Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

In May 2023, the Chinese Stomatological Association promulgated the group standard of "Clinical Practice Specifications for Permanent Tooth Extraction". These specifications were formulated after repeated discussions and revisions guided by relevant literature and the opinions of well-known experts in the field across the country. However, the content of the group standard is not elaborated and is limited to its writing form and requirements. As a consequence, medical workers might not easily understand and comprehend its content and knowledge points, which also limits its dissemination and wide use in primary medical units. This study aims to sort out and interpret the content of the 2023 edition of the "Clinical Practice Specification for Permanent Tooth Extraction" to help medical staff understand and apply it in clinical practice.
Tooth Extraction/standards* ; Humans ; China ; Dentition, Permanent ; Practice Guidelines as Topic

Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus Aspergillus sp. C1. HN-001 dose- and time- dependently reversed palmitic acid (PA)-induced hepatocyte death. This protection was associated with IRE-1α-mediated XBP-1 splicing inhibition, which resulted in suppression of XBP-1s nuclear translocation and transcriptional regulation. Knockdown of XBP-1s attenuated lipotoxicity, but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown hepatocytes. Notably, the ER stress and lipotoxicity amelioration was associated with PLA2. Both HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity, reduced lysophosphatidylcholine (LPC) level, subsequently ameliorated lipotoxicity. In contrast, overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of HN-001. Additionally, HN-001 treatment suppressed the downstream pro-apoptotic JNK pathway. In vivo, chronic administration of HN-001 (i.p.) in mice alleviated all manifestations of MAFLD, including hepatic steatosis, liver injury, inflammation, and fibrogenesis. These effects were correlated with PLA2/IRE-1α/XBP-1s axis and JNK signaling suppression. These data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity, and provide a natural structural basis for developing anti-MAFLD candidates.

INTRODUCTION: This study aimed to assess the effectiveness of the emergency department observation unit (EDOU) for patients with acute pyelonephritis in a Singapore tertiary academic medical centre. METHODS: We reviewed the clinical records of consecutive patients who presented with pyelonephritis between 1 July 2012 and 31 October 2014 to collect information on demographics, symptoms, signs, laboratory and radiological results, treatment, and clinical outcomes. RESULTS: Of 459 emergency department (ED) patients who were identified as having pyelonephritis, 164 (35.7%) were managed in the EDOU. Successful management in the EDOU was achieved in 100 (61.0%) patients. Escherichia coli was the predominant (64.6%) micro-organism in urine cultures and was positive in 106 patients. Patients diagnosed with acute pyelonephritis who were successfully managed in the EDOU had a lower incidence of nausea (32.0% vs. 60.9%, p < 0.001) and vomiting (15.0% vs. 50.0%, p < 0.001) compared to those who were not successful. CONCLUSION EDOU is useful for both observation and treatment of patients with acute pyelonephritis. Urine cultures are sufficient for the identification of the culprit micro-organism. Patients who present with prominent symptoms of vomiting should have routine administration of antiemetics, while consideration for second-line antiemetics is recommended for those with persistent symptoms.

Interleukin ( IL) -38 is the most recently discovered cytokine, which is the tenth member of IL-1 cytokine family. IL-38 shares a high homology with IL-1 receptor antagonist ( IL-1 Ra) and IL-36 Ra. IL-36 R is the specific receptor of IL-38 which is the partial receptor antagonist of IL-36. Now, research has shown that IL-38 not only had relationship with intracellular infection and inflammation, but also with many clinical diseases such as autoimmune diseases, osteoarthritis, tumor and cardiopulmonary diseases. However, the molecular immune regulation mechanism of IL-38 is complicated, involving specific receptor recruitment, apoptosis mediated phagocyte regulation, regulation of Th17 cell differentiation and many other processes. It also provides several new clues to the treatment of diseases. IL-38 is a new cytokine research hot spot with extensive application prospects and need deep exploration.

Objective: To observe the etiology, comorbidities, clinical features and treatment patterns of hospitalized patients with heart failure (HF) in China. Methods: Data were collected prospectively on hospitalized patients with HF who were enrolled in China Heart Failure Center Registry Study from 169 participating hospitals from January 2017 to August 2018. In this cross-sectional study, patients were stratified by left ventricular ejection fraction (LVEF) category: heart failure with reduced ejection fraction (HFrEF, LVEF<40%); heart failure with mid-ranged ejection fraction (HFmrEF, 40%≤LVEF<50%) and heart failure with preserved ejection fraction (HFpEF, LVEF≥50%). The clinical data were collected, including demographic information, diagnosis, signs, electrocardiogram, echocardiography, laboratory tests, and treatment. Results: A total of 31 356 hospitalized patients with HF were included, 19 072 (60.8%) were males and the average age was (67.9±13.6) years old. The common causes of HF were hypertension (57.2%), coronary heart disease (54.6%), dilated cardiomyopathy (14.7%), valvular heart disease (9.2%). The common complications were atrial fibrillation/atrial flutter (34.1%), diabetes (29.2%), and anemia (26.7%). 32.8% of patients had a history of hospitalization for HF within the previous 12 months. There were 11 034 (35.2%) patients with HFrEF, 6 825 (21.8%) patients with HFmrEF and 13 497 (43.0%) patients with HFpEF. Compared with patients with HFpEF, patients with HFrEF had a lower systolic blood pressure ((124.7±21.1)mmHg(1 mmHg=0.133 kPa) vs. (134.9±22.9)mmHg), faster heart rate ((85±19) beats/minutes vs. (81±19)beats/minutes), and higher percentage of New York Heart Association (NYHA) class Ⅳ, smoking, alcohol, left bundle branch block, and QRS time≥130 ms, and higher levels of blood uric acid, BNP, and NT-proBNP (all P<0.05). Compared with patients with HFmrEF and HFrEF, patients with HFpEF were older, more women, and higher comorbidity burden including hypertension, atrial fibrillation/atrial flutter, anemia and chronic obstructive pulmonary disease (all P<0.05). HFmrEF took a mid-position between HFrEF and HFpEF in age, gender, heart rate, systolic blood pressure, hypertension, atrial fibrillation/atrial flutter, anemia, and chronic obstructive pulmonary disease (all P<0.05). Patients with HFmrEF had the highest proportion of coronary heart disease, myocardial infarction and percutaneous coronary intervention (all P<0.05). During hospitalization, loop diuretics were used in 90.2% of patients, and intravenous inotropics were used in 20.4% of patients. The use of ACEI/ARB/ARNI, β blockers and aldosterone receptor antagonists at discharge were 71.8%, 79.1% and 83.6% in HFrEF and 69.9%, 75.5% and 72.4% in HFmrEF, respectively. The use of digoxin at discharge was 25.3% (HFrEF 36.7%, HFmrEF 23.1%, HFpEF 17.0%). The rates of cardiac resynchronization therapy and implantable cardioverter defibrillator in HFrEF were 2.7% and 2.1%. Conclusions Among the hospitalized patients with HF in China, coronary heart disease and hypertension are the mostly prevalent causes. HFpEF accounts for a large proportion of hospitalized patients with HF. HFrEF, HFmrEF and HFpEF have different etiology and clinical features. In real-world, there are still large gaps in the effective application of the guideline recommended therapies to HF patients, especially the non-pharmacological therapy option, which needs to be improved further in China.

【Objective】To form a new PTMAc- PEG- PTMAc triblock（PPP）copolymerhydrogel and to evaluate its sustained released performance and antiproliferative effects as an ocular drug carrier of Pirfenidone（PFD）【Methods】One type triblockcopolymers PPP hydrogel was chosen. The morphology of the material was evaluated by scanning electron microscopy（SEM）. The swelling properties of the PPP hydrogel was analyzed in PBS solution（37 ℃ ，pH 7.4）. The in vitro drug release of the pirfenidone loaded hydrogels were evaluated with non-dialysis method and the curves of drug release were drawed. We evaluated the adhesion，survival of human Tenon′s capsule fibroblasts（HTF）around hydrogels. The cell cytotoxicity of hydrogels and antiproliferative effects were evaluated through CCK-8 assay.【Results】The hydrogel has stable gelation conditions. The swelling rate decreased by increasing hydrogel concentration.The SEM images indicated the fibrous and porous structure. We also observed that the encapsulated pirfenidone were sustained released from hydrogels with an initial burst release at early stage（within 4 d）and then the release rate were declined for all hydrogels during the following 14 d. The PPP hydrogel can inhibit cell adhesion. The cell viability in hydrogels at four time point（24，48，72 and 96 h）were 85.7% ，93.0% ，82.0% ，81.6%. The inhibition rate of drug loaded hydrogel with two drug concentration（1 mg/mL or 2 mg/mL）are 25.8%，21.8%，55.4%，25.6%；44.6%，35.9%，55.5%，31.4%. While that of drug solution are 28.9% ，29.7% ，7.8% ，7.7%. The suppressive effects of the PFD loaded hydrogels on HTF proliferation followed a dose-dependent fashion and time-dependent fashion.【Conclusions】Such biocompatible copolymers hydrogel can be effectively used as an drug sustain released system. It can induce significant inhibition of HTF proliferation. With equal amount of drug，the inhibition effect of drug loaded gel was longer than that of drug solution.

Objective? To explore the effects of perioperative blood glucose management in orthopedic diabetic patients. Methods? Totally 75 diabetic patients receiving surgery and requiring blood glucose monitoring 7 times a day in the Department of Orthopedics, He'nan Provincial People's Hospital from October 2017 to February 2018 were included in the control group, who received blood glucose management using conventional methods. Another 79 patients of the same type hospitalized between March and June 2018 were selected into the observation group for whom a blood glucose team was built and an intervention protocol of perioperative blood glucose management was developed. Self-efficacy, blood glucose detection missing rate, patient's satisfaction and average length of hospital stay of the two groups were analyzed before and after intervention. Results? The self-efficacy score of the observation group was higher than that of the control group after intervention;the blood-glucose detection missing rate was lower in the observation group than in the control group; the average length of hospital stay was shorter in the observation group than in the control group; and patient's satisfaction was higher in the observation group than in the control group (P＜ 0.05). Conclusions? Blood glucose management in orthopedic diabetic patients helps to optimize the blood glucose management process, improve patients' self-management capability, reduce diabetic patients' operative risk, guarantee patients' safety, and improve the quality of medical service.

OBJECTIVETo observe the expressions of caspase-8 and caspase-9 mRNA, and explore the changes of apoptosis of bone marrow hematopoietic cells in patients with chronic mountain sickness (CMS).

METHODSOf 18 CMS patients and 16 controls were enrolled in this study. The apoptotic index (AI) of bone marrow mononuclear cells (BMMNC) was measured by TUNEL technique, the levels of caspase-8 and caspase-9 mRNA in BMMNC of CMS patients and controls were determined by RT-PCR. Results (1)The AI of BMMNC in patients with CMS (8.51 ± 3.35)% was lower than that in controls (16.00 ± 4.28)% (P < 0.01); (2) The values of caspase-8 and caspase-9 mRNA were (0.28 ± 0.07) and (0.23 ± 0.08) respectively, in CMS patients, which were significantly lower than those of (0.45 ± 0.09) and (0.41 ± 0.09) respectively, in the controls (both P < 0.01); (3) Hemoglobin (Hb) value was negatively correlated with levels of caspase-8 and caspase-9 mRNA (r values were -0.52 and -0.61 respectively, both P < 0.05) in CMS patients. There was a negative correlation between AI and Hb (r value was -0.89, P < 0.01) in CMS patients. However, the significant relationship was not found between AI and level of caspase-8 or caspase-9 mRNA (P > 0.05).

CONCLUSIONSThe results showed a decrease apoptosis of BMMNCs and reduced levels of caspase-8 and caspase-9 mRNA in CMS patients, the latter might be involved in the change of BMMNCs apoptosis.

Adult ; Altitude Sickness ; metabolism ; pathology ; Apoptosis ; Bone Marrow Cells ; metabolism ; Case-Control Studies ; Caspase 8 ; metabolism ; Caspase 9 ; metabolism ; Humans ; Male ; Middle Aged

BACKGROUNDAhmed glaucoma valves (AGV) has been used for decades, but there is no detailed report about the efficacy of AGV in Chinese glaucoma patients. This study aimed to compare the intraocular pressure (IOP) lowering efficacy and side effects of S-2 polypropylene and PF-7 silicone AGV implantation in Chinese refractory glaucoma patients.

METHODSPatients were divided into S-2 model AGV group and FP-7 model AGV group. The complete and qualified surgical success rate, change of IOP, number of anti-glaucoma medications used and postoperative complications were recorded and analyzed.

RESULTSAverage follow-up time was comparable between two groups. IOP was reduced from (37.9 ± 12.7) mmHg preoperatively to (17.3 ± 5.3) mmHg at the last follow-up in S-2 group and reduced from (39.9 ± 14.4) mmHg to (17.7 ± 4.9) mmHg in FP-7 group. Anti-glaucoma medications were reduced from 3.8 ± 0.2 to 1.5 ± 0.2 in S-2 group, and 3.5 ± 0.2 to 0.7 ± 0.2 in FP-7 groups. The cumulative success rates were comparable in two groups, which were 61.2% and 72.1% in S-2 group and FP-7 group respectively. When IOP reduction criteria was used, complete success rates were 30.6% and 51.2% for S-2 and FP-7 groups, and qualified success rates were 86.1% and 92.7% separately. In both groups, the major complication was hypotony, and the previous trabeculectomy of patients was the major risk factor for surgery failure.

CONCLUSIONSIn this short-term retrospective study, S-2 AGV is showed at least as effective as FP-7 AGV in IOP reduction, but associated with higher rate of complications. Previous trabeculectomy is a principle risk factor for AGV implantation failure. These clinical outcomes are important for converting use of the FP-7 silicon AGV in Chinese refractory glaucoma patients.

Adult ; Female ; Glaucoma ; physiopathology ; therapy ; Glaucoma Drainage Implants ; Humans ; Intraocular Pressure ; physiology ; Male ; Retrospective Studies