Programming co-assembled peptide nanofiber morphology via anionic amino acid type: Insights from molecular dynamics simulations.

Co-assembling peptides can be crafted into supramolecular biomaterials for use in biotechnological applications, such as cell culture scaffolds, drug delivery, biosensors, and tissue engineering. Peptide co-assembly refers to the spontaneous organization of two different peptides into a supramolecular architecture. Here we use molecular dynamics simulations to quantify the effect of anionic amino acid type on co-assembly dynamics and nanofiber structure in binary CATCH(+/-) peptide systems. CATCH peptide sequences follow a general pattern: CQCFCFCFCQC, where all C's are either a positively charged or a negatively charged amino acid. Specifically, we investigate the effect of substituting aspartic acid residues for the glutamic acid residues in the established CATCH(6E-) molecule, while keeping CATCH(6K+) unchanged. Our results show that structures consisting of CATCH(6K+) and CATCH(6D-) form flatter ß-sheets, have stronger interactions between charged residues on opposing ß-sheet faces, and have slower co-assembly kinetics than structures consisting of CATCH(6K+) and CATCH(6E-). Knowledge of the effect of sidechain type on assembly dynamics and fibrillar structure can help guide the development of advanced biomaterials and grant insight into sequence-to-structure relationships.

Medical expenses of patients with severe mental disorders in Beijing, China.

OBJECTIVES: Mental health has become a significant public health problem that impacts both economic and social development, with severe mental disorders (SMDs) being the top priority. Over recent years, Beijing, China, has introduced several policies to reduce the economic burden on patients with mental health disorders. The aim of this study was to investigate the current status and composition of patients' medical expenses following the introduction of multiple medical policies, explore the factors that may impact the utilisation of medical services and provide a reference and basis for subsequent policy improvements. STUDY DESIGN: Multistage sampling was used to select a representative study population. A retrospective survey was used to collect patient information and data on medical expenses in 2019. METHODS: Descriptive statistics were applied to analyse the current status of patients' medical expenses, and a two-part model was used to examine the factors influencing healthcare utilisation and to model predicted expenses. RESULTS: Among 4940 participants, the average outpatient expenses of patients with SMD who incurred medical expenses were 8373.61 Yuan, and the average hospitalisation expenses were 81,594.05 Yuan. The out-of-pocket expenses were 29.22% of outpatient expenses and 8.13% of inpatient expenses. Factors such as age, household status, economic status, marital status, participation in the Community Free-Medication Service (CFMS) and the type of disease diagnosed influenced the differences in medical expenses and utilisation of services. CONCLUSIONS: The medical expenses of patients with SMD in Beijing are high, but a number of introduced policies have effectively reduced these costs for patients. Future studies should focus on the impact of factors such as age, economic status, participation in the CFMS and the type of disease diagnosed on medical expenses.

T-SPOT.TB Negative and Diagnosed as Interstitial Pulmonary Tuberculosis by NGS: a Case Report and Literature Review.

BACKGROUND: Tuberculosis is an airborne infectious disease with multiple morphologic changes on chest imaging. Tuberculosis-specific enzyme-linked immunospot assay (T-SPOT.TB) is widely used in the diagnosis of tuberculosis. Clinically, pulmonary tuberculosis with T-SPOT.TB negative and interstitial changes is very rare. METHODS: T-SPOT.TB, pathogenetic testing, chest CT scan, next-generation sequencing (NGS). RESULTS: Laboratory tests showed negative T-SPOT.TB and sputum antacid staining, chest CT showed interstitial fibrosis and multiple high-density shadows in both lungs, and sputum NGS showed Mycobacterium tuberculosis infection. CONCLUSIONS: Negative T-SPOT.TB and interstitial lung changes do not exclude Mycobacterium tuberculosis infection. NGS has a high specificity in the detection of pathogens in infectious diseases, especially in complex, mixed infectious diseases.

Positive PPD Test and TB-Ab Misdiagnosed as Tuberculosis Finally Proved as Sarcoidosis by Thoracoscopy: a Case Report.

BACKGROUND: Tuberculosis (TB) is a common infectious disease in developing countries. Tuberculosis and sarcoidosis are difficult to differentiate. We report a case of a patient who was initially misdiagnosed as tuberculosis due to positive tuberculin test (PPD test) and tuberculosis antibody (TB-Ab), which was eventually proven as sarcoidosis by thoracoscopy. METHODS: Appropriate laboratory tests are carried out and a chest CT scan, bronchoscopy, thoracoscopic pathological biopsy were done. RESULTS: Serum sedimentation was increased and tuberculosis antibody was positive. The chest CT scan showed multiple pulmonary nodules in both lungs. The bronchoscopy demonstrated no abnormality. Thoracoscopic pathology showed noncaseating granulomas and acid-fast staining was negative. CONCLUSIONS: When a patient has multiple pulmonary nodules and lymphadenopathy without obvious tuberculosis poisoning symptoms, physicians should pay attention to tuberculosis, sarcoidosis, and lung cancer. Pathology is crucial for the ultimate diagnosis.

Rare Co-Infection of the Lungs with EBV and Pneumocystis Carinii in a Patient with Kidney Cancer: a Case Report.

BACKGROUND: Epstein-Barr virus (EBV) is the primary agent of infectious mononucleosis, lymphoma, and naso-pharyngeal carcinoma, but rarely involves the lungs. Pneumocystis carinii is commonly found in patients with HIV infection and is not pathogenic when the host is healthy, but opportunistic infections can occur when the body is immunocompromised, causing pneumocystis pneumonia (PCP). It is rare for both diseases to occur in the lungs of the same patient. METHODS: Next-generation sequencing (NGS), laboratory examination, chest CT scan, electronic bronchoscopy, and pathogenetic examination were used in this study. RESULTS: Laboratory tests showed (1-3)-ß-D-glucan of 889.47 pg/mL, negative human immunodeficiency virus (HIV) antibody, and negative Aspergillus immunological test. Chest CT showed multiple high-density shadows in both lungs, and EBV infection combined with Pneumocystis carinii pneumonia was confirmed by bronchoscopic biopsy and NGS examination. CONCLUSIONS: Elevated serum (1-3)-ß-D-glucan is not a specific index for infectious diseases. Bronchoscopy and the NGS has high specificity in pathogen detection of infectious diseases.

D-Dimer and Procalcitonin Improve the Sensitivity of BAP-65 Score in Predicting AECOPD Patients Admission to ICU.

BACKGROUND: The study aimed at investigating the effectiveness of the BAP-65 score combined with D-dimer and procalcitonin (PCT) in predicting admission of acute exacerbation chronic obstructive pulmonary disease (AECOPD) patients to the intensive care unit (ICU). METHODS: We conducted a retrospective study. We analyzed data from 369 patients over the age of 40 years ad-mitted to our hospital with AECOPD. All patients received blood routine measurements and BAP-65 score calculation on admission. Receiver operating characteristic curves (ROC) were used to assess the sensitivity and specificity of D-dimer, PCT, and BAP-65 scores and combined metrics in predicting the risk of admissions to the ICU of AECOPD patients. RESULTS: We found that the percentage of patients with AECOPD admitted to the ICU was 32.25% (119/369). The area under the curve (AUC) of D-dimer, PCT, and BAP-65 score in individually predicting the probability of entering the ICU of AECOPD patients were 0.74 (95% CI 0.68 - 0.80), 0.83 (95% CI 0.78 - 0.88), and 0.72 (95% CI 0.66 - 0.79), respectively. The sensitivities of D-dimer, PCT, and BAP-65 score were 0.51, 0.65, and 0.52, respectively. The specificities of D-dimer, PCT, and BAP-65 score were 0.90, 0.91, and 0.92, respectively. The AUC of D-dimer and PCT combined with BAP-65 score was 0.90 (95% CI 0.86 - 0.94), the sensitivity and specificity were 0.90 and 0.80, respectively. CONCLUSIONS: D-dimer and procalcitonin improve the sensitivity of the BAP-65 score in predicting the probability of AECOPD patients entering the ICU while having a good specificity.

Non-Tuberculous Mycobacteria with Enlarged Mediastinal Lymph Node by Next Generation Sequencing: Case Report.

BACKGROUND: A young patient characterized by rapid enlargement of mediastinal lymph nodes was diagnosed as non-tuberculous mycobacterial pulmonary disease (NTM-PD) by bronchoalveolar lavage fluid Next Generation Sequencing (NGS). METHODS: Laboratory examination, Chest CT scan, electronic bronchoscopy, and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) were performed to diagnose non-tuberculous mycobacterium pulmonary disease. RESULTS: Detection of bird-intracellular mycobacterium complex in bronchoalveolar lavage fluid by NGS. Chest CT scan showed multiple enlarged lymph nodes in mediastinum. 4R region TBNA: chronic granulomatous inflammation, positive bacilli were found by acid-fast staining. After the anti-NTM treatment, the symptoms of the patients were relieved. CONCLUSIONS: When the patient shows mediastinal lymph node enlargement of unknown cause, NTM-PD can be considered and NGS can be used to assist in the diagnosis.

Procalcitonin (PCT) Improves the Accuracy and Sensitivity of CURB-65 Score in Predicting CAP Patients Admission to ICU.

BACKGROUND: The CURB-65 scoring system is a simple tool for assessment and prognosis prediction for community-acquired pneumonia (CAP) patients. However, the variations in the performance of CURB-65 in young and elderly patients, underestimation, or overestimation of the severity have often been reported. It is worth noting that the application of biomarkers is helpful for improving the accuracy of the scoring system. In recent years, more and more reports and studies paid attention to procalcitonin (PCT) in respiratory infectious diseases, and its clinical value has attracted increasing attention. The study aimed at investigating the effectiveness of the CURB-65 score combined with PCT in predicting admission of CAP patients to intensive care units (ICU). METHODS: We conducted a retrospective study. We analyzed data from 520 non-immune individuals over the age of 18 in this study. All patients received blood indicators measurement and CURB-65 score calculation on admission. The primary outcome used to assess the probability of a CAP patient was who would get a bed in general ward or ICU. Receiver operating characteristic curves (ROC) were used to evaluate the sensitivity and specificity of the CURB-65 model and PCT combined CURB-65 augmented model in predicting the main outcomes. RESULTS: After analyzing the data from 520 patients, we found that the probability of entering the ICU was 22.1% (115/520). The AUC of Combination 1 (PCT&CURB-65 scores), Combination 2 (WBC&CURB-65 scores), Combination 3 (hs-CRP&CURB-65 scores) and Combination 4 (D-dimer&CURB-65 scores) for predicting CAP patients entering the ICU was 0.92 (95% CI 0.88 - 0.95), 0.91 (95% CI 0.87 - 0.94), 0.89 (95% CI 0.85 - 0.92), and 0.90 (95% CI 0.87 - 0.94), respectively, with statistically significant differences (p = 0.00); the sensitivities were 0.83, 0.82, 0.77 and 0.77, respectively, and the specificities were 0.92, 0.84, 0.90 and 0.91, respectively. PCT was superior to other indexes to improve the sensitivity and specificity of the CURB-65 score. CONCLUSIONS: Procalcitonin improves the accuracy and sensitivity of the CURB-65 score in predicting the probability of CAP patients entering the ICU, and PCT was superior to other indexes to improve the sensitivity and specificity of the CURB-65 score.

Organizing Pneumonia Secondary to Infection with Coxiella Burnetii: a Case Report.

BACKGROUND: Organizing pneumonia is a non-specific inflammatory response to various types of damage to the lungs. It is usually considered bacterial pneumonia that has not been absorbed for more than 4 weeks, accompanied by granulomas and fibrosis. Lung lesions in patients with organizing pneumonia are usually irreversible and the prognosis is relatively poor. Coxiella burnetii can cause Q fever. Acute Q fever usually presents as a self-limiting febrile illness with a good prognosis, but there are few cases of coexisting organizing pneumonia. We report a case of organizing pneumonia secondary to Coxiella burnetii infection. METHODS: Percutaneous lung biopsy, Next-generation sequencing (NGS). RESULTS: Percutaneous lung biopsy showed the existence of organizing pneumonia, and external examination of NGS showed the existence of Coxiella burnetii infection. After symptomatic treatment with azithromycin and glucocorticoids, the patient improved and was discharged from the hospital. CONCLUSIONS: For lesions with obvious heterogeneous enhancement on chest CT imaging, percutaneous lung biopsy or bronchoscopy should be performed promptly to obtain pathological tissue, and NGS should be used for definite diagnosis if necessary.

Mycobacterium Tuberculosis Infection in AECOPD Combined with Pulmonary Embolism: a Case Report.

BACKGROUND: Mycobacterium tuberculosis belongs to the group of mycobacteria, most of which can cause a delayed hypersensitivity reaction in the body and is a bacterium that causes tuberculosis. Mycobacterium tuberculosis infection often presents with symptoms of tuberculosis toxicity and rarely with respiratory distress. At the same time, chest imaging often shows an ill-defined solid shadow in the apical and posterior segments of the upper lobe and, less frequently, in the dorsal segment of the lower lobe, and less frequently a diffuse nodular shadow. We report a case of AECOPD combined with pulmonary embolism infected with Mycobacterium tuberculosis. METHODS: Bronchoscopy, Next-generation sequencing (NGS). RESULTS: Antacid staining of bronchoalveolar lavage fluid suggested that a small amount of Mycobacterium antacid was visible. NGS was sent for examination and it suggested the presence of Mycobacterium tuberculosis with a sequence number of 5 (reference range ≥ 0). Treatment such as bronchodilation and antituberculosis was given. CONCLUSIONS: In patients with dyspnea, it is crucial to find the causative agent and to promptly improve relevant examinations such as pulmonary arteriography and bronchoscopy, and if necessary, to make a definitive diagnosis by NGS.

[Preventive effect of atropine premedication on vagal reflex in patients undergoing suspension laryngoscopy during anesthesia induction].

Objective: To evaluate the preventive effect of atropine premedication during anesthesia induction on vagal reflex in patients undergoing suspension laryngoscopy. Methods: A total of 342 patients (202 males and 140 females) scheduled for suspension laryngoscopy under general anesthesia in Beijing Tongren Hospital from October 2021 to March 2022 were prospectively enrolled, with a mean age of (48.1±11.9) years. The patients were randomly divided into two groups using the random number table method: the treatment group (n=171) and the control group (n=171). Patients in the treatment group were administrated with 0.5 mg atropine intravenously guttae (ivgtt) while patients in the control group were given equivalent volume of normal saline. For all patients, if heart rate (HR)<50 beats/min happened during the insertion of the suspension laryngoscope, the operation should be stopped and the laryngoscope should be removed. Patients without HR recovery after the removal of the laryngoscope should be given 0.5 mg atropine, and the operation should be continued after the HR recovered. The primary outcome was the incidence of HR fluctuation over 20% (ΔHR>20%) before and immediately after suspension laryngoscope fixation, and the secondary outcomes included HR, mean arterial pressure (MAP) of the two groups recorded before and after anesthesia induction, before and immediately after suspension laryngoscope fixation, and the incidences of sinus bradycardia, laryngoscope removal and atropine treatment during operation. Results: The incidences of ΔHR>20% and bradycardia immediately after the suspension laryngoscope fixation were 14.6% (25/171) and 12.9% (22/171) in the treatment group, which were significantly lower than those in the control group [28.1% (48/171) and 29.8% (51/171)] (both P<0.05). The HR immediately after the suspension laryngoscope fixation in the treatment group [(66.4±13.5) beats/min] and in the control group [(60.8±15.7) beats/min] was significantly lower than those before the suspension laryngoscope fixation [(74.7±11.1) beats/min and (67.6±12.8) beats/min, respectively] (both P<0.05). There were no significant differences in MAP between the two groups at each time point (all P>0.05). The incidence of laryngoscope removal once plus 0.5 mg atropine administration, laryngoscope removal twice plus 0.5 mg atropine administration and laryngoscope removal twice plus 1.0 mg atropine administration was 9.9% (17/171), 1.8% (3/171) and 0 (0) in the treatment group, respectively, which was significantly lower than those in the control group [24.0% (41/171), 5.8% (10/171) and 2.3% (4/171), respectively] (all P<0.05). Conclusion: Atropine premedication during anesthesia induction can effectively reduce the occurrence of vagal reflex in patients undergoing suspension laryngoscopy.

[The analysis of a pedigree with hereditary coagulation factor â ¤ deficiency caused by compound heterozygous variation of F5 gene].

Objective: To analyze the gene variation of a genetic coagulation factor Ⅴ (FⅤ) deficiency pedigree and explore the molecular pathogenesis. Methods: The proband was a 32 years old female. The patient was prone to nose bleeding since childhood which was usually self-healed. On March 10, 2021, the proband went to the First Affiliated Hospital of Air Force Medical University for treatment of knee hematoma caused by a fall. None of the family members reported any history of bleeding. The prothrombin time (PT), activated partial thromboplastin time (APTT) and FⅤ activity (FⅤ: C) were detected by clotting method and the FⅤ antigen (FⅤ: Ag) was tested with enzyme-linked immunosorbent assay (ELISA). All exons and flanks of F5 gene were determined by Sanger sequencing. Clustalx-2.1-win, PolyPhen-2 and Swiss-PDBViewer software were used to analyze the conservatism of missense variation sites, whether the variations were harmful and their influences on protein structure and function. MutationTaster and NetGene2 software were used to analyze whether the splice site variation was harmful and its effect on the splice site. Results: The PT and APTT of the proband prolonged to 24.0 s and 69.8 s, respectively. The FⅤ: C and FⅤ: Ag decreased to 6% and 9%, respectively. There were compound heterozygous variations in F5 gene, which included c.911G>A heterozygous missense variation in exon 6 leading to p.Gly276Glu variation and c.5208+1G>A heterozygous missense variation in intron 15. The father and daughter had the p.Gly276Glu heterozygous variation. Her mother and son had the c.5208+1G>A heterozygous variation. Software analysis results of p.Gly276Glu heterozygous variation showed that Gly276 was conserved among homologous species, the variation was harmful, and it could affect the local structure and function of the protein. The c.5208+1G>A heterozygous variation was deleterious and resulted in the disappearance of the splice site, thereby affecting the protein function. Conclusion: The p.Gly276Glu and c.5208+1G>A compound heterozygous variants are deleterious variants associated with the patient's disease and may be the molecular pathogenesis of inherited FⅤ deficiency in this family.

Recurrent ZNF83-E293V Mutation Promotes Bladder Cancer Progression through the NF-κB Pathway via Transcriptional Dysregulation of S100A8.

Urothelial carcinoma (UC) is the predominant form of bladder cancer. Significant molecular heterogeneity caused by diverse molecular alterations brings about large variations in the response to treatment in UC. An improved understanding of the genetic mechanisms underlying the development and progression of UC is essential. Through deep analysis of next-generation sequencing data of 99 UC patients, we found that 18% of cases had recurrent somatic mutations in zinc finger protein gene zinc finger protein 83 (ZNF83). ZNF83 mutations were correlated with poor prognosis of UC. We also found a hotspot mutation, p.E293V, in the evolutionarily well-conserved region of ZNF83. ZNF83-E293V increased tumor growth and reduced the apoptosis of UC cells compared to wild-type ZNF83 both in vitro and in mice xenografted tumors. ZNF83-E293V activated nuclear factor κB (NF-κB) more potently than did the wild-type protein owing to its decreased transcriptional repression for S100A8. The NF-κB inhibitors could pharmacologically block the tumor growth in mice engrafted with ZNF83-E293V-transfected UC cells. These findings provide a mechanistic insight and a potential therapeutic strategy for UC, which established a foundation for using the ZNF83-E293V mutation as a predictive biomarker of therapeutic response from NF-κB inhibitors.

A Predictive Model Based on Blood Indicators for Admission to the ICU with AECOPD.

BACKGROUND: AECOPD is the most common cause of death among infectious diseases in developing countries, and also an important cause of mortality and morbidity in developed countries. In recent years, related scoring systems such as the mMRC score and CAT questionnaire have been widely used to assess the severity of AECOPD. However, they both have some shortcomings in predicting the admission of AECOPD patients to the ICU. This study aimed to develop a new prediction model to predict the admission of AECOPD patients to the ICU based on objective blood indicators. METHODS: This was a retrospective study. Enrolled patients with AECOPD underwent blood gas analysis as well as biomarker testing for serum inflammatory markers, including white blood cell count (WBC), neutrophils, D-dimer, procalcitonin (PCT), high-sensitivity C-reactive protein (hs-CRP), and erythrocyte sedimentation rate (ESR). General characteristics such as age and gender were also recorded. The main observation was admission to the ICU. Univariate analysis and binary logistic regression analysis were used to explore independent risk factors for admission to the ICU in patients with AECOPD, which could be used as components of a new predictive model. Subject receiver operating characteristic curves (ROC) were used to assess the sensitivity and specificity of the new model, which consisted of all independent risk factors predicting the primary outcome. RESULTS: Initially, 369 patients with AECOPD were admitted to the general ward, of which 119 were subsequently transferred to the ICU (119/369). PaCO2, WBC, D-dimer, PCT, and hs-CRP were independent risk factors for admission to the ICU in patients with AECOPD. The AUC of the new prediction model (combined model consisting of PaCO2, WBC, D-dimer, PCT, and hs-CRP) was 0.94 (95% CI 0.92 - 0.97). The sensitivity was 80.7% and the specificity was 94.8%. CONCLUSIONS: The model for predicting the admission of AECOPD patients to the ICU based on blood indicators has a high specificity and sensitivity.

A New Prediction Model for Prolonged Hospitalization in Adult Community-Acquired Pneumonia (CAP) Patients.

BACKGROUND: As a serious and common out-of-hospital infectious disease, community-acquired pneumonia (CAP) ranks among the leading causes of death in both developing and developed countries. In recent years, the increasing incidence of CAP has led to an increase in the number of hospitalizations. Although CURB-65 (or CRB-65) and pneumonia severity Index (PSI) scoring systems are widely used in CAP prognostic scoring systems, each score had some limitations in predicting whether patients with CAP would require prolonged hospitalization. The aim of this study was to analyze serum inflammatory biomarkers combined with age to establish a novel predictive model for predicting prolonged hospitalization in patients with CAP. METHODS: In a retrospective study, serum inflammatory biomarkers were collected from all enrolled CAP patients, including white blood cell count (WBC), high-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), D-dimer, procalcitonin (PCT), fibrinogen (FIB), and ICU treatment. Length of hospital stay and age were also recorded. The 75th percentile of length of stay in the enrolled population was defined as long hospitalization over time, and the primary predictor of outcome was prolonged hospitalization. Univariate analysis and binary logistic regression analysis were used to explore the independent risk factors which could be components of a new predicting model for prolonged hospitalization in CAP patients. ROC curves were used to evaluate the sensitivity and specificity of the new model, which consisted of the combination of all independent risk factors in predicting the main outcomes. RESULTS: The results showed that among 364 patients with CAP, 85 had extended hospitalization (85/364). Further analysis showed that age, white blood cell, fibrinogen, and high-sensitivity C-reactive protein were independent risk factors for extended hospitalization in patients with CAP. Finally, the AUC of the ROC curve of the new prediction model (the joint model consists of age, WBC, FIB, and hs-CRP) was 0.93 (95% CI 0.90 - 0.96), and the sensitivity and specificity were 87.1% and 87.8%, respectively. CONCLUSIONS: Serum inflammatory biomarkers combined age have high specificity and sensitivity in predicting prolonged hospitalization in adult CAP patients.

Carcinoembryonic Antigen Elevation in Broncholithiasis Patients Initially Misdiagnosed as Lung Cancer: a Case Report.

BACKGROUND: We report a case of broncholithiasis with recurrent pulmonary infection accompanied by blood in the sputum, which was initially misdiagnosed as lung cancer after laboratory examination indicating elevated carcinoembryonic antigen. METHODS: Laboratory examination, enhanced chest CT scan, electronic bronchoscopy, and ultra-thin bronchoscopy were performed to diagnose broncholithiasis. RESULTS: Carcinoembryonic antigen levels were elevated. Chest CT scan showed dense nodules and calcification in the middle lobe of the right lung. Ultrathin bronchoscopy demonstrates calcification of the distal bronchus of the lateral middle lobe of the right lung. The symptoms were relieved after the removal of the calculi by electronic bronchoscopy. CONCLUSIONS: It is necessary to pay attention to the calcification of the trachea and the differential diagnosis of lung cancer, especially when the level of carcinoembryonic antigen is increased.

Initial Elevated Myocardial Enzymes were Neglected in Lung Adenocarcinoma ICIS Associated Myocarditis: a Case Report.

BACKGROUND: In recent years, immunotherapy has gradually become the first or second-line drug for non-small cell lung cancer. However, the side effects associated with immunotherapy should not be underestimated. Toxic reactions are commonly seen in the skin, endocrine, and liver, and rarely in the heart and nerves. These effects are often life-threatening when they occur. In this paper, we present a case of ICIs-associated myocarditis in advanced lung adenocarcinoma with unappreciated initial cardiac enzyme elevation in a driver gene negative. METHODS: After electronic bronchoscopy and pathological examination, the patient was diagnosed with driver gene-negative advanced lung adenocarcinoma and treated with ICIs. RESULTS: Driver gene-negative advanced lung adenocarcinoma, effectively treated with ICIs, initially had elevated cardiac enzymes and unilateral ptosis, but was not taken seriously and the patient eventually died after discharge from the hospital. CONCLUSIONS: For patients with driver gene-negative advanced lung adenocarcinoma treated with ICIs, regular and periodic monitoring of myocardial damage markers is a top priority, followed by timely initiation of hormonal therapy as a means to improve prognosis.

[Effects of topical anesthesia with 1% tetracaine on hemodynamic responses in microlaryngosurgery].

Objective: To observe the effects of topical anesthesia with 1% tetracaine on hemodynamic responses in general anesthesia patients undergoing microlaryngosurgery. Methods: From October 2021 to December 2021, 92 patients (46 males and 46 females) in Beijing Tongren Hospital, with a median age [M (Q1, Q3)] of 51 (42, 57) years who scheduled for microlaryngosurgery under general anesthesia, were divided into two groups (n=46 in each group) using the random number table method. Group T received topical anesthesia with 1% tetracaine at the root of the tongue and epiglottis and glottis on the basis of general intravenous anesthesia induction, with 0.5 ml at each position, while the control group (group C) received equal volume of normal saline. Heart rate (HR) and mean arterial pressure (MAP) were recorded at the time of patients entering the operating room (baseline), after induction, after intubation, immediately after suspending laryngoscopy, 1 min after suspending laryngoscopy, 3 min after suspending laryngoscopy, 5 min after suspending laryngoscopy and immediately after extubation. The recovery profiles, including time to recover breathing, time to open eyes, time to extubation and adverse reactions were evaluated during recovery period. Results: The MAP of patients in group T at baseline, after induction, after intubation, immediately after suspending laryngoscopy, 1 min after suspending laryngoscopy, 3 min after suspending laryngoscopy, 5 min after suspending laryngoscopy and immediately after extubation were (99.4±12.9), (78.5±8.8), (79.2±10.2), (100.6±17.0), (101.9±14.7), (100.8±13.9), (97.4±12.1), (107.3±16.8) mmHg (1 mmH=0.133 kPa), respectively, while in group C were (99.5±11.6), (80.9±12.8), (90.5±16.0), (109.5±20.4), (108.0±18.9), (103.7±15.5), (100.1±13.3), (114.2±17.3) mmHg, respectively. The two critical time points of MAP after intubation and immediately suspending laryngoscopy in group C were significantly higher than group T (P<0.05).The HR of patients in group T at baseline, after induction, after intubation, immediately after suspending laryngoscopy, 1 min after suspending laryngoscopy, 3 min after suspending laryngoscopy, 5 min after suspending laryngoscopy and immediately after extubation was (71.3±10.6), (66.0±10.1), (69.5±11.4), (61.3±14.2), (69.8±9.8), (71.0±10.6), (70.6±11.0), (78.8±11.6) bmp, respectively, while in group C were (73.1±10.9), (67.8±9.9), (79.5±12.9), (57.1±18.1), (69.2±12.8), (71.4±11.7), (70.7±11.5), (85.3±13.0) bmp, respectively. The two critical time points of HR after intubation and after extubation in group C were significantly higher than that of group T (P<0.05). The time to recover breathing in the two groups was (11.8±3.5) min and (11.3±4.6) min, respectively. The time to open eyes was (12.0±3.3) min and (11.5±5.0) min, respectively. The time to extubation was (13.2±3.7) min and (12.6±4.9) min, respectively. There were no statistically significant difference in time to recovery between the two groups (P>0.05). Likewise, there were no toxic reactions to local anesthetics, respiratory depression, hypoxemia, laryngospasm and cough occurred in either group. Conclusion: Topical anesthesia with 1% tetracaine can effectively reduce the hemodynamic changes without influencing patient's recovery, and does not increase the incidence of adverse reactions.

The short-term efficacy of electrical pudendal nerve stimulation versus intravesical instillation for the urethral pain syndrome: a randomized clinical trial.

PURPOSE: Urethral pain syndrome is a chronic condition characterized by disturbing feeling or server pain sensed at the urethra without specific treatment. This double-center, two-arm controlled trial aimed to explore the efficacy of electrical pudendal nerve stimulation (EPNS) versus intravesical instillation (II) of heparin and alkalinized lidocaine for urethral pain syndrome (UPS). METHODS: Eighty eligible patients took three sessions of EPNS, or 1 session of II per week, for 6 consecutive weeks. The primary end point was the change of pelvic pain and urgency/frequency symptom (PUF) score from baseline to week 6. Secondary outcome measures included changes of visual analogue scale (VAS) score and three sub-score extracted from PUF score. RESULTS: The enrolled participants were all included in the intention-to-treat analyses, and baseline characteristics between the two groups were well balanced. The post-treatment PUF score decreased by 10.0 (7.00, 16.50) in the EPNS group, and by 7.0 (3.00, 10.00) in the II group. At the closure of treatment, the medians of changes in symptom score, bother score, pain-related score and VAS score were 6.50 (4.25, 10.00), 4.00 (2.00, 6.00), 6.00 (5.00, 8.00),4.50 (2.25, 6.00), respectively, in the EPNS group, and 4.00 (2.00, 7.00), 3.00 (1.00, 3.00), 3.00 (2.00, 6.00), 2.00 (1.00, 4.00), respectively, in the II group. All the between-group differences were statistically significant. CONCLUSION: Compared with the II, the EPNS results in superior pain control and better relief of lower urinary tract symptoms, and deserves further attention. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03671993).

Midterm Outcomes After Reconstruction of Superolateral Acetabular Defects Using Flying Buttress Porous Tantalum Augments During Revision Total Hip Arthroplasty.

BACKGROUND: Porous tantalum augments are versatile tools in reconstructing complex acetabular defects during revision total hip arthroplasty (THA). This study examines the clinical and radiographic outcomes of porous tantalum augments placed in the type I (flying buttress) configuration at two to 17-year follow-up in the largest cohort to-date in the literature. METHODS: We retrospectively analyzed 59 consecutive revision THAs involving the use of flying buttress augments between 2003 and 2018. The mean patient age and follow-up duration were 63.9 ± 11.6 years (range, 35-87) and 8 years (range, 2-17), respectively. The Oxford hip score was used to assess clinical outcome. The modified Moore classification was used to assess acetabular augment and shell osseointegration. Kaplan-Meier survival analysis with 95% confidence interval (CI) was used to assess implant survivorship. RESULTS: The mean Oxford hip score improved from 15.9 ± 6.2 preoperatively to 35.0 ± 6.5 at a mean follow-up of eight years (P < .0001). Radiographic assessment using the modified Moore classification demonstrated five signs of osseointegration in 49 hips (83.1%), four signs in six hips (10.2%), three signs in one hip (1.7%), and one sign in one hip (1.7%). Kaplan-Meier analysis demonstrated ten-year survivorship of 88.9% (95% CI 74.4-95.4) with all-cause revision as end point and 94.3% (95% CI 83.1-98.2) with revision for acetabular aseptic loosening as end point. CONCLUSION: Treatment of superolateral acetabular defects during revision THA using porous tantalum augments placed in the type I (flying buttress) configuration provides excellent implant survivorship and favorable clinical outcomes at mid-term follow-up. LEVEL OF EVIDENCE: Therapeutic Level IV.