Objective:To analyze the clinical characteristics and treatment outcomes of chronic dacryocystitis-related corneal ulcers and to provide a basis for the rational clinical diagnosis and treatment.Methods:An observational case series study was performed.A total of 31 patients (31 eyes) diagnosed with chronic dacryocystitis-related corneal ulcers in Eye Hospital of Shandong First Medical University were enrolled from January 2016 to January 2020, with an average age of (53.0±10.8) years.The typical ocular signs, results of the etiological examination and microbial sensitivity test, treatment process and outcomes were analyzed.This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Eye Hospital of Shandong First Medical University (No.20191020-1).Written informed consent was obtained from each subject before any medical examination.Results:The average history of chronic dacryocystitis was (3.6±1.9) years.Corneal ulcers were mostly located in the peripheral cornea and had a rounded morphology with clear borders.The positive rate of corneal scraping was 74.2%(23/31), with bacteria in 19 eyes, fungal hyphae in 3 eyes, and both gram-positive cocci and fungal hyphae in 1 eye.The positive rate of microbial culture was 74.2%(23/31), with positive bacterial culture in 20 eyes (gram-positive cocci in 16 eyes and gram-negative bacilli in 4 eyes) and fungal growth in 3 eyes.The sensitivity rates of gram-positive cocci to vancomycin, rifampicin, moxifloxacin, and levofloxacin were 100%(16/16), 87.5%(14/16), 81.3%(13/16), and 75.0%(12/16), respectively.All patients were treated with surgery for chronic dacryocystitis, including 22 cases of endoscopic dacryocystorhinostomy, 7 cases of dacryocystectomy, and 2 cases of lacrimal duct probing combined with intubation.Among the 9 cases with an ulcer depth of <1/3 of the corneal thickness (CT), 6 cases were cured after (10.8±3.2) days of drug treatment and 3 cases underwent corneal lesion resection.The 6 patients with an ulcer depth of 1/3-2/3 of the CT underwent conjunctival flap covering surgery.Among the 16 patients with an ulcer depth of >2/3 of the CT, lamellar keratoplasty was performed in 6 cases, penetrating keratoplasty in 8 cases and evisceration in 2 cases with infectious endophthalmitis.Conclusions:Chronic dacryocystitis-related corneal ulcers are mainly located at the periphery of the cornea, and gram-positive cocci infections are the most common pathogenic bacteria.In patients with mild symptoms, corneal ulcers heal gradually after treatment with sensitive antibiotics.For patients with severe infections, appropriate surgery should be selected according to the depth of the corneal ulcer.

The adenosine 5'-triphosphate (ATP)-binding cassette (ABC) transporter, IrtAB, plays a vital role in the replication and viability of Mycobacterium tuberculosis (Mtb), where its function is to import iron-loaded siderophores. Unusually, it adopts the canonical type IV exporter fold. Herein, we report the structure of unliganded Mtb IrtAB and its structure in complex with ATP, ADP, or ATP analogue (AMP-PNP) at resolutions ranging from 2.8 to 3.5 Å. The structure of IrtAB bound ATP-Mg2+ shows a "head-to-tail" dimer of nucleotide-binding domains (NBDs), a closed amphipathic cavity within the transmembrane domains (TMDs), and a metal ion liganded to three histidine residues of IrtA in the cavity. Cryo-electron microscopy (Cryo-EM) structures and ATP hydrolysis assays show that the NBD of IrtA has a higher affinity for nucleotides and increased ATPase activity compared with IrtB. Moreover, the metal ion located in the TM region of IrtA is critical for the stabilization of the conformation of IrtAB during the transport cycle. This study provides a structural basis to explain the ATP-driven conformational changes that occur in IrtAB.
Siderophores/metabolism* ; Iron/metabolism* ; Mycobacterium tuberculosis/metabolism* ; Cryoelectron Microscopy ; Adenosine Triphosphate/metabolism* ; ATP-Binding Cassette Transporters

OBJECTIVE It's known that post-retrieval extinction but not extinction alone could erase fear memory.However,whether the coding pattern of original fear engrams is remod-eled or inhibited remains largely unclear.Here we try to investigate whether the coding pattern of memory engrams is altered during post-retrieval extinction induced memory updating.METHODS To answer the question,by using activity-depen-dent neuronal-tagging technology,neuronal trac-ing technique combined with optogenetic manipu-lation and in vivo calcium imaging,we identified the fear and extinction cells in PrL and BLA and investigated the dynamic encoding of memory engram ensembles in the PrL and BLA during CS versus US initiated memory updating.RESULTS We found increased reactivation of engram cells in the prelimbic cortex and basolat-eral amygdala during memory updating.More-over,conditioned stimulus and unconditioned stimulu sinitiated memory updating depend on the engram cells reactivation in the prelimbic cor-tex or basolateral amygdala respectively.Finally,we found memory updating causes increased overlapping between fear and extinction cells and the original fear engrams encoding was altered during memory updating.CONCLUSION Our data provide the first evidence to show the overlapping ensembles between fear and extinc-tion cells and functional reorganization of original engrams underlying conditioned stimulus and unconditioned stimulus initiated memory updating.

Hereditary spastic paraplegia type 58 is rare, caused by pathogenic variations in KIF1C gene. Here, a case diagnosed in Qilu Hospital, Shandong University, was reported. The 15-year-old female suffered tremor in bilateral upper limbs which was aggravated gradually since age 8. Cerebellar ataxia, positive pyramidal tract sign and dystonic tremor were prominent on physical examination. The brain magnetic resonance imaging showed T 2-hyperintense signals in bilateral pyramidal tracts, optic radiations and superior cerebellar peduncles, with mild cerebellar atrophy. Whole exon sequencing revealed the unreported homozygous c.425_426delTG (p.V142Gfs*10) mutation which was presumed pathogenic.

Objective:To investigate the curative effect of Haikunshenxi capsule combined with losartan potassium tablets on chronic kidney disease (CKD) and its effect on renal function and inflammatory factors.Methods:One hundred patients with chronic kidney disease in Shaoxing Central Hospital from January 2018 to December 2019 were selected and randomly divided into observation group (50 cases) and control group (50 cases). The control group was treated with losartan potassium tablets based on conventional therapy, and the observation group was treated with Haikunshenxi capsulebase on control group. The treatment course of the two groups was 12 weeks. The curative effect, renal function, inflammatory factors, 24h urinary protein (24 h Upro) and glomerular filtration rate (GFR) were compared between the two groups before and after treatment.Results:The total effective rate in the observation group was higher than that in the control group: 90.0%(45/50) vs. 72.0%(36/50), χ2 = 5.26, P<0.05. After treatment, the levels of serum creatinine (Scr) and blood urea nitrogen (BUN) in the two groups were decreased and the levels of Scr and BUN in the observation group were lower than those in the control group: (63.27 ± 2.89) μmol/L vs. (67.89 ± 2.35) μmol/L, (5.23 ± 0.19) mmol/L vs. (5.56 ± 0.16) mmol/L, the differences were statistically significant ( P<0.05). After treatment, the levels of serum C-reactive protein (CRP) , interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the two groups were decreased and the levels of CRP, IL-6 and TNF-α in the observation group were lower than those in the control group: (2.97 ± 0.34) mg/L vs. (3.58 ± 0.42) mg/L, (3.64 ± 0.68) ng/L vs. (4.97 ± 0.96) ng/L, (14.32 ± 2.17) ng/L vs. (17.86 ± 2.06) ng/L, the differences were statistically significant ( P<0.05). After treatment, the level of 24 h Upro in two groups was decreased, while the level of GFR was increased, and the level of 24 h Upro in the observation group was lower than that in the control group: (0.87 ± 0.09) g vs. (1.15 ± 0.13) g , but the level of GFR in the observation group was higher than that in the control group: (101.73 ± 3.12) ml/(min·m 2) vs. (96.75 ± 2.35) ml/(min·m 2), the differences were statistically significant ( P<0.05). Conclusions:Haikunshenxi capsule combined with losartan potassium tablets has obvious curative effect on patients with chronic kidney disease, and can improve renal function and micro inflammation.

Objective:To explore the current situation and influencing factors of stressors among nursing interns.Methods:From September 2020 to June 2021, 750 nursing interns who practiced in the First Affiliated Hospital of Harbin Medical University were selected by convenience sampling for the questionnaire survey. Multiple linear regression was used to analyze the influencing factors of stressors.Results:A total of 750 questionnaires were distributed, and 732 valid questionnaires were recovered. A total of 51.23% (375/732) nursing interns were under high pressure, and 39.89% (292/732) were under medium pressure. The main stressors were the psychological impact brought by the nature of the work in the rotation department, the students' perception of their poor theoretical foundation and the fear of not finding a satisfactory job due to the conflict between study and work. Age, personality, whether to choose nursing specialty voluntarily, whether to like nursing specialty, whether to have nursing practice and probation experience, and the time of practice were the influencing factors of stressors ( P<0.05) . Conclusions:In combination with the stressors and their influencing factors of nursing interns, we should propose targeted measures to relieve the pressure of nursing interns, help them maintain their physical and mental health, quickly complete the role transition, and provide a reference for improving clinical nursing teaching methods and the quality of education of nursing interns.

Objective To systematically evaluate the efficacy and safety of immune checkpoint inhibitors in the treatment of advanced gastric cancer or gastroesophageal junction cancer (GC/GEJC). Methods CNKI, Wanfang, PubMed, EMBASE, ClinicalTrials, Cochrane Library and other databases were searched to collect the clinical trials of immune checkpoint inhibitors in the treatment of advanced GC/GEJC. The retrieval time was from the inception to Nov. 2019. Outcome measures mainly included ORR, DCR, PFS, OS and toxicities. The adoption rate difference and hazard ratio were effect measures. Meta-analysis was performed using RevMan 5.3 software. Results We included seven literatures with a total of 1949 patients. Meta-analysis showed that for the patients with advanced GC/GEJC, the second-line or later immune checkpoint inhibitor therapy improved the overall survival rate at 12 and 18 months; the OS of the patients was prolonged, compared with chemotherapy/placebo therapy (all P < 0.05). The incidence of adverse reactions of any grade or ≥grade 3 caused by immune checkpoint inhibitor therapy was lower than that caused by chemotherapy/placebo. Conclusion Immune checkpoint inhibitor treatment could improve survival endpoints in some patients with advanced GC/GEJC, and the incidence of common adverse reactions is low.

Objective:To understand the sleep quality and mental health status of nurses in public health emergencies, and analyze the correlation between them.Methods:A total of 128 first-line nursing staff participating in public health emergencies on February 22-23, 2020 in Tianjin Beichen Hospital, Tianjin First Central Hospital, Tianjin Fourth Central Hospital were investigated by the general data questionnaire, Pittsburgh Sleep Quality Index (PSQI), and Symptom Checklist 90 (SCL-90).Results:70.3%(90/128) of nursing staff had poor sleep quality, and the total score of PSQI was (9.71±4.01) points, which was statistically significant compared with the domestic norm ( t value was 16.479, P<0.01). The total score of SCL-90 was 1.59±0.52, which was statistically significant compared with the domestic norm ratio ( t value was 4.505, P<0.01). One-way ANOVA showed that the nursing staff's age had a significant impact on sleep quality, and the difference was statistically significant ( F value was 4.092, P<0.05). Pearson correlation analysis showed that the Pittsburgh sleep quality scale index scores and symptom self-assessment scale and somatization, force, sensitive interpersonal relationship, depression, anxiety, hostile, terrorist, paranoia, and psychosis were positively correlated( r values were 0.292-0.444, P< 0.01). Conclusions:The sleep quality and mental health status of nurses in public health emergencies are poor, and the sleep quality is correlated with mental health status.

Objective:To compare the clinical efficacy of transperitoneal robot assisted laparoscopic radical prostatectomy (RARP) versus extraperitoneal single port RARP.Methods:A retrospective analysis was perfoumed on 142 cases of RARP from July 2019 to June 2020 in Robotic Minimally Invasive Center of Sichuan Provincial People's Hospital, including 82 cases(Group A) , aged 70.0(65.6-78.0), undergoing transperitoneal RARP and 60 cases(Group B), aged 68.2 years old(60.1-79.2), undergoing extraperitoneal single port RARP. For group A, PSA was 12.9(5.6-64.0) ng/ml, with 26 cases of less than 10 ng/ml(31.7%), 40 cases of 10-20 ng/ml(48.8%), and 16 cases of more than 20 ng/ml(19.5%), the Gleason score was 7.2(6.0-10.0), with 14 cases(17.1%) of ≤6, 56 cases(68.3%) of 7, and 12 cases(14.6%) of ≥8, and the prostate volume was 61.3(29.0-112.0) ml. There were 49 cases with BMI≤25 kg/m 2, accounting for 59.8%, and 33 cases with BMI>25 kg/m 2, accounting for 40.2%. There were 17 cases(20.7%) of T 1, 44 cases(53.7%) of T 2 and 21 cases(25.6%) of T 3. The proportion of lymph node dissection was 17.1%, and 4 cases(4.9%)had a history of operation. For group B, the PSA was 12.2(1.0-42.6)ng/ml, with 20 cases (33.3%) of <10 ng/ml, 31 cases(51.7%)of 10-20 ng/ml, and 9 cases (15%) of >20 ng/ml. Gleason score was 7.1(6.0-9.0), with 12 cases (20.0%) of ≤6, 42 cases (70.0%) of 7, and 6 cases (10.0%)of ≥8. Prostate volume was 42.4(31.2-72.8)ml on average. There were 37 cases (61.7%) with BMI≤25 kg/m 2, and 23 cases (38.3%)with BMI >25 kg/m 2 . There were 17 cases(28.3%)of T 1, 32 cases(53.3%)of T 2 and 11 cases(18.3%)of T 3.The proportion of lymph node dissection was 11.7% and 4 cases (6.7%) had a history of operation.There was no statistically significant difference in term of age, PSA level, Gleason score, BMI, clinical stage, proportion of lymph node dissection or history of operation between the two groups( P>0.05), but there was statistically significant difference for prostate volume( P<0.05). All operations were performed by the same operator. Four different ways of bladder neck and urethral dissociation was selected according to the intraoperative conditions in Group A, include VIP style, T-shape incision style, VIP plus T-shape incision style or the style along the lateral side of the bladder neck. Small and single anterograde incision stripping of bladder neck was routinely performed in the Group B. Postoperative follow-up was performed to compare the operation time, intraoperative blood loss, bladder neck and urethral anastomosis time, postoperative hospital stay, postoperative exhaust time, postoperative complications, positive rate of surgical margin, indwelling time of urinary catheter, urinary continence satisfaction rate of immediately after operation, 3 months and 6 months after operation, wound healing and aesthetics. Results:All of the operations were successfully completed under robot-assisted laparoscopy, and there was no conversion to open surgery. The operation time was 56.0(45.0-112.0) min in the Group A and 65.4(55.5-96.8) min in the Group B, and there was no statistically significant difference( P>0.05). The intraoperative blood loss was 76.2(30.0-120.5) ml and 55.6(45.5-114.6) ml, respectively, and the difference was not statistically significant( P>0.05). The time of bladder neck urethral anastomosis was 18.9(12.6-25.6) min and 16.2(10.7-19.3) min, respectively, and the difference was not statistically significant( P>0.05). The postoperative hospital stay days were 9.3(8.0-16.0) d and 8.4(7.0-13.0) d, respectively, and the difference was not statistically significant( P>0.05). The postoperative exhaust time was 1.3(0.7-3.0) d and 3.4(2.0-7.0) d, respectively, and the difference was statistically significant( P<0.05). There was 1 case of anastomotic fistula with ureteral injury in Group A, and no serious complication in Group B, and the difference was not statistically significant( P>0.05). The number of positive surgical margin in the two groups was 13(15.9%)and 9(15.0%)respectively, and the difference was not statistically significant( P>0.05). The indwelling time of urinary catheter after operation was 9(7-21) d and 6(4-8) d, respectively, and the difference was statistically significant( P<0.05). The number of patients with satisfactory urinary continence immediately after surgery, 3 months and 6 months after surgery in the two groups were 8(9.8%), 51(62.2%), 62(75.6%) and 17(28.3%), 43(71.7%) and 54(90.0%), respectively. The differences were statistically significant( P<0.05). The total incision lengths in the two groups were 12.1(10.4-13.4) cm and 5.6(5.0-6.0) cm, respectively, and the difference was statistically significant( P<0.05). Conclusions:The extraperitoneal single port RARP is safe and feasible, and the postoperative effect is similar to that of transperitoneal RARP. It has the advantages of shorter recovery time, higher urinary continence satisfaction rate, neater and more beautiful incision. The long-term therapeutic effect needs further confirming by prospective study.

Objective:To explore the association between blood pressure control and risk of ischemic stroke (IS) in patients with hypertension.Methods:A total of 5 488 patients with hypertension from 60 communities were randomly selected from 101 communities in 8 streets of Nanshan District in Shenzhen City by using two-stage sampling method. The social demographic characteristics, behavior and life style, coronary heart disease and diabetes were collected and the physical condition, blood pressure and blood biochemical indexes were measured. From April 1, 2010 to August 31, 2017 as the follow-up period, the incidence of IS was annually collected by using telephone survey. Cox proportional hazard regression model was used to analyze the relationship between blood pressure control, systolic blood pressure (SBP), diastolic blood pressure (DBP) and the risk of IS.Results:The age of all patients was (58.50±12.14) years old, including 2 712 males (49.42%) and 3 112 patients with well-controlled blood pressure (56.71%). During the follow-up period, 358 new cases of IS were confirmed, and the incidence density was 1 346.27/100 000 person-years. Cox proportional hazard regression model analysis showed after adjusting for confounding factors, unstable blood pressure control, SBP≥150 mmHg (1 mmHg=0.133 kPa; compared with SBP<120 mmHg), and DBP≥95 mmHg (compared with DBP<80 mmHg) were associated with risk of IS. The HR (95% CI) was 1.29 (1.04, 1.59), 2.00 (1.26, 3.17) and 1.52 (1.01, 2.64), respectively. Subgroup analyses showed these associations only existed in female patients with hypertension. The HR (95% CI) was 1.39 (1.05, 1.85), 2.53 (1.41, 4.56) and 1.73 (1.00, 3.36), respectively. Conclusion:Unstable blood pressure control increases the risk of IS in female patients with hypertension.