OBJECTIVE: To explore the chronic injury and its possible mechanism of ionizing radiation on multipotent hematopoietic progenitor cells (MPPs) by determining the related indicators of MPPs in bone marrow of mice post-radiation. METHODS: Sixteen C57BL/6 adult mice were randomly divided into normal control and irradiation groups, 8 mice in each group. The mice in irradiation group were exposed to 6 Gy X-ray. The proportion of bone marrow MPPs, their apoptosis and proliferation 2 months after irradiation were detected by flow cytometry. Mitochondrial activity and levels of reactive oxygen species (ROS) in each MPPs population were detected by Mitotracker Red and DCFDA probes, and the senescent state of MPPs in the bone marrow was analyzed. RESULTS: Ionizing radiation could reduce the proportion of MPPs in mouse bone marrow. The proportions and numbers of MPP1, MPP3 and MPP4 in the bone marrow were significantly decreased after whole-body irradiation with 6 Gy X-ray (P<0.05). In addition, radiation significantly reduced the colony-forming capacity of MPPs in bone marrow (P<0.05), the proportions of apoptotic cells in the MPP1 and MPP4 cell populations increased significantly in the bone marrow (P<0.05). The activity of mitochondria was significantly reduced in the bone marrow MPP2, MPP3 and MPP4 cell populations compared with that of the control group (P<0.05). It was also found that the radiation could significantly increase the ROS levels of MPPs in bone marrow, and the content of ROS in the MPP2, MPP3 and MPP4 cell population of the bone marrow was significantly increased(P<0.05). The senescent cells ratios of MPP1, MPP3 and MPP4 cells in the bone marrow after irradiation were significantly higher than those in the control group (P<0.05). CONCLUSION Ionizing radiation can cause chronic MPPs damage in mice, which is closely associated with persistent oxidative stress, cells apoptosis, and cellular senescence.
Mice ; Animals ; Bone Marrow ; Reactive Oxygen Species ; Mice, Inbred C57BL ; Hematopoietic Stem Cells ; Whole-Body Irradiation ; Radiation, Ionizing ; Bone Marrow Cells

OBJECTIVE: To investigate the imaging effect of a near-infrared fluorescent targeted probe ICG-NP41 on the neurovascular bundles (NVB) around the prostate in rats. METHODS: A near-infrared fluorescent targeted probe ICG-NP41 was synthesized. An animal model for NVB imaging was established using Sprague-Dawley rats (250-400 g). Experiments were conducted using a custom-built near-infrared windowⅡ(NIR-Ⅱ) small animal in vivo imaging system, and images collected were processed using ImageJ and Origin. The fluorescence signal data were statistically analyzed using GraphPad Prism. The signal-to-background ratio (SBR) for NVB was quantitatively calculated to explore the effective dosage and imaging time points. Finally, paraffin pathology sections and HE staining were performed on the imaging structures. RESULTS: Except for rats in the control group (n=2), right-sided NVB of the rats injected with ICG-NP41 (n=2 per group) were all observed in NIR-Ⅱ fluorescence mode 2 h and 4 h after administration. At 2 h and 4 h, average SBR of cavernous nerve in 2 mg/kg group in fluorescence mode was 1.651±0.142 and 1.619±0.110, respectively, both higher than that in white light mode (1.111±0.036), with no significant difference (P>0.05); average SBR of 4 mg/kg group in fluorescence mode were 1.168±0.066 and 1.219±0.118, respectively, both higher than that in white light mode (1.081±0.040), with no significant difference (P>0.05). At 2 h and 4 h, the average SBR of 2 mg/kg and 4 mg/kg groups in fluorescence mode were higher than that of the control group (SBR=1), the average SBR of the 2 mg/kg group was higher than that of the 4 mg/kg group, and all the above with no significant difference (P>0.05). The average diameter of the nerve measured by full width at half maxima method was about (178±15) μm. HE staining of paraffin sections showed the right major pelvic ganglion. CONCLUSION The near-infrared fluorescent targeted probe ICG-NP41 can be used for real-time imaging of the NVB around the prostate in rats, providing a potential feasible solution for localizing NVB in real time during nerve-sparing radical prostatectomy.
Male ; Rats ; Animals ; Prostate/diagnostic imaging* ; Paraffin ; Indocyanine Green ; Rats, Sprague-Dawley ; Fluorescent Dyes

OBJECTIVE: To investigate the clinicopathological features and prognostic characteristics of papillary renal cell carcinoma (pRCC). METHODS: The clinical data of 114 patients with pRCC, including 91 males and 23 females, admitted to the Department of Urology, Peking University Third Hospital from May 2012 to May 2021 were retrospectively analyzed. All the cases were operated patients with clear pathological diagnosis and complete follow-up data. The log-rank test was used to analyze the relationship between the patients' clinicopathological characteristics and survival time, the Kaplan-Meier method to draw survival curves, and the Cox regression model for univariate and multifactorial analysis. RESULTS: The mean age of the 114 patients was (57.3±12.6) years. The tumors were located in the left kidney in 49 cases and in the right kidney in 65 cases. In the study, 48 radical nephrectomies and 66 partial nephrectomies were performed, 42 cases were type 1 and 72 cases were type 2, and the mean maximum tumor diameter was (5.5±3.6) cm. pT1a stage 52 cases, pT1b stage 22 cases, pT2 stage 4 cases, pT3 stage 33 cases, and pT4 stage 3 cases were staged. According to the World Health Organization / International Society of Urological Pathology (WHO/ISUP), there were 13 cases of gradeⅠ, 44 cases of grade Ⅱ, 51 cases of grade Ⅲ, and 6 cases of grade Ⅳ. And 34 of the 114 patients had vascular cancer embolism, 30 cases had lymph node metastasis, and 3 cases had adrenal metastasis. The median follow-up time after surgery was 22 months, and the 3-year progression-free survival rate was 95.6%. The patients with type 1 and type 2 pRCC showed statistically significant differences in age (P=0.046), body mass index (P=0.008), surgical approach (P=0.001), maximum tumor diameter (P < 0.001), vascular cancer embolism (P < 0.001), lymph node metastasis (P < 0.001), pT stage (P < 0.001), and nuclear grade (P < 0.001). The 3-year progression-free survival rates for type 1 and type 2 pRCC were 100% and 69.4%, respectively, with type 1 having a significantly better prognosis than with type 2 (P=0.003). Univariate analysis of the patients with type 2 pRCC showed that pT stage (P < 0.001), vascular cancer embolism (P < 0.001) and lymph node metastasis (P < 0.001) were strongly associated with their prognosis. Multifactorial analysis showed that vascular cancer embolism was an independent prognostic factor for progression-free survival in type 2 pRCC (P=0.001). Univariate analysis of the pRCC patients undergoing radical nephrectomy showed that pT stage (P=0.006), vascular cancer embolism (P=0.001), and lymph node metastasis (P=0.008) were significant factors affecting their prognosis, and further multifactorial analysis showed that only vascular cancer embolism was an indepen-dent prognostic factor for their progression-free survival (P=0.006). CONCLUSION Type 2 pRCC has more morbidity, more lymph node metastases, more advanced pT stage, and higher pathologic grading than type 1 pRCC. The presence of vascular cancer embolism is an independent prognostic factor in patients with type 2 pRCC and pRCC undergoing radical nephrectomy.
Adult ; Aged ; Carcinoma, Renal Cell/pathology* ; Female ; Humans ; Kidney Neoplasms/pathology* ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Retrospective Studies

Objective: To analyze the course of disease and epidemiological parameters of COVID-19 and provide evidence for making prevention and control strategies. Methods: To display the distribution of course of disease of the infectors who had close contacts with COVID-19 cases from January 1 to March 15, 2020 in Guangdong Provincial, the models of Lognormal, Weibull and gamma distribution were applied. A descriptive analysis was conducted on the basic characteristics and epidemiological parameters of course of disease. Results: In total, 515 of 11 580 close contacts were infected, with an attack rate about 4.4%, including 449 confirmed cases and 66 asymptomatic cases. Lognormal distribution was fitting best for latent period, incubation period, pre-symptomatic infection period of confirmed cases and infection period of asymptomatic cases; Gamma distribution was fitting best for infectious period and clinical symptom period of confirmed cases; Weibull distribution was fitting best for latent period of asymptomatic cases. The latent period, incubation period, pre-symptomatic infection period, infectious period and clinical symptoms period of confirmed cases were 4.50 (95%CI:3.86-5.13) days, 5.12 (95%CI:4.63-5.62) days, 0.87 (95%CI:0.67-1.07) days, 11.89 (95%CI:9.81-13.98) days and 22.00 (95%CI:21.24-22.77) days, respectively. The latent period and infectious period of asymptomatic cases were 8.88 (95%CI:6.89-10.86) days and 6.18 (95%CI:1.89-10.47) days, respectively. Conclusion: The estimated course of COVID-19 and related epidemiological parameters are similar to the existing data.
COVID-19 ; Cohort Studies ; Contact Tracing ; Humans ; Incidence ; Prospective Studies

This study aims to explore the molecular mechanism of Ganoderma against gastric cancer based on network pharmacology, molecular docking, and cell experiment. The active components and targets of Ganoderma were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and gastric cancer-related targets from GeneCards and Online Mendelian Inheritance in Man(OMIM). The protein-protein interaction(PPI) network of the common targets was constructed with STRING, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis of the common genes based on Bioconductor and R language. The medicinal-disease-component-target network and medicinal-disease-component-target-pathway network were established by Cytoscape. Molecular docking was performed between β-sitosterol(the key component in Ganoderma) and the top 15 targets in the PPI network. Cell experiment was performed to verify the findings. A total of 14 active components and 28 targets of Ganoderma were retrieved, and the medicinal and the disease shared 25 targets, including caspase-3(CASP3), caspase-8(CASP8), caspase-9(CASP9), and B-cell lymphoma-2(BCL2). The common targets involved 72 signaling pathways and apoptosis and p53 signaling pathway may play a crucial role in the effect of Ganoderma against gastric cancer. β-sitosterol had strong binding activity to the top 15 targets in the PPI network. The in vitro cell experiment demonstrated that β-sitosterol inhibited gastric cancer AGS cell proliferation by inducing cell apoptosis and cell cycle arrest in the S phase, which might be related to the regulation of the p53 pathway. This study shows the multi-component, multi-target, and multi-pathway characteristics of Ganoderma against gastric cancer, which lays a scientific basis for further research on the molecular mechanism.
Ganoderma ; Humans ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Network Pharmacology ; Stomach Neoplasms/genetics*

OBJECTIVE: To evaluate the value of Gerota's fascia suspension device in retroperitoneal laparoscopic partial nephrectomy, and to share the operation experience. METHODS: From October 2018 to December 2020, 6 cases of tumor located in the ventral side of the kidney were selected, including 3 males and 3 females, with 3 cases on the right side and 3 cases on the left side, aged 38-60 years, with an average of 52 years. The body mass index (BMI) was 18.3-30.2 kg/m², with an average of 22.9 kg/m². One patient with diabetes mellitus, three patients with renal cysts, and two patients underwent cholecystectomy before. All the patients were found by physical examinations. The course of disease was 7 days to 20 years, with a median time of 1 month. The tumor was in the ventral side of the kidney, 2 cases located in the upper pole, 1 case in the lower pole and 3 cases near the renal hilum. The tumor size was 1.2-7.8 cm, with an average of 4.5 cm. The R.E.N.A.L score was 7 in 1 case, 8 in 3 cases and 9 in 2 cases. After the preoperative examination completed, retroperitoneal laparoscopic partial nephrectomy (Gerota's fascia suspension device) was performed. RESULTS: All the operations were successfully completed. The operation time ranged from 139 to 193 min, with an average of 172 min. The renal artery occlusion time was 7-43 min, with an average of 19 min, only one case was more than 30 min. The blood loss ranged from 10 to 500 mL, with an average of 128 mL. The postoperative hospital stay ranged from 4 to 13 days, with an average of 6.5 days. Postoperative pathology revealed 4 cases of renal angiomyolipoma and 2 cases of renal clear cell carcinoma. The patients were followed up for 2-27 months, with an average of 17 months, without recurrence. CONCLUSION In the operation of retroperitoneal laparoscopic partial nephrectomy, Gerota's fascia suspension device is beneficial to expose the ventral surgical field, and it is convenient for the surgeon to operate with both hands. This technique is an effective method to deal with the ventral renal tumor, which is worthy of promotion.
Angiomyolipoma ; Fascia ; Female ; Humans ; Kidney ; Kidney Neoplasms/surgery* ; Laparoscopy ; Male ; Nephrectomy

BACKGROUND: Innovative coronavirus disease 2019 (COVID-19) vaccines, with elevated global manufacturing capacity, enhanced safety and efficacy, simplified dosing regimens, and distribution that is less cold chain-dependent, are still global imperatives for tackling the ongoing pandemic. A previous phase I trial indicated that the recombinant COVID-19 vaccine (V-01), which contains a fusion protein (IFN-PADRE-RBD-Fc dimer) as its antigen, is safe and well tolerated, capable of inducing rapid and robust immune responses, and warranted further testing in additional clinical trials. Herein, we aimed to assess the immunogenicity and safety of V-01, providing rationales of appropriate dose regimen for further efficacy study. METHODS: A randomized, double-blind, placebo-controlled phase II clinical trial was initiated at the Gaozhou Municipal Centre for Disease Control and Prevention (Guangdong, China) in March 2021. Both younger (n = 440; 18-59 years of age) and older (n = 440; ≥60 years of age) adult participants in this trial were sequentially recruited into two distinct groups: two-dose regimen group in which participants were randomized either to follow a 10 or 25 μg of V-01 or placebo given intramuscularly 21 days apart (allocation ratio, 3:3:1, n = 120, 120, 40 for each regimen, respectively), or one-dose regimen groups in which participants were randomized either to receive a single injection of 50 μg of V-01 or placebo (allocation ratio, 3:1, n = 120, 40, respectively). The primary immunogenicity endpoints were the geometric mean titers of neutralizing antibodies against live severe acute respiratory syndrome coronavirus 2, and specific binding antibodies to the receptor binding domain (RBD). The primary safety endpoint evaluation was the frequencies and percentages of overall adverse events (AEs) within 30 days after full immunization. RESULTS: V-01 provoked substantial immune responses in the two-dose group, achieving encouragingly high titers of neutralizing antibody and anti-RBD immunoglobulin, which peaked at day 35 (161.9 [95% confidence interval [CI]: 133.3-196.7] and 149.3 [95%CI: 123.9-179.9] in 10 and 25 μg V-01 group of younger adults, respectively; 111.6 [95%CI: 89.6-139.1] and 111.1 [95%CI: 89.2-138.4] in 10 and 25 μg V-01 group of older adults, respectively), and remained high at day 49 after a day-21 second dose; these levels significantly exceed those in convalescent serum from symptomatic COVID-19 patients (53.6, 95%CI: 31.3-91.7). Our preliminary data show that V-01 is safe and well tolerated, with reactogenicity predominantly being absent or mild in severity and only one vaccine-related grade 3 or worse AE being observed within 30 days. The older adult participants demonstrated a more favorable safety profile compared with those in the younger adult group: with AEs percentages of 19.2%, 25.8%, 17.5% in older adults vs. 34.2%, 23.3%, 26.7% in younger adults at the 10, 25 μg V-01 two-dose group, and 50 μg V-01 one-dose group, respectively. CONCLUSIONS: The vaccine candidate V-01 appears to be safe and immunogenic. The preliminary findings support the advancement of the two-dose, 10 μg V-01 regimen to a phase III trial for a large-scale population-based evaluation of safety and efficacy. TRIAL REGISTRATION http://www.chictr.org.cn/index.aspx (No. ChiCTR2100045107, http://www.chictr.org.cn/showproj.aspx?proj=124702).
Aged ; Antibodies, Viral ; COVID-19/therapy* ; COVID-19 Vaccines ; Double-Blind Method ; Humans ; Immunization, Passive ; Recombinant Fusion Proteins ; SARS-CoV-2

Magnoliae Officinalis Cortex, a common Chinese medicinal in clinic, should undergo "sweating" process in producing area according to Chinese Pharmacopoeia, which affects its genuineness and quality. In light of the concept and research mode of quality marker(Q-marker) for decoction pieces, the active components of Magnoliae Officinalis Cortex pieces which altered significantly before and after "sweating" were identified in this study. The main pharmacodynamic material basis was clarified by pharmacodynamic, pharmacokinetic and drug property research, followed by the prediction of Q-markers of Magnoliae Officinalis Cortex before and after "sweating", for better improving its quality standard.
Drugs, Chinese Herbal ; Magnolia

Fabrication of conventional complete dentures involves a complex restoration method, requiring significant time and typically involving primary impressions, definitive impressions, jaw relation records, clinic try-in, and complete denture placement, which has been used for nearly a century without change. A novel digital system named Functionally Suitable Denture (FSD) was researched and developed so as to reduce clinical steps, operation difficulties and errors of complete denture restoration. It pioneered a unique diagnostic complete denture aided by computer aided design (CAD) & 3D printing, by which, the functional impression, jaw relation, and try-in (3 steps) were simplified to 1 step, thus the number of visits to the dentist was reduced by 2 times. Moreover, for the first time, it put forward a CAD software of template matching based on the expert design, which was an efficient and intelligent design scheme, and the excellent denture experts' experience and skills could be inherited and iterated. The system included the 3D scanner with appropriate accuracy and high efficiency, the CAD software, the special 3D printer and process software, and the innovative clinical operation process. The Patent Cooperation Treaty (PCT) patent international search report showed that all the 15 claims of the technology were of novelty, creativity and industrial utility. All the digital products were independently developed and made by Peking University School and Hospital of Stomatology, China. The design and manufacture process of denture prosthesis was fast, simple and accurate. At the same time, personalized functional and aesthetic matching of the patients after wearing prosthesis was realized. It effectively solved the global problems of "slow, difficult and inaccurate" of the traditional manual technology of complete denture, and brought good news to edentulous patients. Compared with the traditional complete denture treatment, FSD system has a wide range of applications for different types of edentulous patients, including those with severe resorption of the alveolar ridge or a high occlusal force. Furthermore, the low-cost of 3D printers, compared with expensive milling machines, may make the approach more accessible. This review describes that our research is related to the development of the FSD system, including multi-source data acquisition technology, three generations of complete denture design software, 3D printing systems of individual tray and complete denture pattern, the clinical and laboratory operation process of the FSD system.
China ; Computer-Aided Design ; Creativity ; Denture, Complete ; Humans ; Mouth, Edentulous

OBJECTIVE: To detail a novel technique for marking renal tumors with intravenous indocyanine green (ICG) during laparoscopic partial nephrectomy, and to investigate the feasibility and safety of this technique with the use of near-infrared fluorescence imaging. METHODS: Between July 2019 and January 2020, 25 consecutive cases with renal masses underwent intraoperative ICG tumor marking laparoscopic partial nephrectomy, at the department of urology in Peking University Third Hospital by the same surgeon. The key benefits included quick intraoperative identification of the mass with improved visualization and real-time control of resection margins by the ICG Immunofluorescence imaging technique. Clinical data were prospectively collected in our institutional database. Perioperative, pathological, and clinical outcomes of the partial nephrectomy were assessed. Measurement data with normal distribution and count data were respectively described as M(range) and percentage. Among these cases, 16 cases were male and 9 cases female, The median body mass index was 25.4 (20.0-35.4) kg/m². The average age was 54 (29-77) years. The maximum tumor diameter was 2.75(1.30-5.20) cm. The R.E.N.A.L score was 7.5 (5.0-10.0).The tumor locations were distributed with upper pole (11, 42%), middle (6, 23%), and lower pole (9, 35%).The clinical stages of the tumor were described as follows: T1aN0M0 (23, 88.5%), T1bN0M0(2, 7.7%), T2aN0M0 (1, 3.8%). RESULTS: All the 25 cases were performed 26 times with intraoperative ICG tumor marking laparoscopic partial nephrectomy. There were no allergy, infection and other complications with intravenous indocyanine green. The surgical procedure was successful in all the patients. No conversion and blood transfusion were needed. All the cases of the surgical margin were negative. Overall the operative time was 136 (50-247) min and warm ischemia time was 14 (7-30) min.The estimated blood loss was 50 (10-400) mL and the hospital stay was 5.5 (3.0-31.0) days. One case with perirenal hematoma, one case with urine leak, one with respiratory failure and deep venous thrombosis. All of these cases were cured by the corresponding treatment. The others had no severe complications. There was no tumor recurrence and metastasis during the follow up with 4 to 10 months. CONCLUSION ICG marking and near-infrared fluorescence imaging technology has now emerged as a safe, feasible and useful tool that may facilitate laparoscopic partial nephrectomy.
Adult ; Aged ; Female ; Humans ; Indocyanine Green ; Kidney Neoplasms ; Laparoscopy ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Nephrectomy ; Retrospective Studies