Disposal and utilization of dead animals during breeding in livestock and poultry farming by means of synthetic microbiota.

The disposal of animal remains resulting from breeding is a significant challenge that impacts the industry's growth. To address the issues with current treatment methods, such as the large space required for corpse storage, and the high energy consumption of pyrolysis. Three strains with high protease and lipase production and one strain with high keratinase production were screened. The virulence genes were evaluated, the synthesis gene clusters of degrading enzymes were mined, secondary metabolites of each strain were analyzed, and the bacterial community with both growth rate and enzyme production ability was developed. Therefore, a microbial degradation method with mild reaction conditions and rapid liquefaction of animal residues was developed. The liquid degradation of four common farm-raised animal residues (sheep, cattle, chickens, and pigs) was tested under laboratory conditions. The results showed that the liquid degradation of animal residues was achieved within 144 h, transforming the months-long anaerobic process of traditional compost fermentation process into a mere 6 days' anaerobic process. N, P, K plant nutrients accounted for 15% of the total matrix, pH value was 5.5-6.7, heavy metal content was less than 0.2 mg L-1. Designed and improved fermentation equipment, produced a 3 m³ fermentation equipment, used in chicken, pig two types of animal residues pilot test. The emissions of greenhouse gases such as CO2 in the entire degradation process were 1.6 × 104 ppm, which was 481 times less than that of composting by 7.7 × 106. This study provides a solution for the treatment of dead livestock and poultry, which has promotional and practical value.

Functional study of the soybean stamen-preferentially expressed gene GmFLA22a in regulating male fertility.

China has a high dependence on soybean imports, yield increase at a faster rate is an urgent problem that need to be solved at present. The application of heterosis is one of the effective ways to significantly increase crop yield. In recent years, the development of an intelligent male sterility system based on recessive nuclear sterile genes has provided a potential solution for rapidly harnessing the heterosis in soybean. However, research on male sterility genes in soybean has been lagged behind. Based on transcriptome data of soybean floral organs in our research group, a soybean stamen-preferentially expressed gene GmFLA22a was identified. It encodes a fasciclin-like arabinogalactan protein with the FAS1 domain, and subcellular localization studies revealed that it may play roles in the endoplasmic reticulum. Take advantage of the gene editing technology, the Gmfla22a mutant was generated in this study. However, there was a significant reduction in the seed-setting rate in the mutant plants at the reproductive growth stage. The pollen viability and germination rate of Gmfla22a mutant plants showed no apparent abnormalities. Histological staining demonstrated that the release of pollen grains in the mutant plants was delayed and incomplete, which may due to the locule wall thickening in the anther development. This could be the reason of the reduced seed-setting rate in Gmfla22a mutants. In summary, our study has preliminarily revealed that GmFLA22a may be involved in regulating soybean male fertility. It provides crucial genetic materials for further uncovering its molecular function and gene resources and theoretical basis for the utilization of heterosis in soybean.

Protective effect of Qingjie Huagong decoction on pancreatic tissue of mice with severe acute pancreatitis by regulating the NOD-like receptor protein 3/Toll-like receptor 4/nuclear factor-kappa B signaling pathway / 临床肝胆病杂志

ObjectiveTo investigate the therapeutic effect of Qingjie Huagong decoction （QJHGD） on a mouse model of severe acute pancreatitis （SAP） and the mechanism of action of QJHGD against inflammatory response. MethodsA total of 36 male C57BL/6J mice were randomly divided into blank group， model group， Western medicine group （ulinastatin）， and low-， middle-， and high-dose QJHGD groups， with 6 mice in each group. All mice except those in the blank group were given 5% sodium taurocholate by retrograde pancreaticobiliary injection to establish a model of SAP. After modeling， the mice in the low-， middle-， and high-dose groups were given QJHGD （1， 2， and 4 g/kg， respectively） by gavage， and those in the Western medicine group were given intraperitoneal injection of ulinastatin （5×104 U/kg）， for 7 days in total. HE staining was used to observe the histopathological changes of the pancreas； ELISA was used to measure the levels of α-amylase， lipase， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， interleukin-18 （IL-18）， and tumor necrosis factor-α （TNF-α） in mice； RT-qPCR was used to measure the mRNA expression levels of NOD-like receptor protein3 （NLRP3）， Toll-like receptor 4 （TLR4）， and nuclear factor-kappa B （NF-κB） in pancreatic tissue； immunohistochemistry was used to measure the positive expression rates of NLRP3， TLR4， and NF-κB in pancreatic tissue； Western blot was used to measure the protein expression levels of NLRP3， TLR4， NF-κB， IL-1β， and IL-6. An analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the blank group， the model group had diffuse destruction of pancreatic tissue structure， focal dilatation of pancreatic lobular septum， pancreatic acinar atrophy， and massive inflammatory cell infiltration， as well as significant increases in the content of α-amylase， lipase， IL-1β， IL-6， IL-8， IL-18， and TNF-α （all P<0.05）， the mRNA expression levels and positive expression rates of NLRP3， TLR4， and NF-κB （all P<0.05）， and the protein expression levels of NLRP3， TLR4， NF-κB， IL-1β， and IL-6 （all P<0.05）. Compared with the model group， the low-， middle-， and high-dose QJHGD groups and the Western medicine group had slightly tighter and more intact structure of pancreatic tissue， ordered arrangement of pancreatic acinar cells， a small amount of inflammatory cell infiltration， and hemorrhagic foci of pancreatic lobules， as well as significant reductions in the content of α-amylase， lipase， IL-1β， IL-6， IL-8， IL-18， and TNF-α （all P<0.05）， the mRNA expression levels and positive expression rates of NLRP3， TLR4， and NF-κB （all P<0.05）， and the protein expression levels of NLRP3， TLR4， NF-κB， IL-1β， and IL-6 （all P<0.05）. ConclusionQJHGD may exert a protective effect on the pancreatic tissue of SAP mice by inhibiting the activation of NLRP3/TLR4/NF-κB signaling pathway-related proteins， reducing the release of inflammatory mediators， and preventing the enhancement of inflammatory cascade response.

Research Progress of Traditional Chinese Medicine Intervention in Nrf2/HO-1 Signaling Pathway for Acute Pancreatitis： A Review / 中国实验方剂学杂志

Acute pancreatitis （AP） is a common clinical acute abdominal disease， which is characterized by acute onset， rapid development， severe disease， many complications， and high mortality rate. It can progress to severe AP （SAP） if not treated promptly in the early stage. The pathogenesis of AP is complex and involves multiple cellular and molecular levels. It is now clear that oxidative stress and reactive oxygen species （ROS） production are involved in the physiopathological process of AP， which is associated with a low quantity and activity of antioxidant enzymes in pancreatic cells. Nuclear factor E2-related factor 2 （Nrf2） serves as the ''golden key'' to maintain redox homeostasis in tissue cells and constitutes an important signaling pathway for antioxidant response and inflammation in vivo by collaborating with downstream antioxidant enzymes such as heme oxygenase-1 （HO-1）. Traditional Chinese medicine has unique efficacy in treating diseases due to its multi-component， multi-target， multi-drug delivery， and multi-formulation characteristics. Based on the concept of synergy between traditional Chinese and Western medicine， traditional Chinese medicine is becoming a new craze in the treatment of AP. The level of oxidative stress and Nrf2/HO-1 signaling pathway in AP pancreatic tissue are in a dynamic change process， and the intervention of traditional Chinese medicine can clean ROS production， affect the inflammatory pathway， and reduce oxidative stress damage， so as to protect against pancreatic injury. This suggests that this pathway plays an important role in AP. This article reviews the recent literature on the regulation of the Nrf2/HO-1 signaling pathway by traditional Chinese medicine for AP and summarizes that the monomers of traditional Chinese medicine targeting this pathway are mainly heat-clearing and detoxifying， blood-activating and blood-stasis-removing， and Qi benefiting and middle warming， and the compounds of traditional Chinese medicine include Yinchenhao Decoction and QingYi Ⅱ， so as to provide a new direction for the prevention and treatment of AP and further drug development.

Washed microbiota transplantation for Clostridioides difficile infection: A national multicenter real-world study.

OBJECTIVES: Fecal microbiota transplantation (FMT) has been recommended for the treatment of recurrent Clostridioides difficile infection (CDI). We aimed to evaluate the therapeutic efficacy and safety of washed microbiota transplantation (WMT), a new method of FMT, for CDI across various medical settings. METHODS: This multicenter real-world cohort study included CDI patients undergoing WMT. The primary outcome was the clinical cure rate of CDI within 8 weeks after WMT. Secondary outcomes included the CDI recurrence rate and reduction in total abdominal symptom score (TASS) during the follow-up period. Adverse events related to WMT were recorded. RESULTS: Altogether 90.7% (49/54) of CDI patients achieved clinical cure after treated with WMT. The cure rate was 83.3% for cases with severe and complicated CDI (ScCDI) (n = 30) and 100% for non-ScCDI cases (n = 24) (P = 0.059). No difference was observed in the clinical cure rate between patients with first and recurrent CDI (91.9% vs 88.2%, P = 0.645). One week post-WMT, TASS showed a remarkable decrease compared to that at baseline (P < 0.001). Totally, 8.2% (4/49) of patients suffered CDI recurrence during the follow-up period. A WHO performance score of 4, age ≥65 years, higher TASS score, and higher Charlson comorbidity index score were potential risk factors for efficacy (P = 0.018, 0.03, 0.01, 0.034, respectively). Four (3.8%) transient adverse events related to WMT were observed. CONCLUSIONS: This study emphasizes the attractive value of WMT for CDI. Early WMT may be recommended for CDI, especially for those in serious condition or with complex comorbidities. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT03895593 (registered on 27 March 2019).

PDMS-filled micro-spring Fabry-Perot cavity for temperature sensing.

A highly sensitive fiber-tipped temperature sensor based on polydimethylsiloxane (PDMS)-filled spring Fabry-Perot (FP) cavity has been proposed and experimentally demonstrated. The spring FP cavity is first fabricated on the fiber endface by the two-photon polymerization lithography. After that, PDMS is filled into the cavity to drive the elongation of the flexible spring and thus to functionalize high-performance temperature sensing. Benefiting from the large thermal expansion coefficient of PDMS, the proposed sensor exhibits a maximal temperature sensitivity of 704.3 pm/°C with excellent operating repeatability and stability. Besides, by selecting a proper spring constant k, the FP sensitivity can be precisely adjusted in the range of 100-700 pm/°C. Thanks to the advantages of high fabrication accuracy and designable property, the proposed sensor could promote numerous usages for customizable temperature sensing.

Treatment persistence of bictegravir/emtricitabine/tenofovir alafenamide and efavirenz + lamivudine + tenofovir disoproxil among HIV-1 patients newly starting treatment in Hunan Province in China.

BACKGROUND: Though bictegravir/emtricitabine/tenofovir (BIC/FTC/TAF) have been regulatory approved and included in the National Reimbursement Drug List in China, due to the affordability concern, generic version of efavirenz + lamivudine + tenofovir (EFV + 3TC + TDF) is still recommended as the first-line therapy in the clinical guideline and widely used in clinical practice. The aim of the study is to assess the persistence with first-line BIC/TAF/TAF and EFV + 3TC + TDF in newly treated HIV-1 patients in the real-world setting in Hunan Province in China. METHODS: A retrospective analysis of the medical records of HIV patients initiating first-line antiretroviral therapy in the First Hospital of Changsha in January 1st, 2021-July 31st, 2022 was conducted. Persistence was assessed as the number of days on the therapy from the index until treatment discontinuation or end of data availability. Kaplan-Meier Curves and Cox Proportional Hazard models were used to evaluate the discontinuation rates. Subgroup analysis was performed excluding BIC/FTC/TAF patients with treatment discontinuation due to economic reason, and EFV + 3TC + TDF patients with a viral load > 500,000 copies/mL. RESULTS: A total of 310 eligible patients were included in the study, with 244 and 66 patients in the BIC/FTC/TAF group and EFV + 3TC + TDF group, respectively. Compared with EFV + 3TC + TDF patients, BIC/FTC/TAF patients were older, more living in the capital city currently, and had significantly higher total cholesterol and low-density level (all p < 0.05). No significant difference was shown in the time to discontinuation between BIC/FTC/TAF patients and EFV + 3TC + TDF patients. After excluding BIC/FTC/TAF patients with treatment discontinuation due to economic reason, EFV + 3TC + TDF group were shown to have a significantly higher risk of discontinuation than BIC/FTC/TAF group (hazard ratio [HR] = 11.1, 95% confidence interval [CI] = 1.3-93.2). After further removing the EFV + 3TC + TDF patients with a viral load > 500,000 copies/mL, the analysis showed similar results (HR = 10.1, 95% CI = 1.2-84.1). 79.4% of the EFV + 3TC + TDF patients discontinued treatment due to clinical reasons, while 83.3% of the BIC/FTC/TAF patients discontinued treatment due to economic reasons. CONCLUSIONS: Compared with BIC/FTC/TAF, EFV + TDF + 3TC patients were significantly more likely to discontinue the first-line treatment in Hunan Province in China.

Radiobacillus kanasensis sp. nov., a halotolerant bacterium isolated from woodland soil.

A novel Gram-positive, aerobic, rod-shaped, non-motile, endospore-forming salt-tolerant bacterium strain (80T), was isolated from woodland soil collected near Kanas lake in the Altay region of Xinjiang, PR China. The strain grew at 15-45 °C, pH6.0-9.0 and with 0-14 % (w/v) NaCl. The complete genome size of the novel strain was 4 031 766 bp including a circle chromosome and a circle plasmid. The genomic DNA G+C content was 38.99 mol %. Phylogenetic analysis based on 16S rRNA gene sequence and genome showed that strain 80T has the highest similarity to Radiobacillus deserti TKL69T. However, the novel strain showed an average nucleotide identity value of 78.65 % (lower than 95 %) and a digital DNA-DNA hybridization value of 22.30 % with R. deserti TKL69T based on the genome sequences. The major fatty acids were anteiso-C15 : 0, iso-C15 : 0, anteiso-C17:0 and C16 : 1 ω7c alcohol. The only respiratory quinone was MK-7. The cell wall peptidoglycan was meso-diaminopimelic acid. Diphosphatidylglycerol, phosphatidylglycerol, one unidentified phospholipid, one unidentified aminophospholipid and two unidentified glycolipids were identified as the major polar lipids. The phylogenetic, phenotypic and chemotaxonomic analyses showed that strain 80T represents a novel species of the genus Radiobacillus and the name Radiobacillus kanasensis sp. nov. is proposed. The type strain is 80T (=GDMCC 1.2844T=JCM 35077T).

Advances and applications of quantitative systems pharmacology modeling and virtual clinical trials in modern drug development / 药学学报

Quantitative systems pharmacology (QSP) modeling is an emerging computational medicine approach with growing applications and significance in modern drug development. QSP models are generally formulated based on multiscale disease mechanisms and drug-target interactions, which makes them capable of integrating multimodal data from the preclinical and clinical space. This also enables them to generate quantitative characterization of the dynamic disease progression as well as high-throughput predictions of drug-induced efficacy and toxicity signals. Therefore, QSP modeling and model-based virtual clinical trials have been widely implemented to guide drug development, in scenarios such as target identification and assessment, clinical trial design, evaluation of combination therapy and biomarkers, and personalized medicine. In US and Europe, QSP modeling has been developing rapidly in the past 10 years and is now an integral part of the model-informed drug development paradigm; however, in China it is still a nascent field. Here we will present a comprehensive review of the recent advancements of QSP and its impact in modern drug development through a number of case studies. This review will provide guidance for the future drug development efforts and the growth of QSP practice in China.

Comparison of coagulation function between adrenocorticotropic hormone independent Cushing syndrome and nonfunctional adrenal adenoma and its influence factors / 北京大学学报(医学版)

OBJECTIVE@#To investigate the coagulation function indicators and identify influence factors of hypercoagulability in patients with adrenocorticotropic hormone (ACTH) independent Cushing syndrome (CS).@*METHODS@#In our retrospective study, the electronic medical records system of Peking University First Hospital was searched for the patients diagnosed with ACTH independent CS on discharge from January 2014 to June 2019. Nonfunctional adrenal adenoma patients were chosen as control group and matched 1 ∶1 by body mass index (BMI), gender, and discharge date. Clinical features and coagulation function indicators were compared between the two groups.@*RESULTS@#In the study, 171 patients were included in each group. Compared with control group, activated partial thromboplastin time (APTT), and prothrombin time (PT) in ACTH independent CS group were significantly lower [(29.22±3.39) s vs. (31.86±3.63) s, P < 0.001; (29.22±3.39) s vs. (31.86±3.63) s, P < 0.001], and both D-dimer and fibrin degradation products (FDP) levels were significantly higher (P < 0.05). Percentage of APTT levels under the lower limit of reference range in the CS patients was significantly higher than that in nonfunctional group (21.6% vs. 3.5%, P < 0.001). Percentage of D-dimer levels over the upper limit of reference range in the CS patients was significantly higher than that in nonfunctional group (13.5% vs. 6.6%, P=0.041). There were three patients with deep venous thrombosis and one patient with pulmonary embolism in CS group, however none was in control group. The area under curve (AUC) of serum cortisol rhythm (8:00, 16:00 and 24:00) levels was negatively associated with the levels of PT (r=-0.315, P < 0.001) and APTT (r=-0.410, P < 0.001), and positively associated with FDP (r=0.303, P < 0.001) and D-dimer levels (r=0.258, P < 0.001). There were no differences in coagulation function indicators among different histopathologic subgroups (adrenocortical adenoma, adrenocortical hyperplasia, oncocytic adenoma, adrenocortical carcinoma). With Logistic regression analysis, the AUC of cortisol and glycosylated hemoglobin A1c (HbA1c) levels were independent risk factors for hypercoagulability in the ACTH independent CS patients (P < 0.05).@*CONCLUSION@#ACTH independent CS patients were more likely in hypercoagulable state compared with nonfunctional adrenal adenoma, especially in ACTH independent CS patients with higher levels of cortisol AUC and HbA1c. These patients should be paid attention to for the hypercoagulability and thrombosis risk.

Preparation of chitosan hydrochloride stabilized emulsion and its immunostimulatory effect / 生物工程学报

In order to increase the ability of oil-emulsion adjuvant to stimulate cellular immunity, chitosan hydrochloride with positive charge was selected to stabilize oil-in-water emulsion (CHE). In this paper, model antigen ovalbumin was selected to prepare vaccines with emulsion adjuvant, commercial adjuvant or no adjuvant. The emulsion was characterized by measuring the particle size, electric potential and antigen adsorption rate. BALB/c mice were immunized by intramuscular injection. Serum antibody levels, the numbers of IL-4-secreting cells in splenocytes, cytotoxic T lymphocyte (CTL) response, and the expression of central memory T cells were measured to evaluate the immunostimulatory effect. The results showed that chitosan hydrochloride can effectively stabilize the emulsion. The emulsion size is about 600 nm, and the antigen adsorption rate is more than 90%. After immunization, CHE could increase serum antibodies levels and increase IL-4 secretion. Expression of CTL surface activation molecules was also increased to stimulate CTL response further and to increase the CD44+CD62L+ in T cells proportion. CHE as adjuvant can stimulate humoral and cellular immunity more efficiently, and is expected to extend the duration of protection.

Omics Analysis of Ferroptosis and Establishment of Prognostic Model for multiple myeloma Patients / 中国实验血液学杂志

OBJECTIVE@#To explore the role of ferroptosis-related genes in multiple myeloma(MM) through TCGA database and FerrDb, and build a prognostic model of ferroptosis-related genes for MM patients.@*METHODS@#Using the TCGA database containing clinical information and gene expression profile data of 764 patients with MM and the FerrDb database including ferroptosis-related genes, the differentially expressed ferroptosis-related genes were screened by wilcox.test function. The prognostic model of ferroptosis-related genes was established by Lasso regression, and the Kaplan-Meier survival curve was drawn. Then COX regression analysis was used to screen independent prognostic factors. Finally, the differential genes between high-risk and low-risk patients were screened, and enrichment analysis was used to explore the mechanism of the relationship between ferroptosis and prognosis in MM.@*RESULTS@#36 differential genes related to ferroptosis were screened out from bone marrow samples of 764 MM patients and 4 normal people, including 12 up-regulated genes and 24 down-regulated genes. Six prognosis-related genes (GCLM, GLS2, SLC7A11, AIFM2, ACO1, G6PD) were screened out by Lasso regression and the prognostic model with ferroptosis-related genes of MM was established. Kaplan-Meier survival curve analysis showed that the survival rate between high risk group and low risk group was significantly different(P<0.01). Univariate COX regression analysis showed that age, sex, ISS stage and risk score were significantly correlated with overall survival of MM patients(P<0.05), while multivariate COX regression analysis showed that age, ISS stage and risk score were independent prognostic indicators for MM patients (P<0.05). GO and KEGG enrichment analysis showed that the ferroptosis-related genes was mainly related to neutrophil degranulation and migration, cytokine activity and regulation, cell component, antigen processing and presentation, complement and coagulation cascades, haematopoietic cell lineage and so on, which may affect the prognosis of patients.@*CONCLUSION@#Ferroptosis-related genes change significantly during the pathogenesis of MM. The prognostic model of ferroptosis-related genes can be used to predict the survival of MM patients, but the mechanism of the potential function of ferroptosis-related genes needs to be confirmed by further clinical studies.

Clinical analysis of P2Y2 receptor agonist in the treatment of diabetic dry eye / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the clinical efficacy of P2Y2 agonist diquafosol sodium(DQS)eye drops in the treatment of diabetic dry eye.METHODS: A total of 80 patients(160 eyes)with diabetic dry eye who admitted to our hospital from January 2022 to March 2022 were selected. They were randomly divided into study group and control group. A total of 40 patients(80 eyes)in the study group were treated with 3% DQS eye drops and 40 patients(80 eyes)in the control group were treated with 0.3% sodium hyaluronate eye drops. The ocular surface disease index(OSDI)score, non-invasive tear meniscus height(NITMH), first non-invasive tear film break-up time(NIBUTf), average non-invasive tear film break-up time(NIBUTav), tarsal gland loss score, lipid layer thickness grade and bulbar redness analysis(including conjunctival grade and ciliary grade), were examined before treatment and at 1wk, 1 and 3mo after treatment, respectively. Furthermore, corneal fluorescence staining and conjunctival lissamine green staining were analyzed based on the ocular surface staining score(OSS), and the conjunctival impression cytology and confocal microscopy were evaluated before and 3mo after treatment, respectively.RESULTS: There were no differences in OSDI score, tarsal gland loss score, conjunctival grade score and ciliary grade score between the two groups before and after treatment(P&#x0026;#x003E;0.05). OSS scores in the study group were lower than those in the control group, while NITMH, NIBUTf and NIBUTav were higher than those in the control group at 1 and 3mo after treatment(P&#x0026;#x003C;0.05). After 3mo of treatment, the density of conjunctival goblet cells increased and corneal dendritic cells decreased in the study group compared with the baseline(all P&#x0026;#x003C;0.05), while there were no significant changes in the control group compared with the baseline(all P&#x0026;#x003E;0.05).CONCLUSION: 3% DQS eye drops were effective in treating diabetic dry eye without serious complications.

Safety and efficacy of lacrimal canalicular plug in the treatment of severe chronic ocular graft-versus-host disease / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the safety and efficacy of lacrimal canalicular plug in the treatment of severe chronic ocular graft-versus-host disease(coGVHD).METHODS: Retrospective study. A total of 9 patients with severe coGVHD admitted to the dry eye clinic of the Affiliated Hospital of Xuzhou Medical University from June to September 2022 were included. All patients underwent binocular inferior lacrimal canaliculus plug. Ocular surface disease index(OSDI)score, tear meniscus height(TMH), corneal fluorescein staining(CFS)scores, conjunctival lisamine green staining(CLGS)score, noninvasive breakup time(NIBUT), Schirmer Ⅰ test(SⅠt)and the infiltration of Langerhans cells in the superficial corneal stroma tested by confocal corneal microscopy were observed before treatment and at 1 and 3 mo after treatment. At the same time, the complications related to lacrimal canalicular plug implantation were evaluated.RESULTS: The OSDI score decreased from 67.33±12.64 before treatment to 21.89±6.07 after 3mo of treatment(P&#x003C;0.01); TMH increased from 0.09±0.02mm to 0.21±0.03mm after 3mo of treatment(P&#x003C;0.05), and NIBUT increased from 2.24±0.68s before treatment to 6.77±2.05s after 3mo of treatment(P&#x003C;0.01). In addition, the CFS and CLGS also changed significantly, from 9.11±1.45 and 6.33±1.00 before treatment to 2.22±0.67 and 2.56±0.88 at 3mo after treatment, respectively(all P&#x003C;0.01). The density of Langerhans cells decreased from 140.22±38.18cells/mm2 before treatment to 39.67±9.75cells/mm2 3mo after treatment(P&#x003C;0.01). SⅠt showed no significant difference before and after treatment(F=0.059, P=0.943). During the whole follow-up period, no complications such as plug abscission were observed.CONCLUSION: Lacrimal canalicular plug is safe and effective in the treatment of severe coGVHD. It can significantly improve the symptoms and signs of dry eye patients and reduce inflammatory reaction.

Analysis of interleukin-36 expression in tears of allogeneic hematopoietic stem cell transplantation patients and its correlation with the ocular surface microenvironment / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To detect the expression of interleukin(IL)-36(α, β, γ)in tears of patients undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT), investigate its correlation with ocular surface microenvironment, and further analyze the relationship between its expression and ocular graft-versus-host disease(oGVHD).METHODS: Prospective study. A total of 35 patients(70 eyes)underwent allo-HSCT in the hematology department of our hospital in January 2020 were selected, and 35 healthy volunteers(70 eyes)with appropriate age and gender were selected as normal control group. The patients in the allo-HSCT group were followed up 3 times after operation once every 3mo. The subjects with postoperative ocular symptoms were divided into oGVHD and Non-oGVHD group.Ocular surface disease index(OSDI)questionnaire, Schirmer test, tear break-up time(TBUT), corneal fluorescein staining(FL), and conjunctival impression cytology(CIC)was conducted in three groups. Furthermore, the expression levels of IL-36(α,β,γ)in tears were detected by ELISA.RESULTS: In the normal control group, IL-36(α, β, γ)expression levels were 74.32±5.27, 70.02±8.43, 97.41±8.66 pg/mL, respectively; in the allo-HSCT group, IL-36(α, β, γ)baseline expression levels were 77.27±7.03, 74.53±7.53, 100.77±9.74 pg/mL, with no statistically significant differences between the two groups(t=1.648, 1.954, 1.262, all P&#x003E;0.05). There were no significant differences in IL-36α, IL-36β and IL-36γ in Non-oGVHD group at different time points(P&#x003E;0.05), while there were significant differences in IL-36α, IL-36β and IL-36γ in oGVHD group at different time points(P&#x003C;0.05). Compared with Non-oGVHD group, the levels of IL-36α and IL-36β at different time points were significantly increased in oGVHD group(all P&#x003C;0.05).IL-36(α, β, γ)of oGVHD group was positively correlated with OSDI score, FL and CIC, while it was negatively correlated with TBUT and Schirmer test(all P&#x003C;0.05).CONCLUSION: Evaluation of levels of tear IL-36(α, β, γ)can be of significance in diagnosing oGVHD after allo-HSCT. IL-36(α, β, γ)is highly expressed in the tears of oGVHD patients before the onset of ocular symptoms, and it is correlated with the ocular surface parameters.

Safety and efficacy of intense pulsed light in the treatment of severe chronic ocular graft-versus-host disease / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the safety and efficacy of intense pulsed light in the treatment of severe chronic ocular graft-versus-host disease.METHODS: Prospective randomized controlled study. A total of 35 cases(35 eyes), who had a history of allogenic hematopoietic stem cell transplantation(allo-HSCT), admitted to the Affiliated Hospital of Xuzhou Medical University from January to September 2022 and were diagnosed by our hospital's hematology and ophthalmology departments with severe chronic ocular graft-versus-host disease(coGVHD)were selected. One eye was randomly selected for inclusion in the study if both eyes met the enrollment criteria, and the eye was selected if a single eye met the enrollment criteria. All patients were administrated with Dextran and Hypromellose eye drops 4 times a day and Cyclosporine eye drops twice a day. The experimental group was additionally treated with intense pulsed light, once every two weeks a week, for 4 times in total. The evaluation indicators were evaluated before treatment and 2wk, 1 and 2mo after treatment. The evaluation indicators include ocular surface disease index(OSDI)score, best corrected visual acuity(BCVA), intraocular pressure(IOP), tear meniscus height(TMH), non-invasive break-up time(NIBUT), conjunctival injection score(CIS), meibomian gland area proportion(MGAP), meibomian gland evaluation(MGE), cornea fluorescein staining(CFS), conjunctival lissamine green staining(CLGS), lid margin abnormality score(LMAS), and Schirmer's Ⅰ test(SⅠt).RESULTS: After treatment, OSDI score, TMH, NIBUT, BCVA, CFS, CLGS, and CIS improved in both groups compared with those before treatment(all P&#x003C;0.05), with NIBUT, CFS and CLGS showing more significant improvements in the test group. In the control group, MGAP, MGE of the upper and lower eyelids and LMAS did not change significantly before and after treatment(P&#x003E;0.05), while in the experimental group, MGAP of the lower eyelids, MGE of upper and lower eyelids and LMAS improved compared with those before treatment(P&#x003C;0.05), except for MGAP of the upper eyelids, which did not differ from that before treatment(P&#x003E;0.05). There was no difference in SⅠt and IOP between the two groups before and after treatment(P&#x003E;0.05). Patients did not experience adverse reactions such as skin burns, redness and swelling in the treated area and eyelash loss during the follow-up period.CONCLUSION: Intense pulsed light is safe and effective in the treatment of severe coGVHD, which can significantly improve the symptoms and signs of patients and enhance the stability of tear film.

Construction of a graded post management indicator system for specialist nurses in medical institutions / 中华医院管理杂志

Objective:To establish a graded post management system for specialist nurses in medical institutions, so as to provide a reference for the selection, stratification, employment, and promotion of specialist nurses in China.Methods:Through literature review and brainstorming, the primary screening indicators of the graded post indicator management system for specialist nurses were constructed. Two rounds of Delphi method were used to consult 25 experts to construct the graded post management system for specialist nurses.Results:The effective recovery rates for two rounds of consultation were 100% and 96%, respectively, with expert authority coefficients of 0.86 and 0.89, and Kendall harmony coefficients of 0.31 and 0.54. The final establishment of a specialist nurses graded post management indicator system included 8 first level indicators, 31 second level indicators.Conclusions:The graded post management indicator system for specialist nurse could provide theoretical support for the management of specialist nurse. It was conducive to clarifying the admission standards and hierarchical framework for specialist nurses, standardizing the establishment of positions and responsibilities, and improving the competition and incentive mechanism.

Effect of CKIP-1 on hepatocyte apoptosis in nonalcoholic fatty liver disease / 中华内科杂志

Objective:To explore the effect and underlying mechanism of casein kinase 2 interacting protein-1 (CKIP-1) on hepatocyte apoptosis in nonalcoholic fatty liver disease (NAFLD).Methods:Experimental study. An NAFLD cell model was established by inducing human hepatoma cell line, HepG 2 cells, with oleic acid (OA). Flag-CKIP-1 expression vector and shRNA-CKIP-1 were transfected into HepG 2 cells. Flow cytometry was used to detect the effect of CKIP-1 on the activity and apoptosis of NAFLD hepatocytes. The levels of apoptosis-related proteins were detected by Western blot. CKIP-1 knockout mice in C57BL/6 back-ground were fed with either standard or high-fat diet for 8 weeks. Apoptosis-related signal proteins in NAFLD hepatocytes were detected by immunohistochemistry. Results:After CKIP-1 was transfected into HepG 2 cells, the degree of OA induced cell liposis was significantly reduced ( P<0.05). Annexin V-FITC/PI flow cytometry showed that CKIP-1 reduced the apoptosis of steatotic hepatocytes. Overexpression of CKIP-1 could significantly inhibit the expression of caspase-3 and caspase-9 and increase the expression of Bcl-2/Bax ( P<0.05). Knockdown of CKIP-1 could increase the expression of caspase-3 and caspase-9 ( P<0.05). CKIP-1 knockout could further increase the expression of caspase-3 and caspase-9 in NAFLD mice ( P<0.01, P<0.05), and further decrease the expression of Bcl-2/Bax ( P<0.05). Conclusion:CKIP-1 inhibited the apoptosis of steatotic hepatocytes by up-regulating the expression of apoptosis inhibitor gene, Bcl-2/Bax, and affecting the proteases, caspase-3 and caspase-9.