dongguan, Shenzhen, Zhongshan, Guangzhou, Foshan and Huizhou have high imported risks in the next 4 days, with imported risk indexes of 38.85, 21.59, 11.67, 11.25, 6.19 and 5.92, and the highest risk still comes from Hubei province. Conclusions Cities with a large number of migrants in Guangdong province have a higher risk of import. Hubei province and neighboring provinces in Guangdong province are the main source of the imported risk. Each city must strengthen the health management of migrants in high-risk provinces and reduce the imported risk of Guangdong province.