Macroautophagy (referred to as autophagy hereafter) is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and organelles. Previous studies showed that autophagy protects against acetaminophen (APAP)-induced injury (AILI) via selective removal of damaged mitochondria and APAP protein adducts. The lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with autophagosomes. In the present study, we showed that transcription factor EB (TFEB), a master transcription factor for lysosomal biogenesis, was impaired by APAP resulting in decreased lysosomal biogenesis in mouse livers. Genetic loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI, respectively. Mechanistically, overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2 (NRF2) activation to protect against AILI. We also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB agonists. Among these agonists, salinomycin, an anticoccidial and antibacterial agent, activated TFEB and protected against AILI in mice. In conclusion, genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.

Objective To analyze the medication rules of Professor HUANG Feng for the treatment of low back pain using data mining methods.Methods The information of prescriptions for the effective cases of outpatients with low back pain treated by Professor HUANG Feng were collected and screened.Microsoft Excel 2019 was used to analyze the frequency of medication and the distribution of properties,flavors and meridian tropism of the drugs in the included prescription.IBM SPSS Modeler 18.0 was used for association rule analysis,and IBM Statistics 26.0 was used for cluster analysis.Results A total of 239 prescriptions and 75 Chinese medicines were included.There were 23 high-frequency Chinese medicines with the medication frequency being or over 20 times,and the top 10 Chinese medicines were Glycyrrhizae Radix et Rhizoma,vinegar-processed Corydalis Rhizoma,Cibotii Rhizoma,Atractylodis Macrocephalae Rhizoma,Zanthoxyli Radix,salt-processed Achyranthis Bidentatae Radix,Rehmanniae Radix,Dipsaci Radix,Coicis Semen,and Salviae Miltiorrhizae Radix et Rhizoma.The medicines were mainly warm in nature,and were sweet,bitter and pungent in flavor.Most of the drugs had the meridian tropism of liver,stomach and spleen meridians.Among the drug combinations obtained from association rule analysis with the top 20 highest support,vinegar-processed Corydalis Rhizoma,Cibotii Rhizoma,Atractylodis Macrocephalae Rhizoma and Zanthoxyli Radix were the core drugs.Cluster analysis yielded 6 clustering combinations.Conclusion For the treatment of low back pain,Professor HUANG Feng follows the principle of"treatment adapting to the climate,individuality,and environment"and"treating the root cause of the disease",usually adopts the drugs for activating blood,moving qi and relieving pain,nourishing the liver and kidney,and also uses the medicines for replenishing qi and strengthening the spleen.The ideas of HUANG Feng for the treatment of low back pain can be used as a reference for the clinical treatment.

Immunoassays are widely used in medicine, food, environment and other fields due to having the advantages of simpleness, rapidness and accuracy. Combining immunoassays with nanomaterials can improve the performance of immunoassays. Compared with traditional nanomaterials, upconversion nanoparticles (UCNPs) have excellent optical properties such as good photostability, long luminescence lifetime and narrow and tunable emission bands, which can significantly reduce background noise and improve analytical sensitivity when combined with immunoassay. This paper briefly introduces the luminescence mechanism of UCNPs, summarizes the synthesis and surface modification methods of UCNPs. And then 5 UCNPs-based immunoassay techniques, namely, fluorescence resonance energy transfer, inner filter effect, magnetic separation technique, upconversion-linked immunosorbent assay and upconversion immunochromatography, are discussed in detail. These sensing protocols of UCNPs-based immunoassays have been successfully utilized to detect various targets, including small molecules, macromolecules, and pathogens, all of which closely related to food safety, human health, and environmental pollution. Finally, the challenges and prospects of this technique are summarized and prospected. Although the UCNPs immunoassays based on antibodies and antigens have made great progress, most of the research is still in the stage of laboratory, and there is a long way to go to realize its social applications. There is a series of challenges need to be overcome. (1) Designing excellent water soluble and dispersive upconversion nanomaterials is needed. Hydrophilic ligands are bound to smaller upconversion nanoparticles and removing hydrophobic surface ligands are the most widely used methods to improve solubility and dispersity. (2) Multi-detection technology platforms and multi-mode simultaneous detection platforms have great potential, which will improve the efficiency of point of care detection. (3) The researchers also need to focus on some important problems. For examples, the upconversion luminescence efficiency of UCNPs is difficult to maintain, the synthesis method is complex, and the surface modification degree and functionalization are difficult to control.

【Objective】 To establish an effective quality indicator monitoring system, scientifically and objectively evaluate the quality management level of blood banks, and achieve continuous improvement of quality management in blood bank. 【Methods】 A quality monitoring indicator system that covers the whole process of blood collection and supply was established, the questionnaire of Quality Monitoring Indicators for Blood Collection and Supply Process with clear definition of indicators and calculation formulas was distributed to 17 blood banks in Shandong. Statistical analysis of 21 quality monitoring indicators in terms of blood donation service (10 indicators), blood component preparation (7 indicators ), and blood supply (4 indicators) from each blood bank from January to December 2022 were conducted using SPSS25.0 software The differences in quality monitoring indicators of blood banks of different scales were analyzed. 【Results】 The average values of quality monitoring indicators for blood donation service process of 17 blood banks were as follows: 44.66% (2 233/5 000) of regular donors proportion, 0.22% (11/50) of adverse reactions incidence, 0.46% (23/5 000) of non-standard whole blood collection rate, 0.052% (13/25 000) of missed HBsAg screening rate, 99.42% (4 971/5 000) of first, puncture successful rate, 86.49% (173/200) of double platelet collection rate, 66.50% (133/200) of 400 mL whole blood collection rate, 99.25% (397/400) of donor satisfaction rate, 82.68% (2 067/2 500) of use rate of whole blood collection bags with bypass system with sample tube, and 1 case of occupational exposure in blood collection.There was a strong positive correlation between the proportion of regular blood donors and the collection rate of 400 mL whole blood (P<0.05). The platelet collection rate, incidence of adverse reactions to blood donation, and non-standard whole blood collection rate in large blood banks were significantly lower than those in medium and small blood banks (P<0.05). The average quality monitoring indicators for blood component preparation process of 17 blood banks were as follows: the leakage rate of blood component preparation bags was 0.03% (3/10 000), the discarding rate of lipemic blood was 3.05% (61/2 000), the discarding rate of hemolysis blood was 0.13%(13/10 000). 0.06 case had labeling errors, 8 bags had blood catheter leaks, 2.76 bags had blood puncture/connection leaks, and 0.59 cases had non-conforming consumables. The discarding rate of hemolysis blood of large blood banks was significantly lower than that of medium and small blood banks (P<0.05), and the discarding rate of lipemic blood of large and medium blood banks was significantly lower than that of small blood banks (P<0.05). The average values of quality monitoring indicators for blood supply process of 17 blood banks were as follows: the discarding rate of expired blood was 0.023% (23/100 000), the leakage rate during storage and distribution was of 0.009%(9/100 000), the discarding rate of returned blood was 0.106% (53/50 000), the service satisfaction of hospitals was 99.16% (2 479/2 500). The leakage rate of blood components during storage and distribution was statistically different with that of blood component preparation bags between different blood banks (P<0.05). There were statistically significant differences in the proportion of regular blood donors, incidence of adverse reactions, non-standard whole blood collection rate, 400 mL whole blood collection rate, double platelet collection rate, the blood bag leakage rate during preparation process, the blood components leakage rate during storage and distribution as well as the discarding rate of lipemic blood, hemolysis blood, expired blood and returned blood among large, medium and small blood banks (all P<0.05). 【Conclusion】 The establishment of a quality monitoring indicator system for blood donation services, blood component preparation and blood supply processes in Shandong has good applicability, feasibility and effectiveness. It can objectively evaluate the quality management level, facilitate the continuous improvement of the quality management system, promote the homogenization of blood management in the province and lay the foundation for future comprehensive evaluation of blood banks.

Objective To study the pharmacokinetic characteristics of lamotrigine tablets in Chinese healthy subjects under fasting and fed conditions,and to evaluate the bioequivalence and safety profiles between the domestic test preparation and the original reference preparation.Methods Twenty-four Chinese healthy male and female subjects were enrolled under fasting and fed conditions,18 male and 6 female subjects under fasting conditions,17 male and 7 female subjects under fed conditions.A random,open,single-dose,two preparations,two sequences and double-crossover design was used.Plasma samples were collected over a 72-hour period after give the test or reference preparations 50 mg under fasting and fed conditions.The concentration of lamotrigine in plasma was detected by liquid chromatography-tandem mass spectrometry,and the main pharmacokinetic parameters were calculated to evaluate the bioequivalence by WinNonLin 8.1 program.Results The main pharmacokinetic parameters of single-dose the tested and reference preparations were as follows:The fasting condition Cmax were(910.93±248.02)and(855.87±214.36)ng·mL-1;tmax were 0.50(0.25,4.00)and 1.00(0.25,3.50)h;t1/2 were(36.1±9.2)and(36.0±8.2)h;AUC0_72h were(27 402.40±4 752.00)and(26 933.90±4 085.80)h·ng·mL-1.The fed condition Cmax were(701.62±120.67)and(718.95±94.81)ng·mL-1;tmax were 4.00(1.00,5.00)and 4.00(0.50,5.00)h;t1/2 were(44.2±12.4)and(44.0±12.0)h;AUC0-72h were(30 253.20±7 018.00)and(30 324.60±6 147.70)h·ng·mL-1.The 90％confidence intervals of the geometric mean ratios of Cmax and AUC0-72 hfor the test preparation and reference preparation were all between 80.00％and 125.00％under fasting and fed conditions.Conclusion Two kinds of lamotrigine tablets are bioequivalent,and have similar safety in Chinese healthy male and female subjects under fasting and fed conditions.

Objective To observe clinical outcomes of propofol and remazolam in patients undergoing elective painless fiberoptic bronchoscopic biopsy.Methods Patients who underwent painless fibreoptic bronchoscopic biopsy in our hospital from March 2022 to April 2023 were selected for the study and divided into 2 groups using simple randomisation method.In the control group,anaesthesia was induced with 1 mg·kg-1 propofol,3 μg·kg-1 fentanyl,0.1 mg·kg-1 cis-atracurium,and anaesthesia was maintained with 4-6 mg·kg-1·h-1 propofol.In the treatment group,anaesthesia was induced with 0.2 mg·kg-1 remazolam,3 μg·kg-1 fentanyl,0.1 mg·kg-1 cis-atracurium,and anaesthesia was maintained with 0.2-0.4 mg·kg-1·h-1 remazolam.We compared the awakening time,laryngeal mask removal time,microscopy time,and the proportion of additional anaesthetics in the 2 groups,and detected the levels of S100β,neuron-specific enolase(NSE),interleukin-6(IL-6),tumour necrosis factor-alpha(TNF-α)in the 2 groups preoperatively and at 24 h postoperatively,and statistically counted the occurrences of adverse reactions in the 2 groups.Results The time for pulling out the laryngeal mask in the treatment group was significantly lower than that in the control group,while the time for microscopy,time for awakening,and proportion of additional anaesthesia drugs were not statistically significant when compared with that in the control group(all P＞0.05).The overall anaesthesia effect grading of the test group was not statistically significant when compared with the control group(P＞0.05).S100β were(0.66±0.17)and(0.78±0.21)μg·L-1;NSE were(8.47±1.78)and(11.47±2.06)μg·L-1;IL-6 were(8.64±1.21)and(12.89±1.47)pg·mL-1;TNF-α were(6.27±1.07)and(9.13±1.41)pg·mL-1,respectively,which were higher than that of preoperative period,and the treatment group was lower than that of the control group at 24 h postoperatively,and the difference was statistically significant(all P＜0.05).The incidence of adverse drug reactions in the treatment group and the control group were 13.75％and 22.50％,respectively,and the difference was not statistically significant(P＞0.05).Conclusion The use of remazolam in painless fiberoptic bronchoscopic biopsy is less neurologically damaging,stabilizes hemodynamics.

AIM To study the extraction process,enzymatic properties and practical application of glucuronic hydrolase in Scutellaria baicalensis stems and leaves(sbsl GUS).METHODS With granularity,water consumption,extraction time and extraction frequency as influencing factors,enzymatic activity as an evaluation index,the extraction process was optimized by orthogonal test on the basis of single factor test.The relationship between substrate(baicalin)concentration and enzymolysis rate,after which Vmax and Km were calculated,the effects of pH value,temperature and metal ion on enzymatic activity were investigated,pH stability and heat stability were evaluated.sbsl GUS was adotped in the enzymolysis of baicalin to prepare baicalein,then the effects of pH value,temperature,reaction time,initial substrate concentration and enzyme addition on transfer rate were investigated.RESULTS The optimal extraction process was determined to be 40 mesh for granularity,10 times for water consumption,15 min for extraction time,and 3 times for extraction frequency.The enzymolysis accorded with the kinetics of enzymatic reaction,Km was 0.006 3 mol/L,Vmax was 70.42 μmol/h,the strongest enzymatic activity was found at the pH value of 6.0,temperature of 45℃and metal ion of 100 mmol/L Cu2+,sbsl GUS demonstrated good stability at the ranges of 4.0-7.0 for pH value and 4-30℃for temperature.The optimal preparation process was determined to be 6.0 for pH value,45℃for temperature,more than 12 h for reaction time,67.2 mmol/L for initial substrate concentration,and 1 mL/0.269 mmol baicalin for enzyme addition,the transfer rate was 97.83%.CONCLUSION sbsl GUS enzymolysis exhibits high efficiency and mild condition,which can provide a simple preparation method for obtaining baicalein,and expand the application path of Scutellaria baicalensis stems and leaves.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

Objective To analyze the economic burden due to healthcare-associated infection(HAI)in low birth weight(LBW)infants,and provide theoretical basis for formulating HAI related policies.Methods The data of LBW infants in a tertiary first-class hospital from January 2018 to December 2022 were retrospectively collected.Propensity score matching method and marginal analysis were adopted to evaluate the economic losses in LBW in-fants and hospitals due to HAI.Results A total of 1 048 LBW infants were included in analysis,124 of whom had HAI,with HAI incidence of 11.8％.A total of 109 pairs were successfully matched using the propensity score matching method.The median length of hospital stay for LBW infants in the HAI group and non-HAI group were 34.0 and 11.0 days,respectively,the length of hospital extended 23 days in LBW infants in the HAI group(P＜0.001).The median hospitalization expenses for LBW infants in HAI group and non-HAI group were 38 067.6 and 12 375.7 Yuan,respectively,the hospitalization expense for LBW infants in HAI group was 25 691.9 Yuan more than non-HAI group(P＜0.001).The major increased expenses were examination,treatment and medication fees.The total hospitalization expenses in different birth weight LBW infants in HAI group were all higher than non-HAI group,and the differences were all statistically significant(all P＜0.05).LBW infants with gestational age＜32 weeks had longer length of hospital stay and higher total hospitalization expense,differences were all statistically significant(all P＜0.05).When the marginal profit ratios were 5％,10％,and 15％,respectively,the economic losses caused by HAI were 371 000 Yuan,742 000 Yuan,and 1 114 000 Yuan,respectively;The ratios of loss-profit and loss-profit to infection coefficient were 0.33 and 2.79,respectively.Conclusion HAI cause significant economic losses to both LBW infants and hospitals.Infants with a birth weight ≤1 000 g and those with a gestational age＜32 weeks are key populations for prevention and control.The lost-profit to infection coefficient can be used to estimate the economic loss of the hospital,timely adjust infection control measures,and reduce the incidence of HAI.

Objective To compare the oral cleansing effects of the microbubble toothbrush and the conventional pulsed oral irrigator to provide references for users.Methods Ninety identical 3D-printed resin tooth models were grouped and subjected to repeated experiments,which were divided randomly into five groups including a microbubble toothbrush high-speed gear(GN-H)group,a microbubble toothbrush medium-speed gear(GN-M)group,a microbubble low-speed gear(GN-L)group,a conventional pulsed oral irrigator high-speed gear(W-H)group and a conventional pulsed oral irrigator low-speed gear(W-L)group,with 18 teeth in each group.The cleansing effects of the microbubble toothbrush and the conventional pulsed oral irrigator were evaluated in terms of irrigating strength and abilities for eliminating plaque and debris.Results Both the two types of water flossers were provided with high irrigating strength and effectively reduced plaque and debris on tooth surfaces,and the GN-H,GN-M and GN-L groups behaved better significantly than the remained groups.The order of the five groups was GN-H group＞GN-M group＞W-H group＞GN-L group＞W-L group for irrigating strength,GN-H group＞GN-M group＞GN-L group＞W-H group＞W-L group for plaque removal,GN-H group＞GN-M group＞W-H group＞GN-L group＞W-L group for debris removal,with all the differences being statistically significant(P＜0.05).Conclusion Both the two types of water flossers remove plaque and debris effectively,while the microbubble toothbrush gains advantages over the conventional pulsed oral irrigator.[Chinese Medical Equipment Journal,2024,45(9):67-72]