BACKGROUND:Heterotopic ossification is a dynamic growth process.Diverse heterotopic ossification subtypes have diverse etiologies or induction factors,but they exhibit a similar clinical process in the intermediate and later phases of the disease.Acquired heterotopic ossification produced by trauma and other circumstances has a high incidence. OBJECTIVE:To summarize the molecular biological mechanisms linked to the occurrence and progression of acquired heterotopic ossification in recent years. METHODS:The keywords"molecular biology,heterotopic ossification,mechanisms"were searched in CNKI,Wanfang,PubMed,Embase,Web of Science,and Google Scholar databases for articles published from January 2016 to August 2022.Supplementary searches were conducted based on the obtained articles.After the collected literature was screened,131 articles were finally included and summarized. RESULTS AND CONCLUSION:(1)The occurrence and development of acquired heterotopic ossification is a dynamic process with certain concealment,making diagnosis and treatment of the disease difficult.(2)By reviewing relevant literature,it was found that acquired heterotopic ossification involves signaling pathways such as bone morphogenetic protein,transforming growth factor-β,Hedgehog,Wnt,and mTOR,as well as core factors such as Runx-2,vascular endothelial growth factor,hypoxia-inducing factor,fibroblast growth factor,and Sox9.The core mechanism may be the interaction between different signaling pathways,affecting the body's osteoblast precursor cells,osteoblast microenvironment,and related cytokines,thereby affecting the body's bone metabolism and leading to the occurrence of acquired heterotopic ossification.(3)In the future,it is possible to take the heterotopic ossification-related single-cell osteogenic homeostasis as the research direction,take the osteoblast precursor cells-osteogenic microenvironment-signaling pathways and cytokines as the research elements,explore the characteristics of each element under different temporal and spatial conditions,compare the similarities and differences of the osteogenic homeostasis of different types and individuals,observe the regulatory mechanism of the molecular signaling network of heterotopic ossification from a holistic perspective.It is beneficial to the exploration of new methods for the future clinical prevention and treatment of heterotopic ossification.(4)Meanwhile,the treatment methods represented by traditional Chinese medicine and targeted therapy have become research hotspots in recent years.How to link traditional Chinese medicine with the osteogenic homeostasis in the body and combine it with targeted therapy is also one of the future research directions.(5)At present,the research on acquired heterotopic ossification is still limited to basic experimental research and the clinical prevention and treatment methods still have defects such as uncertain efficacy and obvious side effects.The safety and effectiveness of relevant targeted prevention and treatment drugs in clinical application still need to be verified.Future research should focus on clinical prevention and treatment based on basic experimental research combined with the mechanism of occurrence and development.

Objective:To evaluate the immunogenicity, safety, and immune persistence of the sequential booster with the recombinant protein-based COVID-19 vaccine (CHO cell) in healthy people aged 18-84 years.Methods:An open-label, multi-center trial was conducted in October 2021. The eligible healthy individuals, aged 18-84 years who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, were recruited from Shangyu district of Shaoxing and Kaihua county of Quzhou, Zhejiang province. All participants were divided into three groups based on the differences in prime-boost intervals: Group A (3-4 months), Group B (5-6 months) and Group C (7-9 months), with 320 persons per group. All participants received the recombinant COVID-19 vaccine (CHO cell). Blood samples were collected before the vaccination and after receiving the booster at 14 days, 30 days, and 180 days for analysis of GMTs, antibody positivity rates, and seroconversion rates. All adverse events were collected within one month and serious adverse events were collected within six months. The incidences of adverse reactions were analyzed after the booster.Results:The age of 960 participants was (52.3±11.5) years old, and 47.4% were males (455). The GMTs of Groups B and C were 65.26 (54.51-78.12) and 60.97 (50.61-73.45) at 14 days after the booster, both higher than Group A′s 44.79 (36.94-54.30) ( P value<0.05). The GMTs of Groups B and C were 23.95 (20.18-28.42) and 27.98 (23.45-33.39) at 30 days after the booster, both higher than Group A′s 15.71 (13.24-18.63) ( P value <0.05). At 14 days after the booster, the antibody positivity rates in Groups A, B, and C were 91.69% (276/301), 94.38% (302/320), and 93.95% (295/314), respectively. The seroconversion rates in the three groups were 90.37% (272/301), 93.75% (300/320), and 93.31% (293/314), respectively. There was no significant difference among these rates in the three groups (all P values >0.05). At 30 days after the booster, antibody positivity rates in Groups A, B, and C were 79.60% (238/299), 87.74% (279/318), and 90.48% (285/315), respectively. The seroconversion rates in the three groups were 76.92% (230/299), 85.85% (273/318), and 88.25% (278/315), respectively. There was a significant difference among these rates in the three groups (all P values <0.001). During the sequential booster immunization, the incidence of adverse events in 960 participants was 15.31% (147/960), with rates of about 14.38% (46/320), 17.50% (56/320), and 14.06% (45/320) in Groups A, B, and C, respectively. The incidence of adverse reactions was 8.02% (77/960), with rates of about 7.50% (24/320), 6.88% (22/320), and 9.69% (31/320) in Groups A, B, and C, respectively. No serious adverse events related to the booster were reported. Conclusion:Healthy individuals aged 18-84 years, who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, have good immunogenicity and safety profiles following the sequential booster with the recombinant COVID-19 vaccine (CHO cell).

Objective:To investigate the association of serum fibroblast growth factor 23(FGF23) level with insulin resistance(IR) and sex hormone levels in patients with polycystic ovary syndrome(PCOS).Methods:A retrospective study was performed in eighty-seven patients with PCOS, fifty-seven patients with simple IR, and sixty-one healthy women who were admitted to Affiliated Hospital of Zunyi Medical University during October 2021 and November 2022. According to the homeostasis model assessment-IR index, all subjects were divided into normal control group( n=61), IR group( n=57), PCOS without IR group(PCOS group, n=15), and PCOS+ IR group( n=72). The levels of serum FGF23, adiponectin, and sex hormones in all groups were compared, and their correlations with glucose and lipid metabolism indicators were analyzed. Results:The FGF23 level was significantly elevated in the IR group, while markedly reduced in the PCOS group and PCOS+ IR group, with the PCOS group showing a significantly lower concentration. The adiponectin levels were significantly decreased in the IR group, PCOS group, and PCOS+ IR group(all P<0.05). The correlation analysis showed that FGF23 level was positively correlated with adiponectin and sex hormone binding globulin, and negatively correlated with luteinizing hormone, luteinizing hormone/follicle stimulating hormone, and free testosterone index(all P<0.05). Logistic regression results indicated that both FGF23 and adiponectin could be used as good indicators for the diagnosis of PCOS and PCOS with IR(all P<0.05). Conclusion:FGF23 is closely related to IR and androgen as well, and under certain conditions, it can reflect the severity of IR and hyperandrogenemia in PCOS patients. The cutoff value of FGF23 obtained in this study can provide a good reference for the diagnosis of PCOS diseases.

Objective: The aim of this study was to establish a comprehensive concise health index (CHI) for evaluating adolescents, so as to provide a basis for determining the overall health status of adolescents in China. Methods: On the basis of a literature review and consensus among core researchers, adolescent CHI indicators in the following five dimensions were assessed:physical growth, physical fitness, common diseases, mental health and behavioral health. A total of 24 experts used an analysis hierarcgy process (AHP) to calculate the indicators subjective weights. In addition, from October to December of 2021, two regions, A and B were selected to conduct empirical research, and the CRITIC method was used to calculate the objective weights of the indicators. Finally, the weight coefficients were determined through the AHP-CRITIC combination weight method, and comprehensive evaluation was performed with the TOPSIS method. Results: Across academic period and genders, the combined weighted coefficients of the health indicators were as follows:BMI, 0.081-0.095; waist circumference, 0.070-0.081; relative grip strength, 0.101-0.108; myopia, 0.110-0.128; dental caries, 0.055-0.070; psychological symptoms, 0.240-0.262; physical exercise, 0.085-0.115; screen time, 0.097-0.111; and sleep duration, 0.086-0.103. The health index of middle school students in city A (0.626±0.065) was significantly higher than that in city B(0.613±0.066)( t=6.34, P <0.01). Conclusion The comprehensive adolescent CHI evaluation method has good consistency and application value, and may serve as a reference for adolescent health monitoring.

Objective:To investigate the impact of switching to low iodine drinking water in areas with high water iodine levels on the iodine nutritional status and thyroid function of pregnant women.Methods:A cross-sectional survey was conducted in Gaoqing County, Zibo City, Shandong Province. Pregnant women who underwent prenatal examinations at the Obstetrics Clinic of Gaoqing County People's Hospital from 2019 to 2021 were selected as the survey subjects. With reference to the Criteria for the Classification of Water Source High Iodine Areas and High Iodine Disease Areas (GB/T 19380-2016), pregnant women with drinking water iodine > 100 μg/L were considered as the high water iodine group and ≤100 μg/L was the non-high water iodine group. Basic information, one random urine sample, fasting blood sample, 24-hour urine sample and drinking water sample of pregnant women were collected, and thyroid ultrasound examination was performed on pregnant women. Urinary iodine (UI) concentration (UIC) and drinking water iodine concentration (WIC) were measured by inductively coupled plasma mass spectrometry, and 24-hour urinary iodine excretion (UIE) and daily iodine intake (TII) of pregnant women were calculated. Serum thyroid hormone (TSH), free triiodothyronine (FT 3), free thyroxine (FT 4), thyroid peroxidase antibody (TPOAb) and anti-thyroid autoantibodies (TgAb) were determined by automatic chemiluminescence immunoassay. Creatinine (CR) was determined using deproteinized endpoint microplate method and UI/CR was calculate. Results:A total of 797 pregnant women were included, and the UIC was 150.2 (88.1, 281.3) μg/L, the iodine nutrition was generally at an appropriate level. Among them, 584 pregnant women in the non-high water iodine group had a UIC of 120.9 (74.9, 191.5) μg/L, which was at the iodine deficiency level; 213 pregnant women in the high water iodine group had a UIC of 321.1 (201.9, 569.1) μg/L, which was at the iodine super-appropriate level; the differences in WIC, UIC, UIE, TII, and UI/CR between the two groups were statistically significant ( Z = 21.63, 13.34, 15.14, 15.14, 11.81, P < 0.001). After stratification by different gestational periods, the differences were statistically significant when comparing WIC and TSH in pregnant women in the non-high water iodine group and UI/CR in pregnant women in the high water iodine group by gestational period ( H = 59.13, 7.30, 13.60, P < 0.05). A total of 744 pregnant women were tested for thyroid function, and 128 cases of TSH > 2.5 mU/L, 15 cases of hypothyroxemia, and 19 cases of subclinical hypothyroidism were detected, with detection rates of 17.2%, 2.0%, and 2.6%, respectively. The differences were statistically significant when comparing TSH and TPOAb levels and the proportion of pregnant women with TSH > 2.5 mU/L in the high water iodine and non-high water iodine groups ( Z = 3.04, - 2.17, χ 2 = 6.94, P = 0.002, 0.030, 0.008). The thyroid glands of pregnant women were examined in 720 cases, and 30 cases of goiter and 150 cases of thyroid nodules were detected, with detection rates of 4.2% and 20.8%, respectively. The median thyroid volume was 8.92 ml in the high water iodine group and 8.60 ml in the non-high water iodine group, which were both within the normal range, with no statistically significant difference between the groups ( Z = - 0.75, P = 0.455). Conclusions:After changing to low iodine water, the overall iodine nutrition of pregnant women in Gaoqing County is now at an appropriate level, and the reduction of water iodine effectively reduces the risk of TSH abnormalities in local pregnant women. However, pregnant women in the non-high water iodine group are iodine deficiency, and pregnant women in the high water iodine group are at iodine super-appropriate, and the iodine nutrition level of pregnant women in this area is highly variable, which causes the "illusion" that the overall iodine level of local pregnant women is suitable.

A fundamental challenge that arises in biomedicine is the need to characterize compounds in a relevant cellular context in order to reveal potential on-target or off-target effects. Recently, the fast accumulation of gene transcriptional profiling data provides us an unprecedented opportunity to explore the protein targets of chemical compounds from the perspective of cell transcriptomics and RNA biology. Here, we propose a novel Siamese spectral-based graph convolutional network (SSGCN) model for inferring the protein targets of chemical compounds from gene transcriptional profiles. Although the gene signature of a compound perturbation only provides indirect clues of the interacting targets, and the biological networks under different experiment conditions further complicate the situation, the SSGCN model was successfully trained to learn from known compound-target pairs by uncovering the hidden correlations between compound perturbation profiles and gene knockdown profiles. On a benchmark set and a large time-split validation dataset, the model achieved higher target inference accuracy as compared to previous methods such as Connectivity Map. Further experimental validations of prediction results highlight the practical usefulness of SSGCN in either inferring the interacting targets of compound, or reversely, in finding novel inhibitors of a given target of interest.
Drug Delivery Systems ; Proteins ; Transcriptome

Objective: To observe the efficacy of herbal cake-partitioned moxibustion for lumbar disc herniation (LDH) due to kidney deficiency and blood stasis and observe the influence of this method on lumbar functions and inflammatory factors in patients with this condition. Methods: A total of 120 LDH patients who met the inclusion criteria were randomly divided into three groups, including a herbal cake-partitioned moxibustion group, a flour cake-partitioned moxibustion group, and a Western medication group, with 40 patients in each group. The patients in the Western medication group were treated with diflunisal tablets, 0.5 g per dose, 2 doses a day. Those in the herbal cake-partitioned moxibustion group were treated with additional herbal cake-partitioned moxibustion group at Back-Shu Points and Jiaji (EX-B2) Points once a day. Those in the flour cake-partitioned moxibustion group were treated with the same methods as in the herbal cake-partitioned moxibustion group, except that the herbal cake was replaced by a flour cake. All the patients were treated for 10 d. After treatment, the scores of the visual analog scale (VAS) and Japanese Orthopaedic Association (JOA) and the changes of the interleukin (IL)-6, tumor necrosis factor (TNF)-α, and substance P (SP) levels were observed, and the efficacy was evaluated. Results: After treatment, the VAS score and the levels of IL-6, TNF-α, and SP were lower than those before treatment, and the JOA score was higher than that before treatment in the three groups, indicating intra-group statistical significance (P<0.05). The VAS score and the levels of IL-6, TNF-α, and SP of the herbal cake-partitioned moxibustion group were lower than those of the flour cake-partitioned moxibustion group and the Western medication group, while the JOA score of the herbal cake-partitioned moxibustion group was higher than that of the other two groups, indicating inter-group statistical significance (P<0.05). The total effective rate of the herbal cake-partitioned moxibustion group was 92.5％, higher than that of the flour cake-partitioned moxibustion group (80.0％) and the Western medication group (72.5％), indicating inter-group statistical significance (P<0.05). Conclusion: On the basis of Western oral medication, additional herbal cake-partitioned moxibustion can alleviate the pain and improve the lumbar functions in patients with LDH due to kidney deficiency and blood stasis. The efficacy of the integrated method is better than that of either flour cake-partitioned moxibustion or Western medication alone, which may be related to the reduction of serum inflammatory factors.

OBJECTIVE：To study the improvement effects and mechanism of Polygonum orientale flower extract on hypoxia- reoxygenation injury of H 9c2 cardiomyocytes. METHODS ：H9c2 cardiomyocytes were divided into normal control group ，model group and low- ，medium- and high-concentrations groups of P. orientale flower extract （20，40，80 μg/mL）. Except for normal control group ，other groups were given 800 μmol/L CoCl2 to induce hypoxia-reoxygenation injury model. Cell apoptosis was observed. The levels of Ca 2+（in cytoplasm ），mitochondrial membrane potential （MMP），ATP enzyme （Na+-K+-ATP enzyme ，Ca2+-Mg2+-ATP enzyme） activities， the ratio of cytochrome c （Cyto c ）， protein in cytosol to mitochondria ，phosphorylation levels of reperfusion injury salvage kinase （RISK） signaling pathwayrelated protein [protein kinase B （Akt）and extracellular signal regulated kinase 1/2（ERK1/2）] as well as protein expression of HIF- 1 α were detected respectively. In addition，the cells were divided into normal control group ，model group and P. orientale flower extract group （80 μ g/mL），PI3K inhibitor LY294002+CoCl2 group（15 μmol/L LY294002+80 μmol/L ，LY294002+P. orientale flower extract group （15 μmol/L LY294002+80 μg/mL P. orientale flower extract ），MEK inhibitor PD98059+CoCl2 group（25 μmol/L PD98059+800 μmol/L CoCl2），PD98059+P. orientale flower extract group （25 μmol/L PD98059+80 μg/mL P. orientale flower extract ）. After cultured by the same method ，the phosphorylation levels of Akt protein and ERK1/2 protein in the cells were measured to verify the activation of P. orientale flower extract to RISK signaling pathway. RESULTS：Compared with model group ，nuclear pyknosis and the number of apoptotic bodies were reduced in different concentrations groups of P. orientale flower extract. ROS level ，Ca2+ level（except for low-concentration group ），MMP，ratio of Cyto c in cytoplasm to Cyto c in mitochondria ，protein expression of HIF- 1α were decreased significantly（P＜0.05 or P＜0.01）； the activity of ATP enzyme （except for the low-concentration group ），Akt protein and ERK 1/2 protein phosphorylation level were significantly increased （P＜0.01）. After treated with PI 3K inhibitor LY 294002 and MEK inhibitor PD 98059，Akt protein and ERK 1/2 protein phosphorylation level in cadiomyocyte were decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS ：P. orientale flower extract can improve hypoxia-reoxygenation injury of H 9c2 cardiomyocytes，the mechanism of which may be associated with inhibiting cardiomyocyte apoptosis ，improving ATPase activity ，protecting mitochondria ，regulating RISK signaling pathway related proteins and HIF- 1α protein expression.

Objective: To investigate the associated factors of myopia among primary and secondary school students in Shenzhen, and to provide reference for the prevention and control of myopia. Methods: By stratified cluster sampling, 3 073 students of 14 schools including primary,junior,regular and vocational senior schools from two districts in Shenzhen were selected and investigated. Results: For primary school students, the time of using computer for 2-<3 hours per day (OR=2.23，95%CI=1.19-4.20) , and no physical education class(2 sections per week OR=0.34, 95%CI=0.13-0.91; 4 sections per week OR=0.23, 95%CI=0.08-0.62; 5 sections or more per week OR=0.33, 95%CI=0.11-0.97) were positively associated with myopia. Teachers finishing class on time at break (occasionally delaying OR=1.99, 95%CI=1.51-2.63; frequently delaying OR=2.07, 95%CI=1.29-3.30), taking 0.5-1 hour break when using eyes at close range (1-<2 hours OR=1.33，95%CI=1.03-1.70; ≥3 hours OR=1.87, 95%CI=1.17-3.00), no parents with myopia(one parent with myopia OR=1.69, 95%CI=1.32-2.17; two parents with myopia OR=2.13, 95%CI=1.50-3.02) were negatively associated with myopia. For junior high school students, without parents with myopia (one parent with myopia OR=3.27, 95%CI=2.17-4.94; two parents with myopia OR=5.38, 95%CI=2.78-10.42) was the protective factor of myopia. For senior high school students, male (female OR=1.52, 95%CI=1.07-2.14), doing eye exercises twice a day in school (OR=0.41, 95%CI=0.23-0.75), and accumulating outdoor activities for ≥2 hours a day (OR=0.70, 95%CI=0.49-1.00) were negatively associated with myopia. Conclusion There are different risk factors for myopia among different students in Shenzhen. Students with high risk factors are the key objects of prevention and control.

Objective: To investigate psychological sub-health status and its correlation with suicidal behaviors among middle school students in Shenzhen, so as to provide reference for early prevention of suicide. Methods: A total of 4 014 students from 5 junior high schools and 5 senior high schools in Shenzhen were selected as the subjects. The status of psychological sub-health and suicidal behaviors were assessed, and their correlation was analyzed. Results: The detection rates of psychological sub-health, suicide ideation, suicide plan and suicide attempts were 21.38%, 24.66%, 11.81% and 3.64% respectively. The detection rates of suicidal ideation, suicide plan and suicide attempts among students with high level of psychological sub-health status were significantly higher than those without psychological sub-health status(P<0.01). Correlation analysis showed that the number of psychological sub-health symptoms was positively correlated with the number of suicidal ideations, suicide plans and suicide attempts(P<0.01). Conclusion Psychological health status of adolescents in Shenzhen is not optimistic. There is a correlation between psychological sub-health status and suicidal behaviors. More attention should be paid to suicide prevention among students with psychological sub-health status.