Protocol for combined N-of-1 trials to assess cerebellar neurostimulation for movement disorders in children and young adults with dyskinetic cerebral palsy.

BACKGROUND: Movement and tone disorders in children and young adults with cerebral palsy are a great source of disability. Deep brain stimulation (DBS) of basal ganglia targets has a major role in the treatment of isolated dystonias, but its efficacy in dyskinetic cerebral palsy (DCP) is lower, due to structural basal ganglia and thalamic damage and lack of improvement of comorbid choreoathetosis and spasticity. The cerebellum is an attractive target for DBS in DCP since it is frequently spared from hypoxic ischemic damage, it has a significant role in dystonia network models, and small studies have shown promise of dentate stimulation in improving CP-related movement and tone disorders. METHODS: Ten children and young adults with DCP and disabling movement disorders with or without spasticity will undergo bilateral DBS in the dorsal dentate nucleus, with the most distal contact ending in the superior cerebellar peduncle. We will implant Medtronic Percept, a bidirectional neurostimulator that can sense and store brain activity and deliver DBS therapy. The efficacy of cerebellar DBS in improving quality of life and motor outcomes will be tested by a series of N-of-1 clinical trials. Each N-of-1 trial will consist of three blocks, each consisting of one month of effective stimulation and one month of sham stimulation in a random order with weekly motor and quality of life scales as primary and secondary outcomes. In addition, we will characterize abnormal patterns of cerebellar oscillatory activity measured by local field potentials from the intracranial electrodes related to clinical assessments and wearable monitors. Pre- and 12-month postoperative volumetric structural and functional MRI and diffusion tensor imaging will be used to identify candidate imaging markers of baseline disease severity and response to DBS. DISCUSSION: Our goal is to test a cerebellar neuromodulation therapy that produces meaningful changes in function and well-being for people with CP, obtain a mechanistic understanding of the underlying brain network disorder, and identify physiological and imaging-based predictors of outcomes useful in planning further studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT06122675, first registered November 7, 2023.

[Pulmonary co-infection with Nocardia otitidiscaviarum and Aspergillus: a case report].

Nocardia is a rarely encountered opportunistic gram-positive bacterium that exhibits marked invasiveness and dissemination. Typically, acquired through trauma or inhalation, this pathogen primarily affects immunocompromised individuals and is a potentially life-threatening risk in severe cases. Nocardia otitidiscaviarum is a particularly rare subtype of Nocardia infection, and the occurrence of concurrent Aspergillus infection is extremely rare. In cases where both infections manifest concomitantly, rapid and accurate diagnosis is essential to facilitate the subsequent selection of appropriate anti-infective interventions. This paper reported the diagnostic and therapeutic experience in managing a case of pulmonary co-infection with Nocardia otitidiscaviarum and Aspergillus. The patient presented with an acute onset, rapid progression, and early manifestation of respiratory failure. The diagnostic process included respiratory pathogen culture and bronchoscopy, which was supplemented with targeted next-generation sequencing (tNGS). These comprehensive diagnostic modalities led to the identification of pulmonary co-infection with Nocardia otitidiscaviarum and Aspergillus. After adjustment of the antibiotic regimen, the patient's condition improved rapidly, culminating in a timely discharge.

[Diagnosis and surgical treatment of high-risk anomalous aortic origin of coronary artery].

Objective: To analyze the diagnosis and surgical treatment of high-risk anomalous aortic origin of coronary artery (AAOCA). Methods: This is a retrospective case series study. From January 2016 to July 2023, 24 cases of high-risk AAOCA underwent surgical treatment in Department of Cardiac Surgery, Guangdong Provincial People's Hospital. There were 18 males and 6 females, operatively aged (M (IQR)) 13 (26) years (range: 0.3 to 57.0 years). They were confirmed by cardiac ultrasound and cardiac CT, all of which had anomalous coronary running between the aorta and the pulmonary artery. There were 15 cases of the right coronary artery from the left aortic sinus of Valsalva, 6 cases of left coronary artery from the right aortic sinus of Valsalva, 3 cases of the sigle coronary artery. Only 3 patients had no obvious related symptoms (2 cases were complicated with a positive exercise stress test and 1 case with other intracardiac malformations), 21 cases had a history of chest tightness, chest pain, or syncope after exercise. Three patients suffered syncope after exercise and underwent cardiopulmonary resuscitation (2 cases were treated with an extracorporeal membrane oxygenerator (ECMO)). The gap from the first symptom to the diagnosis was 4.0 (11.5) months (range: 0.2 to 84.0 months). The detection rate of coronary artery abnormalities suggested by the first cardiac ultrasound was only 37.5% (9/24). Seven patients were complicated with other cardiac diseases (4 cases with congenital heart defects, 2 cases with coronary atherosclerotic heart disease, 1 case with mitral valve disease). Results: All 24 patients underwent surgical treatment (23 cases underwent abnormal coronary artery unroofing, 1 case underwent coronary artery bypass grafting), and 5 patients underwent other intracardiac malformation correction at the same time. There were no death or surgery related complications in the hospital for 30 days after the operation. A patient with preoperative extracorporeal cardiopulmonary resuscitation was continuously assisted by ECMO after emergency AAOCA correction and had complications such as limb ischemia necrosis and renal dysfunction after the operation. During the follow-up of 2.2 (3.3) years (range: 1 month to 7.2 years), one patient who previously underwent percutaneous transluminal coronary angioplasty with a stent implant experienced significant postoperative symptomatic relief, and the other discharged patients had no related symptoms. Conclusions: The accurate rate of initial diagnosis for high-risk AAOCA is still low, but the risk of cardiovascular accidents is high. For sports-related chest pain and other symptoms, more attention should be paid to the detection of AAOCA, especially for adolescents. Exercise stress testing can be helpful in evaluating the cardiovascular risk of asymptomatic AAOCA. Instant surgical treatment can achieve satisfactory curative effects.

[A real-world study on the efficacy and safety analysis of paclitaxel liposome in advanced breast cancer].

Objective: To explore the application and efficacy of paclitaxel liposome in the treatment of advanced breast cancer among Chinese population in the real world. Methods: The clinical characteristics of patients with advanced breast cancer who received paclitaxel liposome as salvage treatment from January 1, 2016 to August 31, 2019 in 11 hospitals were collected and retrospectively analyzed. The primary outcome was progression free survival (PFS), and the secondary outcome included objective response rate (ORR) and safety. The survival curve was drawn by Kaplan-Meier analysis and the Cox regression model were used for the multivariate analysis. Results: Among 647 patients with advanced breast cancer who received paclitaxel liposome, the first-line treatment accounted for 43.3% (280/647), the second-line treatment accounted for 27.7% (179/647), and the third-line and above treatment accounted for 29.1% (188/647). The median dose of first-line and second-line treatment was 260 mg per cycle, and 240 mg in third line and above treatment. The median period of paclitaxel liposome alone and combined chemotherapy or targeted therapy is 4 cycles and 6 cycles, respectively. In the whole group, 167 patients (25.8%) were treated with paclitaxel liposome combined with capecitabine±trastuzumab (TX±H), 123 patients (19.0%) were treated with paclitaxel liposome alone (T), and 119 patients (18.4%) were treated with paclitaxel liposome combined with platinum ± trastuzumab (TP±H), 108 patients (16.7%) were treated with paclitaxel liposome combined with trastuzumab ± pertuzumab (TH±P). The median PFS of first-line and second-line patients (5.5 and 5.5 months, respectively) were longer than that of patients treated with third line and above (4.9 months, P<0.05); The ORR of the first line, second line, third line and above patients were 46.7%, 36.8% and 28.2%, respectively. Multivariate analysis showed that event-free survival (EFS) and the number of treatment lines were independent prognostic factors for PFS. The common adverse events were myelosuppression, gastrointestinal reactions, hand foot syndrome and abnormal liver function. Conclusion: Paclitaxel liposomes is widely used and has promising efficacy in multi-subtype advanced breast cancer.

[Treatment strategies for patients with resistant advanced breast cancer to CDK4/6 inhibitors].

CDK4/6 inhibitors have become the standard of care for HR-positive, HER2-negative advanced breast cancer. However, there is still a lack of standard recommendations for the subsequent treatment of patients with CDK4/6 inhibitor resistance, especially those with primary resistance or rapid progression. Currently, appropriate treatment strategies included re-challenge of CDK4/6 inhibitors, combination with PI3K/AKT/mTOR inhibitors, new antibody drug conjugate (ADC), novel endocrine therapy drugs, and chemotherapy. In addition, many new targeted drugs and new combination treatment strategies are also being explored. In the future, precise treatment strategies based on biomarkers should be established, as well as the optimal sequence of use of different therapies.

[Effect of compound chamomile and lidocaine hydrochloride gel on oropharyngeal complications after the use of laryngeal mask airway with positive pressure ventilation].

Objective: To evaluate the effect of compound chamomile and lidocaine hydrochloride gel on oropharyngeal complications after the use of laryngeal mask airway with positive pressure ventilation. Methods: A total of 64 patients undergoing elective surgery under general anesthesia using laryngeal mask airway (LMA) with positive pressure ventilation in Beijing Tongren Hospital Affiliated to Capital Medical University From January to March 2023 were prospectively selected and divided into two groups by the random number table method: normal saline group (n=32), with 18 males and 14 females, aged 28-64 (48.4±10.6) years, and the compound chamomile and lidocaine hydrochloride gel group (chamomile gel group, n=32), with 18 males and 14 females, aged 24-64 (46.3±10.8) years. Patients in both groups received total intravenous anesthesia. Before LMA placement, the front, shoulder and back of LMA were lubricated with normal saline and compound chamomile and lidocaine hydrochloride gel in the normal saline group and the chamomile gel group, respectively. The main outcome measure was the incidence of postoperative oropharyngeal mucosal inflammation at different time points after the removal of the laryngeal mask. Secondary outcome measures included oropharyngeal mucositis score, sore throat score, hoarse voice score, cough score and throat dryness score at different time points after LMA removal, the number of LMA insertion times, time of successful insertion and leakage pressure, as well as stress reactions such as cough and agitation before and after LMA removal, and adverse reactions such as tongue numbness and protective pharyngeal reflex limitation during recovery. Results: The incidence of oropharyngeal mucositis in the chamomile gel group was 25.0% (8/32), 31.3% (10/32), 28.1% (9/32) and 3.1% (1/32) at 0.5, 3, 6 and 24 h after LMA removal, respectively, which were lower than those of normal saline group [53.1% (17/32), 59.4% (19/32), 59.4% (19/32) and 21.9% (7/32)] (all P<0.05). The oropharyngeal mucositis scores of patients in the chamomile gel group were 0 (0, 0.8), 0 (0, 1.0), 0 (0, 1.0) and 0 (0, 0) respectively at 0.5, 3, 6 and 24 h after LMA removal, which were lower than those in the saline group [1.0 (1.0, 1.8), 1.0 (0, 2.0), 1.0 (0, 2.0) and 0 (0, 0)] (all P<0.05). The cough score of the patients in the chamomile gel group was 0 (0, 0) and 0 (0, 0) at 3, 6 h after LMA removal, which were lower than those of the normal saline group [(0, 0) and 0 (0, 0)] (both P<0.05). The throat dryness score of the patients in the chamomile gel group was 0 (0, 1.0) at 3 h after LMA removal, which was lower than that of the normal saline group [1.0 (0.3, 1.0)] (P=0.019). The time of successful LMA insertion in the chamomile gel group was 25.0 (20.3, 29.8) s, which was shorter than that in the saline group [29.0 (25.0, 32.0) s] (P=0.016). There were no significant differences in the number of LMA insertion, leakage pressure, postoperative sore throat and hoarse voice scores between the two groups (all P>0.05). Likewise, there were no stress reactions such as cough and agitation before and after LMA removal, and no adverse reactions such as tongue numbness and limited protective pharyngeal reflex during recovery. Conclusion: Compound chamomile and hydrochloride lidocaine gel can reduce the incidence of postoperative oropharyngeal mucositis, relieve the symptoms of postoperative oropharyngeal mucositis, pharyngeal dryness and cough, and improve the postoperative comfort of patients using the laryngeal mask airway with positive pressure ventilation.

[Efficacy and safety of new systemic therapies in moderate-to-severe atopic dermatitis in the elderly: meta-analysis].

Objective: To systematically evaluate the efficacy and safety of new systemic therapies (biological agents and JAK inhibitors) in moderate-to-severe elderly atopic dermatitis. Methods: The database of Embase, PubMed, Web of Science,Cochrane, the Global Resource of Eczema Trials database, ClinicalTrials. Gov, CNKI, Wanfang, VIP were used to search for literatures of randomized controlled trials (RCTs) and real-world studies of the treatment of moderate-to-severe AD with the new systemic therapies from January 2014 to February 2023. Two reviewers independently screened the literature, extracted the data and evaluated the risk of bias included in the study. Data were analyzed by Review Manager 5.3 software for meta-analysis and odds ratio (OR) and 95% confidence interval were used as the effect statistics. The heterogeneity and publication bias were assessed. Results: A total of five studies (523 elderly patients and 802 young patients) using dupilumab were included for meta-analysis. Dupilumab showed good efficacy in elderly AD, with 74.6%(390/523) of patients whose EASI reached 75, which there was no significant difference with young patients (OR=0.79, 95%CI:0.58-1.07, P=0.122); the proportion of elderly patients with NRS improvement≥4 was 68.7%(244/355), and there was no significant difference with young patients (OR=0.79, 95%CI:0.55-1.14, P=0.213). The most common adverse reactions were conjunctivitis, facial and neck erythema and injection site reactions, and there are no serious adverse events in both groups. The incidence of adverse events in elderly patients was 24.3%(65/267), which was not significantly different from that in young patients (OR=1.07, 95%CI:0.65-1.77, P=0.789). There are few studies on other biological agents and JAK inhibitors in elderly AD patients. We only found 4 studies of elderly AD patients using JAK inhibitors (2 studies on abrocitinib and 2 studies on upadacitinib). The clinical efficacy of abrocitinib in the elderly was not significantly different from that in the young. The incidence of serious adverse events of abrocitinib and upadacitinib increased in the elderly and was dose-related. Conclusion: The efficacy and safety of dupilumab in elderly AD patients were similar to those in the young patients, and the JAK inhibitor needs to be further studied and verified.

[The effect of modified nasopharynx airway with spontaneous breathing under general anesthesia on the postoperative recovery quality of patients undergoing hysteroscopic daytime surgery].

Objective: To explore the impact of a new type of modified nasopharynx airway preserving spontaneous breathing under general anesthesia on the postoperative recovery quality of patients undergoing hysteroscopic daytime surgery. Methods: A total of 80 patients undergoing hysteroscopic daytime surgery at Beijing Tongren Hospital from August to December 2022 was prospectively selected. The patients were randomly divided into two groups using a random number table method: patients in the laryngeal mask mechanical ventilation general anesthesia group (laryngeal mask group, n=40) aged (46.8±10.1) years (20-65 years), while patients in the modified nasopharyngeal airway preserving spontaneous breathing general anesthesia group (nasopharyngeal airway group, n=40) aged (45.5±12.1) years (26-65 years). The main outcome measures were the clinical recovery score (CRS) and modified alertness and sedation score (MOAA/S) of patients at different postoperative time points. Secondary observation indicators included anesthesia induction time, awakening time, and extubation time, changes of hemodynamic indicators between preoperative and intraoperative period, and incidence of adverse reactions during and after surgery. Results: The CRS scores [M (Q1, Q3)] of patients in the nasopharyngeal airway group were 8 (8, 9), 8 (8, 9), 8 (8, 9), 9 (9, 9) and 10 (10, 11) at postoperative awakening, immediately after extubation, 5 minutes after extubation, 15 minutes after extubation, and 30 minutes after extubation, respectively, which were higher than those in the laryngeal mask group [7 (6, 8), 7 (7, 8), 7 (7, 8), 8 (8, 8) and 9 (8, 9)] (all P<0.001). The MOAA/S scores of the nasopharyngeal airway group were 5 (5, 5), 5 (5, 5), 5 (5, 5) and 5 (5, 5) at postoperative awakening, immediately after extubation, 5 minutes after extubation, and 15 minutes after extubation, respectively, which were higher than those in the laryngeal mask group [4 (3, 5), 4 (4, 5), 5 (5, 5) and 5 (5, 5)] (all P<0.05). The anesthesia induction time, awakening time, and extubation time of the nasopharyngeal airway group were (47.8±4.3) s, (4.1±1.7) min and (4.5±1.7) min, respectively, which were shorter than those of laryngeal mask group [(138.8±4.2) s, (7.2±2.9) min and (8.1±2.7) min] (all P<0.05). The mean arterial pressure (MAP) of patients in the nasopharynx airway group during extubation was (84.9±10.2) mmHg (1 mmHg=0.133 kPa), which was lower than that of the laryngeal mask group [(93.2±7.5) mmHg] (P<0.05). The partial pressure of end-tidal carbon dioxide (PetCO2) during cervical dilation was (22.0±5.9) mmHg, which was lower than those of the laryngeal mask group [(37.2±2.2) mmHg] (P<0.05). The PetCO2 during intrauterine operation and extubation were (45.5±6.7) and (41.6±4.5) mmHg, which were higher than those of the laryngeal mask group [(39.2±4.1) mmHg and (38.6±3.6) mmHg] (both P<0.05). The incidence of respiratory depression and body movement during surgery in the nasopharyngeal airway group were 27.5% (11/40) and 17.5% (7/40), respectively, which were higher than those in the laryngeal mask group [0 and 0] (both P<0.05). The incidence of postoperative drowsiness was 2.5% (1/40), which was lower than that of the laryngeal mask group [17.5% (7/40)] (P<0.05). There was no severe physical activity or intraoperative awareness in the two groups. Conclusion: The new modified general anesthesia method of preserving spontaneous breathing through the nasopharynx airway can improve the postoperative recovery quality of patients, and reduce the occurrence of adverse reactions, which facilitates rapid recovery after hysteroscopic daytime surgery.

[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.

[Association between smoking status and mortality risk among elderly people aged 60 and above in Beijing City].

Objective: To examine the association between smoking status and related mortality among elderly people aged 60 and above in urban and rural areas of Beijing City. Methods: Based on Beijing City Elderly Comprehensive Health Cohort Study from 2009 to 2014, a total of 4 499 eligible older adults included in the baseline survey were followed up and investigated to collect information on survival and death. The Cox proportional hazards regression model was used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs), and the dose-response relationship was estimated between the smoking index, the years of quitting and mortality. Results: The median (IQR) age of 4 499 subjects was 70.00 (10.00) years old, including 1 814 (40.32%) males. The proportion of non-smokers, former smokers and current smokers was 69.50% (3 127/4 499), 13.20% (594/4 499) and 17.30% (778/4 499), respectively. After adjusting for confounding factors such as demographic and sociological characteristics, lifestyle, etc., the results of multivariate Cox regression analysis showed that, compared to non-smokers, former smokers had a 30.6% increased risk of all-cause mortality [HR (95%CI): 1.306 (1.043-1.636)] and the HR (95%CI) of all-cause, malignant tumor and lung cancer mortality among current smokers has increased by 50.0% [HR (95%CI): 1.500 (1.199-1.877)], 80.3% [HR (95%CI): 1.803 (1.226-2.652)] and 212.6% [HR (95%CI): 3.126 (1.626-6.012)], respectively. The smoking index was positively associated with the increased risk of all-cause, malignant tumor and lung cancer mortality, while the years of smoking cessation were negatively associated with that risk (P<0.05). Conclusion: Smoking is associated with tobacco-related mortality among elderly people in Beijing City.

[Hsp90 participates in the necroptosis of mouse neural cells induced by aluminum through the RIP1/RIP3/MLKL pathway].

Objective: To investigate whether heat shock protein 90 (HSP90) participates in the necroptosis of C57BL/6 mouse neurons and spatial memory impairment induced by Aluminum maltol [Al (mal) (3)] through RIP1/RIP3/MLKL pathway. Methods: In March 2022, Thirty-two C57 mice were randomly divided into control group, Low dose group, a medium dose group, and a high-dose group, with 8 mice in each group, and injected intraperitoneally with physiological saline, 20, 40, and 80, respectivelyµmol/kgAl (mal) (3) was administered, it was injected 5 days a week and discontinued 2 days for 60 days. Morris water maze test was used to test the spatial learning and memory ability of mice. Nissl staining was used to observe the pathological changes of brain tissue. The protein expression levels of RIP1, RIP3, MLKL and HSP90 in hippocampus were determined by Western blotting. Results: In the water maze experiment, compared with the control group, the number of mice crossing the platform decreased in each dose group, the difference was statistically significant (H=9.50, P=0.023), and the number of mice crossing the platform was statistically significant among each dose group (P <0.05). Compared with the control group, the number of hippocampal nerve cells in each dose group decreased, the arrangement was disordered, and the Nissellite bodies decreased. Western blotting results showed that compared with the control group, the expression level of RIP1 protein in the hippocampus of mice in high-dose group was higher, and the difference was statistically significant (P <0.05). The expression levels of RIP3, MLKL and HSP90 in hippocampal tissue of mice in medium and high dose groups were increased, and the differences were statistically significant (P<0.05). After siRNA intervention decreased the expression of HSP90 protein, the expressions of HSP90, RIP1, RIP3 and MLKL in Al (mal) (3) groups were increased, and the differences were statistically significant (P<0.05) . Conclusion: Through RIP1/RIP3/MLKL pathway, HSP90 is involved in neuronal programmed necrosis and spatial memory impairment induced by maltol aluminum in C57 mice.

Risk factors for progression of Urolith Associated with Obstructive Urosepsis to severe sepsis or septic shock.

INTRODUCTION: To analyze the risk factors for progression of urolith associated with obstructive urosepsis to severe sepsis or septic shock, we had done the retrospective cross-sectional study, which would facilitate the early identification of high-risk patients. MATERIALS AND METHODS: Datas were retrospectively reviewed from 160 patients, suffering from obstructive urosepsis associated with urolith between December 2013 and December 2019. There were 49 patients complicating by severe sepsis (severe sepsis group), 12 patients complicating by septic shock (septic shock group), and 99 patients without progressing to severe sepsis or septic shock (sepsis group). The data covered age, gender, BMI (body mass index), time interval from ED (emergency department) to admission, WBC count (white blood cell count), NLR (neutrophil/lymphocyte ratio), HGB (hemoglobin), etc. Datas were analyzed by univariate analyses and multivariate logistic regression analysis. The corresponding nomogram prediction model was drawn according to the regression coefficients. RESULTS: Univariate analysis showed that the differences of age, the time interval from ED to admission, history of diabetes mellitus, history of CKI (chronic kidney disease), NLR, HGB, platelet count, TBil (total bilirubin), SCr (serum creatinine), ALB (albumin), PT (prothrombin time), APTT (activated partial thromboplastin time), INR (international normalized ratio), PCT (procalcitonin), and positive rate of pathogens in blood culture were statistically significant (P < 0.05). Multivariatelogistic regression analysis showed that age, SCr, and history of CKI were independent risk factors for progression to severe sepsis, or septic shock (P < 0.05). CONCLUSIONS: Aged ≥ 65 years, SCr ≥ 248 mol/L, and history of CKI were independent risk factors for progression of urolith associated with obstructive urosepsis to severe sepsis or septic shock. We need to pay more attention to these aspects, when coming across the patients with urolithic sepsis.

Insights to Human γD-Crystallin Unfolding by NMR Spectroscopy and Molecular Dynamics Simulations.

Human γD-crystallin (HGDC) is an abundant lens protein residing in the nucleus of the human lens. Aggregation of this and other structural proteins within the lens leads to the development of cataract. Much has been explored on the stability and aggregation of HGDC and where detailed investigation at the atomic resolution was needed, the X-ray structure was used as an initial starting conformer for molecular modeling. In this study, we implemented NMR-solution HGDC structures as starting conformers for molecular dynamics simulations to provide the missing pieces of the puzzle on the very early stages of HGDC unfolding leading up to the domain swap theories proposed by past studies. The high-resolution details of the conformational dynamics also revealed additional insights to possible early intervention for cataractogenesis.

[Cardiometabolic disease patterns among elderly patients with colorectal cancer in China].

Objective: To explore the distribution patterns of cardiometabolic diseases (CMD) in elderly patients with colorectal cancer, and provide a reference for the prevention and treatment of cardiovascular metabolic diseases in these patients. Methods: Clinical data of 3 894 elderly patients with colorectal cancer from January 2008 to March 2018 admitted in the Chinese PLA General Hospital were recruited and the incidence rate of CMD was retrospectively analyzed. The influence factors of elderly patients with colorectal cancer combined with CMD were analyzed by multivariate Logistic regression model. Results: The morbidity rate of CMD in elderly patients with colorectal cancer is 33.4% (1 301/3 894), among them, the morbidity rate of the male was 31.9% (768/2 409), and that of the female was 35.9% (533/1 485). There was not significant difference between these two sex (P=0.074). The morbidity rates of CMD in patients of 65-74 years, 75-84 years and ≥85 years were 30.6% (754/2 462), 37.0% (479/1 294) and 49.3% (68/138), respectively, with significant differences (P<0.001). Multiple Logistic regression analysis revealed that female (OR=1.213, 95%CI: 1.056-1.394), age (75-84 years group: OR=1.344, 95%CI: 1.164-1.552; ≥85 years group: OR=2.345, 95%CI: 1.651-3.331) and body mass index (BMI 18.5-24.9 kg/m(2) group: OR=1.319, 95%CI: 1.065-1.638; ≥25 kg/m(2) group: OR=2.041, 95%CI: 1.627-2.561) were independent risk factors for elderly colorectal cancer patients with CMD. Conclusion: The morbidity rate of CMD in elderly patients with colorectal cancer increases with age and it is urgent to strengthen multidisciplinary cooperation and develop reasonable treatment plans to extend the survival and life quality of these patients.

[Analysis on the concept and clinical practice of patient-controlled analgesia in the treatment of cancer pain by Chinese medical providers].

Objective: To investigated the concept and clinical practice of patient-controlled analgesia (PCA) in the treatment of cancer pain. Methods: Doctors, nurses, pharmacists from the oncology department, pain department, or hospice department were investigated using an electronic questionnaire from December 1 to December 31, 2021. In addition to the basic information, there were 26 questions were collected, including the current situation of cancer pain treatment, the concept of medical staff on PCA treatment of cancer pain and the clinical practice of PCA. Results: Questionnaires from 2 872 medical staff were collected from 993 hospitals in 30 provincial administrative units. Only 34.8% (955/2 748) of medical staff considered that the satisfaction rate of cancer pain control was over 75%, and 27.9% (548/1 968) of medical staff convinced that the satisfaction rate of breakthrough pain control was less than 50%. 97.1% (2 439/2 513) of medical staff considered that PCA could be effectively used for cancer pain treatment. The proportion of medical staff in secondary and tertiary hospitals who thought that PCA was applicable to cancer pain that could not be effectively alleviated by standardized non-invasive drug administration was 64.6% (319/494) and 69.1% (1 262/1 826) respectively, which was higher than that in primary hospitals [57.0% (110/193)] (P=0.002). In different occupations, the proportion of nurses who convinced PCA treatment of cancer pain increased the risk of addiction and drug overdose was 62.8% (431/686) and 76.1% (522/686), respectively, which was higher than doctors [39.2% (670/1709) and 58.2% (995/1709), respectively] and pharmacists [49.2% (58/118) and 65.3% (77/118), respectively] (all P<0.001). There was no significant difference in type of pump, route of administration, mode of infusion, protocol for PCA administration and selection of common medication in PCA treatment of cancer pain among different hospitals (all P>0.05). The calculation of continuous infusion dose and rescue dose of PCA was not uniform among different hospitals. After initiation of PCA, 71.7% (1 226/1 709) of hospitals had insufficient analgesia and most of them needed to be adjusted for 1-3 times to achieve satisfactory analgesia. Conclusion: Medical staff have insufficient cognition of PCA treatment of cancer pain and there is a lack of unified guidance in clinical practice. Therefore, it is an urgent need to develop an expert consensus on PCA treatment of cancer pain.

[Association between nutritional status and depression among centenarians in Hainan Province].

Objective: To explore the relationship between nutritional status and depression of centenarians in Hainan Province. Methods: A total of 1 002 elderly people in Hainan Province who were 100 years of age or older on June 1, 2014 were included in the study. The basic condition questionnaire, Mini Nutritional Assessment Short-Form (MNA-SF), Instrumental Activities of Daily Living-Lawton scale (Lawton-IADL) and Geriatric Depression Scale (GDS-15) were used to collect the subjects' demographic characteristics, disease history, nutritional status, functional status of daily activities, and depression, respectively. The restricted cubic spline fitting logistic regression model was used to analyze the relationship between the scores of MNA-SF and depression. The multivariable logistic regression model was used to analyze the relationship between nutritional status and depression in the total population and different subgroups of daily activity function. Results: The M (Q1, Q3) of subjects' age was 102 (101, 104) years old, among which 82.0% (822) were women. The prevalence of malnutrition, impaired daily activities, and depression was 20.8% (208 cases), 64.7% (648 cases) and 28.5%(286 cases), respectively. Restricted cubic spline fitting logistic regression model showed a linear association between the scores of the MNA-SF and depression (P=0.251). The higher the MNA-SF score was, the lower the risk of depression was in centenarians. Multivariable logistic regression model analysis showed that after adjusting for sex, education level, diabetes, hypertension, coronary heart disease, visual function, hearing function, and functional status of daily activities, malnutrition was positively associated with the development of depression in the total population and the subgroup with impaired daily activities [OR (95%CI) was 1.50 (1.07-2.11) and 1.56 (1.09-2.24), respectively], but not in the subgroup with good daily activities [OR (95%CI): 0.77 (0.21-2.80)]. Conclusion: Malnutrition is positively associated with depression, especially in the centenarians with impaired daily activities.

[Imaging features of developmental stenosis of atlas with degenerative cervical myelopathy].

Objective: To investigate the imaging features of patients with developmental stenosis of atlas (small atlas) complicated with degenerative cervical myelopathy and to explore the diagnostic criteria of small atlas. Methods: The clinical data of patients with degenerative cervical myelopathy treated by posterior cervical laminoplasty and resection of posterior arch of atlas from 2006 to 2020 in the Department of Orthopedics, Peking University Third Hospital were retrospectively analyzed. Sixteen cases had spinal cord compression at C1 level after the exclusion of ossification of cervical posterior longitudinal ligament (OPLL) and other pathology. These cases were suspected small atlas (small atlas group). Forty-six cases without posterior arch resection in the same period were selected as control group. The middle sagittal diameter of atlas and the vertical distance from posterior tubercle of atlas to occipitoaxial line under CT in both groups were compared. The sagittal diameter of the spinal canal at the atlas level under MRI, the Japanese Orthopaedic Association (JOA) score for functional state of cervical spine before operation and at last follow-up were also measured. Results: There were 9 males and 7 females in the small atlas group, aged (63±12) years. There were 21 males and 25 females in the control group, aged (57±10) years. The patients in both group were followed-up for at least one year. The sagittal diameter of atlas in the small atlas group was (26.4±3.1) mm, which was significantly smaller than that in the control group [(29.6±2.2) mm, P=0.010]. The vertical distance from the posterior tubercle of atlas to the occipitoaxial line in the small atlas group was larger than that in the control group[(6.79±1.17) mm vs (5.57±1.29) mm, P=0.001]. The diameter of atlas canal in the small atlas group was (8.25±1.44) mm which was significantly smaller than that in the control group [(13.00±1.66) mm, P<0.001]. The JOA score of the small atlas group before operation and at the last follow-up were both slightly lower than that in the control group (both P<0.05), but there was no significant difference in the recovery rate of JOA score between the two groups (61.9% vs 66.0%, P=0.066). Among the 16 cases in the small atlas group, 5 cases of occipital-axial connection were located at the posterior 1/3 of the posterior arch of atlas, and 11 cases of occipital-axial connection were completely located at the posterior arch of atlas. Conclusions: The effective sagittal diameter of atlas is smaller in small atlas group which can lead to more severe cervical myelopathy. The presence of a small atlas should be highly suspected when the sagittal diameter of atlas canal is less than 26 mm under CT. The existence of the small atlas should be alert when the occipitalaxial line is located at the dorsal 1/3 or behind of the posterior arch of atlas.

[Advances in analytical methods of relationship between exposome and health outcomes].

The research on the relationship between single exposure and health outcomes is not comprehensive without a capability of systematically revealing the cause. At present, some studies have explored the relationship between exposome and health outcomes. However, due to the large data of exposome and the correlation among exposure factors, there is still a lack of effective methods to analyze the relationship between exposome and health outcomes. This study reviews the previous literature, combs the analysis methods of the relationship between exposome and health outcomes, and points out that agnosticism combined with middle-level information can significantly reduce the false positive rate, so as to provide a reference for accurately identifying the influencing factors of health outcomes in extensive exposome.

[Adrenal cavernous hemangioma: A case report and literature review].

A 57-year-old male patient was referred to our department with complaints of his right adrenal gland occupancy and hypertension about 6 months. When admitted to the hospital, the blood pressure was about 160/100 mmHg, and the heart rate was 110 beats/min. He was no obvious obesity, acne, abnormal mood, without weakness of limbs, acral numbness, palpitation and headache. He presented with type 2 diabetes for more than 3 years, with oral administration of metformin enteric coated tablets and subcutaneous injection of insulin glargine to control blood glucose, and satisfied with blood glucose control. Enhanced CT showed that: the right adrenal gland showed a kind of oval isodense, slightly hypodense shadow, the edge was clear, lobular change, the size was about 5.8 cm×5.4 cm, uneven density, there were nodular and strip calcification, round lipid containing area and strip low density area, and the CT value of solid part was about 34 HU. Enhanced scan showed heterogeneous nodular enhancement in the solid part of the right adrenal gland, nodular enhancement could be seen inside. The CT values of solid part in arterial phase, venous phase and delayed phase were 45 HU, 50 HU and 81 HU, respectively. Considering from the right adrenal gland, cortical cancer was more likely. No obvious abnormality was found in his endocrine examination. After adequate preoperative preparation, retroperitoneal laparoscopic adrenalectomy was performed under general anesthesia. During the operation, the 6 cm adrenal tumor was closely related to the inferior vena cava and liver, and after careful separation, the tumor was completely removed and normal adrenal tissue was preserved. The operation lasted 180 min and the blood loss was 100 mL, and the blood pressure was stable during and after the operation. There was no obvious complication. The results of pathological examinations were as follows: the size of the tumor was 7.5 cm×6.0 cm×3.5 cm, soft, with intact capsule and grayish-red cystic in section. Pathological diagnosis: (right adrenal gland) cavernous hemangioma, secondary intravascular thrombosis, old hemorrhagic infarction with calcification and ossification. After 6 months of observation, no obvious complications and tumor recurrence were found. In summary, cavernous hemangioma of adrenal gland is a rare histopathological change. Its essence is a malformed vascular mass. Blood retention is the cause of thrombosis and calcification in malformed vessels. The imaging findings were inhomogeneous enhancement of soft tissue masses, and the adrenal function examination showed no obvious abnormalities. Retroperitoneal laparoscopic surgery is feasible after adequate preoperative preparation. It is difficult to diagnose the disease preoperatively and needs to be confirmed by postoperative pathology.

[Preoperative video distraction alleviates separation anxiety and improves induction compliance of preschool children: a randomized controlled clinical trial].

Objective: To explore the effect of video distraction on preoperative separation anxiety and induction compliance of preschool children receiving strabismus surgery under general anesthesia. Methods: In this prospective trial, 80 children aged 3 to 6 years scheduled for strabismus surgery under inhalation anesthesia were randomly allocated to one of two groups, a control group and a video distraction group, with 40 cases in each group. Children in the video distraction group continuously watched videos from waiting in the holding area, separating with parents, entering the operating room and induction of anesthesia, while children in the control group didn't watch videos during the same process. The modified Yale Preoperative Anxiety Scale (mYPAS) of children were recorded upon arriving at the holding area(T1)and separating with parents(T2). Induction Compliance Checklist (ICC) score was recorded when the anesthesia induction was performed. The emergence time, the occurrence rate of adverse events in post-anesthesia care unit (PACU) including nausea and vomiting, laryngospasm, severe cough, hypoxemia and sinus bradycardia, incidence of postoperative adverse reactions such as pain, dizziness, nausea and vomiting and lethargy, the parents' satisfaction of anesthesia were also assessed. Results: There were no significant difference in mYPAS score and the proportion of mYPAS score>30 between 2 groups at T1 (all P>0.05). At T2, the mYPAS score and the proportion of mYPAS score>30 in video distraction group were (34.41±13.23) and 52.50%, which were lower than those in control group (50.64±20.96, 87.50%) with statistically significant difference (all P<0.05). The ICC score of video distraction group was lower than that of the control group, which was (1.83±2.26) vs (4.03±2.99), and the difference was statistically significant (P<0.05). The proportion of children with ICC score=0 in video distraction group was 37.50%, which was higher than that in the control group (12.50%), while the proportion of children with ICC score=4-10 was lower than that of the control group, which was 17.50% vs 45.00%, and the difference was statistically significant (P<0.05). No significant intergroup differences were observed in emergence time, incidence of adverse events in PACU, and incidence of postoperative adverse reactions (P>0.05). The parents' satisfaction of anesthesia in the video distraction group was (9.23±0.89), which was higher than that in the control group (8.63±1.23), with statistically significant (P<0.05). Conclusion: Preoperative video distraction alleviates separation anxiety, improves induction compliance of preschool children receiving strabismus surgery under general anesthesia, and increases the parents' satisfaction of anesthesia.