As a hot spot in clinical research today, immune checkpoint inhibitor has been recommended by guidelines in the first- and second-line treatments of advanced cervical cancer as immune monotherapy or combination therapy. It has also achieved good efficacy in clinical practice. In locally advanced cervical cancer, immune checkpoint inhibitors have been included in the guidelines for adjuvant therapy, and good tumor regression effects have been achieved in clinical practice. Based on the results of existing trials, immune checkpoint inhibitors have also shown good clinical potential as neoadjuvant therapy. Furthermore, the issue of immunotherapy rechallenge has increasingly captured clinicians’ attention, offering a potential new therapeutic strategy for cervical cancer patients with prior immunotherapy exposure. In this article, the clinical application and research progress of immune checkpoint inhibitors in the treatment of cervical cancer in recent years are summarized to provide valuable ideas and directions for clinical treatment.

OBJECTIVE: To explore the correlation between mechanical power normalized to dynamic lung compliance (Cdyn-MP) and weaning outcomes and prognosis in mechanically ventilated patients. METHODS: A prospective, observational cohort study was conducted. Patients who underwent invasive mechanical ventilation (IMV) for more than 24 hours and used a T-tube ventilation strategy for extubation in the intensive care unit (ICU) of Lianyungang First People's Hospital and Lianyungang Second People's Hospital between January 2022 and December 2023 were enrolled. The collected data encompassed patients' baseline characteristics, primary causes of ICU admission, vital signs and laboratory indicators during the initial spontaneous breathing trial (SBT), respiratory mechanics parameters within the 4-hour period prior to the SBT, weaning outcomes and prognostic indicators. Mechanical power (MP) and Cdyn-MP were calculated using a simplified MP equation. Univariate and multivariate Logistic regression analyses were utilized to determine the independent risk factors associated with weaning failure in patients undergoing mechanical ventilation. Restricted cubic spline (RCS) analysis and Spearman rank-sum test were employed to investigate the correlation between Cdyn-MP and weaning outcomes as well as prognosis. Receiver operator characteristic curve (ROC curve) was constructed, and the area under the ROC curve (AUC) was computed to evaluate the predictive accuracy of Cdyn-MP for weaning outcomes in mechanically ventilated patients. RESULTS: A total of 366 patients undergoing IMV were enrolled in this study, with 243 cases classified as successful weaning and 123 cases classified as failed weaning. Among them, 23 patients underwent re-intubation within 48 hours after the successful withdrawal of the first SBT, non-invasive ventilation, or died. Compared with the successful weaning group, the patients in the failed weaning group had significantly increased levels of sequential organ failure assessment (SOFA) score, body temperature and respiratory rate (RR) during SBT, and respiratory mechanical parameters within the 4-hour period prior to the SBT [ventilation frequency, positive end-expiratory pressure (PEEP), platform pressure (Pplat), peak inspiratory pressure (Ppeak), dynamic driving pressure (ΔPaw), fraction of inspired oxygen (FiO₂), MP, and Cdyn-MP], dynamic lung compliance (Cdyn) was significantly reduced, and duration of IMV, ICU length of stay, and total length of hospital stay were significantly prolonged. However, there were no statistically significant differences in age, gender, body mass index (BMI), smoking history, main causes of ICU admission, other vital signs [heart rate (HR), mean arterial pressure (MAP), saturation of peripheral oxygen (SpO₂)] and laboratory indicators [white blood cell count (WBC), albumin (Alb), serum creatinine (SCr)] during SBT of patients between the two groups. Univariate Logistic regression analysis was conducted, and variables with P < 0.05 and no multicollinearity with Cdyn-MP were selected for inclusion in the multivariate Logistic regression model. The results demonstrated that SOFA score [odds ratio (OR) = 1.081, 95% confidence interval (95%CI) was 1.008-1.160, P = 0.030], and PEEP (OR = 1.191, 95%CI was 1.075-1.329, P = 0.001), FiO₂ (OR = 1.035, 95%CI was 1.006-1.068, P = 0.021) and Cdyn-MP (OR = 1.190, 95%CI was 1.086-1.309, P < 0.001) within the 4-hour period prior to the SBT were independent risk factors for weaning failure in patients undergoing IMV. The RCS analysis after adjusting for confounding factors showed that as Cdyn-MP within the 4-hour period prior to the SBT increased, the risk of weaning failure in patients undergoing IMV significantly increased (P < 0.001). The Spearman rank correlation test showed that Cdyn-MP within the 4-hour period prior to the SBT was positively correlated with respiratory mechanical parameters including ΔPaw and MP (r values were 0.773 and 0.865, both P < 0.01), and negatively correlated with Cdyn (r = -0.587, P < 0.01). Cdyn-MP within the 4-hour period prior to the SBT was positively correlated with prognostic indicators such as duration of IMV, length of ICU stay, and total length of hospital stay (r values were 0.295, 0.196, and 0.120, all P < 0.05). ROC curve analysis demonstrated that, within the 4-hour period preceding the SBT, Cdyn-MP, MP, Cdyn, and ΔPaw possessed predictive value for weaning failure in patients undergoing IMV. Notably, Cdyn-MP exhibited superior predictive capability, evidenced by an AUC of 0.761, with a 95%CI ranging from 0.712 to 0.810 (P < 0.001). At the optimal cut-off value of 408.5 J/min×cmH₂O/mL×10^-3, the sensitivity was 68.29%, and the specificity was 71.19%. CONCLUSION Cdyn-MP is related to weaning outcomes and prognosis in mechanically ventilated patients, and has good predictive ability in assessing the risk of weaning failure.
Humans ; Prospective Studies ; Ventilator Weaning ; Prognosis ; Respiration, Artificial ; Intensive Care Units ; Lung Compliance ; Female ; Male ; Middle Aged ; Aged

Objective To analyze the changes in optical coherence tomography angiography (OCTA) parameters in patients with essential hypertension，and to explore the effect of blood pressure on OCTA parameters. Methods A total of 164 patients with essential hypertension were selected and divided into controlled blood pressure group (n=92) and uncontrolled blood pressure group (n=72). OCTA examination was performed on the optic disc and macula of all patients, and the right eyes were selected for analysis. Results There were no significant differences in retinal nerve fiber layer (RNFL) thickness, radial peripapillary capillary (RPC) total vascular density, RPC total small vessel density, perifovea superficial capillary plexus (SCP) vascular density, and perifovea deep capillary plexus (DCP) vascular density between the two groups of patients. There were no significant differences in foveal avascular zone (FAZ) area, FAZ diameter, and fovea retinal thickness between the two groups of patients. The density of the parafovea SCP, parafovea DCP, and fractal dimension (FD) in the uncontrolled blood pressure group were significantly lower than those in the controlled blood pressure group (P＜0.05). Multiple linear regression analysis showed that elevation of blood pressure was a independently related factor of reduced parafovea DCP density (P＝0.026), while there was no correlation between the uncontrolled blood pressure and parafovea SCP density and FD level. Conclusions The blood pressure level is correlated with the parafovea DCP density, while has no correlation with other OCTA parameters in hypertension patients.

[Objective] To explore the feasibility of exemption from radiotherapy after breast-conserving surgery for hormone receptor-negative elderly breast cancer. [Methods] A total of 139 estrogen receptor (ER) and progesterone receptor (PR)-negative older adults with breast cancer who underwent breast-conserving surgery admitted to the Second Affiliated Hospital of Nanchang University from December 1, 2013 to December 1, 2018 were recruited as the subjects of the study, and were divided into a case group of 67 patients who did not undergo postoperative radiotherapy and a control group of 72 ones who underwent postoperative radiotherapy, according to whether they received postoperative radiotherapy or not. Clinicopathological data including age, tumor T stage, tumor N stage, tumor Nottingham grade, pathology type, human epidermal growth factor receptor 2 (HER2) expression status, and chemotherapy regimen were collected and compared between the two groups. The study analyzed the 5-year disease-free survival (DFS) and 5-year overall survival (OS) of two groups of patients. The log-rank test was used to compare the survival rate, and a multifactorial COX proportional hazards regression model was used to analyze the effect of exempted radiotherapy after breast-conserving surgery on DFS and OS of hormone receptor-negative elderly breast cancer mammary carcinoma. [Results] The two groups did not significantly differ in age, tumor T-stage, tumor N-stage, pathological type, tumor Nottingham grade, HER2 status, or chemotherapeutic regimen (all P>0.05). The 5-year DFS rate of 139 hormone receptor-negative elderly breast cancer cases was 74.1% and the 5-year OS rate was 83.5%. The difference in the 5-year DSF rate between the case group and the control group was statistically significant (65.7 vs. 81.9%, P=0.023), but the difference in the 5-year OS rate was not statistically significant (79.1% vs. 87.5%, P=0.186). The results of multifactorial COX proportional risk regression model analysis showed that exemption from radiotherapy after breast-conserving surgery was an independent risk factor for DFS (HR=2.298, 95% CI: 1.113-4.746, P=0.024), but not for OS (HR=1.831, 95% CI: 0.740-4.532, P=0.191). [Conclusion] Hormone receptor-negative elderly breast cancer according to exemption of radiotherapy after breast-conserving surgery has a higher local recurrence rate, but OS has no significant effect. Therefore, whether hormone receptor-negative elderly breast cancer can be exempted from radiotherapy after breast-conserving surgery still needs to be verified by further clinical trials.

BACKGROUND:It has been shown that neural stem cells can differentiate into neurons,astrocytes,and oligodendrocytes.Mesenchymal stem cells-derived extracellular vesicles have also been shown to cross the blood-brain barrier to reach sites of central nervous injury and promote neural repair.However,it is not clear whether neuron-derived extracellular vesicles promote the differentiation of neural stem cells in a direction that is beneficial for neurogenesis. OBJECTIVE:To investigate whether neuron-derived extracellular vesicles facilitate neural stem cell differentiation towards neurogenesis. METHODS:Neurons and neural stem cells were extracted from neonatal SD rat cerebral cortex by trypsin digestion.Cell supernatants of neurons were collected.Neuron-derived extracellular vesicles were extracted.Neural stem cells cultured for 10 days were co-cultured with neuron-derived extracellular vesicles or PBS for 7 days.Immunoblotting,immunofluorescence,and RT-qPCR were used to detect proteins specifically expressed by neurons,neural stem cells,oligodendrocytes,and astrocytes. RESULTS AND CONCLUSION:The neural stem cells co-cultured with neuron-derived extracellular vesicles showed high expression of neuron-specific proteins and oligodendrocyte-specific proteins including β3-tubulin,neurofilament 200 and myelin basic protein,and low expression of astrocyte-specific protein glial fibrillary acidic protein.These results suggest that neuron-derived extracellular vesicles can promote the differentiation of neural stem cells into neurons and oligodendrocytes and prevent the differentiation of neural stem cells into astrocytes.

Objective:To understand the electrocardiogram and echocardiography examination results of population in key areas of unexplained sudden death in Yunnan Province (referred to as Yunnan sudden death).Methods:From 2014 to 2022, electrocardiogram examination was performed on population (including same incident cases, relatives of the cases, villagers of the affected villages, and control individuals) in key areas of Yunnan sudden death from May to October each year. Echocardiography examination was performed on relatives of the cases and villagers of the affected villages, and the types of electrocardiogram and echocardiography changes were sorted out and analyzed.Results:Electrocardiogram examination was conducted on 1 same incident case, 241 relatives of the cases, 464 villagers of the affected villages, and 99 control individuals, respectively. The types of electrocardiogram changes in the same incident case were Q-T interval prolongation and sinus tachycardia. A total of 17 types of electrocardiogram changes were detected in the relatives of the cases, mainly including sinus arrhythmia (12.45%, 30/241), sinus bradycardia (11.20%, 27/241), and left axis deviation (8.30%, 20/241). A total of 21 types of electrocardiogram changes were detected in the villagers of the affected villages, mainly including left axis deviation (9.48%, 44/464), sinus bradycardia (8.19%, 38/464), and T-wave abnormalities (7.76%, 36/464). A total of 10 types of electrocardiogram changes were detected in the control individuals, mainly including sinus arrhythmia (12.12%, 12/99), T-wave abnormalities (9.09%, 9/99), and sinus bradycardia (7.07%, 7/99). Echocardiography examination was conducted on 49 relatives of the cases and 365 villagers of the affected villages, respectively. A total of 12 types of echocardiography changes were detected in the relatives of the cases, mainly including tricuspid regurgitation (18.37%, 9/49), decreased right ventricular diastolic function (8.16%, 4/49), aortic regurgitation (6.12%, 3/49), and atrial septal defect (6.12%, 3/49). A total of 15 types of echocardiography changes were detected in the villagers of the affected villages, mainly including tricuspid regurgitation (8.77%, 32/365), aortic regurgitation (6.85%, 25/365), and decreased left ventricular diastolic function (6.58%, 24/365).Conclusion:There are many types of changes in electrocardiogram and echocardiography in the population of key areas of Yunnan sudden death.

Objective:To investigate the clinical characteristics, risk factors, and prognosis of invasive pulmonary aspergillosis (IPA) in patients with dermatomyositis associated with positive anti-melanoma differentiation-associated gene 5 (MDA5-DM).Methods:A total of 55 patients with MDA5-DM were analyzed. Patients were divided into IPA (+) group (14 cases) and IPA (-) group (41 cases) based on the presence of IPA. Microbiological examination and clinical data were analyzed. Risk factor analysis was performed using Binary Logistic regression, and survival analysis was carried out using Kaplan-Meier method.Results:Aspergillus flavus (5/14, 35.7%) and Aspergillus fumigatus (4/14, 28.6%) were the most common species in MDA5-DM patients with IPA. Compared to the IPA (-) group, IPA (+) group had higher serum level of α-hydroxybutyrate dehydrogenase (246 U/L vs. 191 U/L, Z=-2.02, P=0.043) and ferritin [1 306.7(518.7, 2 977.8)ng/ml vs. 472.6(269.0, 792.1)ng/ml, Z=-2.09, P=0.036], lower CD8 + T lymphocyte counts {[111.5 (68.3, 214.0)]×10 6/L vs. [188.0(141.0, 270.0)]×10 6/L, Z=-2.18, P=0.029}, and more positive BALF GM tests [70.0%(7/10) vs. 18.9%(7/37), χ2=9.82, P=0.004]. Elevated serum ferritin was found to be an independent risk factor for IPA occurrence [adjusted OR (95% CI)=1.001 (1.000, 1.002), P=0.031)]. In addition, the 6-month cumulative survival rate was significantly lower in the IPA (+) group than in the IPA (-) group (78.6% vs. 97.6%, P=0.021). Conclusion:The mortality of MDA5-DM patients is increased after IPA infection. Elevated serum ferritin is an independent risk factor for IPA occurrence, and active prevention and treatment of IPA are expected to improve the prognosis of patients.

Objective:To explore the relevance of a new comprehensive respiratory mechanics parameter, elastic power, to the 28-day prognosis of ARDS patients.Methods:Patients with ARDS hospitalized for at least 48 h with invasive mechanical ventilation in five intensive care units in three local hospitals in Lianyungang City from June 2018 to June 2022 were included in the study. Their baseline data and respiratory mechanics parameters were collected. Elastic power, mechanical power, driving pressure and lung compliance are calculated according to the corresponding formulae. The prognostic risk factors of ARDS patients were analysed using COX multi-factor regression, and the predictive value of EP/Cst on the 28-day prognosis of ARDS patients was evaluated based on ROC curve analysis and Kaplan-Meier survival curve.Results:There was no significantly difference in tidal volume and PEEP settings between the patients in the ARDS survivor and death groups ( P> 0.05). However, the differences in respiratory rate, plateau pressure, driving pressure, lung compliance, mechanical work, elastic work, EP/cst and MP/cst between the two groups were significantly different (all P< 0.01). Multifactorial COX regression analysis showed that EP/cst ( HR=1.211, 95% CI:1.091-1.323) and RR ( HR=1.209, 95% CI:1.046-1.339) were strongly associated with a more severe degree of illness and a worse prognosis in ARDS. And the cumulative survival rate at 28 d was significantly lower in the high Cst-EP group than in the low Cst-EP group (50.00% vs. 82.40%, P < 0.01). Conclusions:The new respiratory mechanics parameters EP and EP/Cst can assess the severity of ARDS with a good predictive effect on patient prognosis at 28 days.

Objective:To evaluate the effect of comprehensive intervention measures on Yunnan unexplained sudden death (YUSD) in Dali Prefecture, Yunnan Province, and to provide scientific basis for improving the prevention and control measures.Methods:Since 2010, Yunnan Province had implemented comprehensive intervention measures in ward areas according to the etiological pattern of YUSD. In July 2019, 47 families with YUSD were selected as case families and 23 families without YUSD were selected as control families in 31 natural villages of Heqing, Xiangyun, Yunlong, Eryuan, Jianchuan, Binchuan and Nanjian counties of Dali Prefecture. A unified questionnaire was used to investigate the basic information, economic status, dietary structure, and health literacy of the families during the two periods of "the first sudden death case" and "the present".Results:The annual household income of the case families at present (median, 20 492.6 yuan) was significantly higher than that of the first sudden death case (3 883.4 yuan), and the difference was statistically significant ( Z = - 5.27, P < 0.001). At present, rice (76.6%, 36/47) was the main diet of the case families; at the time of the first sudden death case, 23.4% (11/47) of the case families could not eat enough, and there was no such situation in the case families at present. Compared with the time of the first sudden death case, the dietary habits of the case families at present were as follows: the proportion of eating Trogia venenata decreased from 19.0% (39/205) to 0 (0/190), the proportion of eating wild fruit decreased from 17.1% (35/205) to 9.5% (18/190), and the proportion of drinking raw water decreased from 55.1% (113/205) to 42.1% (80/190), and the differences were statistically significant (χ 2 = 22.37, 4.90, 6.86, P < 0.05). Lifestyle and health awareness: the proportion of those who washed their hands before meals and after using the toilet increased from 9.8% (20/205) to 41.6% (79/190), those who did not overwork increased from 16.6% (34/205) to 34.2% (65/190), and those who took good protection when spraying pesticides increased from 7.3% (15/205) to 21.6% (41/190), and the differences were statistically significant (χ 2 = 53.17, 33.94, 16.48, P < 0.001). Toilet habits: the proportion of using outdoor toilet decreased from 75.6% (155/205) to 9.5% (18/190), the difference was statistically significant (χ 2 = 175.21, P < 0.001). When the first sudden death case occurred, the proportions of eating Trogia venenata and using outdoor toilet in the case families were higher than those in the control families (χ 2 = 22.37, 23.70, P < 0.001), the proportions of those who washed their hands before meals and after using the toilet and those who did not overwork in the case families were lower than those in the control families (χ 2 = 7.38, 4.93, P < 0.05). Conclusions:The economic conditions, production and living conditions of YUSD areas in Dali Prefecture have been significantly improved, and the health literacy and health prevention awareness of the population have been greatly improved. Economic conditions and living standard, dietary structure and health literacy may be related factors of YUSD.

OBJECTIVE: To develop and validate a mechanical power (MP)-oriented nomogram prediction model of weaning failure in mechanically ventilated patients. METHODS: Patients who underwent invasive mechanical ventilation (IMV) for more than 24 hours and were weaned using a T-tube ventilation strategy were collected from the Medical Information Mart for Intensive Care-IV v1.0 (MIMIC-IV v1.0) database. Demographic information and comorbidities, respiratory mechanics parameters 4 hours before the first spontaneous breathing trial (SBT), laboratory parameters preceding the SBT, vital signs and blood gas analysis during SBT, length of intensive care unit (ICU) stay and IMV duration were collected and all eligible patients were enrolled into the model group. Lasso method was used to screen the risk factors affecting weaning outcomes, which were included in the multivariate Logistic regression analysis. R software was used to construct the nomogram prediction model and build the dynamic web page nomogram. The discrimination and accuracy of the nomogram were assessed by receiver operator characteristic curve (ROC curve) and calibration curves, and the clinical validity was assessed by decision curve analysis (DCA). The data of patients undergoing mechanical ventilation hospitalized in ICU of the First People's Hospital of Lianyungang City and the Second People's Hospital of Lianyungang City from November 2021 to October 2022 were prospectively collected to externally validate the model. RESULTS: A total of 3 695 mechanically ventilated patients were included in the model group, and the weaning failure rate was 38.5% (1 421/3 695). Lasso regression analysis finally screened out six variables, including positive end-expiratory pressure (PEEP), MP, dynamic lung compliance (Cdyn), inspired oxygen concentration (FiO₂), length of ICU stay and IMV duration, with coefficients of 0.144, 0.047, -0.032, 0.027, 0.090 and 0.098, respectively. Logistic regression analysis showed that the six variables were all independent risk factors for predicting weaning failure risk [odds ratio (OR) and 95% confidence interval (95%CI) were 1.155 (1.111-1.200), 1.048 (1.031-1.066), 0.968 (0.963-0.974), 1.028 (1.017-1.038), 1.095 (1.076-1.113), and 1.103 (1.070-1.137), all P < 0.01]. The MP-oriented nomogram prediction model of weaning failure in mechanically ventilated patients showed accurate discrimination both in the model group and external validation group, with area under the ROC curve (AUC) and 95%CI of 0.832 (0.819-0.845) and 0.879 (0.833-0.925), respectively. Furthermore, its predictive accuracy was significantly higher than that of individual indicators such as MP, Cdyn, and PEEP. Calibration curves showed good correlation between predicted and observed outcomes. DCA indicated that the nomogram model had high net benefits, and was clinically beneficial. CONCLUSIONS The MP-oriented nomogram prediction model of weaning failure accurately predicts the risk of weaning failure in mechanical ventilation patients and provides valuable information for clinicians making decisions on weaning.
Humans ; Respiration, Artificial/methods* ; Ventilator Weaning/methods* ; Nomograms ; Lung ; Risk Factors