Objective To systematically evaluate the short-term efficacy and safety of McKeown and Sweet methods in the treatment of esophageal cancer. Methods PubMed, EMbase, The Cochrane Library, Web of Science, Wanfang, VIP, CNKI and Chinese Biomedical Literature database were searched for literature on the short-term efficacy and safety of McKeown and Sweet methods in the treatment of esophageal cancer published from the establishment to May 2023. Newcastle-Ottawa Scale was used to evaluate the quality of researches, and meta-analysis was performed using RevMan5.4. Results A total of 9 articles were included, involving 3687 patients including 1019 in the McKeown group and 2668 in the Sweet group. NOS score was 8-9 points. There were no statistical differences in the age, sex or American Joint Committee on Cancer stage between the two groups (P>0.05). Patients in the McKeown group had longer operative time and hospital stay, more intraoperative blood loss, and higher Eastern Cooperative Oncology Group scores than those in the Sweet group (P<0.05). However, the McKeown operation could remove more lymph nodes (P=0.001). In terms of safety, the incidences of pulmonary complications [OR=2.20, 95%CI (1.40, 3.46), P=0.001] and postoperative anastomotic leakage [OR=2.06, 95%CI (1.45, 2.92), P=0.001] were higher in the McKeown group than those in the Sweet group. In addition, there were no statistical differences between the two groups in the Karnofsky score, cardiac complications, vocal cord injury or paralysis, chylous leakage, or gastric emptying (P>0.05). Conclusion Compared with McKeown, Sweet method has advantages in operation time, intraoperative blood loss and hospital stay, and has lower incidence of postoperative pulmonary complications and anastomotic leakage. However, McKeown has more lymph node dissection.

BACKGROUND:Croton cream can activate ERK pathways and have anti-apoptotic effects on neuronal cells.It is not clear whether it synergistically exerts anti-apoptotic effects by inhibiting the activation of JNK and p38 pathways. OBJECTIVE:To explore the effects and mechanisms of croton cream on neuronal damage and apoptosis in the ischemic cortex of rats with cerebral ischemia-reperfusion injury. METHODS:(1)Ninety Sprague-Dawley rats were randomly divided into sham operation group,model group,croton cream low-dose group,croton cream medium-dose group,croton cream high-dose group and nimodipine group,with 15 rats in each group.Except for the sham operation group,animal models of middle cerebral artery occlusion were prepared in rats by the thread method.Rats in the three croton cream groups were given 20,40,and 60 mg/kg croton cream,respectively.Rats in the sham operation and model groups were given the same amount of normal saline,once a day,for 7 consecutive days.The optimal concentration of croton cream,namely the high dose of croton cream,was selected based on neurological deficit score,TTC staining,brain tissue water content,hematoxylin-eosin staining and Nissl staining.(2)Another 120 Sprague-Dawley rats were randomly divided into sham operation group,model group,croton cream group,JNK inhibitor group,croton cream+JNK inhibitor group,p38 MAPK inhibitor group,croton cream+p38 MAPK inhibitor group,and nimodipine group,with 15 rats in each group.Animal models of middle cerebral artery occlusion were prepared using the thread method in all the groups except in the sham operation group.Thirty minutes before modeling,10 μL of SP600125(JNK inhibitor)and 10 μL of SB203580(p38 MAPK inhibitor)were injected into the lateral ventricle of the rats,respectively.Rats in croton cream groups were intragastrically given 60 mg/kg croton cream.Seven days later,the JNK/p38 MAPK signaling pathway,apoptosis-related proteins and cell apoptosis were detected by western blot,TUNEL staining and flow cytometry,respectively. RESULTS AND CONCLUSION:(1)Compared with the sham operation group,neurological deficit score,cerebral water content,cerebral infarction volume and apoptosis rate were significantly increased in the model group(P<0.05),where nerve cells showed scattered distribution.Compared with the model group,neurological deficit score,water content of brain tissue and cerebral infarction volume were significantly decreased in the croton cream medium-dose group,high-dose group and nimodipine group(P<0.05),and the pathological morphology of nerve cells was significantly improved.(2)Compared with the JNK inhibitor group,p-JNK/JNK,p-p38/p38 and Bax expressions in rat brain tissue and the apoptotic rate were significantly decreased in the croton cream+inhibitor groups(P<0.05),while the expression of and Bcl-2 was significantly increased(P<0.05).To conclude,croton cream may inhibit the activation of JNK/p38 MAPK signaling pathway and reduce neuronal apoptosis to achieve neuroprotective effects in rats with cerebral ischemia-reperfusion injury.

Objective:To investigate the diagnostic value of nucleic acid matrix-assisted laser desorption ionization-time of flight mass spectrometry（MALDI-TOF MS）in sputum smear-negative patients with nontuberculous Mycobacterial（NTM）pulmonary disease.Methods:Clinical data of 123 patients suspected of NTM pulmonary disease admitted in Public Health Clinical Center Affiliated to Shandong University between July 2022 and November 2023 were retrospectively analyzed. Bronchoalveolar lavage fluid（BALF）specimens were collected for MALDI-TOF MS assay and MGIT 960 culture. The diagnostic efficacy of MALDI-TOF MS for NTM pulmonary disease in patients with negative sputum smears for acid-fast bacilli was evaluated with receiver operating characteristic（ROC）curve. Statistical analysis was performed using SPSS 26.0 software and MedCalc statistical software.Results:Diagnosis of NTM pulmonary disease was finally confirmed in 66 out of the 123 suspected patients. It took 8 to 24 h for MALDI-TOF MS to identify NTM species and resistance. By MALDI-TOF MS，72 NTM strains were identified，with the Mycobacterium avium complex being the most prevalent（34 strains，47.22%），followed by the Mycobacterium abscessus complex（13 strains，18.06%）；resistance to macrolides was detected in 6 cases，while no resistance to aminoglycosides was found. It took 9 to 45 days for BALF MGIT 960 culture to identify NTM，and took 7 to 15 days for NTM typing and drug sensitivity testing. By BALF MGIT 960 culture，28 NTM strains were identified；and 1 case was found to be resistant to macrolides. Using confirmed diagnosis as the gold standard，MALDI-TOF MS demonstrated higher sensitivity，negative predictive value，and agreement rate compared to MGIT 960 culture（84.85% vs. 42.42%，81.13% vs. 56.32%，80.49% vs. 62.60%， χ2=25.667，8.998，9.664， P<0.05 or <0.01）. The area under ROC curve（AUC）for MALDI-TOF MS was significantly higher than that of MGIT 960 culture（0.801 vs. 0.642， Z=3.300， P=0.001）. Conclusion:Compared to MGIT 960 culture，MALDI-TOF MS exhibits superior diagnostic efficiency in detecting NTM pulmonary disease in patients with acid-fast bacilli smear-negative sputum，with advantage of rapidly identifying NTM species and resistance.

Objective:To investigate the clinical and electrophysiological characteristics of ANCA-associated vasculitic neuropathy (VN) and analyze the predictors of treatment outcomes.Methods:Retrospective case series. In all, 652 consecutive patients with ANCA-associated vasculitis were admitted to the First Medical Center of the Chinese PLA General Hospital between January 2006 and December 2022. Peripheral neuropathy occurred in 91 patients. Patients were excluded if other known causes of neuropathy were present. Sixty-one patients were eventually enrolled, including 17 with eosinophilic granulomatosis with polyangiitis (EGPA), 11 with granulomatosis polyangiitis (GPA), and 33 with microscopic polyangiitis (MPA). Their clinical data were collected and clinical characteristics, VN manifestations, electrophysiological findings (including interside amplitude ratio [IAR]), and treatment outcomes were compared among the three subsets of AAV. Then, factors influencing the treatment outcomes were analyzed using multivariable logistic regression analysis.Results:Peripheral neuropathy occurred in 62.1%(18/29) of EGPA, 8.3%(15/180) of GPA, and 13.1%(58/443) of MPA patients. The age at onset and examination was higher in patients with MPA than those with EGPA or GPA ( P<0.01). The occurrence of VN was later in patients with GPA than those with EGPA ( P<0.01), and the GPA group had fewer affected nerves than the other two groups ( P<0.016). The abnormal IARs of motor nerves in lower limbs were more detected in the EGPA than the MPA group ( P<0.01). Logistic regression analysis suggested that higher Birmingham vasculitis activity score-version 3 (BVAS-V3) ( OR=6.85, 95% CI 1.33-35.30) was associated with better treatment outcomes of VN. However, central nervous system involvement was a risk factor for poor treatment outcomes ( OR=0.13, 95% CI 0.02-0.89). Conclusions:The clinical and electrophysiological characteristics of VN were slightly different among subsets of AAV. Patients with GPA often presented with polyneuropathy and had fewer nerves affected; mononeuritis multiplex was more common in EGPA than GPA and MPA. Higher BVAS-V3 and central nervous system involvement might predict the treatment outcome of VN.

Objective:To investigate the clinical and electrophysiological characteristics of patients with amyotrophic lateral sclerosis (ALS) with positive repetitive nerve stimulation (RNS) test results on the accessory nerve and negative needle electromyography (EMG) test results on the sternocleidomastoid with the goal to enrich the knowledge of disease progression in patients with ALS.Methods:The clinical data of 612 patients diagnosed with ALS at the Neurology Department of the First Medical Center, Chinese PLA General Hospital from June 2016 to August 2022 were collected. In total, 267 cases had undergone EMG tests on the sternocleidomastoid following a positive 3 Hz RNS test result on the accessory nerve, who were selected as the study subjects. The differences in clinical indicators were compared between RNS (+)/EMG (-) group and RNS (+)/EMG (+) group. A binomial distribution model with multiple variables was built to quantitatively analyze the major factors and their effects.Results:At the initial visit, 15.8% of patients with ALS were 3 Hz RNS (+) on the accessory nerve and EMG (-) on the ipsilateral sternocleidomastoid, accounting for 36.3% of RNS (+) patients. The decremental range of the 3 Hz RNS test delivered to the accessory nerve in these patients [-14% (-19%, -12%)] was lower than that in patients with RNS (+)/EMG (+) [-17% (-23%, -13%)] ( P<0.05), while the ratio of upper limb onset (64.9%) and non-definite diagnosis (28.9%) were higher [54.7% and 13.5% for patients with RNS (+)/EMG (+), P<0.05]. Furthermore, the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score [40 (37, 42)], body mass index (BMI) [23.8 (22.0, 25.4) kg/m 2] and forced vital capacity (FVC) [92.8% (76.6%, 103.8%)] were higher in patients with RNS(+)/EMG(+) ( P<0.05). The multivariate model suggested that, in patients with RNS (+)/EMG (-), the ratio of upper limb onset to lower limb onset was 1.04, while that of upper limb onset to bulbar onset was 2.02, and that of lower limb onset to bulbar onset was 1.94. The ratio of non-definite ALS to definite ALS was 1.13. The ALSFRS-R score, BMI, and FVC had a protective contribution to the electrophysiological function of the motor neurons. The ratio of the effect size of the ALSFRS-R or BMI to that of FVC was 3.37 and 1.14, respectively. Conclusions:Patients with ALS that were 3 Hz RNS (+) on the accessory nerve and EMG (-) on the ipsilateral sternocleidomastoid had a smaller decremental range of the compound muscle action potential amplitude, and a higher proportion of upper limb onset and non-definite ALS. A higher ALSFRS-R score, BMI, and FVC have a protective effect to the electrophysiological function of motor neurons. The effect size of the ALSFRS-R score is the largest, followed by BMI and FVC.

Pulmonary hypertension (PH) is an extremely malignant pulmonary vascular disease of unknown etiology. ADAR1 is an RNA editing enzyme that converts adenosine in RNA to inosine, thereby affecting RNA expression. However, the role of ADAR1 in PH development remains unclear. In the present study, we investigated the biological role and molecular mechanism of ADAR1 in PH pulmonary vascular remodeling. Overexpression of ADAR1 aggravated PH progression and promoted the proliferation of pulmonary artery smooth muscle cells (PASMCs). Conversely, inhibition of ADAR1 produced opposite effects. High-throughput whole transcriptome sequencing showed that ADAR1 was an important regulator of circRNAs in PH. CircCDK17 level was significantly lowered in the serum of PH patients. The effects of ADAR1 on cell cycle progression and proliferation were mediated by circCDK17. ADAR1 affects the stability of circCDK17 by mediating A-to-I modification at the A5 and A293 sites of circCDK17 to prevent it from m1A modification. We demonstrate for the first time that ADAR1 contributes to the PH development, at least partially, through m1A modification of circCDK17 and the subsequent PASMCs proliferation. Our study provides a novel therapeutic strategy for treatment of PH and the evidence for circCDK17 as a potential novel marker for the diagnosis of this disease.

Objective     To systematically evaluate the accuracy of endoscopy-based artificial intelligence (AI)-assisted diagnostic systems in the diagnosis of early-stage esophageal cancer and provide a scientific basis for its diagnostic value. Methods    PubMed, EMbase, The Cochrane Library, Web of Science, Wanfang database, VIP database and CNKI database were searched by computer to search for the relevant literature about endoscopy-based AI-assisted diagnostic systems for the diagnosis of early esophageal cancer from inception to March 2022. The QUADAS-2 was used for quality evaluation of included studies. Meta-analysis of the literature was carried out using Stata 16, Meta-Disc 1.4 and RevMan 5.4 softwares. A bivariate mixed effects regression model was utilized to calculate the combined diagnostic efficacy of the AI-assisted system and meta-regression analysis was conducted to explore the sources of heterogeneity. Results    A total of 17 articles were included, which consisted of 13 retrospective cohort studies and 4 prospective cohort studies. The results of the quality evaluation using QUADAS-2 showed that all included literature was of high quality. The obtained meta-analysis results revealed that the AI-assisted system in the diagnosis of esophageal cancer presented a combined sensitivity of 0.94 (95%CI 0.91 to 0.96), a specificity of 0.85 (95%CI 0.74 to 0.92), a positive likelihood ratio of 6.28 (95%CI 3.48 to 11.33), a negative likelihood ratio of 0.07 (95%CI 0.05 to 0.11), a diagnostic odds ratio of 89 (95%CI 38 to 208) and an area under the curve of 0.96 (95%CI 0.94 to 0.98). Conclusion    The AI-assisted diagnostic system has a high diagnostic value for early stage esophageal cancer. However, most of the included studies were retrospective. Therefore, further high-quality prospective studies are needed for validation.

【Objective】 To investigate the effects of high-dose hyperbaric trioxygen autologous blood therapy (HOT) on oxygenation index (PaO2/FiO2) and serum inflammatory factors in dogs with acute respiratory distress syndrome (ARDS). 【Methods】 Twelve healthy adult beagles were randomly divided into 3 groups (n=4). The blank group was injected with normal saline intravenously. The ARDS model was established by intravenous injection of oleic acid (0.12 mL/kg) in the ARDS group and ARDS+ HOT group. The mark of a successful model is that the oxygen and index (PaO2/FiO2) <300 mmHg. In the ARDS+ HOT group, after the ARDS model was established, 16 G indwelling needle was used to puncture the left femoral vein and connect the line of the HOT device. Venous blood (50 mL/ dog) was collected from the femoral vein under negative pressure to the blood storage bottle (100 mL blood storage bottle), and then the blood collection was stopped and the gas injection switch of the HOT device was turned on. Inject 50 mL of 20ng/dL trioxygen gas into the blood storage bottle. After gas injection, turn the blood storage bottle upside down three times to fully trioxidize the blood and then inject it back into the dog. Repeat this treatment for 10 cycles. PaO2 and PaO2/FiO2 were detected before treatment and at 1, 2, 3, 4, 5 h after treatment. The serum was retained after treatment, and the expressions of inflammatory cytokines (IL-6, IL-8) and myeloperoxidase (MPO) were detected by ELISA. The animals were euthanized, and the gross lung morphology of the dogs was observed at autopsy. The dorsal segment of the left lower lobe of the lung was taken for pathological section HE staining, and the morphological changes of the lung tissue were observed under the microscope. 【Results】 After 5 hours of treatment, the PaO2/FiO2 of blank group was 481.85±35.31, and that of ARDS group was 183.67±20.18, which was significantly lower than that of blank group (P<0.01). The ARDS HOT group was 271.90±21.35, which was significantly higher than the ARDS group (P<0.01). The inflammatory factor IL-6 was (206.49±38.85) pg/mL in the blank group, and (293.12±30.38) pg/mL in the ARDS group, which was significantly higher than that in the blank group (P<0.01). There was a significant difference between the ARDS HOT group and ARDS group (221.56±46.69) pg/mL (P<0.01). The results of inflammatory factor IL-8 detection showed that the IL-8 in ARDS group was increased compared with the blank group (P<0.01); and the IL-8 in ARDS HOT group was decreased compared with ARDS group (P<0.01). Myeloperoxidase MPO test results showed that the blank group was (505.58±73.94) pg/mL, and the ARDS group was (605.69±108.88) pg/mL, which was significantly higher than the blank group (P<0.05). The ARDS HOT group was (476.52±103.85) pg/mL, which was significantly lower than the ARDS group (P<0.05). Microscopic examination of lung pathology showed that the lung tissue injury in ARDS HOT group was significantly reduced compared with ARDS group. 【Conclusion】 HOT can reduce the inflammation and injury of lung in ARDS model dogs through significantly increasing the PaO2/FiO2, down-regulating the expression of MPO, then inhibiting the activity of neutrophils and reducing the levels of IL-6 and IL-8.

Objective:To investigate the association between split foot and electrophysiology in patients with amyotrophic lateral sclerosis (ALS).Methods:The clinically definite or clinically probable ALS patients hospitalized in the Department of Neurology, the First Medical Center of Chinese People′s Liberation Army General Hospital from April 2021 to December 2022 were prospectively collected. From April 2021 to December 2022, patients who visited the Chinese People′s Liberation Army General Hospital for other reasons without abnormal electrophysiological examination were collected as the control group. The incidence of split leg [the limb whose modified Medical Research Council Muscle Strength Scale (mMRC) score of ankle dorsiflexors was lower than that of ankle plantarflexors] in ALS patients was calculated, and the incidence of split foot (the limb whose mMRC score of hallux dorsiflexors was lower than that of hallux plantarflexors) in ALS patients was calculated. The amplitude of compound muscle action potential (CMAP) of common peroneal nerve and tibial nerve was detected to observe the involvement of motor neurons innervating ankle dorsiflexors and ankle plantarflexors. The characteristics of split leg and split foot in ALS patients were analyzed from the perspective of muscle strength, and the characteristics of split foot in ALS patients were analyzed from the perspective of electrophysiology. Receiver operating characteristic (ROC) curve was used to analyze the sensitivity and specificity of peroneal nerve/tibial nerve CMAP amplitude ratio in distinguishing ALS patients from controls.Results:A total of 101 ALS patients with lower limb involvement and 110 controls with normal lower limb muscle strength were collected. Among the 101 ALS patients with lower limb involvement, strength of ankle plantarflexors was greater than that of ankle dorsiflexors in 35.64% (36/101) patients, strength of ankle dorsiflexors was greater than that of ankle plantarflexors in 5.94% (6/101) patients, and strength of ankle plantarflexors and ankle dorsiflexors was equal in 58.42% (59/101) patients. Strength of hallux dorsiflexors was lower than that of hallux plantarflexors in 53.47% (54/101) patients, strength of hallux dorsiflexors was greater than that of hallux plantarflexors in 1.98% (2/101) patients, and the strength of hallux dorsiflexors and hallux plantarflexors was equal in 44.55% (45/101) patients. The incidence of split leg was negatively correlated with age ( OR=0.25, 95% CI 0.16-0.40, P<0.05), course of disease ( OR=0.52, 95% CI 0.38-0.80 P<0.05) and ALS functional revised scores ( OR=0.29, 95% CI 0.12-0.67, P<0.05). The incidence of split foot was negatively correlated with the onset time of lower limb symptoms ( OR=0.96, 95% CI 0.93-0.99, P<0.05). Compared with the control group, the differences of the decrease of CMAP amplitude in the common peroneal nerve and tibial nerve [the common peroneal nerve (6.45±2.56) mV vs (3.63±1.83) mV, tibial nerve (12.87±4.72) mV vs (9.18±6.22) mV] were statistically significant ( t=-4.65, t=-3.44, both P<0.001) and the differences of the peroneal nerve/tibial nerve CMAP amplitude ratio (0.54±0.24 vs 0.36±0.18) decrease was statistically significant ( t=-4.31, P<0.001) in patients with split foot. ROC curve analysis showed that the area under the ROC curve of CMAP amplitude ratio of common peroneal nerve/tibial nerve in ALS patients with split foot was 0.70, indicating that the accuracy of CMAP amplitude of common peroneal nerve/tibial nerve in distinguishing ALS patients from controls was low. Conclusions:In ALS patients with lower limb involvement, strength of ankle dorsiflexors is weaker than that of ankle plantarflexors, and strength of hallux dorsiflexors is weaker than that of hallux plantarflexors. At the diagnostic level, the CMAP amplitude ratio of common peroneal nerve/tibial nerve in ALS patients with split foot has a lower accuracy in the diagnosis of ALS.

OBJECTIVE To analyze the clinical characteristics of liraglutide-induced pancreatitis， and to provide reference for clinical rational drug use. METHODS Retrieved from CNKI， VIP， Wanfang database， PubMed， Web of Science and Medline， case reports about liraglutide-induced pancreatitis were collected from the inception to December 31st， 2022. Demographic characteristics， drug use， clinical manifestations， intervention and outcome were analyzed using descriptive statistical method. RESULTS A total of 17 pieces of literature were collected and 17 patients were involved， including 7 males and 10 females. The patients aged from 25 to 75 years. All 17 patients had drug indications， including 14 cases of type 2 diabetes mellitus， 3 cases of obesity or overweight. Among 17 patients， liraglutide was used alone in 5 cases， and combined with other drugs in 12 cases. Time from liraglutide administration to pancreatitis occurrence ranged from 1 day to 11 months after medication in 17 patients， with 14 cases less than 6 months. The clinical manifestations mainly included abdominal pain， nausea and vomiting， etc. After the diagnosis of pancreatitis， liraglutide discontinuation occurred in 16 patients； 1 case did not receive any other interventions and the other 15 cases were managed with symptomatic supportive treatment； the symptoms of all 16 patients resolved； however， 2 patients suffered from second episode of severe pancreatitis several weeks after liraglutide discontinuation， pancreatitis recurred after liraglutide rechallenge in 1 case. The results of correlation evaluation showed that 1 case was “positive”， 4 cases were “possible”， and the remaining patients were “very likely”. CONCLUSIONS Liraglutide-induced pancreatitis mainly occurred within 6 months after drug administration. The majority of liraglutide-induced pancreatitis cases are mild to moderate， but there are also severe and even fatal cases. It is advisable to periodically monitor the level of pancreatic enzymes and closely observe patients’ clinical mani-festations. In case of suspected liraglutide-induced pancreatitis，drug withdrawal and symptomatic treatment should be taken immediately.