Macrophage migration inhibitory factor reversed senescent phenotype in human chondrocytes in vitro.

BACKGROUND: The senescence of chondrocytes, which is closely linked to the development of osteoarthritis (OA), has been found to be influenced by the inflammatory environment of joint cavity. However, there remains a lack of comprehensive understanding regarding the specific mechanisms through which cytokine impacts chondrocytes senescence. PURPOSE: To investigate the effects of MIF on the chondrocytes senescence and explore the underlying mechanism. METHODS: Human cytokine array and ELISA were used for the level of MIF in synovium fluid. CCK-8 was used for chondrocytes viability. IF, WB, SA-ß-gal staining and flow cytometry were used for the chondrogenic, apoptotic and senescent phenotype of chondrocytes. RESULTS: The level of MIF was significantly increased in OA patients. MIF significantly reversed the senescent phenotype induced by LPS pretreatment in human chondrocytes. MIF significantly enhanced the expression of Col II, SOX9, and ACAN in LPS pre-treated human chondrocytes. Furthermore, MIF significantly inhibited the apoptosis of LPS-induced senescent chondrocytes. CONCLUSION: Increased level of MIF in osteoarthritic joint cavity might effectively suppress the senescent phenotype and simultaneously improve the chondrogenic phenotype in chondrocytes, the underlying mechanism was likely to be independent of apoptosis.

The association between ferroptosis and autophagy in cardiovascular diseases.

Autophagy is a process in which cells degrade intracellular substances and play a variety of roles in cells, such as maintaining intracellular homeostasis, preventing cell overgrowth, and removing pathogens. It is highly conserved during the evolution of eukaryotic cells. So far, the study of autophagy is still a hot topic in the field of cytology. Ferroptosis is an iron-dependent form of cell death, accompanied by the accumulation of reactive oxygen species and lipid peroxides. With the deepening of research, it has been found that ferroptosis, like autophagy, is involved in the occurrence and development of cardiovascular diseases. The relationship between autophagy and ferroptosis is complex, and the association between the two in cardiovascular disease remains to be clarified. This article reviews the mechanism of autophagy and ferroptosis and their correlation, and discusses the relationship between them in cardiovascular diseases, which is expected to provide new and important treatment strategies for cardiovascular diseases.

The association between sleep duration and lung cancer: a meta-analysis.

PURPOSE: The link between sleep duration and lung cancer risk has been suggested by some epidemiological studies. This meta-analysis was performed to further understand this relationship. METHODS: MEDLINE and EMBASE entries up to December 2022 were searched for eligible publications. A random effects model was used to calculate pooled relative risks (RRs) with 95% confidence intervals (95% CIs). Publication bias was estimated using Begg's and Egger's regression asymmetry test. RESULTS: The meta-analysis included 11 studies (including 10 cohort studies and 1 case-control study). The pooled adjusted RRs were 1.13 (95% CI: 1.03-1.24) for short sleep duration and 1.21 (95% CI: 1.07-1.37) for long sleep duration. CONCLUSION: The findings of this meta-analysis suggested that both short and long sleep duration are associated with an increase in lung cancer risk. These findings need to be corroborated through large-scale prospective studies.

Comparing biweekly single-dose actinomycin D with multiday methotrexate therapy for low-risk gestational trophoblastic neoplasia (FIGO Score 0-4): study protocol for a prospective, multicentre, randomized trial.

BACKGROUND: Single-agent chemotherapy using methotrexate or actinomycin D is the first-line treatment for patients with low-risk gestational trophoblastic neoplasia. Various methotrexate-based and actinomycin D-based single-agent regimens can be used. However, there is insufficient evidence to determine the superior regimen. To guide doctors in selecting a single-agent chemotherapy regimen for patients with low-risk gestational trophoblastic neoplasia, we will compare two regimens. METHODS: We will conduct a multicentre, randomized, prospective clinical trial. Selected low-risk gestational trophoblastic neoplasia patients (FIGO score 0-4) will be randomized 1:1 to a biweekly single-dose actinomycin D group or a multiday methotrexate therapy group. The actinomycin D group will receive IV pulse actinomycin D (1.25 mg/m2) every 14 days, and the methotrexate group will receive methotrexate (50 mg) intramuscularly on days 1, 3, 5, and 7 (4 doses per cycle) and leucovorin (15 mg) intramuscularly on days 2, 4, 6, and 8. This process will be repeated every 14 days. The primary endpoints will include the complete remission rate by single-agent therapy and the overall complete remission rate. The secondary endpoints will include the duration needed to achieve complete remission after single-agent chemotherapy, number of courses needed to achieve complete remission after single-agent chemotherapy, incidence and severity of adverse effects, effects on menstrual conditions and ovarian function based on the anti-Mullerian hormone level, and patient-reported quality of life. DISCUSSION: Previous clinical trials comparing biweekly single-dose actinomycin D with multiday methotrexate therapy for treating low-risk gestational trophoblastic neoplasia patients failed to meet the expected case number. Through this multicentre study, the complete remission ratio and efficacy difference between biweekly single-dose actinomycin D and multiday methotrexate therapy will be obtained. This study will also provide the basis for formulating a preferred regimen for treating patients with low-risk gestational trophoblastic neoplasia. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04562558, Registered on 13 September 2020 (Protocol version 2020-9-24, version 1.0).

Retrospective analysis of clinical features and fertility outcomes with fertility-sparing treatment of placental site trophoblastic tumor.

OBJECTIVE: To analyze the methods, feasibility, efficiency, and fertility outcomes of fertility-sparing treatment for patients with placental site trophoblastic tumor (PSTT). METHODS: Clinical data of patients diagnosed with PSTT between April 1998 and April 2020 from Peking Union Medical College Hospital (PUMCH) were retrospectively collected. The clinical features, treatment, and outcomes of patients received fertility-sparing treatment were analyzed and compared with patients suffered hysterectomy. RESULTS: In total, 126 patients were included in the study and 29 of them received fertility-sparing treatment. Besides significantly younger age and lower proportion of antecedent term delivery were seen in fertility-sparing group than hysterectomy group, no significant differences were observed in stage, serum ß-hCG level, or interval from antecedent pregnancy between the two groups. Conservative surgery was selected individualized and none of them suffered salvage hysterectomy. Patients with clinical or pathological high-risk factors received adjuvant chemotherapy, yet the fertility-sparing treatment did not significantly lengthen chemotherapy duration. All patients in fertility-sparing group achieved complete remission without relapse after 36 to 176 months of follow-up and had sixteen healthy term delivery more than one year after the treatment. CONCLUSIONS: Fertility-sparing treatment for PSTT can be considered for young patients with localized uterine lesions who strongly desire to preserve their fertility potential. With individualized conservative surgery and selected adjuvant chemotherapy, fertility-sparing treatment will not influence the risk of relapse or overall survival and patients will achieve favorable pregnancy and live birth outcomes.

Testing Together Behaviors in Secondary Distribution of HIV/Syphilis Self-testing Program Among Men Who have Sex with Men in China.

HIV self-testing (HIVST) is recommended as a promising way to increase HIV testing uptake among MSM. MSM sometimes used HIVST kits together with their sexual partners or friends. However, limited data was reported on MSM's testing together behaviors with sexual partners and non-sexual contacts. Data were collected among MSM in China from June 2018 to June 2019. Eligible participants (referred to as "index participants") finished a baseline survey and applied for HIVST kits. They were encouraged to distribute the kits to other people (referred to as "alters"). Index participants finished a 3-month follow-up survey on the distribution and usage of the kits. Alters finished an online survey on the usage of HIVST kits after they returned the photographed testing results. Results were reported based on index participants and alters, respectively. Based on follow-up data, 138 index participants successfully motivated others for HIVST, most of them (77.5%) tested together with at least one alter. Around half of alters (52.3%) reported testing together with index participants. Index participants distributed more HIVST kits to friends than sexual partners. MSM who had ever tested for HIV were more likely to test together. Our study demonstrated that the testing together behaviors during HIVST distribution among sexual partners and social network contacts were common. The social network-based approach is essential in promoting testing together and HIV status disclosure among MSM.

Are people living with HIV have a low vulnerability to omicron variant infection: results from a cross-sectional study in China.

BACKGROUND: A surge of more than 80 million Omicron variant infected cases was reported in China less than a month after the "zero COVID" strategy ended on December 7, 2022. In this circumstance, whether people living with HIV (PLWH) in China experience a similar risk is not clear. METHODS: A cross-sectional study was conducted in the Wuchang District of Wuhan between December 20, 2022, and January 18, 2023 through a self-administered online survey. PLWH and HIV-negative people aged ≥ 18 years old who volunteered for this survey were eligible. The prevalence of Omicron variant infection between PLWH and HIV-negative people was compared, and the factors associated with the Omicron variant infection among PLWH and HIV-negative people were further evaluated, respectively. RESULTS: In total, 890 PLWH and 1,364 HIV-negative adults from Wuchang District were enrolled. Among these participants, 690 PLWH (77.5%) and 1163 HIV-negative people (85.3%) reported SARS-CoV-2 infection. Gender, chronic disease conditions, and COVID-19 vaccination status significantly differed between the two groups. After adjusting gender, age, comorbidities, and COVID-19 vaccination status, the risk of SARS-CoV-2 infection among PLWH was significantly lower than among HIV-negative people (aOR 0.56, 95%CI 0.42-0.76). Multivariable logistic regression analysis showed that PLWH with older age and detectable HIV-viral load (HIV-VL) had decreased risk of SARS-CoV-2 infection (aOR 0.98, 95%CI 0.96-0.99; aOR 0.59, 95%CI 0.36-0.97). Compared with PLWH receiving one/two doses of COVID-19 vaccines, no significant differences in the risk of SARS-CoV-2 infection were observed among PLWH receiving three doses of inactivated vaccines and four doses of vaccines (three doses of inactivated vaccines plus one dose of inhaled recombinant adenovirus type 5 (AD5)-vectored vaccine). Among HIV-negative people, those receiving four doses of COVID-19 vaccines had a lower risk of SARS-CoV-2 infection than those receiving one/two doses (aOR 0.14, 95%CI 0.08-0.25). CONCLUSIONS: Our study proves that PLWH have a lower risk of Omicron variant infection than HIV-negative people. However, even PLWH with younger age and virological suppression should strengthen the prevention against SARS-CoV-2 infection. Three doses of inactivated vaccines plus one dose of inhaled recombinant AD5-vectored COVID-19 vaccine may provide better protection for HIV-negative people.

Pulmonary resection of residual lesions of pulmonary metastasis from gestational trophoblastic neoplasia.

OBJECTIVE: To evaluate the prognosis and recurrence in patients with residual lesions of pulmonary metastasis from gestational trophoblastic neoplasia after initial treatment, and to explore the clinical significance of pulmonary resection. METHODS: A retrospective analysis was performed on 606 patients with residual lesions from pulmonary metastasis after receiving standardized chemotherapy as initial treatment in Peking Union Medical College Hospital from January 2002 to December 2018. Patients were divided into surgery (51 patients) and non-surgery (555 patients) groups. The prognosis of these patients was compared. Risk factors affecting recurrence were analyzed to explore the effect of pulmonary resection. RESULTS: Among low risk patients, complete remission rate was 100% and recurrence rate was <1% in both groups. Among high risk patients, complete remission and recurrence rates were 93.5% and 10.3% in the surgery group and 94.7% and 14.3% in the non-surgery group, respectively. There was no significant difference in prognostic features between the two groups (all p>0.05). No significant difference was found in recurrence rates based on recurrence risk factors (≥3.2 cm residual lung lesions, prognosis score ≥9.0, and drug resistance) between the two groups (all p>0.05). CONCLUSION: After standardized chemotherapy, pulmonary resection was not necessary for initially treated stage III gestational trophoblastic neoplasia patients whose blood ß human chorionic gonadotropin levels normalized and residual lung lesions remained stable. These patients should be closely monitored during follow-up, regardless of the size of the residual lung lesions or high/low risk score, especially within a year after complete remission.

Effect of actinomycin D on ovarian reserve in low-risk gestational trophoblastic neoplasia.

OBJECTIVE: This study aimed to explore the single-agent chemotherapy actinomycin D on ovarian reserve by measuring the anti-Mullerian hormone (AMH) levels before, during, and after chemotherapy. METHODS: This study recruited premenopausal women aged 15 to 45 with a newly diagnosed low-risk gestational trophoblastic neoplasia needing actinomycin D. AMH was measured at baseline, during chemotherapy, and 1, 3, and 6 months after the last chemotherapy. The reproductive outcomes were also documented. RESULTS: Of the 42 women recruited, we analyzed 37 (median: 29 years; range 19-45) with a complete dataset. The follow-up was 36 months (range 34-39). Actinomycin D significantly decreased AMH concentrations during treatment, from 2.38±0.92 ng/mL to 1.02±0.96 ng/mL (p<0.05). Partial recovery was seen at 1 month and 3 months after treatment. Full recovery was reached 6 months after treatment among patients younger than 35 years. The only factor correlated with the extent of AMH reduction at 3 months was age (r=0.447, p<0.05). Notably, the number of courses of actinomycin D was not associated with the extent of AMH reduction. A total of 18 (90%) of 20 patients who had a desire to conceive had live births with no adverse pregnancy outcomes. CONCLUSION: Actinomycin D has a transient and minor effect on ovarian function. Age is the only factor that impacts the patient's rate of recovery. Patients will achieve favorable reproductive outcomes after actinomycin D treatment.

Clinical characteristics and oncological outcomes of recurrent adult granulosa cell tumor of ovary: A retrospective study of seventy patients.

INTRODUCTION: This study aimed to describe the clinicopathological characteristics of recurrent adult granulosa cell tumor and identify the risk factors for recurrence. MATERIAL AND METHODS: Seventy recurrent adult granulosa cell tumor patients treated in Peking Union Medical College Hospital between 2000 and 2020 were retrospectively reviewed. The primary outcomes were progression-free survival after first recurrence (PFS-R), overall survival after first recurrence (OS-R) and recurrence frequency. The Kaplan-Meier analysis, univariate and multivariate Cox proportional hazard analysis, and the Prentice, Williams and Peterson counting process (PWP-CP) model were adopted. RESULTS: There were 70 patients included in the study, and recurrence occurred twice in more than 71% of patients, and 49.9% of patients relapsed ≥ three times. The recurrence pattern in over half of the patients at first recurrence was multifocal and distant disease, and abdominal or pelvic mass and liver metastasis were the most common. The 5-year PFS-R was 29.3%, and the 10-year PFS-R was 11.3%; the 5-year OS-R was 94.9%, and the 10-year OS-R was 87.9%. Kaplan-Meier analysis demonstrated that patients with distant recurrence and PFS1 (PFS when first recurrence occurred) ≤60 months had worse PFS-R (p = 0.017, 0.018), and patients with PFS-R ≤ 34 months had worse OS-R (p = 0.023). It demonstrated that PFS1 ≤ 60 months (hazard ratio, HR 1.9, 95% confidence interval [CI]: 1.1-3.4, p = 0.028) was an independent risk factor for PFS-R, and local lesion at recurrence (HR 0.488, 95% CI: 0.3-0.9, p = 0.027) was an independent protective factor for PFS-R. In addition, it demonstrated that PFS-R ≤ 33 months (HR 5.5, 95% CI: 1.2-25.3, p = 0.028) was an independent risk factor for OS-R. The PWP-CP analysis showed that laparoscopic operation (at each operation) could significantly increase recurrence times (p = 0.002, HR = 3.4), and no existence of gross residual lesion (R0) at each recurrence operation could significantly decrease recurrence frequency (p < 0.001, HR <0.001). CONCLUSIONS: The recurrence pattern in patients with recurrent adult granulosa cell tumor was characterized as late and repeated, multifocal, and distant relapse. It has been demonstrated that PFS1 ≤ 60 months and distant lesion at recurrence are independent risk factors for PFS-R, and PFS-R ≤ 33 months is an independent risk factor for OS-R. The PWP-CP model showed that the transabdominal approach and surgery reaching R0 could significantly decrease the recurrence frequency.

De novo myeloid sarcoma mimicking gynecological tumors: a retrospective case series of eight patients.

OBJECTIVE: To describe myeloid sarcoma (MS) that mimic gynecological tumors and provide guidelines for improving the diagnosis and treatment of patients. METHODS: This case series study retrospectively analyzed the clinicopathological characteristics and oncological outcomes of female patients who were histologically diagnosed with MS after initially presenting with reproductive-system tumors at the Peking Union Medical College Hospital between January 2000 and March 2022. RESULTS: There were eight cases in which MS mimicked cervical cancer, ovarian cancer, or hysteromyoma. Six patients had isolated MS, and the other two had acute myeloid leukemia (AML)-M2. The average age was 39.00 ± 14.26. They each sought advice from a gynecological oncologist at the initial visit, complaining of irregular bleeding (3/8), low abdominal pain (3/8), dysmenorrhea (1/8), or an accidentally found mass (1/8). CT/MRI exams revealed that the average tumor size reached 5.65 ± 2.35 cm, with 50% of the tumors being larger than 8 cm. The final diagnoses were confirmed by biopsy (2/8) or postoperative pathology (6/8); the most frequent positive immunohistochemical markers were Ki-67 (60-90%), MPO (100%), LCA (62.5%), CD43 (62.5%), CD117 (62.5%), CD99 (50%), vimentin (37.5%), and lysozyme (25%). MLL/AF9 gene fusions and CEBPA, JAK2, NRAS, and FLT3-TKD mutations were found in the patients. Six (75%) of the patients showed a complete response after upfront treatment using chemotherapy + surgery and experienced no recurrence during follow-up. The overall survival (OS) rate was 72.9%, and the 5-year OS rate was 72.9% (95%CI: 0.4056-1.000). The median OS was 26 months (range: 3-82). CONCLUSION: For patients with isolated MS, treatment by chemotherapy and surgery are radical procedure, and initial treatment using chemotherapy alone should be considered for MS with synchronous intramedullary AML. Poor response to chemotherapy, short interval to leukemia occurrence, and heavy tumor burden (> 10 cm) could indicate a poor prognosis for patients with MS.

Cerebral Protection of Intraoperative Infusion of Dexmedetomidine in Patients with Chronic Cerebrovascular Stenosis Undergoing Endovascular Interventional Therapies: A Prospective Randomized Controlled Trial.

BACKGROUND: To investigate the cerebral protective effect of intraoperative dexmedetomidine infusion on patients with chronic cerebral vascular stenosis receiving endovascular interventional therapy. METHODS: Sixty patients with carotid artery or cerebral artery stenosis or occlusion stenting under elective general anesthesia were divided into dexmedetomidine group (group D) and normal saline group (group N). Group D was given dexmedetomidine loading dose 1.0 µg/kg after peripheral vein opening for 10 min, and then adjusted infusion rate to 0.5 µg/kg/h until stopped 30 min before end. RESULTS: At 7 days after operation, the contents of S100ß, neuron-specific enolase (NSE) and interleukin-6 (IL-6) in group D were apparently lower than those in group N (P < 0.05), while the contents of IL-1ß and tumor necrosis factor-α in 2 groups showed no statistical significance (P > 0.05). Additionally, at 4 days and 7 days after operation, the scores of Mini-Mental State Scale (MMSE) and Wechsler Memory Scale (WMS) in group D were significantly higher than those in group N (P < 0.05). Thirty days after surgery, the cerebral hemodynamic indexes (relative mean transit time, relative time to peak) in group D were significantly improved, and obviously better than those in group N (P < 0.05). CONCLUSIONS: The S-100ß, NSE, and inflammatory mediator IL-6 in group D were significantly decreased compared with group N, the MMSE and WMS cognitive function scores, and the cerebral blood perfusion were apparently improved in group D, clarifying dexmedetomidine has protective effect on nerve tissue injury by inhibiting inflammation.

Study on the correlation between early three-dimensional gait analysis and clinical efficacy after robot-assisted total knee arthroplasty.

PURPOSE: Robot-assisted technology is a forefront of surgical innovation that improves the accuracy of total knee arthroplasty (TKA). But whether the accuracy of surgery can improve the clinical efficacy still needs further research. The purpose of this study is to perform three-dimensional (3D) analysis in the early postoperative period of patients who received robot-assisted total knee arthroplasty (RATKA), and to study the trend of changes in gait parameters after RATKA and the correlation with the early clinical efficacy. METHODS: Patients who received RATKA in the Center of Joint Surgery, the First Hospital Affiliated to Army Military Medical University from October 2020 to January 2021 were included. The imaging parameters, i.e., hip-knee-ankle angle, lateral distal femoral angle, medial proximal tibial angle, posterior condylar angle were measured 3 months post-TKA. The 3D gait analysis and clinical efficacy by Western Ontario Mac Master University Index (WOMAC) score were performed pre-TKA, 3 and 6 months post-TKA. The differences in spatiotemporal parameters of gait, kinetic parameters, and kinematic parameters of the operated limb and the contralateral limb were compared. The correlation between gait parameters and WOMAC scores was analyzed. Paired sample t-test and Wilcoxon rank-sum test were used to analyze the difference between groups, and Spearman correlation coefficient was used to analyze the correlation. RESULTS: There were 31 patients included in this study, and the imaging indexes showed that all of them returned to normal post-TKA. The WOMAC score at 3 months post-TKA was significantly lower than that pre-TKA, and there was no significant difference between at 3 and 6 months. The 3D gait analysis results showed that the double support time of the operated limb reduced at 3 and 6 months (all p < 0.05), the maximum extension and maximum external rotation of the knee joint increased at stance phase, and the maximum flexion angle, the range of motion and the maximum external rotation increased at swing phase. Compared with the preoperative data, there were significant improvements (all p < 0.05). Compared with the contralateral knee joint, the maximum external rotation of the knee joint at swing phase was smaller than that of the contralateral side, and the maximum flexion and extension moment was greater than that of the contralateral knee. The maximum external rotation moment of the joint was greater than that of the contralateral knee joint (p < 0.05). There was a negative correlation between the single support time pre-TKA and the WOMAC score at 3 months (p = 0.017), and the single support time at 3 months was negatively correlated with the WOMAC score at 6 months (p = 0.043). The cadence at 6 months was negatively correlated with the WOMAC score at 6 months (p = 0.031). The maximum knee extension at stance phase at 6 months was negatively correlated with the WOMAC score at 6 month (p = 0.048). The maximum external rotation at stance phase at 6 months was negatively correlated with the WOMAC score at 6 months (p = 0.024). CONCLUSION: The 3D gait analysis of RATKA patients is more sensitive than WOMAC score in evaluating the clinical efficacy. Trend of changes in gait parameters shows that the knee joint support, flexion and extension function, range of motion, external rotation and varus deformity moment of the patient were significantly improved at 3 months after surgery, and continued to 6 months after surgery. Compared with the contralateral knee, the gait parameters of the operated limb still has significant gaps in functionality, such as the external rotation and flexion and extension. The single support time, cadence, knee extension, and knee external rotation of the operated limb have a greater correlation with the postoperative WOMAC score. Postoperative rehabilitation exercises should be emphasized, which is of great value for improving the early efficacy of RATKA.

Efficacies of FAEV and EMA/CO regimens as primary treatment for gestational trophoblastic neoplasia.

BACKGROUND: Guidelines recommend etoposide, methotrexate, actinomycin D (EMA)/cyclophosphamide, vincristine (CO) as first-line treatment for high-risk gestational trophoblastic neoplasia (GTN). However, the floxuridine, actinomycin D, etoposide and vincristine (FAEV) regimen is commonly used to treat these patients in China. We conducted a randomised controlled trial to compare the efficacies and toxicities of FAEV and EMA/CO. METHODS: Ninety-four patients with GTN were enrolled between May 2015 and April 2019 and randomly assigned to the FAEV or EMA/CO regimen. The rates of complete remission and relapse and the toxicities were compared in August 2021. RESULTS: Five patients were excluded from the analysis. There were 46 patients in the FAEV group and 43 patients in the EMA/CO group. The complete remission rates following primary treatment were 89.1% and 79.1% (P = 0.193), respectively. The relapse rates were 8.7% and 9.3% (P = 0.604). The apparent incidences of grade 4 myelosuppression were 60.9% and 32.6% (P = 0.008), respectively; however, they became both 32.6% (P = 0.996) after granulocyte colony-stimulating factor support. Other adverse reactions were similar in the two groups. No patient died of disease. CONCLUSION: FAEV has comparable efficacy and toxicity to EMA/CO as the primary treatment for high-risk GTN, and may thus be another first-line choice of chemotherapy. CLINICAL TRIAL REGISTRATION: chictr.org.cn: ChiCTR1800017423.

Oncological and reproductive outcomes after fertility-sparing surgery in patients with seromucinous borderline ovarian tumor: Results of a large retrospective study.

OBJECTIVE: To evaluate the oncological and reproductive outcomes in patients with seromucinous borderline ovarian tumors (SMBOT) treated with fertility-sparing surgery (FSS). METHODS: We retrospectively reviewed the medical records of patients with SMBOT who underwent surgery between 2000 and 2019. A centralized histological review was performed and recurrence rates were compared between different surgical procedures. RESULTS: A total of 105 patients fulfilled the inclusion criteria, of whom 65 underwent FSS and 40 were treated with radical surgery (RS). Fourteen patients had recurrent disease after a median follow-up time of 59.6 months (range: 22.1-256.8 months). All but one relapsed with SMBOT. There was no significant difference in disease-free survival (DFS) between the two groups (P = 0.141). Multivariate analysis showed that only bilateral involvement was associated with increased recurrence (P = 0.008). In the subgroup of patients treated with conservative surgery, there was no significant difference in DFS with regard to surgical procedures (ovarian cystectomy vs salpingo-oophorectomy, P = 0.487). Of the 12 patients in the FSS group who developed recurrence, 11 underwent a second round of FSS and all remained alive with no evidence of disease at the end of follow-up. Of 20 patients desiring pregnancy, 16 patients were successful and resulted in 17 term deliveries. CONCLUSIONS: FSS is feasible for young patients who wish to preserve their fertility. Patients initially treated with ovarian cystectomy may be managed by close surveillance if post-operative imaging are negative. Repeat FSS remains a valuable alternative for young patients with recurrent SMBOT after thorough communication.

MRI-derived radiomics analysis improves the noninvasive pretreatment identification of multimodality therapy candidates with early-stage cervical cancer.

OBJECTIVES: To develop and validate a clinical-radiomics model that incorporates radiomics signatures and pretreatment clinicopathological parameters to identify multimodality therapy candidates among patients with early-stage cervical cancer. METHODS: Between January 2017 and February 2021, 235 patients with IB1-IIA1 cervical cancer who underwent radical hysterectomy were enrolled and divided into training (n = 194, training:validation = 8:2) and testing (n = 41) sets according to surgical time. The radiomics features of each patient were extracted from preoperative sagittal T2-weighted images. Significance testing, Pearson correlation analysis, and Least Absolute Shrinkage and Selection Operator were used to select radiomic features associated with multimodality therapy administration. A clinical-radiomics model incorporating radiomics signature, age, 2018 Federation International of Gynecology and Obstetrics (FIGO) stage, menopausal status, and preoperative biopsy histological type was developed to identify multimodality therapy candidates. A clinical model and a clinical-conventional radiological model were also constructed. A nomogram and decision curve analysis were developed to facilitate clinical application. RESULTS: The clinical-radiomics model showed good predictive performance, with an area under the curve, sensitivity, and specificity in the testing set of 0.885 (95% confidence interval: 0.781-0.989), 78.9%, and 81.8%, respectively. The AUC, sensitivity, and specificity of the clinical model and clinical-conventional radiological model were 0.751 (0.603-0.900), 63.2%, and 63.6%, 0.801 (0.661-0.942), 73.7%, and 68.2%, respectively. A decision curve analysis demonstrated that when the threshold probability was > 20%, the clinical-radiomics model or nomogram may be more advantageous than the treat all or treat-none strategy. CONCLUSIONS: The clinical-radiomics model and nomogram can potentially identify multimodality therapy candidates in patients with early-stage cervical cancer. KEY POINTS: • Pretreatment identification of multimodality therapy candidates among patients with early-stage cervical cancer helped to select the optimal primary treatment and reduce severe complication risk and costs. • The clinical-radiomics model achieved a better prediction performance compared with the clinical model and the clinical-conventional radiological model. • An easy-to-use nomogram exhibited good performance for individual preoperative prediction.

Serpentine-Inspired Strain Sensor with Predictable Cracks for Remote Bio-Mechanical Signal Monitoring.

Flexible strain sensors have attracted intense interest due to their application as intelligent wearable electronic devices. However, it is still a huge challenge to achieve a flexible sensor with simultaneous high sensitivity, excellent durability, and a wide sensing region. In this work, a crack-based strain sensor with a paired-serpentine conductive network is fabricated onto flexible film by screen printing. The innovative conductive network exhibits a controlled crack morphology during stretching, which endows the prepared sensor with outstanding sensing characteristics, including high sensitivity (gauge factor up to 2391.5), wide detection (rang up to 132%), low strain detection limit, a fast response time (about 40 ms), as well as excellent durability (more than 2000 stretching/releasing cycles). Benefiting from these excellent performances, full-range human body motions including subtle physiological signals and large motions are accurately detected by the prepared sensor. Furthermore, wearable electronic equipment integrated with a wireless transmitter and the prepared strain sensor shows great potential for remote motion monitoring and intelligent mobile diagnosis for humans. This work provides an effective strategy for the fabrication of novel strain sensors with highly comprehensive performance.

Camrelizumab plus apatinib in patients with high-risk chemorefractory or relapsed gestational trophoblastic neoplasia (CAP 01): a single-arm, open-label, phase 2 trial.

BACKGROUND: Treatment options for patients with high-risk chemorefractory or relapsed gestational trophoblastic neoplasia are scarce. The synergistic antitumour effect of immunotherapy and antiangiogenic drugs has been shown in many solid tumours. This phase 2 trial evaluated the activity and safety of camrelizumab (PD-1 inhibitor) plus apatinib (VEGF receptor inhibitor) in patients with high-risk chemorefractory or relapsed gestational trophoblastic neoplasia. METHODS: This was a single-arm, open-label, phase 2 trial, done at a single tertiary health-care centre in Beijing, China. Women (18-70 years) with high-risk (International Federation of Gynecology and Obstetrics score ≥7) chemorefractory or relapsed gestational trophoblastic neoplasia who had received at least two lines of previously unsuccessful multidrug chemotherapy regimens and had an Eastern Cooperative Oncology Group performance status of 0-2 were eligible for inclusion. Patients received 4-week cycles of intravenous camrelizumab 200 mg every 2 weeks plus oral apatinib 250 mg once per day until disease progression or unacceptable toxicity. The primary endpoint was objective response rate assessed according to serum human chorionic gonadotrophin concentration. Activity and safety were analysed in all patients who received at least one dose of study drug. The study is ongoing, but recruitment is complete. The study is registered with ClinicalTrials.gov, NCT04047017. FINDINGS: Between Aug 7, 2019, and March 18, 2020, 20 patients enrolled; 19 (95%) were diagnosed with choriocarcinoma and one (5%) had placental site trophoblastic tumour. The median follow-up duration was 18·5 months (IQR 14·6-20·9). The objective response rate was 55% (95% CI 32-77); ten (50%; 95% CI 27-73) patients had complete response. The most common grade 3 treatment-related adverse events were hypertension (five [25%] patients), rash (four [20%] patients), neutropenia (two [10%]), leukocytopenia (two [10%]), and aspartate aminotransferase increase (two [10%]). One patient had a treatment-related serious adverse event (aspartate aminotransferase 19-times higher than the upper limit of normal). No grade 4 or 5 treatment-related adverse events were reported. INTERPRETATION: Camrelizumab plus apatinib showed promising antitumour activity and acceptable toxicity and could be a salvage therapy option for the treatment of high-risk chemorefractory or relapsed gestational trophoblastic neoplasia. Immune checkpoint inhibitors combined with chemotherapy for heavily-treated patients and upfront use of camrelizumab plus apatinib for patients with high-risk gestational trophoblastic neoplasia are under investigation in phase 2 trials. FUNDING: National Natural Science Foundation of China, Jiangsu Hengrui Pharmaceuticals.

Results with Floxuridine, Actinomycin D, Etoposide, and Vincristine in Gestational Trophoblastic Neoplasias with International Federation of Gynecology and Obstetrics Scores ≥5.

BACKGROUND: 5-fluorouracil-based multiagent chemotherapy has been used as the primary treatment for high-risk gestational trophoblastic neoplasia (GTN) in China for a few decades. This study aims to assess the efficacy and toxicity of floxuridine, actinomycin D, etoposide, and vincristine (FAEV) as a primary treatment for patients with GTN who had International Federation of Gynecology and Obstetrics (FIGO) scores ≥5. MATERIALS AND METHODS: A total of 207 patients with GTN who had FIGO scores ≥5 were treated with FAEV as first-line chemotherapy at Peking Union Medical College Hospital between January 2002 and December 2017. Complete remission (CR), resistance, survival, toxicity, and reproductive outcomes were analyzed. RESULTS: Of the 207 patients treated with FAEV, 9 (4.3%) required a change of chemotherapy owing to toxicity and 1 (0.5%) died of cerebral hernia 5 weeks after commencing treatment. The remaining 197 patients were assessable to determine the response to FAEV; among them, 168 (85.3%) achieved CR with FAEV and 29 (14.7%) developed resistance to FAEV. The 5-year overall survival rate of the entire cohort was 97.4%. Grade 3-4 neutropenia, thrombocytopenia, and anemia occurred in 28.4%, 6.8%, and 6.2% of cycles, respectively. No acute toxicity-related deaths occurred. Five patients developed acute myeloid leukemia 10-50 months after exposure to chemotherapy; another patient developed duodenal cancer 2 years after completing therapy. Sixty-one patients who preserved fertility wanted to become pregnant; 56 of them conceived. CONCLUSION: The FAEV regimen is an effective primary treatment for patients with GTN who have FIGO scores ≥5 and has predictable and manageable toxicity. IMPLICATIONS FOR PRACTICE: The most commonly used multiagent chemotherapy for high-risk gestational trophoblastic neoplasia (GTN) is etoposide, methotrexate and actinomycin D/cyclophosphamide and vincristine (EMA/CO) worldwide. However, 5-fluorouracil-based multiagent chemotherapy has been used as a primary treatment for high-risk GTN in China for a few decades. This study evaluated the efficacy and toxicity of floxuridine, actinomycin D, etoposide, and vincristine (FAEV) as a primary treatment for patients with GTN who have International Federation of Gynecology and Obstetrics (FIGO) scores ≥5. The study's data demonstrated that FAEV as a primary treatment achieved favorable outcomes for patients with FIGO scores ≥5. Toxicities that result from the FAEV regimen are predictable and manageable. The FAEV regimen may provide another option for the treatment of GTN.

QTL mapping for foxtail millet plant height in multi-environment using an ultra-high density bin map.

KEY MESSAGE: Using a fixed RIL population derived from a widely used foxtail millet backbone breeding line and an elite cultivar, we constructed a high-density bin map and identified six novel multi-environment effect QTLs and seven candidate genes for dwarf phenotype. Plant height is an important trait that determines tradeoffs between competition and resource allocation, which is crucial for yield potential. To improve the C4 model plant foxtail millet (Setaria italica) productivity, it is necessary to isolate plant height-related genes that contribute to ideal plant architecture in breeding. In the present study, we generated a foxtail millet population of 333 recombinant inbred lines (RILs) derived from a cross between a backbone line Ai 88 and an elite cultivar Liaogu 1. We evaluated plant height in 13 environmental conditions across 4 years, the mean plant height of the RIL population ranged from 89.5 to 149.9 cm. Using deep re-sequencing data, we constructed a high-density bin map with 3744 marker bins. Quantitative trait locus (QTL) mapping identified 26 QTLs significantly associated with plant height. Of these, 13 QTLs were repeatedly detected under multiple environments, including six novel QTLs that have not been reported before. Seita.1G242300, a gene encodes gibberellin 2-oxidase-8, which was detected in nine environments in a 1.54-Mb interval of qPH1.3, was considered as an important candidate gene. Moreover, other six genes involved in GA biosynthesis or signaling pathways, and fifteen genes encode F-box domain proteins which might function as E3 ligases, were also considered as candidate genes in different QTLs. These QTLs and candidate genes identified in this study will help to elucidate the genetic basis of foxtail millet plant height, and the linked markers will be useful for marker-assistant selection of varieties with ideal plant architecture and high yield potential.