[Effects of pelvic-abdominal mechanics exercises during pregnancy on improving perinatal pelvic floor function in primiparous women].

Objective: To explore the effects of pelvic-abdominal mechanics exercises during pregnancy on improving pelvic floor function in primiparous women during the perinatal period. Methods: A single-center prospective study selected 200 primipara of singleton pregnancies with prenatal care and delivery established at Shanghai Tongren hospital from June 2022 to June 2023 as the study subjects. Participants were divided into two groups: the exercise group (100 cases) and the control group (100 cases) by using a random number table method, five participants dropped out of the study due to reasons such as follow-up failure. Ultimately, the exercise group consisted of 97 cases, while the control group consisted of 98 cases. Participants who engaged in pelvic-abdominal mechanics exercises for at least 3 months, exercising once a week, were included in the exercise group. Those who did not engage in exercise were included in control group. Comparing the two groups in terms of pregnancy discomfort symptoms, delivery outcomes, postpartum pelvic floor electromyography results, postpartum quality of life, and pelvic floor disease incidence. The statistical methods utilized included independent t-test, Pearson chi-square test, Fisher's exact test, and Mann-Whitney U test. Results: In the late stage of pregnancy, the VAS score for low back pain was 5.05±1.22 in the exercise group and 5.47±1.55 in the control group, with a statistically significant difference (t=2.090, P<0.05). The PFDI-20 score was 23.33±8.41 in the exercise group and 25.76±8.34 in the control group, with a statistically significant difference (t=2.026, P<0.05). The PFIQ-7 score was 19.21±7.69 in the exercise group and 26.66±6.19 in the control group, with a statistically significant difference (t=6.851, P<0.05). There was no statistically significant difference in sleep quality and incidence of urinary incontinence between the two groups in late pregnancy (t=1.252, P=0.396, P>0.05). In terms of childbirth outcomes, the exercise group had a vaginal delivery rate of 81.44% (79 cases), while the control group had a rate of 64.28% (63 cases), with a statistically significant difference (χ2=9.022, P<0.05). The duration of the second stage of labor was (42.68±21.38) minutes in the exercise group and (50.54±21.33) minutes in the control group, with a statistically significant difference (t=2.178, P<0.05). At 42 days postpartum, the evaluation of pelvic floor function showed that the vaginal pressure in the exercise group was 62.19±10.04, while in the control group it was 52.68±15.55, with a statistically significant difference (t=-5.074, P<0.05). The MOS grading in the exercise group was 3.82±1.26, whereas in the control group it was 2.34±1.55, with a statistically significant difference (t=-7.355, P<0.05). In terms of the incidence of postpartum pelvic floor disorders, the occurrence of pelvic organ prolapse was 7.22% in the exercise group and 12.24% in the control group, with no statistically significant difference (χ2=1.402, P>0.05). The occurrence rate of stress urinary incontinence was 13.4% in the exercise group and 30.61% in the control group, with a statistically significant difference (P=0.015, P<0.05). Conclusion: Pelvic-abdominal mechanics exercises may have some advantages in reducing symptoms related to perinatal pelvic floor dysfunction, enhancing pelvic floor function, and preventing the occurrence of pelvic floor disease.

[Efficacy and safety of eltrombopag in the treatment of primary immune thrombocytopenia: real-world data from a single medical center].

Objective: This study aimed at investigating the efficacy and safety of eltrombopag in the treatment of adult primary immune thrombocytopenia (ITP) and evaluated the factors influencing its efficacy and side effects. Methods: A total of 198 patients with adult ITP who were admitted to Tianjin Medical University General Hospital between January 2018 and March 2022 were retrospectively analyzed. The efficacy of each starting dose of eltrombopag was evaluated, and adverse events were analyzed. The factors influencing efficacy were investigated, including sex, age, adult ITP type, platelet antibodies, and combined drug treatments. Results: Of the 198 patients, 70 males and 128 females with a median age of 45 years (18-88 years) were included; 130 (65.7%) had newly diagnosed adult ITP, 25 (12.6%) had persistent adult ITP, and 43 (21.7%) had chronic adult ITP. The bleeding event scores at baseline were assessed; 84.3% had scores of<4 and 15.7% had scores of ≥4. The eltrombopag response rate (initial response) at 6 weeks was 78.8% (complete response [CR]: 49.0%; CR1: 14.6%; CR2: 15.2%). The median response time to eltrombopag was 7 (7, 14) days. The initial response rates to 25, 50, and 75 mg eltrombopag were 74.1%, 85.9%, and 60.0%, respectively (P=0.031). The initial response rate to the 50 mg dose was significantly higher than that of the 25-mg and 75-mg doses. Two patients received 100 mg as the starting dose, and their initial response was 0. Regarding dose adjustment, 70.7% of the patients remained on the starting dose, 8.6% underwent dose adjustment to 50 mg, and 6.1% underwent dose adjustment to 75 mg. Another two patients underwent dose adjustment to 100 mg. After dose adjustment, the persistent response rates were 83.6%, 85.3%, and 85.7% for the 25-, 50-, and 75-mg doses, respectively, with no significant difference. After dose adjustment, the sustained efficacy rate for the 100-mg dose (4 patients) was 100.0%. After 6 weeks of treatment with eltrombopag, the overall bleeding score of patients with ITP decreased. The number of patients with a score of ≥4 decreased to 0, the number of patients with a score of<4 decreased, and there was no significant change in the number of patients with a score of 1-2. The most common adverse event associated with eltrombopag was impaired liver function (7.7%). No thrombosis events or other adverse events were observed. ITP type and number of megakaryocytes significantly affected the initial response to eltrombopag. The initial response rates to eltrombopag for newly diagnosed adult ITP, persistent adult ITP, and chronic adult ITP were 85.3%, 56.0%, and 76.2%, respectively (P=0.003). For megakaryocytes, the initial response rates were 61.8%, 87.1%, and 84.3% (P=0.009) for the decreased, normal, and increased megakaryocyte groups, respectively. Conclusion: Eltrombopag, as a second-line or higher treatment for adult ITP, has a rapid onset of action and good safety. The initial response rate is significantly higher with a dose of 50 mg than with a dose of 25 mg. Patients with newly diagnosed ITP and those with normal or increased megakaryocyte numbers have a higher initial response rate to eltrombopag.

Multiple maxillofacial desmoid tumours: a case report.

Desmoid tumors (DTs) are rare benign neoplasms but cause significant mortality due to their locally infiltrative nature and propensity to recur. Most DTs occur in the extremities and trunk. Head and neck DTs are uncommon but can have a significant impact on a patient's facial appearance. However, there is limited information available about the diagnosis and treatment for multiple DTs located in head and neck. We report the first case of multiple maxillofacial DTs in a 14-year-old boy. He had painless submandibular masses for three months and MRI imaging reveals abnormal high signals on the submandibular and bilateral zygomatic regions. Considering facial aesthetics, via intraoral incision we obtained a biopsy from the largest mass. Pathological examination confirmed a diagnosis of DT. We selected the wait-and-see strategy and clinically monitored the rest of the masses. During the subsequent 1-year follow-up, the masses were stagnant and appeared to involute. According to the development and outcome of this case, a conservative treatment for craniofacial DTs is suggested; however, greater clarity concerning management and prognosis could derive from prospective study of a larger patient cohort in the future.

[The overdiagnosis of thyroid cancer should not be overinterpreted].

Recently, the topic of "overdiagnosis" of thyroid cancer has once again sparked controversy in the medical academic community, as well as extensive discussions from patients and the general population. To some extent, the overdiagnosis of thyroid cancer has been over interpreted. This article provides a detailed discussion on how to correctly understand the overdiagnosis of thyroid cancer from the perspective of a thyroid surgeon. The author believes that there are two elements to the occurrence of overdiagnosis of thyroid cancer: the presence of a large "silent pool" of inert tumors in the human body and medical methods to improve detection rates. In recent years, thyroid cancer has become the fastest growing malignant tumor in the world in terms of incidence rate. The exponential growth mode makes thyroid cancer over diagnosed and inevitably becomes a hot topic in academia. However, the overdiagnosis of thyroid cancer is not contradictory to the early screening and diagnosis of thyroid cancer. The overdiagnosis of thyroid cancer should be viewed scientifically and rationally, especially avoiding overinterpretation.

[Phase â ¡ clinical trial of PD-1 inhibitor combined with chemotherapy for locally advanced resectable oral squamous cell carcinoma].

Objective: To explore the effectiveness and safety of programmed death 1(PD-1) inhibitory combined with chemotherapy as a neoadjuvant therapy for locally advanced resectable oral squamous cell carcinoma. Methods: This study was a randomized controlled phase Ⅱ trial. Patients recruited from Tianjin Medical University Cancer Institute and Hospital from July 2021 to February 2023 were randomly divided into two groups in a 1∶1 ratio: the experimental group (Toripalimab combined with albumin paclitaxel and cisplatin) and the control group (albumin paclitaxel and cisplatin); patients in both groups underwent three cycles of neoadjuvant therapy. After completion of neoadjuvant therapy, patients were evaluated and subsequent surgical treatment was performed. According to the completion of treatment, the analysis was conducted on both the full analysis set and the protocol set. The effectiveness and safety of treatments were evaluated. SPSS 20.0 software was used for statistical analysis. Results: A total of 41 cases with oral cancer were enrolled, including 26 males and 15 females, aged between 34 and 74 years old. There were 23 cases in the experimental group and 18 cases in the control group. A total of 23 cases completed neoadjuvant therapy and surgery according to the protocol. Experimental group and control group showed respectively the complete response rates of 1/19 and 0/17, the partial response rates of 13/19 and 8/17, the stage-down rates of 4/19 and 3/17, the pathologic complete response rate of 8/14 and 2/9, with no statistically significant differences in individual rates between two groups (P>0.05). The major pathological response rate of 13/14 in experimental group was higher than that of 2/9 in control group (P<0.05). The incidence of grade 3-4 adverse reactions related to treatment was low in both groups (4/23 vs. 3/18, χ2=0.13, P=0.72), and the most common serious adverse reactions in the experimental group were granulocyte deficiency and electrolyte disorder. There were no adverse reactions that affected subsequent surgical treatment or caused death, and the safety and tolerability were good. The median follow-up time was 15 months, and the one-year disease-free survival rate of the experimental group was higher than that of control group (92.86% vs. 77.78%, χ2=0.62, P=0.42), with a relative decrease of 87% in the risk of disease progression or death (P=0.029). For patients with programmed death-ligand 1(PD-L1) protein expression combined positive score≥20, the experimental group showed higher major pathological response rate than control group (5/5 vs. 0/4, P=0.03). Conclusion: The neoadjuvant therapy of immunotherapy combined with chemotherapy can improve the pathological remission of oral squamous cell carcinoma and the long-term survival benefits and the prognosis of patients.

[Prognostic performance of pulmonary effective arterial elastance in patients with heart failure].

Objective: To explore the predictive value of pulmonary effective arterial elastance (Ea) in patients with heart failure (HF). Methods: This is a retrospective cohort study, which retrospectively included 284 patients with HF who underwent right heart catheterization at Heart Failure Center in Fuwai Hospital between September 2013 and February 2022. Data regarding baseline clinical characteristics, hemodynamic profiles, and prognosis were collected. Ea was calculated as mean pulmonary arterial pressure/stroke volume. Patients were divided into Ea<0.555 group and Ea≥0.555 group according to the median value of Ea (0.555 mmHg/ml, 1 mmHg=0.133 kPa). The primary outcome was the primary clinical event, set as the first occurrence of a series of composite events, including all-cause death, heart transplantation, left ventricular assist device implantation, and HF rehospitalization. Event-free survival was defined as the absence of primary clinical events. Spearman correlation analysis was used to calculate the correlation coefficient between Ea and parameters reflective of right heart function. The Kaplan-Meier analysis was used to compare the different groups for the estimation of outcomes with the log-rank test. We used Cox proportional-hazards regression models to estimate hazard ratios (HR) for primary clinical event. Subgroup analysis was performed based on the age, gender, New York Heart Association (NYHA) functional class, left ventricular ejection fraction, presence of pulmonary hypertension, and serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) values. We used receiver operating characteristic (ROC) curve to calculate the area under the curve (AUC) of Ea for predicting event-free survival in patients with HF. Results: The median age was 51 years, and 206 (72.5%) patients were male. Ea and pulmonary vascular resistance (PVR) were significantly correlated (r=0.698, P<0.001). The correlation between Ea and pulmonary arterial elastance (PAC) were even more significant (r=-0.888, P<0.001). Compared with Ea<0.555 group, Ea≥0.555 group presented with higher serum NT-proBNP values (4 443 (1 792, 8 554) ng/L vs. 1 721 (480, 4 528)ng/L,P<0.001), higher PVR (3.4 (2.5, 4.7) Wood vs. 1.4 (0.9, 2.2) Wood, P<0.001), lower cardiac output (3.0 (2.3, 3.9) L/min vs. 4.3 (3.8, 4.9) L/min, P<0.001), and lower PAC (1.6 (1.3, 2.0) ml/mmHg vs. 4.0 (3.0, 6.0) ml/mmHg, P<0.001). The median follow-up time was 392 (166, 811) days. The Kaplan-Meier survival curve demonstrated a lower event-free survival rate in the Ea≥0.555 group compared to the Ea<0.555 group (Plog-rank<0.001). After multivariate adjustment, Ea (HR=1.734, P<0.001) remained significantly associated with the primary outcome. Subgroup analysis indicated that Ea was associated with the primary outcome across all subgroups. The AUC was 0.724 (P<0.001) for Ea to predict event-free survival calculated from ROC analysis. Conclusions: Ea is closely related to parameters reflective of right ventricular afterload. Increased Ea is an independent predictor of adverse outcomes in patients with HF.

Multi-center Dose Prediction Using Attention-aware Deep learning Algorithm Based on Transformers for Cervical Cancer Radiotherapy.

AIMS: Accurate dose delivery is crucial for cervical cancer volumetric modulated arc therapy (VMAT). We aimed to develop a robust deep-learning (DL) algorithm for fast and accurate dose prediction of cervical cancer VMAT in multicenter datasets and then explore the feasibility of the DL algorithm to endometrial cancer VMAT with different prescriptions. MATERIALS AND METHODS: We proposed the AtTranNet algorithm for three-dimensional dose prediction. A total of 367 cervical patients were enrolled in this study. Three hundred twenty-two cervical patients from 3 centers were randomly divided into 70%, 10%, and 20% as training, validation, and testing sets, respectively. Forty-five cervical patients from another center were selected for external testing. Moreover, 70 patients of endometrial cancer with different prescriptions were further selected to test the model. Prediction precision was evaluated by dosimetric difference, dose map, and dose-volume histogram metrics. RESULTS: The prediction results were all clinically acceptable. The mean absolute error within the body in internal testing was 0.66 ± 0.63%. The maximum |δD| for planning target volume was observed in D98, which is 1.24 ± 2.73 Gy. The maximum |δD| for organs at risk was observed in Dmean of bladder, which is 4.79 ± 3.14 Gy. The maximum |δV| were observed in V40 of pelvic bones, which is 4.77 ± 4.48%. CONCLUSION: AtTranNet showed the feasibility and reasonable accuracy in the dose prediction for cervical cancer in multiple centers. The model can also be generalized for endometrial cancer with different prescriptions without any transfer learning.

[Evaluation of the efficacy and safety of intravenous infusion of ferric derisomaltose in the treatment of iron deficiency anemia: a single-center retrospective analysis].

Objective: To investigate the clinical efficacy and safety of ferric derisomaltose injection versus iron sucrose injection in the treatment of iron deficiency anemia (IDA) . Methods: A total of 120 patients with iron deficiency anemia admitted from June 2021 to March 2023 were given intravenous iron supplementation with ferric derisomaltose to assess the efficacy and safety of hemoglobin (HGB) elevation before and after treatment. Simultaneously, the clinical effects of iron supplementation with iron sucrose were compared to those of inpatient patients during the same period. Results: Baseline values were comparable in both groups. Within 12 weeks of treatment, the elevated HGB level in the ferric derisomaltose group was higher than that of the iron sucrose group, with a statistical difference at all time points, and the proportion of HGB increased over 20 g/L in the patients treated for 4 weeks was higher (98.7%, 75.9% ). During the treatment with ferric derisomaltose and iron sucrose, the proportion of mild adverse reactions in the ferric derisomaltose group was slightly lower than that of the iron sucrose group, and neither group experienced any serious adverse reactions. The patients responded well to the infusion treatment, with no reports of pain or pigmentation at the injection site. Conclusion: The treatment of IDA patients with ferric derisomaltose has a satisfactory curative effect, with the advantages of rapidity, accuracy, and safety. Therefore, it is worthy of widespread clinical use.

[The predictive value of dynamic changes of neutrophil/lymphocyte ratio (NLR) combined with the model of end-stage liver disease (MELD) score in patients with acute-on-chronic hepatitis B liver failure].

Objective: To determine the predictive value of dynamic changes of neutrophil/lymphocyte ratio (NLR) combined with the model of end-stage liver disease (MELD) score in patients with acute-on-chronic hepatitis B liver failure. Methods: Patients with acute-on-chronic hepatitis B liver failure who were hospitalized in the Department of Hepatology of Qilu Hospital of Shandong University from January 2010 to July 2023 were retrospectively enrolled. According to the clinical outcomes of patients within 30 days of admission, they were divided into the survival group and the death group. The dynamic changes in NLR and initial values on day 3, 5, 8, and 12 in two groups were analyzed for the diagnostic value of 30-day prognosis in patients with acute-on-chronic hepatitis B liver failure. Logistic regression analysis and machine learning XGBoost algorithm were used to evaluate the risk factors influencing the prognosis of patients at 30 days. Receiver operating characteristic(ROC) curve was used to evaluate the diagnostic value of NLR and initial value change combined with MELD score on day 12 of admission in patients with chronic acute hepatitis B liver failure. Results: A total of 243 patients were enrolled in the study, including 145 patients in the survival group [115 males, 30 females, aged 25-74 (47±11)] and 98 patients in the death group [80 males, 18 females, aged 22-80 (49±13) ]. The median initial NLR of survival group and death group were 3.5 (2.1, 5.3) and 4.9 (2.9, 8.3), respectively, and the difference was statistically significant (P=0.003). The variation of NLR from the initial value on day 3, 5, 8, and 12 in the survival group [1.6 (0, 4.3), 1.9 (-0.2, 4.1), 2.0 (-0.1, 4.3) and 2.9 (0.3, 7.0), respectively] were lower than that in the death group [3.2 (0.9, 7.5), 5.1 (1.8, 7.6), 5.8 (2.0, 10.6) and 9.6 (3.5, 16.4), respectively] (all P<0.001). Logistic regression multivariate analysis showed that the changes in NLR on the 12th day and initial value (OR=1.07,95%CI:1.01-1.14, P=0.014), the changes in NLR on the 3rd day and initial value (OR=2.71, 95%CI: 1.32-5.55, P=0.007), the initial value of NLR (OR=1.18,95%CI:1.01-1.37,P=0.035) and fibrinogen (OR=0.21,95%CI:0.05-0.96,P=0.044) were related factors for death within 30 days. Machine learning XGBoost algorithm showed that the weight of the change between the NLR on the 12th day and the initial value was the highest. The area under the ROC curve of the combined MELD score was 0.812 (95%CI: 0.728-0.895), the specificity was 67.78%, and the sensitivity was 82.35%. Conclusion: Dynamic change of NLR combined with MELD score has high predictive value for the short-term prognosis of patients with acute-on-chronic hepatitis B liver failure.

A time-averaged serum bicarbonate-based nomogram to predict the probability of residual kidney function preservation for patients undergoing peritoneal dialysis.

OBJECTIVE: Residual kidney function (RKF) is an important prognostic indicator in peritoneal dialysis (PD) patients. So far, there are no prediction tools available for RKF, and the association between serum bicarbonate and RKF has received little attention in patients with PD. We aimed to develop a nomogram for the preservation of RKF based on the time-averaged serum bicarbonate (TA-Bic) levels. PATIENTS AND METHODS: A prediction model was established by conducting a retrospective cohort study of 151 PD patients who had been treated at the First Affiliated Hospital of Anhui Medical University. The nomogram was developed using a multivariate Cox regression model. The discrimination, calibration, and clinical utility of the model were evaluated by the C-index, receiver operating curve (ROC) curve, calibration curve, and decision curve analysis. RESULTS: In the elderly PD onset, higher baseline values of residual glomerular filtration rate, total Kt/V and higher TA-Bic levels were identified as protective predictors of RKF loss. The nomogram was conducted on the basis of the minimum value of the Akaike Information Criterion and Bayesian Information Criterion with a reasonable C-index of 0.766, showing great discrimination, proper calibration, and high potential for clinical practice. Through the total score of the nomogram, the patients were classified into the high-risk group and low-risk group, and a higher cumulative incidence of complete RRF loss was found in the high-risk group compared with the patients in the low-risk group. CONCLUSIONS: The novel predictive nomogram model can predict the probability of RKF preservation in long-term PD patients with high accuracy. Future studies are needed to externally validate the current nomogram before clinical application.

Single-cell analysis reveals a unique microenvironment in peri-implantitis.

AIM: This study aimed to reveal the unique microenvironment of peri-implantitis through single-cell analysis. MATERIALS AND METHODS: Herein, we performed single-cell RNA sequencing (scRNA-seq) of biopsies from patients with peri-implantitis (PI) and compared the results with healthy individuals (H) and patients with periodontitis (PD). RESULTS: Decreased numbers of stromal cells and increased immune cells were found in the PI group, which implies a severe inflammatory infiltration. The fibroblasts were found to be heterogeneous and the specific pro-inflammatory CXCL13+ sub-cluster was more represented in the PI group, in contrast to the PD and H groups. Furthermore, more neutrophil infiltration was detected in the PI group than in the PD group, and cell-cell communication and ligand-receptor pairs revealed most neutrophils were recruited by CXCL13+ fibroblasts through CXCL8/CXCL6-CXCR2/CXCR1. Notably, our study demonstrated that the unique microenvironment of the PI group promoted the differentiation of monocyte/macrophage lineage cells into osteoclasts, which might explain the faster and more severe bone resorption in the progression of PI than PD. CONCLUSIONS: Collectively, this study suggests a unique immune microenvironment of PI, which may explain the differences between PI and PD in the clinic. These outcomes will aid in finding new specific and effective treatments for PI.

An Acid-Responsive Iron-Based Nanocomposite for OSCC Treatment.

Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, characterized by invasiveness, local lymph node metastasis, and poor prognosis. Traditional treatment and medications have limitations, making the specific inhibition of OSCC growth, invasion, and metastasis a challenge. The tumor microenvironment exhibits mildly acidity and high concentrations of H2O2, and its exploitation for cancer treatment has been widely researched across various cancers, but research in the oral cancer field is relatively limited. In this study, by loading ultra-small Prussian blue nanoparticles (USPBNPs) into mesoporous calcium-silicate nanoparticles (MCSNs), we developed an acid-responsive iron-based nanocomposite, USPBNPs@MCSNs (UPM), for the OSCC treatment. UPM demonstrated excellent dual enzyme activities, generating toxic ·OH in a mildly acidic environment, effectively killing OSCC cells and producing O2 in a neutral environment to alleviate tissue hypoxia. The results showed that UPM could effectively inhibit the proliferation, migration, and invasion of OSCC cells, as well as the growth of mice solid tumors, without obvious systemic toxicity. The mechanisms may involve UPM inducing ferroptosis of OSCC cells by downregulating the xCT/GPX4/glutathione (GSH) axis, characterized by intracellular iron accumulation, reactive oxygen species accumulation, GSH depletion, lipid peroxidation, and abnormal changes in mitochondrial morphology. Therefore, this study provides empirical support for ferroptosis as an emerging therapeutic target for OSCC and offers a valuable insight for future OSCC treatment.

Realizing Synthetic Dimensions and Artificial Magnetic Flux in a Trapped-Ion Quantum Simulator.

Synthetic dimension is a potent tool in quantum simulation of topological phases of matter. Here we propose and demonstrate a scheme to simulate an anisotropic Harper-Hofstadter model with controllable magnetic flux on a two-leg ladder using the spin and motional states of a single trapped ion. We verify the successful simulation of this model by comparing the measured dynamics with theoretical predictions under various coupling strength and magnetic flux, and we observe the chiral motion of wave packets on the ladder as evidence of the topological chiral edge modes. We develop a quench path to adiabatically prepare the ground states for varying magnetic flux and coupling strength, and we measure the chiral current on the ladder for the prepared ground states, which allows us to probe the quantum phase transition between the Meissner phase and the vortex phase. Our work demonstrates the trapped ion as a powerful quantum simulation platform for topological quantum matter.

Circular RNA ath-circ032768, a competing endogenous RNA, response the drought stress by targeting miR472-RPS5 module.

CircRNAs (circular RNAs) reduce the abundance of miRNAs through ceRNA (competing endogenous RNA), to regulate many physiological processes and stress responses in plants. However, the role of circRNA in drought stress is poorly understood. Through ring identification and sequencing verification of ath-circ032768, bioinformatics analysis predicted the interaction of ath-circ032768-miR472-RPS5, and further obtained transgenic plants overexpressing ath-circ032768 and silencing STTM-miR472. The change in drought stress was analysed using biochemical and molecular biological methods. Sequencing and biological analysis confirmed that ath-circ032768, miR472 and RPS5 were responsive to drought stress, and changes in gene expression were consistent with the prediction of ceRNA. The silencing vectors ath-circ032768 and STTM-miR472 were constructed using molecular biology techniques, and stable transgenic plants with drought tolerance obtained. Further physiological and biochemical studies showed that ath-circ032768 could bind to miR472, and that miR472 could bind to the RPS5 gene, resulting in decreased expression of RPS5. Hence, ath-circ032768 can competitively inhibit degradation of RPS5 by miR472 through ceRNA. This process is accompanied by increased expression of DREB2A, RD29A and RD29B genes. Through the ath-circ032768-miR472-RPS5 pathway, the RPS5 stress resistance protein interacts with DREB2A protein to enhance expression of downstream drought resistance genes, RD29A and RD29B, and participate in the regulation mechanism of plant drought resistance, thereby improving drought tolerance of plants.

[Evaluation of semicircular canal and otolith graviceptive pathway function in patients diagnosed with motion sickness disorder based on the diagnostic criteria of the Bárány society].

Objective: To investigate the altered function of the semicircular canal and otolith graviceptive pathway in patients diagnosed with motion sickness disorder (MSD) based on the diagnostic criteria of the Bárány society, and explore its relevance to the pathogenesis of MSD. Methods: This is a case-control study. Twenty patients with MSD and age-and sex-matched healthy controls without a history of MSD from the Department of Neurology of Aerospace Center Hospital between March and August 2022 were recruited. All subjects completed the motion sickness susceptibility questionnaire-short version (MSSQ-short) and the motion sickness assessment questionnaire (MSAQ). Canal function was evaluated using caloric stimulation test and video head impulse test (vHIT), and subjective visual vertical/horizontal (SVV/SVH) and vestibular evoked myogenic potential (VEMP) were employed to assess otolith graviceptive function. Differences in vestibular function and correlations between the two groups were analyzed. Results: Each group consisted of 20 cases (9 males and 11 females). The mean age of the MSD and control groups was (26.9±3.9) years and (27.0±3.4) years, respectively. The scores of MSSQ-short [27.0 (22.5, 38.8) vs 1.2 (0, 3.2), P<0.001] and MSAQ [70.1 (54.5, 78.1) vs 11.8 (11.1, 13.9), P<0.001] were significantly higher in the MSD group compared with those of the control group. Evaluation of canal function revealed a significantly higher incidence of caloric stimulation intolerance in MSD patients (60.0%, 12/20) compared with that of the control group (20.0%, 4/20) (P=0.010). Evaluation of otolith graviceptive pathway indicated no significant difference in SVV, SVH and cervical VEMP (cVEMP) abnormality rates between the two groups (all P>0.05). The ocular VEMP (oVEMP) abnormality rate was significantly higher in the MSD group (55.0%, 11/20) than that of the control group (10.0%, 2/20) (P=0.002), with a delayed P1-wave latency compared with the control group [(18.4±1.2) ms vs (17.6±0.8) ms, P=0.018]. Further correlation analysis revealed that P1-wave latency in oVEMP was positively correlated with MSSQ-short (r=0.486, P=0.002) and MSAQ (r=0.391, P=0.015) scores, and duration of caloric intolerance symptoms (r=0.377, P=0.004). Conclusion: The presence of hypersensitivity to caloric stimulation and delayed latency of otolith function in patients with MSD suggests a "separation" between semicircular canal and otolithic function, which may be related to sensory conflict.

[Study of proanthocyanidin promotes osteogenic differentiation of human periodontal ligament stem cells through the transcription factor EB-induced autophagy-lysosome pathway].

Objective: To investigate the mechanism of proanthocyanidin (PA) in regulating the osteogenic differentiation of human periodontal ligament stem cells (PDLSCs), and to explore the effects of PA on the expression and nuclear translocation of transcription factor EB (TFEB) and on the autophagy-lysosome pathway. Methods: PDLSCs were divided into control group and PA group, which were subjected to RNA sequencing analysis (RNA Seq) to detect differentially expressed genes. The osteogenic differentiation ability and autophagy level were observed by real-time fluorescence quantitative PCR (RT-qPCR) analysis, alkaline phosphatase (ALP) staining and transmission electron microscope (TEM), respectively. Scratch assay and Transwell assay were used to detect the migration ability of PDLSCs. Lysotracker and immunofluorescence staining were used to detect the biogenesis of lysosomes. The total protein expression of transcription factor EB (TFEB) as well as that in cytoplasm and nucleus were detected by Western blotting. Confocal laser scanning microscope (CLSM) was used to observe the nuclear translocation of TFEB. The PDLSCs were treated with small interfering RNA (siRNA) technology to knock down the expression levels of TFEB gene with or without PA treatment. Western blotting was used to analyze the expressions of autophagy-related proteins Beclin1 and microtubule-associated protein 1 light chain 3 (LC3B), as well as osteogenic-related proteins runt-related transcription factor 2 (RUNX2), ALP, and osteocalcin in PDLSCs. Results: Compared with the control group, the osteogenic-related and autophagy-related genes showed differential expression in PDLSCs after PA treatment (P<0.05). The mRNA expression levels of osteogenic-related genes RUNX2 (2.32±0.15) and collagen type Ⅰ alpha 1 (COL1α1) (1.80±0.18), as well as the autophagy related genes LC3B (1.87±0.08) and Beclin1 (1.63±0.08) were significantly increased in the PA group, compared with the control group (1.01±0.16, 1.00±0.10, 1.00±0.07, 1.00±0.06, respectively, all P<0.01). Compared with the control group, the PA group had higher ALP activity, and more autophagosomes and autophagolysosomes observed by TEM. PA promoted the migration of PDLSCs (P<0.05) and the increased number of lysosomes and the expression of lysosomal associated membrane protein 1 (LAMP1). In the PA group, the relative expression level of total TFEB protein (1.49±0.07) and the nuclear/cytoplasmic expression of TFEB protein (1.52±0.12) were significantly higher than the control group (1.00±0.11, 1.00±0.13, respectively) (t=6.43, P<0.01; t=5.07, P<0.01). The relative nuclear/cytoplasmic fluorescence intensity of TFEB in the PA group (0.79±0.09) was increased compared with the control group (0.11±0.08) (t=8.32, P<0.01). Knocking down TFEB significantly reduced the expression of TFEB (1.00±0.15 vs 0.64±0.04), LAMP1 (1.00±0.10 vs 0.69±0.09), Beclin1 (1.00±0.05 vs 0.60±0.05), and LC3B Ⅱ/Ⅰ (1.00±0.06 vs 0.73±0.07) in PDLSCs (P<0.05, P<0.05, P<0.01, P<0.01). When TFEB gene was knocked down, the expression levels of Beclin1 (1.05±0.11), LC3B Ⅱ/Ⅰ (1.02±0.09), RUNX2 (1.04±0.10), ALP (1.04±0.16), and osteocalcin (1.03±0.15) proteins were significantly decreased in the PA group compared with the pre-knockdown period (1.28±0.03, 1.44±0.11, 1.38±0.11, 1.62±0.11, 1.65±0.17, respectively) (P<0.05, P<0.01, P<0.05, P<0.01, and P<0.01, respectively). Conclusions: PA promotes the osteogenic differentiation of PDLSCs through inducing the expression and nuclear translocation of TFEB and activating the autophagy-lysosome pathway.

[Study based on the acetaldehyde dehydrogenase 2 gene polymorphism and acetaminophen-induced liver injury].

Objective: To explore the association between aldehyde dehydrogenase 2 (ALDH2) gene polymorphisms and abnormal liver function-induced by acetaminophen (APAP) drugs. Methods: An ALDH2 gene knockout mouse model was constructed using CRISPR/Cas9 gene editing technology. The obtained heterozygous mice were mated with opposite sex of heterozygotes. Genomic DNA was extracted from the tail of the offspring mouse. The polymerase chain reaction (PCR) method was used to determine the ALDH2 genotype. APAP was further used to induce acute drug-induced liver injury models in wild-type and ALDH2 knockout mice. Blood and liver tissues of mice were collected for liver function index, HE staining, F4/80 immunohistochemistry, and other detections. The intergroup mean was compared using a one-way ANOVA. The LSD- t test was used for pairwise comparison. Results: ALDH2 knockout mice were bred successfully. The genotyping of the offspring was segregated into the wild-type (ALDH2(+/+)), heterozygous mutant (ALDH2(+/-)), and homozygous mutant (ALDH2(-/-)), respectively. Biochemical and histological results after APAP modeling showed that the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBil) was not significantly increased in the blank control group (P < 0.05), while the ALT, AST,ALP, and TBil were all elevated in the APAP experimental group. The levels of ALT (P  = 0.004), AST (P = 0.002), and TBil (P = 0.012) were significantly elevated among the mutant group compared to those in the wild-type group, and the expression levels of these indicators were also significantly elevated among the homozygous mutant group compared to those in the heterozygous mutant group (P = 0.003, 0 and 0.006). In addition, the ALP levels were higher in the heterozygous mutation group than those in the homozygous mutant group (P = 0.085) and wild-type group mice, but the difference was only statistically significant compared to wild-type mice (P = 0.002). HE staining results showed that mice in the APAP experimental group had hepatocyte degeneration, necrosis, and increased inflammatory cell infiltration, which was mostly evident in mutant mice. Simultaneously, the F4/80 immunohistochemical staining results showed that brown granules were visible in the liver tissue of APAP experimental group mice, and its expression levels were significantly enhanced compared to the blank control group. Conclusion: APAP-induced liver function abnormalities were associated with the ALDH2 gene polymorphism. The liver injury symptoms were increased in ALDH2 mutant mice following APAP modeling, and the ALDH2 gene defect may alleviate, to some extent, APAP-induced liver function abnormalities.

[Progress in research of rash and fever syndrome surveillance and early warning].

Objective: To introduce the progress in research of rash and fever syndrome (RFS) surveillance and early warning both at home and abroad, and provide reference for surveillance and prevention of RFS in China. Methods: The keywords "fever" "rash" and "surveillance" and others were used for a literature retrieval by using China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, PubMed and Web of Science. The languages of literatures were limited in Chinese and English. The key information of the literatures were collected and analyzed with Excel. Results: A total of 36 study papers (21 in Chinese and 15 in English) were included. The studies mainly focused on the pathogen surveillance of RFS (n=19). The pathogens included measles virus, varicella-zoster virus, rubella virus, enterovirus, human B19 virus, dengue virus, streptococcus group A, Salmonella typhi and Salmonella paratyphoid,human herpesvirus, mumps virus and adenovirus. Eight studies were about the surveillance in major events, such as sport game, World Expo and religious gathering, or sudden natural disasters, such as earthquake and tropical storm, during 2010-2015. Eight studies focused on case or epidemic surveillance, most of which were studies from other counties. The surveillance sites were medical institutions. RFS was diagnosed according to the International Classification of Diseases, 9th (ICD-9) and symptoms descripted in chief-complaint. Only one study in Mongolia conducted RFS epidemic prediction. The analysis methods of 36 papers included simple descriptive analysis, time-based early warning models (such as regression analysis, fixed threshold method, Hugh Hart control chart method and cumulative sum control chart method) and time series analysis method. Conclusions: In the future, RFS surveillance system should cover both known pathogens and emerging pathogens. Automatic surveillance using information capture and intelligent modelling can be applied to improve the sensitivity and specificity of RFS surveillance and early warning.

[Single non-blood-related umbilical cord blood transplantation using a reduced-intensity conditioning regimen for the treatment of severe aplastic anemia].

Objective: To evaluated the clinical efficacy of a reduced-intensity preconditioning regimen for single non-blood-related umbilical cord blood transplantation (sUCBT) in the treatment of severe aplastic anemia (SAA) . Methods: The clinical data of 63 patients with SAA who underwent sUCBT from January 2021 to July 2023 at the Department of Hematology of the First Affiliated Hospital of USTC were retrospectively analyzed. Fifty-two patients received total body irradiation/total bone marrow irradiation (TMI) combined with fludarabine or a cyclophosphamide- conditioning regimen (non-rATG group) , while 11 patients received rabbit anti-human thymocyte immunoglobulin (rATG) combined with TMI, fludarabine, or the cyclophosphamide-conditioning regimen (rATG group) . All patients received cyclosporine A and mycophenolate mofetil for graft-versus-host disease (GVHD) prophylaxis. Complications post-transplantation and long-term survival were compared between the two groups. Results: The baseline parameters were balanced between the two groups (P>0.05) . In the rATG group, all patients achieved stem cell engraftment, and in the non-rATG group, five patients had primary graft failure. There was no significant difference in the cumulative incidence of neutrophil engraftment at 42 days after transplantation or platelet engraftment at 60 days between the two groups. The incidence of grade Ⅱ-Ⅳ acute GVHD in the rATG group was significantly lower than in the non-rATG group (10.0% vs. 46.2% , P=0.032) , and the differences in the cumulative incidences of grade Ⅲ/Ⅳ acute GVHD and 1-year chronic GVHD were not statistically significant (P=0.367 and P=0.053, respectively) . There were no significant differences in the incidences of pre-engraftment syndrome, bacterial bloodstream infections, cytomegalovirus viremia, or hemorrhagic cystitis between the two groups (P>0.05 for all) . The median follow-up time for surviving patients was 536 (61-993) days, and the 1-year transplantation related mortality (TRM) of all patients after transplantation was 13.0% (95% CI 6.7% -24.3% ) . Among the patients in the non-rATG and rATG groups, 15.5% (95% CI 8.1% -28.6% ) and 0% (P=0.189) , respectively, had mutations. The 1-year overall survival (OS) rate of all patients after transplantation was 87.0% (95% CI 75.7% -93.3% ) . The 1-year OS rates in the rATG group and non-rATG group after transplantation were 100% and 84.5% , respectively (95% CI 71.4% -91.9% ) (P=0.198) . Conclusion: The preliminary results of sUCBT with a low-dose irradiation-based reduced-intensity conditioning regimen with fludarabine/cyclophosphamide for the treatment of patients with SAA showed good efficacy. Early application of low-dose rATG can reduce the incidence of acute GVHD after transplantation without increasing the risk of implantation failure or infection.