Objective:This study aimed to explore the performance of renal resistive index (RRI), semiquantitative power Doppler ultrasound (PDU) score, and renal venous Doppler waveform (RVDW) pattern in predicting 28-day renal dysfunction in critically ill patients and establish nomogram model.Methods:This was a prospective, observational study. Critically ill patients admitted to the emergency intensive care unit (ICU) of Cangzhou Central Hospital from January 2018 to October 2022 were included. Patients underwent renal ultrasound examination to obtain RRI, PDU score and RVDW pattern within 24 h after ICU admission. The following clinical variables were collected during the renal ultrasound examination session, including heart rate, mean arterial pressure, type and dose of vasoactive drugs, oxygen therapy parameters, and average urine volume per hour derived from a period of 6 h prior to the ultrasound examination. The data on duration of AKI and mortality were recorded on the 28th day of follow-up. Patients were divided into 28-day normal renal function group and 28-day renal dysfunction group according to 28-day renal dysfunction. 28-days of renal dysfunction was defined as failure to achieve renal function recovery within 28 days of ICU admission. The difference of each index between the two groups was compared. Associated factors for 28-day renal dysfunction were determined by univariate and multivariate COX regression analyses. A nomogram was developed based on the independently factors associated with 28-day renal dysfunction. Survival receiver operator characteristic (ROC) curves were plotted to assess diagnostic performance in predicting 28-day renal dysfunction. Delong’s test was used to compare area under the curves (AUC) between each predictor.Results:187 patients were enrolled for the final analysis: 97 with no AKI, 48 with AKI stage 1, 24 with AKI stage 2, and 18 with AKI stage 3 upon enrollment. At 28-day follow up, 16 patients had renal dysfunction and 2 required continuous renal replacement therapy (CRRT). The multivariate COX regression showed that RVDW and SCr upon enrollment were the independent risk predictors. Nomogram based on RVDW and SCr upon enrollment showed the best performance in predicting 14-day renal dysfunction (AUC = 0.918, 95% CI:0.871-0.964, P<0.05), and the AUC was statistically significantly higher than single index (all P<0.05). Nomogram also showed the best performance in predicting 28-day renal dysfunction (AUC = 0.924, 95% CI:0.865-0.983, P<0.05), and the AUC was statistically significantly higher than single index (all P<0.05) except for SCr upon enrollment. The optimal cutoff for nomogram in predicting 28-day renal dysfunction was ≤89.5 (sensitivity, 81.2%; specificity, 90.6%; Youden index, 0.719). Kaplan-Meier analysis showed that the median duration of renal dysfunction in the groups with total nomogram score >85.9 and ≤85.9 was 0 and 22 days (HR=0.220, 95% CI:0.129-0.376, P<0.001). Conclusions:SCr and RVDW pattern within 24 h from ICU admission were independent factors associated with 28-day renal dysfunction in critically ill patients. The value of the nomogram model based on these two factors in predicting 28-day renal dysfunction is superior to each single intrarenal Doppler spectrum indicator and clinical indicator.

AIM: To investigate the clinical efficacy and safety of XEN drainage tube implantation combined with mitomycin C(MMC)for open angle glaucoma(OAG).METHODS:A total of 37 OAG patients(37 eyes)were retrospectively included, grouped by anti-glaucoma surgical treatment as the first choice or not, with 17 patients(17 eyes)in the group with primary surgical treatment, and 20 patients(20 eyes)in the group with the numerous surgeries. The intraocular pressure(IOP), kinds of IOP-lowering drugs, and complications were collected and analyzed in 1 a follow-up postoperatively.RESULTS:Upon the one-year follow-up, IOP had decreased from 27.56±9.94, 28.43±14.18 mmHg to 15.16±3.65, 17.18±5.83 mmHg in both groups, respectively, representing a reduction of 55.01% and 60.43%, respectively(t=4.863, P<0.001; t=3.255, P=0.004). The IOP at various follow up points were lower than preoperative points in both groups(Ftime=6.876, Ptime<0.001; Fintergroup=0.242, Pintergroup=0.626; Ftime×intergroup=0.959, Ptime×intergroup=0.458). The complete success rate was 47% and 45%, the qualified success rate was 76% and 75%(Z=-0.115, P=0.909), respectively, and there was no significant difference in the cumulative survival rate between two groups(χ2=0.042, P=0.838; χ2=0.004, P=0.949). At the last follow up, IOP-lowering drugs were reduced from 3(2, 3)to 1(0, 2)in both groups(Z=-3.289, -3.796, all P<0.001), and no significant difference between groups(Z=-0.581, P=0.561). Hypotony is the most common short-term complications, anterior chamber haemorrhage followed, while, filtering bleb encapsulation is the most frequent long-term complication, no serious complications occurred, but with XEN drainage tube exposure in 1 eye and drop in 1 eye.CONCLUSION:Initial XEN drainage tube implantation combined with MMC and numerous glaucoma surgeries are both safe and effective treatment for OAG patients, while the incidence of filtering bleb encapsulation is high in those with numerous glaucoma surgeries.

Objective To explore the effects of long non-coding RNA(lncRNA)small nucleolar molecule RNA host gene 12(SNHG12)targeting inhibition of miR-495-3p/phospholipinositol-3-kinase(PI3K)/protein kinase B(Akt)signaling pathway on the proliferation,migration and invasion of prostate cancer cells.Methods The expressions of SNHG12 and miR-495-3p in prostate cancer tissues and cells(LNCaP,C4-2,DU145)were detected with real-time fluorescence quantitative PCR(qRT-PCR).After DU145 cells were divided into si-NC,si-SNHG12,si-SNHG12+anti-miR-NC and si-SNHG12+anti-miR-495-3p groups,the expressions of SNHG12 and miR-495-3p were detected with qRT-PCR;the targeting relationship between SNHG12 and miR-495-3p was determined with dual luciferase assay;cell proliferation was assessed with MTT assay;cell migration and invasion were evaluated with Transwell assay;the protein expressions of proliferating cell nuclear antigen(PCNA),N-cadherin,and E-cadherin were detected with Western blot.Results The expressions of SNHG12 were significantly increased,while the expression of miR-495-3P was significantly decreased in prostate cancer tissues and cells(LNCaP,C4-2,DU145)(P＜0.05).Knockdown of SNHG12 decreased DU145 cell activity,lowered the protein expressions of PCNA and N-cadherin,reduced the number of migrating and invading cells,but increased the protein expression of E-cadherin(P＜0.05).SNHG12 targeted and negatively regulated miR-495-3p,and down-regulation of miR-495-3p reversed the effects of SNHG12 knockdown on the proliferation,migration and invasion of prostate cancer cells.Compared with the si-NC group,the si-SNHG12 group had significantly decreased expressions of p-PI3K and p-Akt(P＜0.05).Compared with the si-SNHG12+anti-miR-NC group,the si-SNHG12+anti-miR-495-3p group had significantly increased protein expressions of p-PI3K and p-Akt(P＜0.05).Conclusion lncRNA SNHG12 can promote the proliferation,migration and invasion of prostate cancer cells through targeted inhibition of miR-495-3p/PI3K/Akt signaling pathway.

Objective:To investigate the efficacy and safety of ab externo or ab interno transluminal trabeculotomy in the treatment of secondary glaucoma following pars plana vitrectomy (PPV).Methods:An observational case series method was performed.Seventeen eyes of 17 patients with glaucoma following PPV were enrolled in Henan Eye Hospital and Beijing Tongren Hospital from May 2016 to Feburary 2022.Primary conditions of patients receiving PPV included retinal detachment in 13 eyes, vitreous hemorrhage in 3 eyes, and entophthalmia in 1 eye.All the subjects underwent ab externo (11 eyes) or ab interno (6 eyes) transluminal trabeculotomy.The scope of all cases accepted trabeculotomy was ≥300°(11 cases of 360°, 4 cases of 330° and 2 cases of 300°).Before and at 1 week, 1 month, 6 months and 12 months after surgery, the intraocular pressure (IOP) was evaluated by Goldmann Tonometer and the best corrected visual acuity (BCVA) was measured using a standard visual acuity chart and converted to logrithm of minimal angle of resolution (LogMAR).The number of anti-glaucoma drug applications and surgery-related complications were recorded.The primary outcomes evaluated were IOP and surgical success rate.Secondary outcomes were medication quantity, BCVA (LogMAR) changes, and complications.Surgical success was defined as IOP reduction to <21 mmHg (1 mmHg=0.133 kPa) with or without the use of IOP-lowering medication.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2021[41]).Written informed consent was obtained from each subject.Results:Preoperative, 1-week, 1-month, 6-month, and 12-month postoperative mean IOP was (34.41±5.11), (21.88±11.72), (20.77±7.67), (19.50±7.01), and (16.32±4.68)mmHg, respectively, with an statistically significant overall difference ( F=20.779, P<0.001).IOP at difference time points after surgery were lower than that before surgery, showing statistically significant differences (all at P<0.01).Compared with before surgery, IOP was reduced more than 40% at 12 months after surgery in 14 eyes.Surgical success rates at 6 and 12 months after surgery were both 76.5%.The number of IOP-lowing drugs decreased significantly after operation ( Z=-4.580, P<0.001).The difference in BCVA between before and 6 months after surgery was not statistically significant ( Z=-1.311, P=0.190).No serious complications were seen in any of the operated eyes postoperatively. Conclusions:Ab externo or ab interno transluminal trabeculotomy is safe and effective in the treatment of secondary glaucoma after PPV.

Objective:To explore whether the optic nerve sheath diameter (ONSD) within 24 hours of intensive care unit (ICU) admission is the predictor of 28-day delirium or coma and death in etiologically diverse critically ill patients.Methods:A prospective, observational study was conducted. The critically ill patients admitted to the emergency ICU of Cangzhou Central Hospital from January 2021 to October 2022 were enrolled. Bedside ultrasound monitoring ONSD was performed within 24 hours of ICU admission. The consciousness status was assessed daily during ICU hospitalization. Coma was defined as Glasgow coma scale (GCS) score < 8 or Richmond agitation-sedation scale (RASS) score -4 or -5. Delirium was defined as responsiveness to verbal stimulation and with a positive confusion assessment method-intensive care unit (CAM-ICU). A positive result of CAM-ICU was defined as acute change or fluctuating course of mental status+inattention+altered level of consciousness or disorganized thinking. X-tile software analysis was used to visualize the best cut-off value for creating divisions in predicting 28-day coma or delirium and death, and then Kaplan-Meier curves were plotted. ONSD≥the optimal cut-off value from X-tile analysis was defined as ONSD broadening. ONSD broadening and related indicators were enrolled, and multivariate Cox regression analysis was used to analyze the risk factors of 28-day coma or delirium and 28-day death in etiologically diverse critically ill patients.Results:A total of 321 critically ill patients were enrolled. Of them, 49 had primary brain injury, 54 had hypoxic ischemic brain injury (HIBI) after cardiac arrest, 70 had acute heart failure, 73 had sepsis, and 75 had other causes. Coma affected 184 patients (57.3%), and delirium affected 173 patients (53.9%). At 28 days of follow-up, 100 patients died, 16 patients remained comatose and 20 patients remained delirious. In all patients, as the GCS score decreased upon admission to the ICU, there was a gradually increasing trend in ONSD [GCS score 15 group: 5.20 (4.93, 5.43) mm, GCS score 10-14 group: 5.30 (4.90, 5.65) mm, GCS score 6-9 group: 5.40 (5.10, 5.80) mm, GCS score < 6 group: 5.70 (5.20, 5.96) mm, P < 0.05]. X-tile software analysis showed that in all patients and five etiological subgroups, ONSD broadening was a predictor for 28-day coma or delirium, and the optimal cut-off value was obtained (5.60 mm for all patients, 4.90 mm for primary brain injury, 5.75 mm for HIBI after cardiac arrest, 5.40 mm for acute heart failure, 5.90 mm for sepsis, and 5.75 mm for other causes). The Kaplan-Meier curves were plotted according to the optimal cut-off values, and the results showed that the higher the ONSD, the higher the incidence and duration of coma or delirium within 28 days in above patient population. X-tile software analysis showed that in all patients, and HIBI after cardiac arrest, sepsis and other causes patients, ONSD was a predictor for 28-day death, and the optimal cut-off value was obtained (6.20 mm for all patients, 5.85 mm for HIBI after cardiac arrest, 5.35 mm for sepsis, and 6.10 mm for other causes). The Kaplan-Meier curves were plotted according to the optimal cut-off values, and the results showed that the higher the ONSD, the higher the 28-day survival rate and the shorter survival duration in above patient population. Multivariate Cox regression analysis showed that ONSD broadening was an independent risk factor for 28-day coma or delirium in all patients [hazard ratio ( HR) = 1.513, 95% confidence interval (95% CI) was 1.093-2.095, P = 0.013] and patients with primary brain injury ( HR = 5.739, 95% CI was 2.112-15.590, P = 0.001). However, ONSD broadening was not independently associated with 28-day death in all patients or in the five etiological subgroups. Conclusions:ONSD within 24 hours of ICU admission is an independent risk factor for 28-day coma or delirium in etiologically diverse critically ill patients. It serves as a predictor for 28-day coma or delirium in 5 subgroups of etiology including primary brain injury, HIBI after cardiac arrest, acute heart failure, sepsis, and other causes, but not for 28-day death.

Objective:To explore the predictive value of bedside ultrasound monitoring of optic nerve sheath diameter (ONSD) for short-term neurological prognosis in critically ill patients without primary brain injury.Methods:An observational prospective study was conducted to enroll critically ill patients without primary brain injury admitted to the emergency intensive care unit (ICU) of Cangzhou Central Hospital from January 2021 to April 2022. The exclusion criteria were as follows: age < 18, combined ocular and optic nerve pathology or injuries, impaired consciousness due to prior neuropathy, primary brain injury, ICU stay < 3 days, death or loss of follow-up within 28 days. Bedside ultrasound measurements of ONSD were performed within 24 hours of ICU admission and on day 3 of ICU admission. The consciousness status was assessed daily during ICU hospitalization. If the Glasgow Coma Scale (GCS) is 15 and the confusion assessment method intensive care unit (CAM-ICU) is negative, the consciousness status will be defined as nonconsciousness disorder. While if the GCS score is less than 15 or the CAM-ICU is positive, the consciousness status will be defined as consciousness disorder. According to the status of consciousness at 28 days, patients were divided into a nonconscious disorder group and a conscious disorder group, and the difference in each index was compared between the two groups. Univariate and multivariate Cox regression were used to analyze the factors influencing 28-day neurological function prognosis, and a Kaplan?Meier survival curve was plotted to analyze the relationship between ONSD and 28-day neurological function prognosis.Results:Sixty-one critically ill patients without primary brain injury (48 in the nonconscious disorder group and 13 in the conscious disorder group) were recruited. Compared to patients in the unconscious disorder group, those in the conscious disorder group had lower GCS upon ICU admission [7(4, 8) vs. 8(6, 14), P<0.05], longer length of mechanical ventilation (MV) [28(15, 28) days vs. 10(4, 14) days, P<0.001], and longer length of ICU stay [28(28, 28) days vs. 12(7, 20) days, P<0.001]. Patients in the conscious disorder group had a higher ONSD within 24 hours of ICU admission [(5.75±0.53) mm vs. (5.45±0.60) mm, P=0.114] and a higher ONSD 3 days after ICU admission [(5.54±0.64) mm vs. (5.22±0.65) mm, P=0.124] than patients in the unconscious disorder group, but the differences were not statistically significant. Multivariate Cox regression analysis showed that use of MV, GCS upon ICU admission and ONSD on day 3 of ICU admission were independent risk factors. Kaplan?Meier survival analysis showed that patients with an ONSD < 5.30 mm on day 3 had a better 28-day neurological prognosis. Moreover, among the patients with ONSD within 24 hours ≥5.30 mm, the patients with ONSD decreased to < 5.30 mm on day 3 had significantly better 28-day neurological prognosis than those with ONSD ≥ 5.30 mm on day 3 ( P=0.042). Conclusions:ONSD within 24 hours of ICU admission, especially ONSD levels and changes in ONSD on day 3, had predictive value for the short-term neurological prognosis of critically ill patients without primary brain injury.

OBJECTIVE: To explore the regulatory mechanism of human hepatocyte apoptosis induced by lysosomal membrane protein Sidt2 knockout. METHODS: The Sidt2 knockout (Sidt2^-/-) cell model was constructed in human hepatocyte HL7702 cells using Crispr-Cas9 technology.The protein levels of Sidt2 and key autophagy proteins LC3-II/I and P62 in the cell model were detected using Western blotting, and the formation of autophagosomes was observed with MDC staining.EdU incorporation assay and flow cytometry were performed to observe the effect of Sidt2 knockout on cell proliferation and apoptosis.The effect of chloroquine at the saturating concentration on autophagic flux, proliferation and apoptosis of Sidt2 knockout cells were observed. RESULTS: Sidt2^-/- HL7702 cells were successfully constructed.Sidt2 knockout significantly inhibited the proliferation and increased apoptosis of the cells, causing also increased protein expressions of LC3-II/I and P62(P < 0.05) and increased number of autophagosomes.Autophagy of the cells reached a saturated state following treatment with 50 μmol/L chloroquine, and at this concentration, chloroquine significantly increased the expressions of LC3B and P62 in Sidt2^-/- HL7702 cells. CONCLUSION Sidt2 gene knockout causes dysregulation of the autophagy pathway and induces apoptosis of HL7702 cells, and the latter effect is not mediated by inhibiting the autophagy-lysosomal pathway.
Humans ; Lysosome-Associated Membrane Glycoproteins/metabolism* ; Autophagy ; Apoptosis ; Hepatocytes ; Lysosomes/metabolism* ; Chloroquine/pharmacology* ; Nucleotide Transport Proteins/metabolism*

OBJECTIVE To investigate the treatment plan for az treonam-resistant metallo- β-lactamase（MBL）-producing Enterobacteriaceae infection in pediatric solid organ transplant recipients. METHODS The clinical data of aztreonam-resistant MBL-producing Klebsiella pneumoniae caused intra-abdominal infection of an infant after liver transplantation were retrospectively analyzed. Abdominal infection occurred after operation. The pathogenic bacterium was MBL-producing K. pneumoniae . The drug sensitivity results showed that the infant was resistant to aztreonam. Based on the results of sensitivity test ，polymyxin B combined with tigecycline were selected as initial regimen. The treatment effect was poor ，with recurrent disease and shock spots. The clinical pharmacist assisted the clinician to formulate treatment regimen of ceftazidime avibactam 0.5 g，q8 h combined with aztreonam 0.18 g，q6 h. Relevant domestic and foreign literature were reviewed ，and the treatment plan of MBL-producing Enterobacteriaceae infection after solid organ transplantation was summarized. RESULTS & CONCLUSIONS The infant was finally cured and discharged with ceftazidime avibatan combined and aztreonam. Several foreign literature reported that ceftazidime avibactam combined with aztreonam could effectively treat the infection caused by aztreonam-resistant MBL-producing Enterobacteriaceae infection in patients with organ transplantation. It is expected to be an effective treatment for aztreonam-resistant MBL-producing Enterobacteriaceae infection in pediatric solid organ transplant recipients.

Osteoporotic thoracolumbar fracture in the elderly will seriously reduce their quality of life and life expectancy. For osteoporotic thoracolumbar fracture in the elderly, spinal reconstruction is necessary, which should comprehensively consider factors such as the physical condition, fracture type, clinical characteristics and osteoporosis degree. While there lacks relevant clinical norms or guidelines on selection of spinal reconstruction strategies. In order to standardize the concept of spinal reconstruction for osteoporotic thoracolumbar fracture in the elderly, based on the principles of scientificity, practicality and progressiveness, the authors formulated the Clinical guideline for spinal reconstruction of osteoporotic thoracolumbar fracture in elderly patients ( version 2022), in which suggestions based on evidence of evidence-based medicine were put forward upon 10 important issues related to the fracture classification, non-operative treatment strategies and surgical treatment strategies in spinal reconstruction after osteoporosis thoracolumbar fracture in the elderly, hoping to provide a reference for clinical treatment.

Objective:To explore the predictive value of renal resistive index (RRI) joint with semiquantitative power Doppler ultrasound (PDU) score to acute kidney injury (AKI) in non-septic critically ill patients.Methods:This prospective observational study enrolled non-septic critically ill patients admitted to the Emergency Intensive Care Unit of Cangzhou Central Hospital from January 2018 to August 2019. In addition to general data, RRI and PDU scores were measured with medical ultrasonic instrument within 6 h after admission. Renal function was assessed on the 5th day in accordance with kidney disease: Improving Global Outcomes criteria. The patients who progressed to AKI stage 3 within 5 days after admission were classified into the AKI 3 group, and the rest were classified into the AKI 0-2 group. The difference of each index was compared between the two groups in non-septic critically ill patients and patients with acute heart failure (AHF). Normal distributed continuous variables were compared using independent sample t-tests, whereas Mann-Whitney U tests were used to examine the differences in variables without a normal distribution. Categorical data were compared with the Chi-square test. Receiver operator characteristic curves were plotted to examine the values of RRI, PDU score, RRI-RDU/10 (subtraction of RRI and 1/10 of PDU score), RRI/PDU (the ratio of RRI to PDU score), and RRI+PDU (the prediction probability of the combination of RRI and PDU score for AKI stage 3 obtained by logistic regression analysis) in predicting AKI 3. Delong's test was used to compare the area under the curve (AUC) between predictors. Results:A total of 110 non-septic critically ill patients (51 patients with no AKI, 21 with AKI stage 1, 11 with AKI stage 2, and 27 with AKI stage 3) were recruited. Among them, there were 63 patients with AHF (21 patients with no AKI, 15 with AKI stage 1, 7 with AKI stage 2, and 20 with AKI stage 3). Among the non-septic critically ill patients as well as its subgroup of AHF, compared with the AKI 0-2 group, acute physiology and chronic health evaluation-Ⅱ score, sequential organ failure assessment score, arterial lactate concentration, mechanical ventilation rate, proportion of vasoactive drugs, 28-day mortality, serum creatinine, RRI, RRI-RDU/10, RRI/PDU, RRI+PDU, and rate of continuous renal replacement therapy were higher in the AKI 3 group, and urine output and PDU score were lower ( all P<0.05). As for non-septic critically ill patients, RRI/PDU [AUC=0.915, 95% confidence interval ( CI): 0.846-0.959, P<0.01] and RRI+PDU (AUC=0.914, 95% CI: 0.845-0.959, P<0.01) performed best in predicting AKI 3, and the AUCs were higher than RRI (AUC=0.804, 95% CI: 0.718-0.874, P<0.01) and PDU score (AUC=0.868, 95% CI: 0.791-0.925, P<0.01). The optimal cutoff for RRI/PDU was > 0.355 (sensitivity 92.6%, specificity 81.9%, Youden index 0.745). The predictive value of RRI-RDU/10 for AKI 3 (AUC=0.899, 95% CI: 0.827-0.948, P<0.01) was also better than RRI and PDU scores, but slightly worse than RRI/PDU and RRI+PDU, with statistically difference only between RRI and RRI-RDU/10 ( P<0.05). As for patients with AHF, RRI/PDU (AUC=0.962, 95% CI: 0.880-0.994, P<0.01) and RRI+PDU (AUC=0.962, 95% CI: 0.880-0.994, P<0.01) also performed best in predicting AKI 3, and the AUCs were higher than RRI (AUC=0.845, 95% CI: 0.731-0.924, P<0.01) and PDU score (AUC=0.913, 95% CI: 0.814-0.969, P<0.01) with statistically differences (all P<0.05). The optimal cutoff for RRI/PDU was > 0.360 (sensitivity 95.0%, specificity 90.7%, Youden index 0.857). The predictive value of RRI-RDU/10 for AKI 3 (AUC=0.950, 95% CI: 0.864-0.989, P<0.01) was also better than RRI and PDU score, but slightly worse than RRI/PDU and RRI+PDU, with statistically difference only between RRI and RRI-RDU/10 ( P<0.05). Conclusions:The combination of RRI and PDU score could effectively predict AKI 3 in non-septic critically ill patients, especially in patients with AHF. The ratio of RRI to PDU score is recommended for clinical application because of its excellent predictive value for AKI and its practicability.