BACKGROUND:Increasing studies have shown that autophagy plays an important role in the treatment of osteoarthritis,and moderate autophagy can preserve the normal physiological function of osteoarticular chondrocytes.Traditional Chinese medicine(TCM)monomers can target and modulate autophagy to treat osteoarthritis,and their characteristics such as single components,clear efficacy,low price,and easy availability have obvious benefits in the treatment of osteoarthritis.OBJECTIVE:To review the effects of TCM monomers on the targeted regulation of autophagy in the treatment of osteoarthritis and the research progress,with a view to laying a foundation for the treatment of osteoarthritis and even other bone metabolic diseases.METHODS:Relevant literature published from January 2012 to October 2022 was retrieved in PubMed,Web of Science,CNKI,and WanFang using the keywords of"traditional Chinese medicine,Chinese herbal monomer,autophagy,osteoarthritis"in English and Chinese.Inclusion and exclusion criteria were developed,and 63 relevant articles were finally included by screening through reading the title,abstract,and full-text content.RESULTS AND CONCLUSION:TCM monomers can treat osteoarthritis by targeting autophagy to inhibit chondrocyte apoptosis,protect cartilage extracellular matrix,reduce inflammation and antagonize oxidative stress injury.Different TCM monomers can regulate autophagy in the same way,and the same TCM monomers can affect autophagy in different ways.The combination of multiple monomers and the multi-target and multi-pathway regulation of autophagy by TCM monomers remain to be explored.The regulation of autophagy by TCM monomers can provide new ideas and strategies for the prevention and treatment of osteoarthritis.Moderate regulation of autophagy by TCM monomers to keep the autophagic flux unimpeded may be the key to treating osteoarthritis.

BACKGROUND:More and more studies have shown that oxidative stress should play an important role in the treatment of osteoporosis.Oxidative stress should cause the accumulation of oxidation activity,which will damage bone-related cells.Finally,it causes the imbalance of bone resorption and bone formation,resulting in a decrease in bone volume and the destruction of the slight structure.Research in recent years has found that some natural products can regulate oxidative stress to treat osteoporosis.The characteristics of extensive sources and small side effects have obvious advantages in the treatment of osteoporosis,and the efficacy is objective. OBJECTIVE:To discuss the mechanism of natural product regulation of oxidation stress in treatment of osteoporosis,conduct a review based on the latest related research progress,provide reference and ideas for more natural products to treat osteoporosis in the future,and provide data support for the clinical application of natural compounds in the treatment of osteoporosis. METHODS:"oxidative stress,free radical,antioxidant,phytotherapy,plant extracts,medicinal plants,herbal medicine,osteoporosis,bone density,bone loss"were used as the keywords in PubMed,Web of Science,Embase,Cochrane,VIP,CBM,WanFang,and CNKI databases to search relevant articles published from January 2010 to February 2023.Inclusion and exclusion criteria were developed,and 64 relevant articles were selected by reading titles,abstracts,and full texts. RESULTS AND CONCLUSION:(1)Some natural products have antioxidant effects and can regulate osteogenic differentiation,osteoblast bone matrix mineralization,osteoclast-mediated bone resorption,proliferation,differentiation,activity,and apoptosis of bone-related cells by improving oxidative stress,thus affecting bone metabolism.(2)These natural products with antioxidant effects play a role in treating osteoporosis by improving bone remodeling balance.(3)The research on the combination of a variety of natural products to improve osteoporosis remains to be explored.(4)The use of natural products to regulate oxidative stress may become a powerful weapon for the clinical treatment of osteoporosis in the future.

Objective:The treatment of head and neck in plexiform neurofibroma (PNF) is a major clinical problem, lacking consensus on surgical treatment, classification, operation timing, and treatment method. The purpose of this study was to provide a basis for further consensus formation by analyzing the clinical manifestations, surgical conditions, tumor recurrence, post-operation satisfaction, and changes in quality of life of patients undergoing PNF surgery in head and neck.Methods:Through medical record review and telephone follow-up, a retrospective analysis was conducted on neurofibromatosis type 1 (NF1) patients admitted for surgical treatment for PNF patient in head and neck from May 2012 to July 2022 in Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine. Complete collection and statistical analysis of patients’clinical data, using telephone follow-up to investigate the immediate postoperative satisfaction and long-term surgical satisfaction of patients and/or their families, as well as standardized quality of life questionnaires HRQol(health related quality of life) and PlexiQol(plexiform neurofibroma quality of life). Based on the data about changes in quality of life before and after surgery and long-term surgical satisfaction, patients were divided into surgical benefit and non-benefit groups. Binary and multivariate logistic regression analysis were used to analyze the clinical characteristics of patients with long-term surgical benefit.Results:Totally 512 patients with head and neck NF1 were admitted for surgery with complete medical records. 121 patients were identified as NF1 related PNF diagnosed by medical history and radiological examination, and effective follow-up was obtained. There were 70 males and 51 females, aged (25.60±12.85) years old, ranging from 7 to 63 years old, with 41 patients who were ≤ 18 years old and 80 patients over 18 years old. 62.81%(76/121) of patients exhibiting clinical dysfunctions, and the tumor mass were mainly characterized by invasive growth. 41.32%(50/121) of patients underwent multiple surgical treatments, with a total of 215 surgeries performed on 121 patients. The surgical objective included appearance improvement and functional repair. The incidence of postoperative complications was 6.05%(13/215). The follow-up period after last operation was (51.41±27.66) months, and 42.15%(51/121) of patients reported postoperative tumor recurrence. 76.03%(92/121) of patients were satisfied with immediate postoperative result, while the rate decreased to 46.28%(56/121) during long-term follow-up. Family members of patients who were ≤ 18 years old had a higher proportion of dissatisfaction with the scars caused by surgery and a stronger willingness to undergo another surgery. The tumor recurrence was closely related to surgical benefits ( OR=2.32, P<0.05). Further analysis found that the gender and age of patients were the main risk factors for the recurrence. The recurrence risk in patients ≤ 18 years old was significantly higher than in that over 18 years old( OR=3.49, P=0.004), and the highest in the 7-12 year-old group, reaching 68.42%(13/19). The recurrence risk in male patients was significantly lower than that in females ( OR=0.40, P=0.026). Conclusion:The clinical manifestations of PNF patients in head and neck region are complex. Clinical diagnosis and treatment in PNF should focus on the applications in comprehensive method such as full preoperative evaluation, active multi-disciplinary treatment cooperation and combined therapies in order to improve the safety and effectiveness of treatment and reduce tumor recurrence.

Objective:The treatment of head and neck in plexiform neurofibroma (PNF) is a major clinical problem, lacking consensus on surgical treatment, classification, operation timing, and treatment method. The purpose of this study was to provide a basis for further consensus formation by analyzing the clinical manifestations, surgical conditions, tumor recurrence, post-operation satisfaction, and changes in quality of life of patients undergoing PNF surgery in head and neck.Methods:Through medical record review and telephone follow-up, a retrospective analysis was conducted on neurofibromatosis type 1 (NF1) patients admitted for surgical treatment for PNF patient in head and neck from May 2012 to July 2022 in Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine. Complete collection and statistical analysis of patients’clinical data, using telephone follow-up to investigate the immediate postoperative satisfaction and long-term surgical satisfaction of patients and/or their families, as well as standardized quality of life questionnaires HRQol(health related quality of life) and PlexiQol(plexiform neurofibroma quality of life). Based on the data about changes in quality of life before and after surgery and long-term surgical satisfaction, patients were divided into surgical benefit and non-benefit groups. Binary and multivariate logistic regression analysis were used to analyze the clinical characteristics of patients with long-term surgical benefit.Results:Totally 512 patients with head and neck NF1 were admitted for surgery with complete medical records. 121 patients were identified as NF1 related PNF diagnosed by medical history and radiological examination, and effective follow-up was obtained. There were 70 males and 51 females, aged (25.60±12.85) years old, ranging from 7 to 63 years old, with 41 patients who were ≤ 18 years old and 80 patients over 18 years old. 62.81%(76/121) of patients exhibiting clinical dysfunctions, and the tumor mass were mainly characterized by invasive growth. 41.32%(50/121) of patients underwent multiple surgical treatments, with a total of 215 surgeries performed on 121 patients. The surgical objective included appearance improvement and functional repair. The incidence of postoperative complications was 6.05%(13/215). The follow-up period after last operation was (51.41±27.66) months, and 42.15%(51/121) of patients reported postoperative tumor recurrence. 76.03%(92/121) of patients were satisfied with immediate postoperative result, while the rate decreased to 46.28%(56/121) during long-term follow-up. Family members of patients who were ≤ 18 years old had a higher proportion of dissatisfaction with the scars caused by surgery and a stronger willingness to undergo another surgery. The tumor recurrence was closely related to surgical benefits ( OR=2.32, P<0.05). Further analysis found that the gender and age of patients were the main risk factors for the recurrence. The recurrence risk in patients ≤ 18 years old was significantly higher than in that over 18 years old( OR=3.49, P=0.004), and the highest in the 7-12 year-old group, reaching 68.42%(13/19). The recurrence risk in male patients was significantly lower than that in females ( OR=0.40, P=0.026). Conclusion:The clinical manifestations of PNF patients in head and neck region are complex. Clinical diagnosis and treatment in PNF should focus on the applications in comprehensive method such as full preoperative evaluation, active multi-disciplinary treatment cooperation and combined therapies in order to improve the safety and effectiveness of treatment and reduce tumor recurrence.

Abstract: Objective　To genotype and analyze whole genomic features of Coxsackievirus B3 (CVB3) isolated in Tianjin, to improve evolution information of CVB3 virus in Tianjin, and to provide basis for surveillance and early warning of related diseases. Methods　Viral RNA was extracted from five CVB3 strains isolated in Tianjin, whole genome sequence of the virus was amplified by RT-PCR and sequenced by next-generation sequencing method, and phylogenetic and recombinant analysis were carried out. Results　The open reading frame 1(ORF) of the five CVB3 strains contained 6 555 nucleotides and encoded 2 185 amino acids, and ORF2 was composed of sequences encoding 68 amino acids. The nucleotide sequence similarity ranged from 78.3%-100%, and the amino acid sequence similarity ranged from 95.7%-100%. Compared with the CVB3 prototype strain, the nucleotide sequence similarity of the five viruses was between 78.2%-79.1%, and the similarity of amino acid sequences was 94.9%-95.3%. All five viruses exhibited a T151A mutation on the VP2 protein. Additionally, the encephalitis isolate showed a K158E mutation on the VP2 protein, while one of the sewage isolates had a C234T mutation in 5' noncoding region. The five strains belonged to two different genotypes, among which the encephalitis isolate in 2016 belonged to the D genotype, while the sewage isolates in 2021 belonged to the E genotype. This is also the first report of E genotype CVB3 in northern China. The CVB3 strain may have recombinant events in non-structural protein regions, in which encephalitis isolate may recombine with a Coxsackievirus B5 (CVB5) strain, while sewage isolates may have recombinant events with a strain of ECHO virus 18 (E18). Conclusions　The CVB3 isolates in Tianjin belong to D and E genotypes, and recombination events may exist in non-structural protein region of the viral genome. The results of CVB3 virus genome analysis in sewage suggests presence of CVB3 infection in the population of Tianjin, and its epidemic dominant genotype may have changed.

Osteoporosis， a common metabolic bone disease， is caused by the imbalance of bone homeostasis. Bone homeostasis depends on the dynamic balance between bone resorption by osteoclasts and bone matrix formation by mesenchymal lineage osteoblasts and involves a series of complex and highly regulated steps. When bone resorption is faster than bone formation， bone homeostasis will be destroyed， which will lead to osteoporosis. Autophagy is a protein and organelle degradation pathway important for the maintenance of cytoplasmic homeostasis. The basal level of autophagy is present in all the three types of bone cells. Autophagy is a process whereby damaged organelles are recycled and bone remodeling continues， and thus it plays an important role in bone maintenance. Therefore， it is possible to regulate bone metabolism by targeting specific autophagy-related molecules. At the same time， as the research on the treatment of osteoporosis by Chinese medicine advances， it is found that the monomers isolated from traditional Chinese medicinals have the potential of regulating autophagy in the treatment of osteoporosis. Thus， this paper discusses the relationship between autophagy and osteoporosis and summarizes six different mechanisms of 22 Chinese medicine monomers in the treatment of osteoporosis through targeting autophagy： increasing osteogenic differentiation of mesenchymal stem cells， promoting osteoblast mineralization， inhibiting osteoclasts differentiation， reducing apoptosis of bone cells， antagonizing oxidative stress injury， and coordinating inflammation and autophagy levels. The review is expected to provide a reference and ideas for future research on the treatment of osteoporosis by Chinese medicine monomers.

Objective:To analyze the whole genome traceability and variation analysis of SARS-CoV-2 in local COVID-19 outbreaks in Binhai New Area, Tianjin.Methods:The whole-genome high-throughput sequencing was performed on throat swab samples collected from one local asymptomatic infected person and five confirmed cases of COVID-19 in Binhai New Area of Tianjin from November 7 to December 5, 2020. The sequencing data were assembled by De novo. MAFFT v7.0 multiple sequence alignment program and MEGA X software were used to compare the above data and construct phylogenetic tree (Neighbor-joining method).Results:The genetic similarity between the sequences of 6 SARS-CoV-2 strains and Wuhan reference sequence (Wuhan-Hu-1) was greater than 99.9%. Two of six strains were genetically identical, conform to the L-Lineage European Branch Ⅱ.1(America Branch)/B.1; The other four strains had the same genes and were in line with the characteristics of L-Lineage European Branch Ⅰ/B.1.1.These six strains belonged to different evolutionary branches and two different transmission chains. There were 18 nucleotide mutation sites in sequences of six SARS-CoV-2 strains, eight of which were synonymous mutation sites, nine of which were missense mutation sites, resulting in nine amino acid mutation sites, and important mutation sites of RDRP-P323L and S-D614G were found in all of the six samples.Conclusions:In this study, there were two COVID-19 outbreaks in Binhai New Area of Tianjin, and the sequences of six SARS-CoV-2 strains belonged to different evolutionary branches and two different transmission chains. It might come from porters′ contact with imported cold chain items contaminated with SARS-CoV-2 from different sources. All the sequences of six SARS-CoV-2 strains had P323L and D614G mutations, which indicated that the virus mutation and transmission ability were stronger. The surveillance of important employees of the cold chain in Tianjin and local and imported cases should be continuously strengthened.

Objective:To collect the upper respiratory tract specimens from both domestically-spread and imported Coronavirus Disease 2019 (COVID-19) confirmed cases, sequence the whole genome of 2019 novel coronavirus (2019-nCoV) and analyze the genetic variation and the phylogenetic characteristics.Methods:The viral nucleic acids of all specimens were extracted, the sequencing library was constructed following the manufacturing instructions, and the sequencing data were analyzed by bioinformatics software.Results:The whole genomes of 2019-nCoV strains from 24 samples were all obtained and had high similarity with the genome of the reference strain Wuhan-Hu-1 (GenBank ID: NC_045512) and the similarity rates were all greater than 99.9%. Six 2019-nCoV strains from domestically-spread cases were classified into L-lineage and the others were S-lineage. The 2019-nCoV strains from the imported cases had 48 nucleotide mutation positions, but those from the domestically-spread cases only had 14 mutation positions. Most of 2019-nCoV strains from the imported cases (15/16) had the specific D614G mutation site in spike protein, while those from the domestically-spread cases had none.Conclusions:The 2019-nCoV strains from the imported cases in Tianjin city had more mutation sites than those from the domestically-spread cases, and most of 2019-nCoV strains from the imported cases had D614G mutations in spike protein which had more transmissive rates and were easier to spread among humans.

To establish a three-dimensional finite element model (FEM) of the neck, to analyze the differences in neck biomechanics between patient with cervical spondylotic myelopathy (CSM) and healthy subject and to provide biomechanics basis for the pathogenesis of CSM.
 Methods: A patient with CSM was enrolled in a mechanical simulation experiment. Three-dimensional CT scan was performed, and three-dimensional FEM of the neck was constructed. A heathy subject was selected as a control according to the patient's age, gender, height, and weight. Three-dimensional FEM was used to compare the stress differences in the vertebral body, intervertebral disc, ligament and spinal cord under the normal stress of the cervical spine and the maximum stress of the posterior reclining motion.
 Results: Successfully constructed FEM model of CSM patient and control, and performed mechanical analysis, the most obvious difference in cervical vertebral body force was at C5-C6 segment in CSM patients. The maximum stress site of control and patient was at the anterior edge of the vertebral body. The maximum stress of the vertebral body in the CSM patient was less than that of the control. The stress distribution of the intervertebral disc was irregular in the CSM patient, and the maximum stress was concentrated on both sides of the posterior edge of the intervertebral disc. The stress distribution of the ligaments of the CSM patient was uneven. The maximum stress was in the posterior longitudinal ligament. The range of neck movement in extension of the CSM patient was restricted.
 Conclusion: Compared with the healthy subject, the balance of the vertebral body, intervertebral disc, ligament and limited range of motion of the CSM patient has been changed, which may be related to the mechanical pathogenesis of cervical spondylotic myelopathy.
Cervical Vertebrae ; Finite Element Analysis ; Humans ; Intervertebral Disc ; Spinal Cord Diseases

Objective: To investigate the efficacy and safety of anlotinib hydrochloride capsules for the treatment of advanced soft tissue sarcoma based on the data from Department of Bone and Soft Tissue Tumor, Peking University Cancer Hospital&Institute. Methods: Patients were randomized allocated at 2:1 ratio for the anlotinib treatment and placebo group. The treatment group received 12 mg/day of anlotinib for 14 consecutive days in a 21-day cycle. The primary end-point was progression-free survival (PFS), and the secondary end-points were disease control rate (DCR), overall survival (OS), and adverse event rate. Results: A total of 46 patients were enrolled in this study; 7 of them were excluded from per protocol set (PPS). Among the remaining 39 patients, 28 were included in the anlotinib group and 11 in the placebo group. In the anlotinib group, 4 patients had partial remission and 13 had stable disease (SD), whereas in the placebo group, 3 patients had SD. The difference in DCR between the 2 groups was statistically significant (60.7% vs . 27.3%, P=0.082). The DCR of the advanced soft tissue sarcoma in the anlotinib group was 78.6% (11/14). The median PFS in the anlotinib group was 12.4 (95% confidence interval [CI]: 7.6 to 17.2) months, which was significantly longer than 4 months in the placebo group (95% CI: 1.7 to 6.3 months, P=0.043); however, the difference in OS between the 2 groups was not significant (19.4 vs . 17.6 months, P=0.961). Regarding the safety, 2 patients had severe adverse events (7.14%) possibly related with treatment in the anlotinib group; one of them had pneumothorax. The other adverse events were grade 1 to 2. Conclusions: Soft tissue sarcoma is highly responsive to anlotinib, with prolonged PFS. Anlotinib is well tolerated and can be used as a treatment option for advanced soft tissue sarcoma.