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 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 investigate the role and mechanism of molecular hydrogen in lipopolysaccharide (LPS)-induced acute lung injury (ALI).Methods:Balb/c male mice were randomly(random number) divided into control group, control+H 2, LPS and LPS+H 2 group with 6 mice in each group. The levels of malondialdehyde (MDA) and Fe 2+ in lung tissue were detected by kits. The lung tissue morphology was observed. The infiltration levels of F4/80 positive macrophages in lung tissue were detected by immunofluorescence staining. A549 cells were divided into control, control+H 2, erastin and erastin+H 2 group. The reactive oxygen species (ROS), malondialdehyde, (MDA), lactate dehydrogenase (GSH), number of cell death and lactate dehydrogenase (LDH) release in each group were detected by kits. Nrf2, GPX4, and HO-1mRNA were quantified by real-time PCR, the protein expression level of Nrf2 was detected by western blot, and the nuclear translocation level of Nrf2 was observed by immunofluorescence. The chi-square test was performed before the measurement data were counted. One-way analysis of variance was used to compare differences between multiple groups. Results:Compared with the control group, the histopathological damage was aggravated, and the levels of MDA, Fe 2+ significantly increased in the LPS group, and F4/80 positive immune cells infiltration significantly increased (all P<0.05). Compared with LPS group, the degree of lung injury in LPS+H 2 group significantly reduced (all P<0.05). In vitro experiments, compared with the control group, the ROS, MDA levels, number of cell death and LDH release significantly increased in erastin group (all P<0.05), while GSH, and GPX4 mRNA levels decreased (all P<0.05). HO-1mRNA and Nrf2 nuclear translocation levels increased (all P<0.05). Compared with erastin group, ROS, MDA levels, cell death number and LDH release decreased in earstin+H 2 group (all P<0.05). The levels of GSH, GPX4 mRNA, Nrf2 mRNA, HO-1 mRNA and Nrf2 nuclear translocation levels increased (all P<0.05). Conclusions:Molecular hydrogen attenuates LPS-induced ALI by promoting Nrf2 nuclear translocation to inhibit ferroptosis of alveolar epithelial cells.

Objective:To analyze the effectiveness and safety of robot-assisted percutaneous endoscopic posterior/transforaminal lumbar interbody fusion (RPE-P/TLIF) in the treatment of lumbar spinal stenosis with instability.Methods:From September 2018 to April 2022, 26 patients with lumbar spinal stenosis combined with lumbar segmental instability were treated with RPE-P/TLIF at the Department of Minimally Invasive Spine Surgery, Guangdong Provincial Hospital of Chinese Medicine. There were 13 males and 13 females, with a mean age of 57.92±7.09 years (range, 44 to 75 years) and a mean body mass index of 24.05±2.64 kg/m 2 (range, 19.38 to 29.06 kg/m 2). A total of 31 segments were included, including 21 cases of single-segment surgery (L 3, 4 in 2 cases, L 4, 5 in 18 cases, and L 5S 1 in 1 case) and 5 cases of two-segment surgery (all L 3-L 5). Before surgery and at 1, 6, and 12 months after surgery, as well as at the final follow-up, the visual analogue scale (VAS) was used to assess back pain and lower limb pain, and the Oswestry disability index (ODI) was used to evaluate spinal nerve function. Clinical efficacy was evaluated using the MacNab criteria at the final follow-up. Imaging evaluation indicators included pre- and post-operative intervertebral space height, lumbar lordosis angle, fusion rate, and accuracy of pedicle screw placement. Results:The follow-up time for the 26 patients was 42.88±10.09 months (range, 12 to 55 months). The mean operation time was 156.54±33.50 min, and the mean postoperative drainage volume was 27.23±20.20 ml. The VAS scores for back pain and lower limb pain before surgery were 4.35±1.23 and 6.08±0.63, respectively. These scores decreased to 2.08±0.69 and 1.85±0.54 at 1 month postoperatively, 1.85±0.54 and 0.77±0.59 at 6 months, 0.96±0.53 and 0.62±0.57 at 1 year, and 0.88±0.52 and 0.58±0.50 at the final follow-up, respectively. The differences were statistically significant ( F=85.943, P=0.001; F=547.946, P=0.014). The ODI scores before surgery and at 1, 6, 12 months after surgery, and at the final follow-up were 55.38%±5.89%, 28.38%±3.849%, 17.77%±2.67%, 12.58%±1.88% and 12.12%±2.27% respectively, with statistically significant differences ( F=783.289, P=0.010). According to the MacNab criteria, at the final follow-up, there were 18 cases of excellent, 6 cases of good, and 2 cases of fair, with an excellent and good rate of 92.3%. A total of 114 percutaneous pedicle screws were implanted with grades A, B and C being 109, 4 and 1, respectively. The preoperative, postoperative, and final follow-up intervertebral space heights were 10.55±1.96, 13.53±1.37, and 12.54±1.42 mm respectively, with statistically significant differences ( F=42.190, P<0.001). And the lumbar lordosis angles were 35.81°±10.80°, 35.69°±11.07°, and 36.08°±11.29° respectively, with no statistically significant differences ( P>0.05). At 12 months postoperatively, bone fusion was achieved in 25 cases, with a fusion rate of 96% (25/26). Conclusion:RPE-P/TLIF for lumbar spinal stenosis combined with lumbar instability were favorable. Being a safe and effective minimally invasive surgical option, it effectively enhanced the intervertebral space height in the surgical segment with fewer complications.

Intra-abdominal infection is the second common infectious disease in intensive care unit and inhospital patients, with the mortality rate of 20%-30%. Advances in medicine have not improved the outcomes of patients with intra-abdominal infection, and the increasing multi-drug resistance organism may lead to a deterioration in the prognosis of patients with intra-abdominal infection. Gut microbiota dysbiosis and abdominal cavity infections show an interdependent and mutually aggravating relationship. Intestinal microecological preparations regulate gut flora and are potential therapeutic measures for intra-abdominal infections. The authors review the changes in gut flora during intra-abdominal infection, the effect of gut flora on the prognosis of intra-abdominal infections and the role of intestinal microecological preparations in intra-abdominal infections.

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

Objective:To explore the diagnostic value of mechanical power (MP) in patients with moderate to severe acute respiratory distress syndrome (ARDS) based on the Medical Information Mart for Intensive Care-Ⅲv1.4 (MIMIC-Ⅲ v1.4).Methods:The information of ARDS patients undergoing invasive mechanical ventilation for no less than 48 hours who were hospitalized at Beth Israel Deaconess Medical Center in Boston, Massachusetts from June 2001 to October 2012 in the MIMIC-Ⅲ v1.4 were collected. The demographics of patients, disease severity scores, ARDS etiology, prognostic indicators, pre-ventilation arterial blood gas analysis and respiratory parameters within 48 hours of ventilation were extracted. According to the lowest oxygenation index (PaO 2/FiO 2) before ventilation, the patients were divided into mild to moderate ARDS group (> 150 mmHg, 1 mmHg≈0.133 kPa) and moderate to severe ARDS group (≤ 150 mmHg), and the differences in baseline characteristics between the two groups were compared. The independent predictors associated with the severity of ARDS were analyzed using Logistic regression. The receiver operator characteristic curve (ROC curve) was plotted. The area under ROC curve (AUC) was calculated to evaluate the diagnostic value of MP for moderate to severe ARDS. The Youden index was used to determine the diagnostic threshold of MP for moderate to severe ARDS. According to the cut-off value of MP based on Youden index, all ARDS patients were divided into high and low MP groups. Kaplan-Meier survival curve was used to analyze the 28-day survival status of patients. Results:A total of 403 ARDS patients were enrolled in the study, including 107 subjects with mild to moderate ARDS and 296 with moderate to severe ARDS. There were significant differences in age, sequential organ failure assessment (SOFA) score, the lowest PaO 2/FiO 2 before ventilation, the last PaO 2/FiO 2 before ventilation, 28-day mortality, the length of intensive care unit (ICU) stay, duration of mechanical ventilation, lung dynamic compliance (Cdyn) in the second 24 hours of ventilation and positive end-expiratory pressure (PEEP), plateau pressure (Pplat), driving pressure (ΔP), respiratory rate (RR), lung static compliance (Cst), MP, inspired fraction of oxygen (FiO 2) within 48 hours of ventilation between the two groups. After adjusting variables such as age, SOFA score, the last PaO 2/FiO 2 before ventilation, and related respiratory mechanics parameters, multivariate Logistic regression analysis showed that higher ΔP, PEEP and MP, and lower last PaO 2/FiO 2 before ventilation were independently associated with moderate to severe ARDS [odds ratio ( OR) and 95% confidence interval (95% CI) was 1.137 (1.032-1.252), 1.333 (1.139-1.561), 1.102 (1.030-1.179), and 0.996 (0.993-0.998), respectively, all P < 0.01]. The ROC curve analysis showed that the best cut-off value of MP for the diagnosis of moderate to severe ARDS was 18.1 J/min with sensitivity of 81.42% and specificity of 60.75%, and the AUC was 0.745 (95% CI was 0.690-0.799). According to the cut-off value of MP obtained by ROC curve, all ARDS patients were divided into high MP group (> 18.1 J/min) and low MP group (≤ 18.1 J/min). The Kaplan-Meier survival curve showed that the 28-day cumulative survival rate in the high MP group was significantly lower than that in the low MP group (73.8% vs. 85.1%; Log-Rank test: χ2 = 5.660, P = 0.017). Conclusion:MP is an independent predictor of the severity of ARDS, and it can be used to diagnose moderate to severe ARDS.

Background: Tigecycline, eravacycline, and omadacycline are recently developed tetracyclines. Susceptibility of microbes to these tetracyclines and their molecular mechanisms have not been well elucidated. We investigated the susceptibility of Moraxella catarrhalis to tigecycline, eravacycline, and omadacycline and its resistance mechanisms against these tetracyclines. Methods: A total of 207 non-duplicate M. catarrhalis isolates were collected from different inpatients. The minimum inhibitory concentrations (MICs) of the tetracyclines were determined by broth microdilution. Tigecycline-, eravacycline-, or omadacycline-resistant isolates were induced under In Vitro pressure. The tet genes and mutations in the 16S rRNA was detected by PCR and sequencing. Results: Eravacycline had a lower MIC50 (0.06 mg/L) than tigecycline (0.125 mg/L) or omadacycline (0.125 mg/L) against M. catarrhalis isolates. We found that 136 isolates (65.7%) had the tetB gene, and 15 (7.2%) isolates were positive for tetL; however, their presence was not correlated with high tigecycline, eravacycline, or omadacycline ( ≥ 1 mg/L) MICs.Compared with the initial MIC after 160 days of induction, the MICs of tigecycline or eravacycline against three M. catarrhalis isolates increased ≥ eight-fold, while those of omadacycline against two M. catarrhalis isolates increased 64-fold. Mutations in the 16S rRNA genes (C1036T and/or G460A) were observed in omadacycline-induced resistant isolates, and increased RR (the genes encoding 16SrRNA (four copies, RR1-RR4) copy number of 16S rRNA genes with mutations was associated with increased resistance to omadacycline. Conclusions Tigecycline, eravacycline, and omadacycline exhibited robust antimicrobial effects against M. catarrhalis. Mutations in the 16S rRNA genes contributed to omadacycline resistance in M. catarrhalis.

Objective:To evaluate the effect of remote endarterectomy in the treatment of complex lower extremity ischemia.Methods:Twenty-one limb ischemic patients underwent remote endarterectomy in Beijing Hospital from Sep 2016 to Feb 2020. Clinical data including general condition, the lesion of lower artery before operation and follow up outcomes were collected. Then the patency rate and limb salvage rate were calculated.Results:The technique success rate was 71.4% (15/21). The 3, 6, 12 month patency rate were 93.3%, 85.6% and 74.1%, respectively. The 1-year limb salvage rate was 93.3% (14/15). In the 6 patients converted to artificial vessel bypass, the 3,6,12 months patency rates were 76.7%, 66.7% and 46.8%, respectively. The 1-year limb salvage rate was 66.7%.Conclusions:Remote endarterectomy of the lower extremity artery is an alternative option in the treatment of complex ischemic lesions of the lower extremity artery, other than artificial vessel bypass.