Objective:To investigate the impacts of the radiosensitivity of cell lines on a microdosimetric kinetic model (MKM) used in carbon-ion radiotherapy.Methods:The saturation-corrected specific energy ( ) of monoenergetic carbon ions was calculated using the Kiefer-Chatterjee (K-C) track structure model. Correction curve f(LET) was derived from experimental data on relative biological effectiveness (RBE) (RBE DSB-LET) defined based on the double-strand DNA break of the Chinese hamster ovary (CHO) and Fibroblast cell lines irradiated using carbon ions with varying linear energy transfer (LET) values. Then, based on the MKM, the D10-LET curves, as well as α and β databases, of the CHO and Fibroblast cell lines with varying radiosensitivity were determined. Results:Compared to the clinically applied MKM, the predicted D10 after correction while accounting for cell line radiosensitivity agreed better with experimental D10 values of the CHO and Fibroblast cell lines. Specifically, compared to experimental values in the literature, the D10 values calculated in the study and determined using the MKM showed mean squared errors (MSEs) of 0.04 and 0.71, for the CHO cell line and 0.35 and 0.55, respectively, for the Fibroblast cell line. For monoenergetic carbon ions with varying LET values, the calculated α and β values generally increased with cellular radiosensitivity. Conclusions:Incorporating cellular radiosensitivity into the MKM framework serves as a more specific method for RBE assessment while also providing a reference for advancing MKM applications and achieving the fine-scale calculations of RBE in carbon-ion radiotherapy.

This review aimed to provide a comprehensive analysis of the etiology, epidemiology, pathology, and conventional treatment of heterotopic ossification (HO), especially emerging potential therapies. HO is the process of ectopic bone formation at non-skeletal sites. HO can be subdivided into two major forms, acquired and hereditary, with acquired HO predominating. Hereditary HO is a rare and life-threatening genetic disorder, but both acquired and hereditary form can cause severe complications, such as peripheral nerve entrapment, pressure ulcers, and disability if joint ankylosis develops, which heavily contributes to a reduced quality of life. Modalities have been proposed to treat HO, but none have emerged as the gold standard. Surgical excision remains the only effective modality; however, the optimal timing is controversial and may cause HO recurrence. Recently, potential therapeutic strategies have emerged that focus on the signaling pathways involved in HO, and small molecule inhibitors have been shown to be promising. Moreover, additional specific targets, such as small interfering RNAs (siRNAs) and non-coding RNAs, could be used to effectively block HO or develop combinatorial therapies for HO.
Humans ; Ossification, Heterotopic/genetics*

Objective:To investigate the impacts of the radiosensitivity of cell lines on a microdosimetric kinetic model (MKM) used in carbon-ion radiotherapy.Methods:The saturation-corrected specific energy ( ) of monoenergetic carbon ions was calculated using the Kiefer-Chatterjee (K-C) track structure model. Correction curve f(LET) was derived from experimental data on relative biological effectiveness (RBE) (RBE DSB-LET) defined based on the double-strand DNA break of the Chinese hamster ovary (CHO) and Fibroblast cell lines irradiated using carbon ions with varying linear energy transfer (LET) values. Then, based on the MKM, the D10-LET curves, as well as α and β databases, of the CHO and Fibroblast cell lines with varying radiosensitivity were determined. Results:Compared to the clinically applied MKM, the predicted D10 after correction while accounting for cell line radiosensitivity agreed better with experimental D10 values of the CHO and Fibroblast cell lines. Specifically, compared to experimental values in the literature, the D10 values calculated in the study and determined using the MKM showed mean squared errors (MSEs) of 0.04 and 0.71, for the CHO cell line and 0.35 and 0.55, respectively, for the Fibroblast cell line. For monoenergetic carbon ions with varying LET values, the calculated α and β values generally increased with cellular radiosensitivity. Conclusions:Incorporating cellular radiosensitivity into the MKM framework serves as a more specific method for RBE assessment while also providing a reference for advancing MKM applications and achieving the fine-scale calculations of RBE in carbon-ion radiotherapy.

Objective:To elucidate the recent therapeutic efficacy of the intelligent fracture reduction robotic system in managing pelvic fractures.Methods:A retrospective evaluation of 49 pelvic fracture patients treated using the intelligent fracture reduction robotic system at Beijing Jishuitan Hospital's trauma orthopedics department between March 2021 and December 2022 was conducted. The cohort included 30 males and 19 females, with a mean age of 51.51±18.71 years (20-92 years range). Fractures were classified according to the Tile system: B1 type in 2 cases, B2 in 7, B3 in 3, C1 in 30, and C2 in 3. The median interval between injury and surgery was 6 days, with a range of 2-22 days. The robotic system assisted in pelvic fracture reduction and stabilization surgeries. Preoperative and postoperative evaluations involved pelvic CT scans, anteroposterior, inlet, and outlet radiographic images. Fracture displacement and reduction outcomes were assessed via X-ray imagery. Data captured included intraoperative blood loss, duration of surgery, fracture stabilization techniques, and postoperative monitoring period. The Majeed scoring system gauged functional outcomes.Results:Of the patients, 48 underwent minimally invasive interventions with robotic assistance, while one case necessitated open reduction and internal fixation due to an unsuccessful reduction. The duration between injury and operation ranged from 2 to 22 days. Average surgical time stood at 206.5±7.1 minutes (105-440 min range), and median intraoperative blood loss was 100ml (10-600 ml range). Using the Matta reduction criteria, 30 postoperative cases exhibited excellent and 9 good outcomes for posterior pelvic ring displacement, translating to a 93% (38/41) positive rate. For anterior pelvic ring shifts, 45 showed excellent and 3 good outcomes, culminating in a 100% (48/48) success rate. Follow-up for the 48 cases lasted 11.0 months (3-23 months range), with the Majeed functional score averaging 81.9±17.0 points (42-100 point range). 27 cases scored excellent, and 11 good, yielding a combined positive outcome rate of 79.2% (38/48).Conclusion:Employing the intelligent fracture reduction robotic system in pelvic fracture treatments facilitates minimally invasive interventions and yields favorable short-term clinical results.

Objective: To establish a rapid GeXP-based multiplex reverse transcription-PCR assay (GeXP assay) for simultaneous detection of 5 subtypes of diarrheogenic Escherichia coli. Methods: Specific primers were designed according to reserved sequences of 12 virulence genes in enterotoxigenic E. coli (ETEC), enterinvasive E. coli (EIEC), enteropathogenic E. coli (EPEC), enteroaggregative E. coli (EAEC) and enterohemorrhagic E. coli (ETEC), and PCR amplification was performed with a single pair of primers to validate the specificity of PCR assay with a single template and a single pair of primers. The specificity of the GeXP assay was evaluated with the genomic DNA of 5 subtypes of diarrheogenic E. coli as the template in a mixture of 12 pairs of primers, and the sensitivity of the GeXP assay was evaluated with the mixed suspensions of 5 subtypes of diarrheogenic E. coli at concentrations of 106, 105, 104 and 103 CFU/mL as the template. Foods purchased from supermarkets and agricultural retail markets were prepared into 34 spiked samples, and 5 subtypes of diarrheogenic E. coli were detected using the GeXP assay and compared with the fluorescent real-time multiple PCR assay. Results: The sizes of sth, pic, bfpB, astA, lt, escV, aggR, stx1, uidA, invE, stx2 and stp genes amplification products were consistent with expected sizes using a single template and a single pair of primers, with a fluorescent signal intensity of more than 25 000 A.U. The sizes of the GeXP assay amplification products of 12 virulence genes in 5 subtypes of diarrheogenic E. coli were consistent with expected sizes, with a high specificity. If the concentration of the mixed suspensions of 5 subtypes of diarrheogenic E. coli was 103 CFU/mL, the GeXP assay was effective for simultaneous detection of 12 virulence genes, with a high fluorescent signal intensity, consistent repeated detection results and a less than 10% coefficient of variation. The GeXP assay detected 3 ETEC isolates, 12 EAEC isolates, one EIEC isolate, one EPEC isolate and one EHEC isolate among the 34 spiked samples, which was in agreement with the detection of 5 subtypes of diarrheogenic E. coli with commercial fluorescent real-time multiple PCR assay kits. Conclusions A GeXP assay has been successfully established for simultaneous detection of 12 virulence genes in diarrheogenic E. coli, which is effective for clinical differential diagnosis and epidemiological surveys of diarrheogenic E. coli.

Objective: To investigate the contamination status and assess the potential consumption risk of Listeria monocytogenes ( L. monocytogenes ) in cooked meat products in bulk in Zhejiang Province, so as to provide strategy for food safety supervision and management. Methods: A total of 2 320 cooked meat products were sampled from eleven cities in Zhejiang Province during 2018-2020. The detection of L. monocytogenes was carried out in accordance with the national standard GB/T 4789.30-2016. Risk Ranger software was used for the semi-quantitative risk assessment on the whole population and pregnant women. Results: The total detection rate of L. monocytogenes in cooked meat products in bulk in Zhejiang Province was 2.97% ( 69/2 320 ). The detection rates in stewed, smoked/roasted, fried, dried products and others were 3.85%, 1.81%, 0.59%, 0% and 0.94%, which were significantly different ( P<0.05 ). There were 28 positive samples in 1 069 samples collected in 2020, with the concentration ranging from 5 to 590 CFU/g and averaging 6.8 CFU/g. The estimated number of listeriosis cases each year caused by consumption of cooked meat products in bulk was 131 in the whole population with a risk score of 42, and 1.44 in pregnant women with a risk score of 54. The risk coefficient could reduce to approximate zero after sufficient heating before intake. Conclusion The prevalence of L. monocytogenes in cooked meat products in bulk in Zhejiang Province during 2018-2020 poses a potential risk in food safety. Pregnant women should avoid eating.

Objective:To summarize our experience in prevention of COVID-19 infection in emergency and confined operations during the first 3 weeks after Spring Festival in 2020.Methods:From February 3rd to 23rd, 2020, 151 patients were admitted to Department of Orthopaedic Trauma, Beijing Jishuitan Hospital for emergency and confined operations. In this cohort, 125 patients were admitted to ordinary wards. They were 70 males and 55 females with an age of 51.1 years ± 14.9 years. Of them, 2 were subjected to emergency operation and 123 to confined operation. The mean time from injury to operation was 9.9 days ± 6.1 days. There were 26 cases in the senile wards, 7 males and 19 females with an age of 80.8 years ± 7.0 years all of whom underwent confined operations. The mean time from injury to operation was 8.4 days ± 6.3 days. The protocols for emergency diagnosis, admission, emergency and confined operations, postoperative rehabilitation and management of suspects with COVID-19 during the epidemic of COVID-19 were optimized according to Diagnosis and Treatment Protocols for Novel Coronavirus Pneumonia (Trial version 5), emergency responding pre-plans of our hospital, and our experience in Enhanced Recovery After Surgery (ERAS) as well.Results:The patients in the ordinary wards had a hospital stay of 6.8 days ± 4.6 days while those in the senile wards 5.1 days ± 2.0 days. Abnormal temperature (≥37.3 ℃) was observed perioperatively in 17 cases in the ordinary wards. It was absorption fever in all and appeared in 4 cases upon admission. Fever appeared in 11 patients in the senile wards and upon admission in 3 of them. One senile patient who had been diagnosed of normal pneumonia returned to normal temperature and remained stable conditions after antibiotic therapy. The other patients were free of complications related to COVID-19 during their hospital stay.Conclusion:The first-line medical staff working at emergency department, wards and surgical theaters must heighten their vigilance against COVID-19 infection and rigorously follow protocols for prevention of COVID-19 infection in their daily clinical practice.

OBJECTIVE: To explore the clinical characteristics and outcomes of adult critically ill patients with COVID-19 and identify the risk factors correlated with in-hospital deaths. METHODS: This study was conducted among 20 confirmed adult cases of COVID-19 in the Intensive Care Unit (ICU) of Honghu People's Hospital in Jingzhou City, Hubei Province. According to the final outcome, the patients were divided into survivor group and death group with 10 patients each. The demographic data, clinical manifestations and signs, laboratory findings, treatment measures and clinical outcomes were obtained from electronic medical records to compare the clinical characteristics and outcomes between the two groups. Univariate logistic analysis was used to analyze the risk factors associated with in-hospital death. RESULTS: The mean age of patients with confirmed COVID-19 was 70 ± 12 years, and 40% of them were male. The patients were admitted to ICU 11 ± 9 days after symptom onset. The most common symptoms on admission were cough (19 cases), fatigue or myalgia (18 cases), fever (17 cases) and dyspnea (16 cases). Eleven (55%) of the patients had underlying diseases, among which hypertension was the most common (11 cases), followed by cardiovascular disease (4 cases) and diabetes (3 cases). Six (30%) of the patients received invasive mechanical ventilation and continued renal replacement therapy but eventually died. Acute cardiac injury was the most common complication (19 cases). Half of the patients died between the 2nd and 19th day after ICU admission. Compared with dead patients, the surviving patients had a lower average body weight (61.70±2.36 68.60±7.15 kg, =0.01) and a higher Glasgow Coma Index (14.69 ± 0.70 12.70 ± 2.45, =0.03), and were less likely to develop shock (2 10, =0.001) or acute respiratory distress syndrome (2 10, =0.001). CONCLUSIONS Critically ill patients with COVID-19 are generally older. A higher body weight and a lower lymphocyte count are potentially associated with a greater likeliness of fatality in ICU patients with COVID-19.
Aged ; Aged, 80 and over ; Betacoronavirus ; Coronavirus Infections ; Critical Illness ; Female ; Humans ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; Retrospective Studies

Objective: To establish real-time recombinase polymerase amplification（RPA）for the rapid detection of Vibrio parahaemolyticus（VP）. Methods: An exo probe and primers were designed according to the conserved sequence of thermolabile hemolysin（tlh）gene of VP and then RPA for detection of VP was established. The sensitivity of the assay was evaluated by detecting different concentration of VP;the specificity was evaluated by detecting different bacteria;the stability was evaluated by repeat trials;the application effect was evaluated by detecting food samples which were simultaneously tested with traditional culture method according to GB 4798.7-2013 Detection of VP. Results: A real-time RPA was established to complete VP amplification within 20 min at a constant temperature of 39 ℃. The analytical sensitivity of the assay was five pg per reaction and no cross-reactivity with other pathogenic bacteria observed. The RPA detection results with different concentration of VP and E. coli DNA templates at three time points were consistent. The detection results of 51 food samples by RPA were the same as those by traditional culture method. Conclusion The established real-time RPA can qualitatively detect VP,with simple operation and interpretation of results,which is suitable for rapid detection of VP in public health emergencies and food safety supervision.

Objective: To explore age-related clinical characteristics, early responses and outcomes in non-senile adults with de novo acute myeloid leukemia (AML). Methods: Data of consecutive cases of 18-65 years adults with de novo AML (non-acute promyelocytic leukemia) were reviewed retrospectively. Clinical characteristics at diagnosis, early responses and outcomes across different age groups of patients were analyzed. Results: 1 097 patients were enrolled. 591 (53.9%) were male. Median age was 42 years. Increasing age was significantly associated with decreasing WBC count (P=0.003), increasing PLT count (P=0.034), lower blast proportions in bone marrow (P=0.021). The incidence of NPM1⁺/FLT3-ITD^- increased with age (P<0.001). Multivariate analyses showed that increasing age was associated with low probabilities of achieving morphologic leukemia free state (MLFS) (P=0.053) and complete remission (CR) (P=0.004) and poor overall survival (OS) (P=0.070) in the whole patients population. However, increasing age was not associated with low MLFS rate and poor OS, except low CR rate (P=0.075) in those receiving standard induction regimen instead of low-intensity regimen. Conclusions There were significant differences on clinical characteristics, cytogenetics and molecular genetics across different age groups in non-senile adults with de novo AML. In the patients receiving standard induction regimen, age was not associated with MLFS rate and OS.