BACKGROUND:With the continuous advancement of medical technology,stem cell therapy has been used to treat a variety of diseases,including amyotrophic lateral sclerosis. OBJECTIVE:To review the research progress of stem cell therapy for amyotrophic lateral sclerosis,and prospect the development trend of this field. METHODS:PubMed,China National Knowledge Infrastructure(CNKI),and WanFang Data were searched for articles published from 1995 to 2024 using the key words"amyotrophic lateral sclerosis,mesenchymal stem cells,neural stem/progenitor cells,pluripotent stem cells."A total of more than 1 700 articles were retrieved,and 58 articles were finally included in this review. RESULTS AND CONCLUSION:Amyotrophic lateral sclerosis is a neurodegenerative disease that affects lower motor neurons in the brainstem and spinal cord and upper motor neurons in the motor cortex.The related research of stem cells in the treatment of amyotrophic lateral sclerosis has become a research hotspot.In this review,we summarize the application of different types of stem cells in amyotrophic lateral sclerosis research,including mesenchymal stem cells,neural stem progenitor cells,and induced pluripotent stem cells,and evaluate the key points of preclinical research such as stem cell source,cell volume,stem cell modification methods,and drug delivery routes,which lays the foundation for the future application of stem cell therapy.

Objective:To analyze the efficacy and safety of nalbuphine for analgesia in patients with non-mechanical ventilation in intensive care unit (ICU).Methods:From December 2018 to August 2021, a multicenter randomized controlled clinical study was conducted to select non-mechanical ventilation patients with analgesic needs admitted to ICU of four hospitals in Henan Province and Guizhou Province. Patients were randomly assigned to nalbuphine group and fentanyl group. The nalbuphine group was given continuous infusion of nalbuphine [0.05~0.20 mg/(kg·h)], and the fentanyl group was given continuous infusion of fentanyl [0.5~2.0 μg/(kg·h)]. The analgesic target was critical-care pain observation tool (CPOT) score<2. The observation time was 48 hours. The primary endpoint was CPOT score, the secondary endpoints were Richmond agitation-sedation score (RASS), ICU length of stay, adverse events, and proportion of mechanical ventilation. The quantitative data of the two groups were compared by t test or Mann-Whitney U test. The enumeration data were compared by chi square test or Fisher exact probability method. The data at different time points between groups were compared by repeated measures analysis of variance. Results:A total of 210 patients were enrolled, including 105 patients in the nalbuphine group and 105 patients in the fentanyl group. There was no significant difference in baseline data between the two groups (all P>0.05). There was no significant difference in CPOT score between nalbuphine group and fentanyl group at each time point after medication ( P>0.05), the CPOT score of both groups at each time point after medication was significantly lower than that before medication, and the analgesic target could be achieved and maintained 2 hours after medication. There was no significant difference in RASS between the two groups at each time point after medication ( P>0.05), which was significantly lower than that before medication, and the target sedative effect was achieved 2 hours after medication. There was no significant difference in ICU length of stay between nalbuphine group and fentanyl group [5.0(4.0,7.5) d vs. 5.0(4.0,8.0) d, P=0.504]. The incidence of delirium, nausea and vomiting, abdominal distension, pruritus, vertigo and other adverse events in the nalbuphine group was lower than that in the fentanyl group (all P<0.05). There was no significant difference in the incidence of other adverse events such as deep sedation, hypotension and bradycardia between the two groups (all P>0.05). The incidence of respiratory depression in nalbuphine group was not significantly different from that in fentanyl group ( P>0.05), but the proportion of mechanical ventilation was significantly lower than that in the fentanyl group [1.9% (2/105) vs. 8.6%(9/105), P=0.030]. Conclusions:Nalbuphine could be used for analgesia in ICU patients with non-mechanical ventilation. The target analgesic effect could be achieved within 2 hours, and it had a certain sedative effect with a low incidence of adverse reactions.

Objective:Investigate the prognostic value of high density lipoprotein (HDL) level in patients with streptococcal bloodstream infection.Methods:A total of 698 patients with streptococcal bloodstream infection admitted to the First Affiliated Hospital of Zhengzhou University from January 2015 to December 2019 were enrolled. Serum lipid and other clinical data of patients with positive blood culture within 48 h were recorded. The patients were followed up by telephone from January to March in 2020, and the end-point events were recorded, which were all-cause death 60 days after the diagnosis of streptococcal bloodstream infection. The patients were divided into two groups according to the levels of HDL: low HDL group (HDL ≤0.84 mmol/L) and high HDL group (HDL > 0.84 mmol/L). Univariate and multivariate Cox regression analysis were used to analyze the 60-day prognostic factors of patients with streptococcus bloodstream infection. The receiver operating characteristic (ROC) curve was used to explore predictive value of HDL level for 60-day prognosis of patients. Kaplan-Meier survival curve was used to compare the cumulative survival of patients with different HDL levels.Results:(1) A total of 491 patients were enrolled according to the inclusion criteria, and 461 patients were followed up successfully, with a follow-up rate of 93.89%. There were 373 survival patients and 88 death patients at 60 days, with a 60-day mortality rate of 19.09% (88/461). (2) There were significant differences in age, total cholesterol (TC), HDL, low density lipoprotein (LDL), platelets, albumin, fibrinogen, triglyceride (TG), creatinine, alanine aminotransferase, aspartate aminotransferase, white blood cell, PCT, total bilirubin, direct bilirubin, and respiratory failure and shock between the survival group and death group. (3) Multivariate Cox regression analysis showed that HDL ( RR=1.922, 95% CI: 1.186-3.117, P=0.008), aspartate aminotransferase ( RR=1.953, 95% CI: 1.233-3.094, P=0.004), shock ( RR=15.196, 95% CI: 6.953-33.211, P< 0.001), and respiratory failure ( RR=9.509, 95% CI: 4.232-21.367, P < 0.001) were independent risk factors for 60-day mortality of patients with streptococcal bloodstream infection. (4) The ROC curve analysis showed that HDL alone had a certain value in predicting the 60-day prognosis of patients with streptococcal bloodstream infection. The area under ROC curve (AUC) was 0.602, and the AUC of the combined predictive value of HDL, aspartate aminotransferase, shock and respiratory failure was 0.960, with a sensitivity of 92% and a specificity of 92%. (5) Kaplan-Meier survival curve analysis showed that the cumulative survival rate of patients without endpoint event in the HDL > 0.84 mmol/L group was higher than that in the HDL ≤ 0.84 mmol/L group, but without statistically significant difference (Log-Rank test: χ20.843, P<0.358). Conclusions:Patients with low HDL level of streptococcal bloodstream infection have an increased risk of 60-day death. HDL is an independent risk factor for 60-day death in patients with streptococcal bloodstream infection, and can be used as an indicator to evaluate the prognosis of patients with streptococcal bloodstream infection.

Background::Sepsis is a serious disease caused by infection. Aminophylline has anti-asthma and anti-inflammatory effects. We aimed to explore the safety and effect of aminophylline in sepsis.Methods::We conducted a clinical randomized controlled trial involving 100 patients diagnosed with sepsis within 48 h after intensive care unit (ICU) admission in two sites. All patients were randomized in a 1:1 ratio to receive standard therapy with or without aminophylline. The primary clinical outcome was all-cause mortality at 28 days.Results::From September 27, 2018 to February 12, 2020, we screened 277 septic patients and eventually enrolled 100 patients, with 50 assigned to the aminophylline group and 50 to the usual-care group. At 28 days, 7 of 50 patients (14.0%) in the aminophylline group had died, compared with 16 of 50 (32.0%) in the usual-care group ( P = 0.032). Cox regression showed that the aminophylline group had a lower hazard of death (hazard ratio = 0.312, 95% confidence interval: 0.129-0.753). Compared with the usual-care group, patients in the aminophylline group had a longer survival time ( P = 0.039 by the log-rank test). The effects of aminophylline on vasopressor dose, oxygenation index, and sequential organ failure assessment score were time-dependent with treatment. There were no significant differences in total hospitalization days, ICU hospitalization days, and rates of serious adverse events (all P > 0.05). No adverse events were observed in the trial. Conclusions::Aminophylline as an adjunct therapy could significantly reduce the risk of death and prolong the survival time of patients with sepsis.Trial registration::ChiCTR.org.cn, ChiCTR1800019173.

Objective:To investigate the relationship between serum cholinesterase (SChE) level and the prognosis of patients with septic shock (SS).Methods:A total of 594 patients with SS admitted to the First Affiliated Hospital of Zhengzhou University from June 2013 to June 2017 were enrolled. General data such as gender, age, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score were recorded as well as routine blood test, procalcitonin (PCT), hepatic function, renal function, coagulation function and blood gas analysis parameters within 48 hours of SS diagnosis. The patients were followed by telephone from September to October in 2019, and the outcome was recorded. The primary outcome was all-cause death 28 days after discharge. The secondary outcomes were all-cause death in intensive care unit (ICU) and 2 years after discharge, and the length of ICU stay. The patients were divided into two groups according to prognosis of 28 days: the survival group and the death group. The clinical data of the two groups were compared. Multivariate Cox regression analysis was used to screen prognostic risk factors of 28 days in patients with SS. The receiver operating characteristic (ROC) curve was used to explore predictive value of liver function parameter SChE for 28-day prognosis of patients with SS. The patients were divided into two groups according to the levels of SChE: the low SChE group (SChE ≤ 4 000 U/L) and the normal SChE group (SChE > 4 000 U/L). Kaplan-Meier survival curves were used to compare the cumulative survival rates without endpoint event of patients with different SChE levels.Results:A total of 385 patients with SS were enrolled according to the inclusion and exclusion criteria, and a total of 356 patients were followed up successfully, with a follow-up rate of 92.5% (356/385). There were 142 survival patients and 214 death patients at 28 days, with a 28-day mortality rate of 60.1% (214/356). There were 116 survival patients and 240 death patients at 2 years, with a 2-year mortality rate of 67.4% (240/356). Compared with the 28-day survival group, the patients in the death group were older and had higher APACHEⅡ score, partial hepatic and renal function parameters, higher level of blood lactate (Lac) and lower levels of white blood cell count (WBC), platelet count (PLT) and SChE with statistically significant differences. Multivariate Cox regression analysis showed that the age [relative risk ( RR) = 1.444, 95% confidence interval (95% CI) was 1.090-1.914, P = 0.010], APACHEⅡ score ( RR = 2.249, 95% CI was 1.688-2.997, P = 0.000), SChE ( RR = 1.469, 95% CI was 1.057-2.043, P = 0.022), and Lac ( RR = 2.190, 95% CI was 1.636-2.931, P = 0.000) were independent risk factors for 28-day mortality of patients with SS. The ROC curve analysis showed that SChE had a weak prognostic value for 28-day prognosis of patients with SS [the area under ROC curve (AUC) was 0.574]. However, the combined predictive value of SChE, APACHEⅡ score and Lac was greater than APACHEⅡ score or Lac alone for prediction (AUC: 0.807 vs. 0.785, 0.697), with a sensitivity of 79.9% and a specificity of 68.5%. Compared with the normal SChE group ( n = 88), the 28-day mortality of patients in the low SChE group ( n = 268) was significantly increased [63.1% (169/268) vs. 51.1% (45/88), P < 0.05], but ICU mortality [59.7% (160/268) vs. 48.9% (43/88)], 2-year mortality [69.8% (187/268) vs. 60.2% (53/88)] or the length of ICU stay [days: 4 (2, 7) vs. 5 (2, 9)] between the two groups showed no statistical significance (all P > 0.05). Kaplan-Meier survival curve analysis showed that the cumulative survival rate without endpoint event of patients in the low SChE group was significantly lower than that in the normal SChE group (Log-Rank test: χ 2 = 5.852, P = 0.016). Conclusions:Increased risk of 28-day mortality in patients with SS whose SChE is below normal. The level of SChE is an independent risk factor for 28-day death in SS patients, and it is one of the indicators to evaluate the short-term prognosis of patients with SS.

Objective:To analyze the cause of myofascial trigger points(MTrPs)in the infraspinatus muscle misdiagnosed as cervical spondylotic radiculopathy(CSR).Methods:Clinical data of patients with MTrPs in the infraspinatus muscle misdiagnosed as CSR were collected in Peking University Third Hospital from October 2016 to September 2019.Results:A total of 28 cases with MTrPs in the infraspinatus muscle were misdiagnosis as CSR.All patients received CT or magnetic resonance imaging evaluation of cervical spine, while none of them received physical examination in posterior shoulder area before confirming MTrPs in the infraspinatus muscle.The pain range was mainly located in the radial side of the shoulder, upper arm and forearm(89.3%)and was mainly unilateral(89.3%). The MTrPs in the supraspinatus muscle were mostly 2~3 points(67.8%). The visal analogue scale(VAS) score was significantly decreased after dry acupuncture as compared with pre-treatment[(2.7±1.4) vs.(6.1±1.3), P<0.05], and the overall treatment efficiency defined as VAS score decrement by more than 50%, was 82.1%. Conclusions:The neglect of medical history inquire and physical examination, and over-reliance on imaging findings are the important factors for misdiagnosis of MTrPs in the infraspinatus muscle as CSR.

Objective To evaluate the safety and efficacy of transcatheter arterial embolization (TAE) in the management of refractory hematuria of prostatic origin (RHPO). Methods This retrospective study from 6 hospitals in china consisted of 31 patients (mean age 75.0±7.5 years, range 58 to 84 years) who underent transcatheter arterial embolization (TAE) for RHPO between February 2011 and January 2017. Patients with RHPO who had complete imaging and clinical data were enrolled. Patients with incomplete clinical data, inability to assess hemostasis, and contraindications to TAE were excluded. The cause of RHPO was benign prostatic hyperplasia (BPH) in nine patients, prostate cancer in twelve, transurethral resection of prostate in four, open prostatectomy in two and prostatic sarcoma in four. Superselective arterial embolization, non-superselective arterial embolization or intra-arterial infusion chemotherapy was performed according to the etiology and angiography. Angiographic findings, technical success rate, clinical success rate, complications were recorded. Results Of the 31 patients, 6 patients (19.4％) were with active bleeding, 4 (12.9％) with aneurysm and 27 (87.1％) with abnormal neovascularization on the angiogram. The 31 patients underwent a totle of 37 TAE, the technical success rate was 100.0％(37/37) and the recent hemostasis success rate was 90.3％(28/31). The incidence of mild complications was 38.7％(13/31), there was no serious complication associated with TAE. Conclusion TAE is a safe and effective method for the treatment of refractory hematuria of prostatic origin.

Objective To analyze the efficacy and safety of nalbuphine in patients with sedative analgesia in intensive care unit (ICU). Methods A prospective observation was conducted. The adult patients with mild and moderate analgesia in general ICU of the First Affiliated Hospital of Zhengzhou University from January to November in 2017 were enrolled, and they were divided into nalbuphine group and sufentanil group in proper order. The nabobrown group was given 40 mg nabobrown, the sufentanil group was given 0.1 mg sufentanil, both of which were injected with 50 mL normal saline for continuous intravenous infusion in micro-pump. Infusion speed was checked according to pain level. The analgesic target was critical-care pain observation tool (CPOT) score < 2. The change in hemodynamics of patients in both groups were observed, and CPOT score and Richmond agitation-sedation scale (RASS) score were recorded before and l, 3, 5, 12, 24 hours after administration. The analgesic and sedative effects of two drugs were evaluated. Results A total of 141 patients were enrolled, including 71 patients in nalbuphine group and 70 in sufentanil group. There was no significant difference in general data including gender, age, body weight, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) or pain source, as well as baseline hemodynamics parameter between the two groups. At 1 hour and 3 hours after administration, nalbuphine had no effect on blood pressure, but the heart rate was decreased slightly, while the heart rate and blood pressure of the sufentanil group were decreased obviously. The two drugs could make the heart rate and blood pressure fluctuate obviously with the time of medication, but there was no statistical difference between the two drugs. The two drugs had no significant effect on pulse oxygen saturation (SpO2) during analgesia. The average dosage of nalbuphine was 0.03 (0.02, 0.05) mg·kg-1·h-1in the nalbuphine group, and the patient was satisfied with the analgesic effect until 3 hours after the use of the drug, and CPOT score was significantly decreased as compared with that before administration [1.0 (1.0, 2.0) vs. 3.0 (2.0, 4.0), P < 0.01], and the sedative effect was increased, RASS score was significantly lower than that before administration [0 (0, 1.0) vs. 1.0 (1.0, 2.0), P < 0.01]. No patients in naporphine group were treated with sufentanil due to unsatisfactory analgesia. The average dosage was 0.11 (0.06, 0.14) μg·kg-1·h-1in the sufentanil group, the patient was satisfied with the analgesic effect until 5 hours after administration, and the CPOT score was significantly lower than that before administration [1.0 (1.0, 2.0) vs. 4.0 (3.0, 6.0), P < 0.01], and the sedative effect was significantly increased, RASS score was significantly lower than that before administration [0 (-1.0, 0) vs. 2.0 (1.0, 2.0), P < 0.01]. The scores of CPOT and RASS in the sufentanil group were significantly higher than those of the naporphine group before use, so the decrease in the CPOT and RASS scores of the two drugs was further analyzed, which indicated the decrease in CPOT score of naporphine group was significantly lower than that in sufentanil group from 3 hours on [1.0 (0, 2.0) vs. 2.0 (1.0, 3.0), P < 0.05], and the decrease in RASS score of naporphine group was significantly lower than that in sufentanil group from 1 hour on [0 (0, 1.0) vs. 1.0 (0, 2.0), P < 0.01]. It suggested that naporphine could achieve sustained and stable analgesic effect and avoid excessive sedation caused by sufentanil. Conclusions Naporphine had a sustained and stable analgesic effect on patients with mild and moderate ICU analgesia. The onset time of naporphine was equivalent to sufentanil, and it had a certain sedative effect and less influence on hemodynamics.

Objective To evaluate the efficacy and safety of terlipressin for septic shock.Methods A randomized double-blind placebo-controlled pilot study was carried out in the general ICU of the First Affiliated Hospital of Zhengzhou University from June 1st 2015 to May 31st 2016.The septic shock patients with a mean arterial pressure below 65 mmHg despite adequate volume resuscitation were enrolled.Patients were randomized (random number) to give continuous infusions of either terlipressin[0.6-2.6 μg/(kg·h)] or norepinephrine(7-30 μg/min).Open label norepinephrine or other catecholamines were additionally infused if the mean arterial pressure failed to reach 65 mmHg.Treatment was continued until shock corrected,death or withdrawn from this study.Correcting rate of shock was the primary end point,the secondary end points included open labeled norepinephrine requirements,the 28 d survival rate and adverse events.The quantitative data of the two groups were compared by t test or Wilcoxon rank sum test.The enumeration data were compared by chi square test or Fisher exact probability method,and the survival data were analyzed by Kaplan-Meier method.Results A total of 28 patients were enrolled.The full analysis set was 28,the per-protocol set was 25,and the safety set was 28.The key demographics and baseline characteristics were similar between the two groups(P＞0.05).The results for the per-protocol set were followed up.The correcting rate of shock between the two groups were similar at the end of treatment[81.82％(9/11)vs.57.14％(8/14),P=0.190].The open label norepinephrine requirements of the trial group and control group for the 0,6,12,24,48 h time point were 0.661,0.921,1.583,1.241,2.143,1.371,1.071,1.261,0.370,1.001 μg/(kg·min),respectively with no significant difference(P＞0.05).The 28 d survival rate of the trial group and control group were 63.64％(7/11)and 50.00％(7/14) respectively with no statistical significance(P＞0.05).There was no significant difference in 28 d survival analyzed using Kaplan-Meier plot between two groups(P=0.470).There were two patients with ischemia of fingers,one patient with hyponatraemia and one patient with ischemia of intestine accompanied by hyponatraemia occurred after treatment with terlipressin,and one patient with isehemia of fingers occurred after treatment with norepinephrine.The incidence of adverse event for the trial group and control group were 30.77％(4/13) and 6.67％(1/15) with no significant difference(P=0.122).Conclusions Terlipressin is an effective agent for treating septic shock.The total adverse event rate of terlipressin was similar to that ofnorepinephrine.

Objective To explore the effect of 5-ethynyl-2'-deoxyuridine (EdU) -labeled adipose-derived stem cells (ADSCs) on lung colonization, TNF-α and IL-4 in rats induced by lipopolysaccharide (LPS) with acute lung injury. Methods Thirty male Sprague-Dawley (SD) rats were randomly divided into the normal control group (n=10), LPS model group (n=10), and LPS+ADSCs intervention group (n=10). The ALI model rats were intraperitoneally injected with 8 mg/kg LPS, rats in the normal control group were intraperitoneally injected with 4 mL/kg physiological saline, and rats in the LPS+ADSCs group were intravenously injected with 300 μL ADSCs by tail vein after 30 minutes for the ALI model establishment, and rats in the normal control group and LPS group were intravenously injected with 300μL physiological saline by tail vein. The time of death in rats was observed, lung tissue and blood from left ventricular were collected, and the serum tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-4) were detected by Enzyme-linked immunosorbent assay (ELISA). Lung wet/dry weight (W/D) ratio was detected by thoracotomy, the pathological changes of lung tissue were observed under optical microscope, and the colonization of ADSCs in the lungs were observed under immunofluorescence microscopy. LSD-t method was used to compare between every two groups. Results There was no significant difference in mortality between the LPS group and LPS + ADSCs group (50％ vs. 70％, P> 0.05); EdU-labeled ADSCs were extensively colonized in the lungs by tail vein injection after 24 h; Compared with the normal control group, the lung injury of the LPS group was heavier, the ratio of lung W/D and TNF-α were significantly increased (all P< 0.01), and IL-4 level was significantly decreased (P< 0.01). Compared with the LPS model group, the degree of lung injury in the LPS + ADSCs group was significantly reduced, lung W/D ratio (5.57±0.27 vs. 5.98±0.28) and TNF-α level of blood [(41.51±4.14)ng/L vs. (45.52±3.74)ng/L] were significantly reduced (all P< 0.05), whereas the IL-4 levels were significantly increased [(7.01±1.11)pg/mL vs. (3.27±0.54)pg/mL, P< 0.05]. Conclusions EdU-labeled ADSCs could be colonized in the lungs of LPS-induced ALI rats, reduce the inflammatory response from TNF-α and improve the anti-inflammatory response from IL-4.