Booster vaccinations are highly recommended in combating the SARS-CoV-2 Omicron variant and its subvariants. However, the optimal booster vaccination strategies and related immune mechanisms with different prior vaccinations are under-revealed. In this study, we systematically evaluated the immune responses in mice and hamsters with different prime-boost regimens before their protective efficacies against Omicron were detected. We found that boosting with Ad5-nCoV, S_WT-2P or S_Omicron-6P induced significantly higher levels of neutralization activities against Omicron variants than CoronaVac and ZF2001 by eliciting stronger germinal center (GC) responses. Specifically, S_Omicron-6P induced even stronger antibody responses against Omicron variants in CoronaVac and Ad5-nCoV-primed animals than non-Omicron-specific vaccines but with limited differences as compared to Ad5-nCoV and S_WT-2P. In addition, boosting with a specific vaccine has the potential to remodel the existing immune profiles. These findings indicated that adenovirus-vectored vaccines and mRNA vaccines would be more effective than other types of vaccines as booster shots in combating Omicron infections. Moreover, the protective efficacies of the vaccines in booster vaccinations are highly related to GC reactions in secondary lymphatic organs. In summary, these findings provide timely important information on prime-boost regimens and future vaccine design.

Objective:To develop and validate a novel PET tracer, N-cyclohexyl-4-((2, 4-dichlorophenyl)(4-(fluoro- 18F)phenyl)methyl)piperazine-1-carboxamide ( 18F-SQKJ-2), targeting cannabinoid type 1 (CB1) receptors for diagnosing psychiatric disorders associated with fear memory. Methods:18F-SQKJ-2 was prepared using a nucleophilic substitution radiochemical synthesis method. For the CB1 receptor blocking experiment, 7 ICR mice were divided into blocking group ( n=4; rimonabant for blocking treatment) and control group 1 ( n=3; no rimonabant blocking treatment). The affinity and specificity of 18F-SQKJ-2 for CB1 receptors were analyzed based on the differences in 18F-SQKJ-2 uptake (percentage injected dose per gram of tissue, %ID/g) by various organs between two groups. The metabolic stability of 18F-SQKJ-2 in vitro was studied using animal tissue homogenates. Ten C57 mice were used to establish fear memory mouse models (fear group, n=6; control group 2, n=4), and the percentage of freezing time was compared between 2 groups. MicroPET scans were used to detect the intracranial distribution of 18F-SQKJ-2, and the relative uptake in each brain region compared to total brain uptake was calculated. Statistical analysis was conducted to compare the differences in CB1 receptor relative total brain uptake in fear-related brain regions between 2 groups. Independent-sample t test and Mann-Whitney U test were used to analyze the data. Results:18F-SQKJ-2 was successfully synthesized with a radiochemical purity ≥98.0% and a corrected radioactive yield of (12.3±6.0)%( n=4). In vitro metabolic stability experiments showed that 18F-SQKJ-2 was basically stable in the liver, blood, and brain within 60min. The CB1 receptor blocking experiment demonstrated that the uptake of 18F-SQKJ-2 in the brains of mice in blocking group was significantly lower than that in control group 1 ((0.95±0.28) vs (3.44±1.16) %ID/g; t=-3.57, P=0.023). The percentage of freezing time in fear group was significantly higher than that in control group 2 (43.28%(39.46%, 52.93%) vs 2.74%(1.52%, 4.85%); Z=-2.45, P=0.010). 18F-SQKJ-2 microPET imaging showed that the uptake of 18F-SQKJ-2 in the cerebral cortex of mice in fear group was significantly increased compared with that in control group 2 ((5.83±0.47)% vs (5.00±0.52)%; t=2.42, P=0.046). Conclusion:18F-SQKJ-2 is successfully prepared with acceptable radiochemical purity and metabolic stability, demonstrating potential for visualizing and quantifying fear memory.

Objective:To develop and validate a novel PET tracer, N-cyclohexyl-4-((2, 4-dichlorophenyl)(4-(fluoro- 18F)phenyl)methyl)piperazine-1-carboxamide ( 18F-SQKJ-2), targeting cannabinoid type 1 (CB1) receptors for diagnosing psychiatric disorders associated with fear memory. Methods:18F-SQKJ-2 was prepared using a nucleophilic substitution radiochemical synthesis method. For the CB1 receptor blocking experiment, 7 ICR mice were divided into blocking group ( n=4; rimonabant for blocking treatment) and control group 1 ( n=3; no rimonabant blocking treatment). The affinity and specificity of 18F-SQKJ-2 for CB1 receptors were analyzed based on the differences in 18F-SQKJ-2 uptake (percentage injected dose per gram of tissue, %ID/g) by various organs between two groups. The metabolic stability of 18F-SQKJ-2 in vitro was studied using animal tissue homogenates. Ten C57 mice were used to establish fear memory mouse models (fear group, n=6; control group 2, n=4), and the percentage of freezing time was compared between 2 groups. MicroPET scans were used to detect the intracranial distribution of 18F-SQKJ-2, and the relative uptake in each brain region compared to total brain uptake was calculated. Statistical analysis was conducted to compare the differences in CB1 receptor relative total brain uptake in fear-related brain regions between 2 groups. Independent-sample t test and Mann-Whitney U test were used to analyze the data. Results:18F-SQKJ-2 was successfully synthesized with a radiochemical purity ≥98.0% and a corrected radioactive yield of (12.3±6.0)%( n=4). In vitro metabolic stability experiments showed that 18F-SQKJ-2 was basically stable in the liver, blood, and brain within 60min. The CB1 receptor blocking experiment demonstrated that the uptake of 18F-SQKJ-2 in the brains of mice in blocking group was significantly lower than that in control group 1 ((0.95±0.28) vs (3.44±1.16) %ID/g; t=-3.57, P=0.023). The percentage of freezing time in fear group was significantly higher than that in control group 2 (43.28%(39.46%, 52.93%) vs 2.74%(1.52%, 4.85%); Z=-2.45, P=0.010). 18F-SQKJ-2 microPET imaging showed that the uptake of 18F-SQKJ-2 in the cerebral cortex of mice in fear group was significantly increased compared with that in control group 2 ((5.83±0.47)% vs (5.00±0.52)%; t=2.42, P=0.046). Conclusion:18F-SQKJ-2 is successfully prepared with acceptable radiochemical purity and metabolic stability, demonstrating potential for visualizing and quantifying fear memory.

The adjacent anatomy of the pelvis is complicated, with digestive, urinary, reproductive and other organs as well as important blood vessels and nerves. Therefore, accurate resection of pelvic tumors and precise reconstruction of defects after resection are extremely difficult. The development of medical 3D printing technology provides new ideas for precise resection and personalized reconstruction of pelvic tumors. The “triune” application of 3D printing personalized lesion model, osteotomy guide plate and reconstruction prosthesis in pelvic tumor limb salvage reconstruction treatment has achieved good clinical results. However, the current lack of normative guidance standards such as preparation and application of 3D printing personalized lesion model, osteotomy guide plate and reconstruction prosthesis restricts its promotion and application. The formulation of this consensus provides normative guidance for 3D printing personalized pelvic tumor limb salvage reconstruction treatment.

Objective: To analyze the epidemiological and clinical characteristics of patients with 2019 novel coronavirus (2019-nCoV) infection in Shenyang. Methods: The epidemiological and clinical characteristics of 30 patients diagnosed with 2019-nCoV infection admitted to Shenyang sixth people's hospital on January 22, 2020 and February 8, 2020 were retrospectively analyzed. Results: Among the 30 cases, 21 were imported, including 17 from Hubei Province and four from other provinces. Nine cases were local infections. There were 18 men and 12 women, aging from 21 to 72 years with the median of 43 years. Eight cases had underlying diseases including hypertension, diabetes, coronary heart disease and bronchitis. On admission, two (7%) cases were mild, 19 (63%) cases were ordinary, eight (27%) cases were severe, and one (3%) case was critical. Clinical manifestations mainly include fever, with or without upper respiratory tract symptoms, normal, decreased or slightly increased white blood cell counts, mainly decreased lymphocyte counts, normal or increased c-reactive protein, and normal procalcitonin. The computed tomography (CT) of the early stage of the lungs showed that multiple patchy ground glass shadows were mainly accompanied by consolidation, which often involved both lungs or multiple lobes of one lung. At the moment, the clinical treatment mainly included respiratory support, symptomatic treatment, antiviral treatment adn anti-bacterial treatment. By February 15, a total of nine cases were cured and discharged, including one mild case, six ordinary cases, and two severe cases. In the comparisons between mild/ordinary patients and severe/critical patients, the fever duration in the severe/critical group (median 11.5 d) was significantly longer than that in the light/normal group (median 2 d) (Z=-2.292, P=0.022), and the laboratory tests indicated elevated d-dimer levels (Z=-2.669, P=0.008) and more cases with neutrophilic/lymphocyte ratio > 3 (Z=-4.071, P<0.01). Conclusions In Shenyang, the early cases with 2019-nCoV infection are mainly imported cases, and expanding local infections gradually develop. Clinical manifestations are mainly characterized by fever and cough. Lung CT performance shows multiple ground glass shadows, mainly accompanied by consolidation. CT changes in the lungs should be closely monitored during the treatment, and CT findings in the lungs may change earlier than the clinical manifestations. Prolonged fever duration, elevated d-dimer level and neutrophil/lymphocyte ratio >3 could be used as early warning indicators for severe cases.

Objective:To propose and verify a surgical classification system for the axial primary malignant and aggressive benign tumor.Methods:The CZH surgical classification system was originally developed for the axial primary malignant and aggressive benign tumor. The CZH surgical classification system includes seven types, according to the anatomic features and the extension of tumor violation. A total of 136 patients (79 males and 57 females) with axial primary malignant and aggressive benign tumor from multiple tertiary centers who received surgery from July 2006 to July 2019 were included. The average age was 44.40±17.55 years (8-83 years) old. There were 99 malignant tumors and 37 aggressive benign tumors included. The number of patients with each classification was presented as followed, Type I 13, Type II 15, Type IIIa 3, Type IIIb 20, Type IVa 43, Type IVb 12, Type Va 21, Type Vb 3, Type VI 2, Type VIIa 3 and Type VIIb 1. Surgical procedures were selected according to different types in classification. The inter- and intra-observer consistencies were evaluated by the Kendall's W test. The VAS, Frankel score, overall survival and recurrence free survival were recorded during the follow-up. Results:The inter- and intra-observer consistent coefficient was 0.973 and 0.996, respectively ( P<0.05). The single posterior approach was adopted for the Type II tumors. Other patients underwent surgery by the combined antero-posterior approach. The majority in anterior approach (113 cases) was the modified submandibular approach. The reconstruction modes included anterior "T" shape titanium mesh (112 cases) or the 3D printed prothesis (7 cases) combined with the posterior occipto-cervical fusion (92 cases) or the pedicle screw system (44 cases). The average surgical duration and the volume of intraoperative bleeding was 348.40±136.14 min (60-760 min) and 1 225.69±859.40 ml (80-4 000 ml), respectively. The operation duration and volume of intraoperative bleeding among each type were with statistical difference. The patients with Type IV, V tumors had longer operation duration than those with Type II tumors. Those with Type V and VII tumors had longer operation duration than those with Type I tumors. The patients with Type V tumors had more intraoperative bleeding than those with Type I-IV tumors. The average preoperative VAS score was 4.15±2.25 and then was reduced significantly to 0.62±0.71 and 0.38±0.59 at one and three months after operation, respectively. The Frankel score was also significantly ameliorated at one and three months postoperatively. There were 22 postoperative complications (16.2%). The complications included cerebral spinal fluid leak (12.5%), dysphagia and/or dysphonia (7.4%), dyspnea (5.1%), wound infection (3.7%), wound hemorrhage (2.2%) and pharyngeal dehiscence (1.5%). The incidence of postoperative complication was 25.9% in Type IV-VII tumors, while 11.8% in Type I-III tumors. Conclusion:CZH surgical classification system was verified with high observer consistency. This classification system could assist surgeons to select proper surgical approaches, resection modes and reconstruction modes, and thus ensure the safety of surgery and reduce the recurrence. The tumors in Type IV, V and VII may be with more challenging for surgeons. The incidence of postoperative complication in Type IV-VII tumors may be higher than that in Type I-III tumors.

Objective:To analyze the safety and efficacy of percutaneous vertebroplasty combined with interstitial implantation 125I of seeds (PVPI) in the treatment of thoracic vertebroplasty with posterior vertebra defect. Methods:A retrospective analysis of the clinical data of 64 patients with thoracic spine metastases admitted to Yunnan Cancer Hospital from November 2017 to May 2019 was conducted, including 32 patients with posterior vertebra defect (experimental group) and 32 cases without (control group). Forty-two vertebral bodies of 32 patients in the experimental group were treated with improved PVPI surgery, which performed with the secondary sealing method and inclined puncture needle injection bone cement rotary filling technology, to reduce leakage. The 54 vertebral bodies of 32 patients in control group underwent PVPI. The two groups of patients were followed up on the second day, one month, three months and six months after the operation, and the short-term efficacy, long-term efficacy and safety indicators of the two groups were compared.Results:All 64 patients successfully completed the surgical treatment. The visual analogue scores and Karnofsky scores of the experimental group and the control group were improved to varying degrees on the second day, 1 month, 3 months and 6 months after the operation. There was no statistically significant difference between the two groups ( P>0.05). The amount of bone cement in the experimental group and control group was (2.36±0.20) ml and (2.39±0.17) ml, and the difference was not statistically significant ( P=0.482). The amount of 125I seed implantation was (30.63±0.91) and (32.56±0.68), respectively, the difference was not statistically significant ( P=0.925). The partial response rates of the study group and the control group were 81.3% and 87.5%, the stable disease rates were 12.5% and 9.4%, the differences were not statistically significant ( P>0.05). The median overall survival (mOS) of the study group was 13 months, and the median progression-free survival (mPFS) was 8 months. The mOS of the control group was 14 months, and the mPFS was 8 months. The differences were not statistically significant ( P>0.05). In the experimental group, 6 (14.3%) vertebral bodies had cement leakage, of which 2 (4.8%) were cement leakage at posterior vertebra, 4 (9.5%) were paravertebral cement leakage. Seven (13.0%) paravertebral cement leakage occurred in the control group. There was no significant difference in bone cement leakage between the two groups ( P=0.097). Bone cement leakage in both groups did not cause serious complications such as spinal cord injury and paraplegia. Conclusion:The application of PVPI in the treatment of thoracic metastatic tumor patients with posterior vertebra defect can acquire better clinical efficacy and safety through conduction of the improved intraoperative technology and paying more attention to the control of bone cement distribution and other issues.

Objective:To analyze the safety and efficacy of percutaneous vertebroplasty combined with interstitial implantation 125I of seeds (PVPI) in the treatment of thoracic vertebroplasty with posterior vertebra defect. Methods:A retrospective analysis of the clinical data of 64 patients with thoracic spine metastases admitted to Yunnan Cancer Hospital from November 2017 to May 2019 was conducted, including 32 patients with posterior vertebra defect (experimental group) and 32 cases without (control group). Forty-two vertebral bodies of 32 patients in the experimental group were treated with improved PVPI surgery, which performed with the secondary sealing method and inclined puncture needle injection bone cement rotary filling technology, to reduce leakage. The 54 vertebral bodies of 32 patients in control group underwent PVPI. The two groups of patients were followed up on the second day, one month, three months and six months after the operation, and the short-term efficacy, long-term efficacy and safety indicators of the two groups were compared.Results:All 64 patients successfully completed the surgical treatment. The visual analogue scores and Karnofsky scores of the experimental group and the control group were improved to varying degrees on the second day, 1 month, 3 months and 6 months after the operation. There was no statistically significant difference between the two groups ( P>0.05). The amount of bone cement in the experimental group and control group was (2.36±0.20) ml and (2.39±0.17) ml, and the difference was not statistically significant ( P=0.482). The amount of 125I seed implantation was (30.63±0.91) and (32.56±0.68), respectively, the difference was not statistically significant ( P=0.925). The partial response rates of the study group and the control group were 81.3% and 87.5%, the stable disease rates were 12.5% and 9.4%, the differences were not statistically significant ( P>0.05). The median overall survival (mOS) of the study group was 13 months, and the median progression-free survival (mPFS) was 8 months. The mOS of the control group was 14 months, and the mPFS was 8 months. The differences were not statistically significant ( P>0.05). In the experimental group, 6 (14.3%) vertebral bodies had cement leakage, of which 2 (4.8%) were cement leakage at posterior vertebra, 4 (9.5%) were paravertebral cement leakage. Seven (13.0%) paravertebral cement leakage occurred in the control group. There was no significant difference in bone cement leakage between the two groups ( P=0.097). Bone cement leakage in both groups did not cause serious complications such as spinal cord injury and paraplegia. Conclusion:The application of PVPI in the treatment of thoracic metastatic tumor patients with posterior vertebra defect can acquire better clinical efficacy and safety through conduction of the improved intraoperative technology and paying more attention to the control of bone cement distribution and other issues.

Objective: To study the mechanism of Heshi-Gejiugao on the nerve endocrine immune network in the treatment of perimenopausal syndrome. Methods: A total of 100 patients with perimenopausal syndrome were randomly divided into treatment group and control group, 50 cases in each group. The control group was only given general treatment, while the treatment group was treated with Heshi-Gejiugao on the basis of general treatment for 30 days. The clinical efficacy, Kupperman score, nerve, endocrine and immune related indexes of the two groups before and after treatment were observed. Results: The total effective rate was 96.0% (48/50) in the treatment group and 50.0% (25/50) in the control group. There was significant difference between the two groups (χ²=37.639, P<0.01). The Kupperman score (17.52 ± 2.73 vs. 24.22 ± 6.87, t=6.409) in the treatment group was significantly lower than that in the control group (P<0.01). After treatment, NE (1 878.08 ± 931.57 ng/m vs. 1 278.43 ± 866.32 ng/ml, t=3.331), DA (1 568.56 ± 597.15 ng/ml vs. 1 183.62 ± 798.72 ng/ml, t=2.729) in the treatment group were significantly higher than those in the control group (P<0.05); E₂ (42.12 ± 9.77 pg/ml vs. 35.91 ± 12.55 pg/ml, t=2.761), FSH (62.70 ± 15.96 mIU/ml vs. 72.67 ± 30.18 mIU/ml, t=2.065), LH (33.88 ± 12.18 mIU/ml vs. 42.93 ± 9.83 mIU/ml, t=4.089) were significantly lower than those of the control group (P<0.05). CD3⁺ (1 087.34/μl ± 432.19/μl vs. 918.27/μl ± 199.72/μl, t=2.511), CD4⁺ (738.16/μl ± 326.75/μl vs. 588.43/μl ± 212.55/μl, t=2.716) and CD4/CD8 (1.87 ± 0.56 vs. 1.16 ± 0.55), t=6.483) were significantly higher than those of the control group (P<0.05); CD8⁺ (788.32/μl ± 214.56/μl vs. 976.37/μl ± 318.62/μl, t=3.462) was significantly lower than that of the control group (P<0.05). Conclusions Heshi-Gejiugao can reduce the symptoms and improve the quality of life by regulating the multi target and multi direction of the neuroendocrine immune network of perimenopausal patients.

Objective To study the feasibility and safety of total en bloc spondylectomy (TES) for bone tumors of the fourth lumbar spine and evaluate the clinical outcomes.Methods From March 2011 to December 2013,21 patients undergone total en bloc spondylectomy in posterior-only approach were retrospectively reviewed.The patients included 9 males and 12 females,with a mean age of 47.1± 15.6 years old (range,15-71 years old).This series included 12 cases of primary bone tumors and 9 cases of solitary metastases.Preoperative evaluation according to clinical,imaging and pathologic features was performed meticulously to select patients.The length of surgery,estimated blood loss,surgical margins,instrumentation failure,perioperative complications,Frankel scale,visual analogue scale (VAS) for pain,local control rate and overall survival were reviewed and analyzed.Results Total en bloc spondylectomy was performed successfully in all patients.Average operative time and estimated blood loss were 297.6±44.6 min (range,225-420 min) and 2 247.1±904.5 ml (range,900-4100 ml),respectively.The mean follow-up time was 50.4± 17.1 mons (range,24-79 mons).All patients encountered nerve roots stretch and 5 patients (23.8％) showed lower extremeties neurological dysfunction.All of them improved in 2-4 weeks postoperatively and recovered completely at 6-month follow -up.Cerebrospinal fluid leak was found in 4 patients (19.0％).The VAS score was 1.5±1.4 at post-operation,which was significantly lower than the 6.2± 1.6 in average at operation (P=0.008).Three patients with metastatic tumors died during the follow-up.Titanium mesh cage subsidence was observed in 7 patients (33.3％).No implant failure was occurred during the follow-up.Conclusion Total en bloc spondylectomy for tumors of the fourth lumbar spine in a posterior-only approach is feasible.However,there are many intraoperative neurological complications and the indications for TES are extremely limited.