[The efficacy and safety of anlotinib combined with niraparib in treating patients with platinum-resistant recurrent ovarian cancer].

Objectives: To investigate the efficacy and safety of anlotinib combined with niraparib in treating patients with platinum-resistant ovarian cancer. Methods: Thirty-five patients with pathological confirmed platinum-resistant ovarian cancer who experienced progression after receiving at least two lines of standard treatment were eligible. All of them were treated with anlotinib combined with niraparib between September 2019 and October 2021. The primary endpoint was progression-free survival (PFS). The second endpoints included overall survival, objective response rate (ORR), disease control rate (DCR) and safety. Survival analysis was performed using the Kaplan-Meier method and Log-rank test, and influence factor analysis was performed using Cox proportional risk regression models. Results: The best overall response showed that partial response was observed in 14 patients, stable disease was noted within 13 patients, and progressive disease was found in 8 patients. Therefore, the ORR and DCR of these 35 patients were 40.0% (95% CI:22.9%-57.1%) and 77.1% (95% CI:62.9%-91.4%), respectively. The median follow-up duration was 18.9 months (6.9-32.2). The median PFS was 6.5 months (95% CI:5.35-7.66). Multivariate Cox regression analysis for PFS indicated that age, Eastern Cooperative Oncology Group performance status (ECOG PS) score, International Federation of Gynecology and Obstetrics (FIGO) stage, and BRCA mutation status were independent factors influencing PFS (P＜0.05). Additionally, the PFS in patients with BRCA mutation who have never received PARP inhibitor treatment was significantly longer than that in patients without BRCA mutation who have been exposed to prior PARPi treatment (15.0 vs 6.0 month, P=0.029). The most common treatment-related adverse reactions were fatigue (85.7%), hematologic toxic (85.7%) and hypertension (74.3%). There were no treatment-related deaths. Conclusion: Anlotinib combined with niraparib shows a promising efficacy and tolerable safety in platinum-resistant ROC patients.

[Conjunctival fungal infection mimicking a recurrent conjunctival mass: a case report].

A 40-year-old man presented with recurrent ocular surface masses in his left eye persisting for over a year. Despite undergoing resection of the conjunctival mass and receiving anti-inflammatory treatment at another hospital, the mass reappeared within a week post-surgery. Over the past 6 months, the mass gradually increased in size, accompanied by a decline in vision. Following conjunctival mass excision combined with amniotic membrane transplantation at Beijing Tongren Hospital, Capital Medical University, histopathological examination revealed a fungal infection of the conjunctiva, resulting in a diagnosis of fungal conjunctivitis and conjunctival granuloma in the left eye. The patient received systemic antifungal medications and local therapy, resulting in a stable condition with no recurrence of the mass.

[The value of minimal residual disease and IKZF1 deletion for predicting prognosis in adult patients with B-cell acute lymphoblastic leukemia].

Objective: To reassess the prognostic value of minimal residual disease (MRD) and IKZF1 gene deletions in adults with B-cell acute lymphoblastic leukemia (B-ALL) who received pediatric-specific chemotherapy regimens during the Nanfang Hospital PDT-ALL-2016 trial. Methods: We retrospectively analyzed the prognosis of 149 adult patients with B-ALL who were admitted to Nanfang Hospital from January 2016 to September 2020. Prognostic factors were identified using Cox regression models. Results: The complete remission rate was 93.2% in 149 patients, with a 5-year overall survival (OS) rate of (54.3±5.0) % and a cumulative incidence of relapse (CIR) of (47.5±5.2) %. The Cox regression analysis revealed that MRD positivity at day 45 (MRD(3)) after induction therapy was independently associated with relapse risk (HR=2.535, 95%CI 1.122-5.728, P=0.025). Deletion of IKZF1 gene was independently associated with mortality risk (HR=1.869, 95%CI 1.034-3.379, P=0.039). Based on MRD(3) and IKZF1 gene status, we categorized adult patients with B-ALL into the low-risk (MRD(3)-negative and IKZF1 gene deletion-negative) and high-risk (MRD(3)-positive and/or IKZF1 gene wild type) groups. The 5-year OS and CIR rates were (45.5±6.0) % vs (69.4±8.6) % (P<0.001) and (61.6±8.3) % vs (25.5±6.5) % (P<0.001), respectively, in the high-risk and low-risk groups, respectively. The multivariate analysis showed that the high-risk group was an independent risk factor for OS (HR=3.937, 95%CI 1.975-7.850, P<0.001) and CIR (HR=4.037, 95%CI 2.095-7.778, P<0.001) . Conclusion: The combined use of MRD and IKZF1 gene in prognostic stratification can improve clinical outcome prediction in adult patients with B-ALL, helping to guide their treatment.

[Effect of information-knowledge-attitude-practice theory-based health education on clonorchiasis control among community residents and primary school students in Zhongshan City].

OBJECTIVE: To evaluate the effect of information-knowledge-attitude-practice (IKAP) theory-based health education interventions on clonorchiasis control among community residents and primary school students in Torch High-tech Development Zone of Zhongshan City, so as to provide insights into formulation of clonorchiasis control strategies among different types of populations. METHODS: Residents were randomly sampled from two communities and students from two primary schools using a random cluster sampling method in Torch High-tech Development Zone, Zhongshan City from 2019 to 2021, and health education pertaining to clonorchiasis control was performed based on the IKAP theory. The changes in the awareness of basic clonorchiasis control knowledge and belief, self-reported risk of Clonorchis sinensis infections and dietary behaviors were compared among community residents and primary school students before and after health education interventions. RESULTS: The participants included 146 male and 151 female community residents and 158 male and 153 female primary school students, with no significant difference detected in gender distribution (χ2 = 0.16, P > 0.05). The mean awareness of basic clonorchiasis control knowledge increased by 44.71% and 43.28% among primary school students and community residents 6 months following health education, and there were significant differences in the awareness of each item of basic clonorchiasis control knowledge before and after health education (χ2 = 41.53 to 284.44, all P values < 0.05). The proportions of primary school students and community residents thinking very high and high risks of C. sinensis infections increased from 9.35% and 6.71% before health education to 22.15% and 37.75% after health education, but only the difference of the attitudes in community residents achieve statistical significance (χ2 = 92.18, P < 0.05). The frequency of separation of raw and cooked foods with chopping board and knife significantly increased among community residents and primary school students following health education (χ2 = 16.04 to 62.65, all P values < 0.05). The frequency of eating raw freshwater fish (χ2 = 32.85, P < 0.05), fish congee (χ2 = 7.02, P < 0.05) and fish fillet hot pot (χ2 = 4.88, P < 0.05) significantly reduced among primary school students following health education, while only the frequency and proportions of eating raw freshwater fish have significantly reduced in community residents (χ2 = 11.77, P < 0.05). CONCLUSIONS: Health education interventions based on the IKAP theory are effective to increase the awareness of clonorchiasis control knowledge and improve dietary behaviors associated with C. sinensis infections among community residents and primary school students in Zhongshan City.

[Predictive value of aMAP risk score for early recurrence of small hepatocellular carcinoma after microwave ablation].

Objective: To explore the value of the aMAP risk score (age, male, albumin-bilirubin, and platelets) to predict early recurrence within one year after microwave ablation in patients with small hepatocellular carcinoma. Methods: This was a retrospective study that enrolled 142 patients diagnosed with hepatocellular carcinoma who were treated with microwave ablation in the Department of Hepatology Unit of Nanfang Hospital, Southern Medical University from July 2016 to July 2021. The cohort enrolled 121 male and 21 female patients, including 110 patients that were <60 years old. All the patients were followed-up after microwave ablation to evaluate residual tumor and recurrence of tumor by computed tomography or magnetic resonance imaging. The observation indices mainly included general data and imaging data of patients. Using the X-tile tools, patients were divided into two groups: a high aMAP score group and a low aMAP score group. Multivariate Cox regression analysis was conducted for comparison of independent risk factors. Results: Multivariate Cox regression showed that high aMAP score, maximum tumor diameter >20 mm, and high AFP were the independent risk factors of early recurrence (all P<0.05). Kaplan-Meier survival curves showed that the median recurrence-free survival was 25.5 months in the low aMAP score group and 6.1 months in the high aMAP score group (P=0.001). Conclusions: The aMAP score could predict the early recurrence within 1 year of small hepatocellular carcinoma after microwave ablation. Patients with high aMAP score should undergo rigorous postoperative follow-up evaluations..

[Efficacy and safety of programmed death-1 inhibitor in the treatment of relapsed/refractory classical Hodgkin's lymphoma].

Objective: This retrospective, single-center study aimed to evaluate the efficacy and safety of programmed death-1 (PD-1) inhibitors, either as monotherapy or in combination with chemotherapy, in the management of relapse/refractory classical Hodgkin's lymphoma (R/R cHL) . Methods: A total of 35 patients with R/R cHL who received treatment at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College from September 2016 to December 2020 were enrolled in this study. Among them, 17 patients received PD-1 inhibitor monotherapy (PD-1 inhibitor group), while 18 patients received a combination of PD-1 inhibitor and chemotherapy (PD-1 inhibitor + chemotherapy group). Clinical data and follow-up information were retrospectively analyzed, and survival analysis was conducted using the Kaplan-Meier method and Cox proportional hazards model. Results: The median age of the 35 patients with R/R cHL was 29 years (range: 11-61 years), with 54.3% being male. According to the Ann Arbor staging system, 62.9% of patients presented with advanced (stage Ⅲ/Ⅳ) disease, and 48.6% had extranodal involvement. Before PD-1 inhibitor therapy, the median number of prior lines of therapy was 2 (range: 1-3). Objective responses were observed in 28 patients, including 22 complete response (CR) cases, resulting in an overall response rate (ORR) of 80.0% and a CR rate of 62.9%. Specifically, the ORR and CR rates were 64.7% and 58.8%, respectively, in the PD-1 inhibitor group and 94.4% and 66.7%, respectively, in the PD-1 inhibitor + chemotherapy group. Among the 18 patients who underwent sequential autologous hematopoietic stem cell transplantation (auto-HSCT) [13 CR and five partial response (PR) cases], eight patients received PD-1 inhibitor therapy after auto-HSCT as consolidation therapy. All patients maintained a CR status after transplantation, and they exhibited significantly improved progression-free survival (PFS) rates compared with those who did not undergo sequential auto-HSCT (4-year PFS rates: 100% vs 53.5% ; P=0.041). The incidence of immune-related adverse events was 29%, with only one patient experiencing grade≥3 adverse reactions, which indicated a favorable safety profile for the treatment approach. Conclusions: PD-1 inhibitor monotherapy demonstrates notable efficacy and sustained response in patients with R/R cHL. PD-1 inhibitors combined with chemotherapy significantly improve response rates. Additionally, for salvage therapy-sensitive patients, consolidation treatment with PD-1 inhibitors after auto-HSCT exhibits the potential for prolonging PFS.

[Clinical analysis of corneal interface infection].

Objective: To analyze the clinical features of corneal interface infection. Methods: A retrospective case series study was conducted to explore the clinical features of interstitial corneal infection. The data of eight patients (eight eyes) who were diagnosed with interstitial corneal infection after undergoing corneal transplant or corneal refractive surgery and visited Beijing Tongren Eye Center from January to December 2018 were collected, including two male and six female patients aged between 18 and 55 years (median age, 27 years). The patients' general information, surgical type, onset time, and clinical manifestations were recorded. The lesions were examined by in vivo corneal laser confocal microscopy (IVCM), and microbial cultures and drug sensitivity tests were performed. Results: Among the 8 patients, 4 had undergone small-incision lenticule extraction (SMILE), 2 had undergone lamellar keratoplasty, and 2 had undergone endothelial keratoplasty. The onset of infection occurred between 2 and 30 days after surgery, with a mean of 9.8 days. Among the 3 patients who had undergone SMILE, the treatment outcome was corneal haze or opacity, while the remaining 5 cases required corneal transplantation for interstitial infections. The pathogens of the 4 cases of interstitial infection after corneal transplantation were all Candida species. Under the IVCM, patients with corneal interstitial bacterial infections showed a large amount of necrotic tissue with no normal tissue structure in the corneal stroma, with infiltration of inflammatory cells and local aggregation of inflammatory cells, but no typical pathogen was observed. Patients with fungal infections showed fungal hyphae under the corneal cap (filamentous fungal infection) or dense, punctate, high-reflection structures in the corneal interstitial space (yeast-like fungal infection). Conclusions: Corneal interlayer infection is difficult to diagnose early and has a poor prognosis. IVCM can assist in early diagnosis. The pathogen spectrum of corneal interlayer infection may differ from that of corneal infection caused by trauma.

Avelumab or talazoparib in combination with binimetinib in metastatic pancreatic ductal adenocarcinoma: dose-finding results from phase Ib of the JAVELIN PARP MEKi trial.

BACKGROUND: Combinations of avelumab [anti-programmed death-ligand 1 (anti-PD-L1)] or talazoparib [poly(adenosine diphosphate ribose) polymerase (PARP) inhibitor] with binimetinib (MEK inhibitor) were expected to result in additive or synergistic antitumor activity relative to each drug administered alone. Here, we report phase Ib results from JAVELIN PARP MEKi, which investigated avelumab or talazoparib combined with binimetinib in metastatic pancreatic ductal adenocarcinoma (mPDAC). PATIENTS AND METHODS: Patients with mPDAC that had progressed with prior treatment received avelumab 800 mg every 2 weeks plus binimetinib 45 mg or 30 mg two times daily (continuous), or talazoparib 0.75 mg daily plus binimetinib 45 mg or 30 mg two times daily (7 days on/7 days off). The primary endpoint was dose-limiting toxicity (DLT). RESULTS: A total of 22 patients received avelumab plus binimetinib 45 mg (n = 12) or 30 mg (n = 10). Among DLT-evaluable patients, DLT occurred in five of 11 patients (45.5%) at the 45-mg dose, necessitating de-escalation to 30 mg; DLT occurred in three of 10 patients (30.0%) at the 30-mg dose. Among patients treated at the 45-mg dose, one (8.3%) had a best overall response of partial response. Thirteen patients received talazoparib plus binimetinib 45 mg (n = 6) or 30 mg (n = 7). Among DLT-evaluable patients, DLT occurred in two of five patients (40.0%) at the 45-mg dose, necessitating de-escalation to 30 mg; DLT occurred in two of six patients (33.3%) at the 30-mg dose. No objective responses were observed. CONCLUSIONS: Combinations of avelumab or talazoparib plus binimetinib resulted in higher-than-expected DLT rates. However, most DLTs were single occurrences, and the overall safety profiles were generally consistent with those reported for the single agents. CLINICAL TRIAL REGISTRATION: ClinicalTrials.govNCT03637491; https://clinicaltrials.gov/ct2/show/NCT03637491.

[Comparison of maternal-fetal outcomes between laparoscopic cervicoisthmic cerclage and McDonald cerclage in women with cervical insufficiency].

Objective: To compare the maternal and fetal outcomes of women with cervical insufficiency (CI) undergoing McDonald cerclage (MC) and laparoscopic cervicoisthmic cerclage (LCC), so as to provide evidence for the selection of cerclage methods. Methods: A retrospective trial was carried out in the First Affiliated Hospital of Sun Yat-sen University from January 2010 to December 2020. A total of 221 women who underwent the prophylactic cerclage were divided into MC group (n=54), LCC with MC history group (n=28) and LCC without MC history group (n=129) by the mode of operation and whether the pregnant women who underwent LCC had MC history. General clinical data, pregnancy complications and pregnancy outcomes were compared between the three groups. Results: (1) General clinical data: the proportion of women accepted cervical cerclage during pregnancy in MC group, LCC with MC history group and LCC without MC history group were 100.0% (54/54), 7.1% (2/28) and 27.1% (35/129), respectively (P<0.001). The indications of the three groups showed statistical significance (P=0.003), and the main indication was the history of abortion in the second and third trimester [75.9% (41/54) vs 89.3% (25/28) vs 84.5% (109/129)]. (2) Pregnancy complications: the incidence of abnormal fetal position [7.8% (4/51) vs 17.4% (4/23) vs 19.8% (24/121)], placenta accrete [5.9% (3/51) vs 13.0% (3/23) vs 11.6% (14/121)], uterine rupture [0 vs 4.3% (1/23) vs 5.8% (7/121)] in the MC group were all lower than those in LCC with MC history and LCC without MC history groups. However, there were no statistical significances (all P>0.05). Intrauterine inflammation or chorioamnionitis [15.7% (8/51) vs 0 vs 0.8% (1/121)] and premature rupture of membrane [23.5% (12/51) vs 4.3% (1/23) vs 0] were both significantly higher in MC group than those in LCC with MC history and LCC without MC history groups (all P<0.001). (3) Pregnancy outcomes: the cesarean section rate was significantly lower in MC group (41.2%, 21/51) than that in LCC with MC history group (100.0%, 23/23) and LCC without MC history group (100.0%, 121/121; P<0.001). MC group was associated with lower expenditure than LCC with MC history and LCC without MC history groups (12 169 vs 26 438 vs 27 783 yuan, P<0.001). The success rates of live birth cerclage did not differ significantly in MC (94.4%, 51/54), LCC with MC history (82.1%, 23/28) and LCC without MC history (93.8%, 121/129) groups (χ2=5.649, P=0.059). There was no significant difference in neonatal intensive care unit occupancy, neonatal birth weight and neonatal asphyxia between the three groups (all P>0.05). Conclusions: Both LCC and MC are the treatment choice for women with CI, which may get similar liver birth. However, MC has the advantages of low cesarean section rate, economical and easy operation. Therefore, MC is recommended as the first choice for CI patients, and LCC is for women with failed MC.

Analysis of SOD1 variants in Chinese patients with familial amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, and genetic contributors exert a significant role in the complicated pathogenesis. Identification of the genetic causes in ALS families could be valuable for early diagnosis and management. The development of potential drugs for patients with genetic defects will shed new light on ALS therapy. AIM: To identify causative variants in three Chinese families with familial ALS (FALS), reveal the pathogenic mechanism and look for the targeted drug for ALS. DESIGN AND METHODS: Whole-exome sequencing and bioinformatics were used to perform genetic analysis of the ALS families. Functional analysis was performed to study the variants' function and search for potential drug targets. RESULTS: Three heterozygous missense variants of the superoxide dismutase 1 gene (SOD1) were identified in families with FALS. The clinical manifestations of these patients include spinal onset, predominant lower motor neurons presentation and absence of cognitive involvement. Functional analysis showed that all three SOD1 variants led to increased reactive oxygen species (ROS) levels, reduced cell viability and formation of cytoplasmic aggregates. Remarkably, the decreased cell viability induced by variants was rescued after treatment with the ROS inhibitor N-acetylcysteine. CONCLUSIONS: This study identified three SOD1 variants in three families with FALS. The variant SOD1 toxicity was associated with oxidative damage and aggregation, and N-acetylcysteine could rescue the decreased cell viability induced by these variants. Our findings support a pathogenic role for ROS in SOD1 deficiencies and provide a potential drug N-acetylcysteine for ALS therapy, especially in SOD1 patients with limb onset.

[Research progress in radiomics based on CT and MRI images for prediction of microvascular invasion in hepatocellular carcinoma].

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Microvascular invasion (MVI) is considered the major risk factor for postoperative recurrence and metastasis in HCC. The diagnosis of MVI relies on the postoperative pathological assessment of the tumor tissues. Seeking non-invasive methods and biomarkers for evaluation of MVI before surgery has important clinical implications for guiding surgical treatment and improving patients' survival. Recent studies have reported the applications of radiomics technique in prediction of MVI in HCC and showed promising results. Herein we summarized the research progress in CT- or MRI-based radiomics models for prediction of MVI in HCC to provide helpful thinking for further research in this field.

[Application of liquid biopsy in early screening and recurrence prediction of hepatocellular carcinoma].

The incidence and mortality of HCC in China account for approximately 50% of all cases worldwide. Low early diagnosis rate and high postoperative recurrence rate are two major causes for poor 5-year survival rate of HCC patients in China. At present, multiple problems such as low performance and compliance of screening technology and lack of effective markers for predicting postoperative recurrence, remain to be resolved. Due to the simplicity and accuracy, new molecular markers, such as liquid biopsy, are expected to serve as supplementary tools to traditional screening and early warning approaches, thereby realizing early detection and accurate treatment of HCC. In this article, research progress upon the clinical application of liquid biopsy in early screening and prediction of postoperative recurrence of HCC was reviewed, and prospects the future research.

[Efficacy and prognosis of newly diagnosed multiple myeloma patients treated with bortezomib, lenalidomide and dexamethasone].

Objective: To evaluate the efficacy of VRD (bortezomib+lenalidomide+dexamethasone) in newly diagnosed multiple myeloma (NDMM) patients as well as the effect of the regimen on the long-term prognosis. Methods: The clinical characteristics, survival rates, response rates and minimal residual disease (MRD) of patients with NDMM at Institute of Hematology & Blood Diseases Hospital from January 1, 2013 to January 1, 2020 were retrospectively analyzed. Subgroup analysis was also performed among groups according to the cytogenetics and autologous stem cell transplantation (ASCT) of patients. Results: A total of 87 patients were retrospectively analyzed. The age[M(Q1,Q3)] of all patients was 56 (51, 61) years and males and females accounted for 58.6% (51/87) and 41.4% (36/87), respectively. The overall response rate (ORR) was 95.9% (71/74) after 2 courses of induction therapy, with 13.5% (10/74) achieving the deep response [complete response (CR) or better] and 51.3% (38/74) of patients achieving a very good partial response (VGPR) or better. After 4 courses of induction therapy, the ORR achieved 95.2% (60/63), and the proportions of the deep response and VGPR or better grew up to 46.0% (29/63) and 77.7% (49/63). According to the treatment, the patients (≤65 years old) were divided into transplantation group and non-transplantation group. After the induction therapy, 88.8% (32/36) of patients in the transplantation group achieved VGPR or better, and 55.5% (20/36) reached the deep response. After the transplantation, the proportion increased to 97.1% (34/35) and 77.2% (27/35), respectively(88.8% vs 97.1%,P=0.174;55.5% vs 77.2%,P=0.055), with the rate of undetectable MRD increasing from 44.4% (16/36) to 77.8% (28/36) (P=0.004). In the non-transplantation group, 74.2% (23/31) of patients achieved VGPR or better after 4 courses of induction therapy, 35.5% (11/31) of the patients achieved deep response and the rate of undetectable MRD was 37.0% (10/27). Compared with the non-transplantation group, transplantation was associated with a higher rate of complete response (89.5% vs 53.1%, P<0.001) and a lower rate of MRD detection(78.4% vs 55.2%, P=0.045). The median follow-up time of all patients was 26.3 months (20.8, 33.8). The median progression-free survival and overall survival were not reached. The three-year PFS and OS rates were 78.4% and 87.2%, respectively. None of the standard-risk group, the high-risk group, the transplantation group and non-transplantation group achieved the median PFS and OS. Conclusions: VRD regimen has a promising efficacy and results in a substantial survival benefit. ASCT after VRD induction therapy is associated with higher rate of deep response, higher rate of undetectable MRD and longer survival.

[Clinicopathological features and prognostic analysis of papillary renal cell carcinoma].

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.

[Clinical characteristics and prognosis of 46 patients with macrofocal multiple myeloma].

The clinical characteristics, laboratory results, response to treatment, and prognosis of 46 macrofocal multiple myeloma(MFMM) patients at our center from January 2013 to December 2019 were analyzed retrospectively. The other 92 patients were selected as matched-controls based on diagnostic period and treatment. Among the 1 137 MM patients, 46 patients met the definition criteria of MFMM (4.0%), with median age 56 years, which was not statistically different from whole MM population (P=0.066). According to the international staging system (ISS) and Revised ISS, the proportion of patients with advanced stage in MFMM group was less common than that of controls (P<0.05). More plasmacytomas in MFMM patients were presented (43.5% vs. 18.5%, P<0.05). Regarding cytogenetic abnormalities, there were minor patients manifesting high-risk features in MFMM group (15.8% vs. 32.2%, P=0.058). Translocation(11;14) could be detected in 32.4% MFMM patients and 9.4% typical myeloma patients (P<0.05). The treatment regimens were comparable. As to the best response of treatment, the complete response (CR) rate in MFMM group was significantly higher than that of controls (78.3% vs. 60.9%, P<0.05). The median follow-up time was 37.9 months. The median progression-free survival in MFMM and control groups were 77.5 vs. 39.8 months, respectively (P<0.05). The overall survival (OS) of MFMM patients was significantly longer (not reached vs. 68.2 months, P<0.05).

[Characteristics of amino acid metabolism in myeloid-derived suppressor cells in septic mice].

OBJECTIVE: To explore the amino acid metabolomics characteristics of myeloid-derived suppressor cells (MDSCs) in mice with sepsis induced by the cecal ligation and puncture (CLP). METHODS: The sepsis mouse model was prepared by CLP, and the mice were randomly divided into a sham operation group (sham group, n = 10) and a CLP model group (n = 10). On the 7th day after the operation, 5 mice were randomly selected from the surviving mice in each group, and the bone marrow MDSCs of the mice were isolated. Bone marrow MDSCs were separated to measure the oxygen consumption rate (OCR) by using Agilent Seahorse XF technology and to detect the contents of intracellular amino acids and oligopeptides through ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) technology. Different metabolites and potential biomarkers were analyzed by univariate statistical analysis and multivariate statistical analysis. The major metabolic pathways were enriched using the small molecular pathway database (SMPDB). RESULTS: The proportion of MDSCs in the bone marrow of CLP group mice (75.53% ± 6.02%) was significantly greater than that of the sham group (43.15%± 7.42%, t = 7.582, P < 0.001), and the basal respiratory rate [(50.03±1.20) pmol/min], maximum respiration rate [(78.07±2.57) pmol/min] and adenosine triphosphate (ATP) production [(25.30±1.21) pmol/min] of MDSCs in the bone marrow of CLP group mice were significantly greater than the basal respiration rate [(34.53±0.96) pmol/min, (t = 17.41, P < 0.001)], maximum respiration rate [(42.57±1.87) pmol/min, (t = 19.33, P < 0.001)], and ATP production [(12.63±0.96) pmol/min, (t = 14.18, P < 0.001)] of sham group. Leucine, threonine, glycine, etc. were potential biomarkers of septic MDSCs (all P < 0.05). The increased amino acids were mainly enriched in metabolic pathways, such as malate-aspartate shuttle, ammonia recovery, alanine metabolism, glutathione metabolism, phenylalanine and tyrosine metabolism, urea cycle, glycine and serine metabolism, ß-alanine metabolism, glutamate metabolism, arginine and proline metabolism. CONCLUSION: The enhanced mitochondrial oxidative phosphorylation, malate-aspartate shuttle and alanine metabolism in MDSCs of CLP mice may provide raw materials for mitochondrial aerobic respiration, thereby promoting the immunosuppressive function of MDSCs. Blocking the above metabolic pathways may reduce the risk of secondary infection in sepsis and improve the prognosis.

Extracellular miR-6723-5p could serve as a biomarker of limbal epithelial stem/progenitor cell population.

BACKGROUND: Dysfunction or loss of limbal stem cells can result in limbal stem cell deficiency (LSCD), a disease that cause corneal opacity, pain, and loss of vision. Cultivated limbal epithelial transplantation (CLET) can be used to restore stem cell niche homeostasis and replenish the progenitor pool. Transplantation has been reported with high success rate, but there is an unmet need of prognostic markers that correlate with clinical outcomes. To date, the progenitor content in the graft is the only parameter that has been retrospectively linked to success. METHODS: In this study, we investigate extracellular micro RNAs (miRNAs) associated with stem/progenitor cells in cultivated limbal epithelial cells (cLECs). Using micro RNA sequencing and linear regression modelling, we identify a miRNA signature in cultures containing high proportion of stem/progenitor cells. We then develop a robust RNA extraction workflow from culture media to confirm a positive miRNA correlation with stem/progenitor cell proportion. RESULTS: miR-6723-5p is associated with cultures containing high proportion of stem/progenitor cells, and is detected in the basal layer of corneal epithelium. CONCLUSIONS: These results indicate that miR-6723-5p could potentially serve as a stem/progenitor cell marker in cLECs.

[Dose-enhanced immunochemotherapy followed by first-line autologous peripheral blood stem cell transplantation for young patients with high-risk aggressive B-cell lymphoma: an efficacy and prognostic factor analysis].

Objective: This study aimed to determine the efficacy of dose-enhanced immunochemotherapy followed by autologous peripheral blood stem cell transplantation (ASCT) in young patients with newly diagnosed high-risk aggressive B-cell lymphoma. Methods: A retrospective study was conducted to examine the clinical and survival data of young patients with high-risk aggressive B-cell lymphoma who received dose-enhanced immunochemotherapy and ASCT as first-line treatment between January 2011 and December 2018 in Blood Diseases Hospital. Results: A total of 63 patients were included in the study. The median age range was 40 (14-63) years old. In terms of the induction therapy regimen, 52 cases received R-DA-EP (D) OCH, and the remaining 11 received R-HyperCVAD/R-MA. Sixteen (25.4% ) patients achieved partial response in the mid-term efficacy assessment, and ten of them were evaluated as complete response after transplantation. The median follow-up was 50 (8-112) months, and the 3-year progression-free survival (PFS) rate and overall survival (OS) rate were (83.9±4.7) % and (90.4±3.7) % , respectively. Univariate analysis demonstrated that age-adjusted international prognostic index ≥2 scores was a negative prognostic factor for OS (P=0.039) , and bone marrow involvement (BMI) was an adverse prognostic factor for OS (P<0.001) and PFS (P=0.001) . However, multivariate analysis confirmed that BMI was the only independent negative predictor of OS (P=0.016) and PFS (P=0.001) . Conclusions: The use of dose-enhanced immunochemotherapy in combination with ASCT as first-line therapy in the treatment of young, high-risk aggressive B-cell lymphoma results in good long-term outcomes, and BMI remains an adverse prognostic factor.

[The effect of large-conductance calcium-activated potassium channels on the migration of pericytes in the mice of senile cochlear stria vascularis].

Objective: To investigate whether large conductance calcium-activated potassium channel (BK(Ca)) was involved in the migration of pericytes (PC) in the mice of senile cochlear stria vascularis capillaries PC. Methods: C57BL/6J mice were divided into 3-month (n=10) and 12-month groups (n=10). Auditory brainstem response (ABR) was used to test the hearing threshold of each group. The immunofluorescence was used to detect the expression changes of osteopontin (OPN) and ß-BK(Ca) channels on cochlear stria vascularis PC. The morphological changes of perivascular cells in cochlea were observed by transmission electron microscope (TEM). Cell experiment: The PC, which were in the stria vascularis of the cochlea were primary cultured and identified. A cell senile model was made with D-gal. The appropriate intervention concentration of low galactose (D-gal) was determined by CCK8. ß-galactosidase (SA-ß-gal) staining was used to evaluate the cell decrept level. The change of BK(Ca) channels current on PC were recorded by whole cell patch clamp technique. The expression of BK(Ca) channels on PC was detected by immunofluorescence. The migration and invasion ability of two groups were detected by using Scratch test and Transwell. The levels of OPN and ß-BK(Ca) channels were detected by Western blot. SPSS 22.0 software was used to analyze the data. Results: The ABR threshold in the 12-month group was higher than 3-month group (t=12.66, P<0.01). In the 12-month group, the expression of ß-BK(Ca) channel was lower and the expression of OPN was increased (t=14.64, P<0.01; t=20.73, P<0.01). In TEM, cochlear stria vascularis PC were tightly connected to endothelial cells in 3-month group, while PC were loosely connected to endothelial cells or PC soma were separated from the capillary in 12-month group. Cell experiment: The positive rate of PC in the primary cultured cochlear stria vascularis is above 95%. Compared with the SA-ß-gal stained cells in the control group, the positive rate of 15 mg/ml D-gal intervention PC was 85% (t=36.90, P<0.01). Whole cell patch clamp BK(Ca) channels current decreased in the D-gal group compared with the young group PC (t=12.18, P<0.05). The OPN expression in the senile group was higher than control group (t=16.30, P<0.01), while the ß-BK(Ca) channels expression was decreased (t=11.98, P<0.01; t=15.72, P<0.05), and migration ability raised (t=7.91, P<0.01;t=7.59, P<0.01). After intervened of BK(Ca) channels specific blocker IBTX in the D-gal group, the expression of OPN and migration were increased (t=4.26, P<0.05; t=5.88, P<0.01; t=21.97, P<0.01). Conclusion: PC migration capacity were increased during the senile period, and the expression of ß-BK(Ca) channel was decreased. The administration of IBTX, a specific blocker of BK(Ca) channel, at the cell level could increase the migration capacity, suggesting that BK(Ca) might be involved in the migration of PC in the stria vascularis of the aging cochlea.