Objective To evaluate the effect of driving pressure(DP)-guided individualized positive end-expiratory pressure(PEEP)combined with regular lung recruitment maneuvers(RMs)on atelectasis in elderly patients undergoing laparoscopic surgery in the Trendelenburg position using lung ultrasound.Methods A total of 62 patients aged 65-85 years old and classified by ASA status Ⅰ-Ⅲ undergoing laparoscopic radical resection of colorectal cancer were included and randomly divided into the experimental group(n=31)and the control group(n=31).Both groups received one RM after the beginning of pneumoperitoneum,followed immediately by titration of individualized PEEP with the lowest DP,and both groups received another RM after the end of pneumoperitoneum.The experimental group received additional RM every 30 min from the beginning of pneumoperitoneum,while the control group received no intervention.Recording time points for observation were:before induction of anesthesia(T0),30 min after pneumoperitoneum(T1),90 min after pneumoperitoneum(T2),at the end of surgery(T3)and 45 min after entering the postanesthesia care unit(PACU,T4).Lung ultrasound score(LUS)was recorded at T0,T3 and T4.Dynamic lung compliance(Cdyn)was recorded at T1-T3.Oxygenation index(OI),mean arterial pressure(MAP)and heart rate(HR)were recorded at T0-T4.Hypotension during RM,hypoxic saturation events in PACU and the incidence of pulmonary complications(POPC)within the first 7 days after surgery were recorded.Results Compared with the control group,LUSs at T3 and T4 were significantly decreased in the experimental group(P<0.05),and OI and Cdyn at T2 and T3 were significantly increased(P<0.05).In addition,the incidence of hypoxia saturation events in PACU was lower in the experimental group than that in the control group(P<0.05).There were no significant differences in the incidence of hypotension during lung recruitment and the incidence of POPC within 7 days after surgery between the two groups.Conclusion The individualized PEEP combined with regular RMs can effectively reduce the atelectasis observed by lung ultrasound immediately after laparoscopic radical resection of colorectal cancer and in PACU in elderly patients.

Bruton's tyrosine kinase(BTK)inhibitors are novel drugs targeted for the treatment of B-cell lymphoma.BTK inhibitors have pro-duced strong curative effects,especially for mantle cell lymphoma(MCL),chronic lymphocytic leukemia/small lymphocytic lymphoma(CLL/SSL),and Waldenstr?m's macroglobulinemia(WM).However,the adverse effect of bleeding has gradually been noted with the wide-spread use of BTK inhibitors in clinical practice.Bleeding events are caused by the off-target effects of BTK inhibitors,which affect platelet function through multiple signaling pathways during use.Bleeding affects patient treatment and threatens their quality of life.As such,the clinical management of bleeding should be strengthened.This paper provides a review of the mechanisms of action and clinical manage-ment of bleeding caused by BTK inhibitors.

Auditory neuropathy spectrum disorder (ANSD) represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function, but with the preservation of outer hair cell function. ANSD represents up to 15% of individuals with hearing impairments. Through mutation screening, bioinformatic analysis and expression studies, we have previously identified several apoptosis-inducing factor (AIF) mitochondria-associated 1 (AIFM1) variants in ANSD families and in some other sporadic cases. Here, to elucidate the pathogenic mechanisms underlying each AIFM1 variant, we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and constructed AIF-wild type (WT) and AIF-mutant (mut) (p.‍T260A, p.‍R422W, and p.‍R451Q) stable transfection cell lines. We then analyzed AIF structure, coenzyme-binding affinity, apoptosis, and other aspects. Results revealed that these variants resulted in impaired dimerization, compromising AIF function. The reduction reaction of AIF variants had proceeded slower than that of AIF-WT. The average levels of AIF dimerization in AIF variant cells were only 34.5%‍‒‍49.7% of that of AIF-WT cells, resulting in caspase-independent apoptosis. The average percentage of apoptotic cells in the variants was 12.3%‍‒‍17.9%, which was significantly higher than that (6.9%‍‒‍7.4%) in controls. However, nicotinamide adenine dinucleotide (NADH) treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells. Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD, and introduce NADH as a potential drug for ANSD treatment. Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.
Humans ; Apoptosis Inducing Factor/metabolism* ; NAD/metabolism* ; Dimerization ; Apoptosis

Auditory neuropathy spectrum disorder (ANSD) represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function, but with the preservation of outer hair cell function. ANSD represents up to 15％ of individuals with hearing impairments. Through mutation screening, bioinformatic analysis and expression studies, we have previously identified several apoptosis-inducing factor (AIF) mitochondria-associated 1 (AIFM1) variants in ANSD families and in some other sporadic cases. Here, to elucidate the pathogenic mechanisms underlying each AIFM1 variant, we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and constructed AIF-wild type (WT) and AIF-mutant (mut) (p.T260A, p.R422W, and p.R451Q) stable transfection cell lines. We then analyzed AIF structure, coenzyme-binding affinity, apoptosis, and other aspects. Results revealed that these variants resulted in impaired dimerization, compromising AIF function. The reduction reaction of AIF variants had proceeded slower than that of AIF-WT. The average levels of AIF dimerization in AIF variant cells were only 34.5％?49.7％ of that of AIF-WT cells, resulting in caspase-independent apoptosis. The average percentage of apoptotic cells in the variants was 12.3％?17.9％, which was significantly higher than that (6.9％?7.4％) in controls. However, nicotinamide adenine dinucleotide (NADH) treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells. Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD, and introduce NADH as a potential drug for ANSD treatment. Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.

Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)-DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.

Oridonin is one of the main anti-tumor active ingredients of Rabdosiae Rubescentis Herba. In the development process of a variety of malignant tumors, such as liver cancer, breast cancer, cervical cancer, pancreatic cancer, lung cancer, gastric cancer, esophageal cancer, colon cancer, etc, it has a significant inhibitory effect. Oridonin plays the rold of anti-tumor effect mainly by inhibiting tumor cell proliferation, inducing tumor cell apoptosis, inhibiting tumor cell invasion and migration, inducing tumor cell autophagy, reducing telomerase activity and reversing the drug resistance of the tumor cell.

Brucellosis is a kind of animal epidemic disease that can be transmitted to human beings through skin, mucous membrane, digestive tract, respiratory tract and other ways. In recent years, the incidence of brucellosis has increased. Its pathogenesis is relatively complicated. In addition to bacteria, toxins and other factors, genetic susceptibility has gradually attracted the attention of scholars. In this paper, we summarized the previous reports and reviewed the relationship between interleukin gene polymorphism and susceptibility to brucellosis.

Brucellosis is an zoonosis, humans can be infected by Brucella through skin, mucous membrane, digestive tract, respiratory tract and so on. In the past, most of them recorded the infection of brucellosis from animal to human, but rarely reported the transmission of brucellosis between humans. This paper retrospectively reviews previous reports describing the spread of brucellosis between humans.

Objective: To describe eraly and midterm outcome of the Rastelli repair in Fuwai hospital Patients. Methods: From May 2010 to March 2017, 71 patients with transposition of the great arteries(TGA)with ventricular septal defect(VSD)and right ventricular outflow tract obstruction(RVOTO) or double outlet right ventricle(DORV)with VSD and RVOTO underwent Rastelli repair. 48 cases male , 23 cases female . Age at operation is(4.7±2.7) years. There are 10 TGA cases, 27 DORV cases, 34 CTGA cases in this group. 30 patients(42.3% , 30/71)received palliative operation prior to the Rastelli procedure, including 13 BT shunt and 17 bi-Glenn operation. 31 patients(43.7%, 31/71 )underwent the Rastelli procedure with VSD enlargement. Right ventricle-to-pulmonary artery connection were created with the use of 9 homografts, 56 valved bovine jugular vein, 6 man-made valved Gore-Tex conduit. The overall mean right ventricle-to-pulmonary artery conduit size was(17.9±3.3)mm. Results: CPB time was(209.0±83.4)minutes, aortic crossclamping time was(132.0±71.1)minutes, mechanical ventilation time was(102.6±81.7)h. Early mortality was 1.4%(1/71). morbidity in hospital was 16.9%, 4 patients with Ⅲ AVB implanted permanent pacemaker, Subxiphoid pericardial window drainage in 3 cases, delayed sternal closure in 3 and re-thoratomy for hemaostsis in 2.Follow up is from 4 months to 6.8 years. Overall survival was 97.2% and 97.2% at 1 and 5 years, respectively. Freedom from RVOTO was 98.6% and 84.1% at 1 and 5 years, respectively. Freedom from reintervention was 98.6% and 90.0% at 1 and 5years, respectively. 1 patients performed a conduit replacement. Seven patients performed 10 times balloon dilatation . Time-related freedom from recurrent LVOTO on echocardiogram in all patients, and the pressure gradient of the LV to the aorta was(10.5±8.8 )mmHg at the most recent follow-up. Conclusion The Rastelli operation remains the preferred procedure for part of the DORV , CTGA , TGA with VSD and severe fixed valvular or subvalvular PS. The Rastelli procedure can be performed with low early mortality. There is frequent need for late reoperation, especially for conduit replacement.

Bow hunter′s syndrome, also known as vertebral basilar artery insufficiency, is a rare disease characterized by post?circulation blood supply insufficiency caused by mechanical or stenosis of the vertebral artery when the head and neck rotate or over?extend. To date, few cases regarding the bilateral hunter′s bow syndrome concurrent with epilepsy have been reported. A 29?year?old man was admitted to the First Hospital of Jilin University due to seizures. Results from transcranial Doppler ultrasound and carotid ultrasound showed that the patient had bilateral hunter′s bow syndrome. Further imaging examination showed that the syndrome was caused by congenital bone fusion which resulted in mechanical occlusion of C1-C2 vertebral artery. This case indicates that seizures are closely related to hunter′s bow syndrome.