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.

Relationship between hemoglobin and serum uric acid in adults with various glucose metabolism status / 中华预防医学杂志

Objective: To investigate the relationship between hemoglobin and serum uric acid in adults with various glucose metabolism status. Methods: The demographic data and biochemical indicators of the adult population who had received physical examination in the Second Medical Center of the PLA General Hospital from January 2018 to December 2021 were collected. The subjects were divided into two groups according to the level of serum uric acid: the normal uric acid group and the hyperuricemia group. The relationship between hemoglobin (stratified into four levels of Q1 to Q4 by the quartile) and serum uric acid was quantified by using Pearson correlation and logistic regression analysis. The effects of age and glucose metabolism status on the relationship between hemoglobin and serum uric acid were analyzed. Results: A total of 33 183 adults were enrolled with age (50.6±10.0) years. The level of hemoglobin in the normal uric acid group (142.61±14.24) g/L was significantly lower than that in the hyperuricemia group [(151.79±11.24) g/L, P<0.001]. Univariate Pearson correlation analysis showed that hemoglobin was positively associated with serum uric acid (r=0.444, P<0.001). After adjusting for related confounding factors, multivariate logistic regression analysis showed that hemoglobin was associated with serum uric acid, and the OR values (95%CI) of hemoglobin Q2 to Q4 group were 1.29 (1.13-1.48), 1.42 (1.24-1.62) and 1.51 (1.32-1.72), respectively (Ptrend<0.001) when compared with hemoglobin Q1 group. Subgroup analysis and hierarchical interaction analysis suggested that with the increase of hemoglobin, the serum uric acid in the age<60 years subgroup, normal glucose subgroup and prediabetes subgroup increased gradually (Ptrend<0.05 and Pinteraction<0.001). Conclusion: The association between hemoglobin and serum uric acid in adults is affected by age and glucose metabolism status.

Infiltration and significance of M1 macrophage in breast cancer: an analysis of METABRIC database and clinical validation / 中华肿瘤杂志

Objective: To investigate the differences of immune microenvironment between stage T1N3 and stage T3N0 breast cancer patients and explore the relationship between M1 macrophage infiltration and lymph node metastasis in breast cancer. Methods: Clinical information and RNA-sequencing (RNA-Seq) expression data of stage T1N3 (n=9) and stage T3N0 (n=11) breast cancer patients were extracted from Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases. Using CIBERSORT, the proportions of 22 types of immune cells were calculated, and then the differences of immune cell infiltration between stage T1N3 and T3N0 patients were compared. From 2011 to 2022, pathologic specimens were collected from breast cancer patients who underwent curative resection at the Cancer Hospital, Chinese Academy of Medical Sciences, including 77 at stage T1N3 and 58 at stage T3N0.The METABRIC database analysis results were verified by examining the density of M1 macrophages in tissues using dual-staining immunohistochemistry. Results: METABRIC data analysis showed M1 macrophage was the highest proportion, 15.85% in stage T1N3 breast cancer; M2 macrophage was the highest proportion, 13.07% in stage T3N0 breast cancer.M1 macrophage proportions were statistically different between patients with stage T1N3 and stage T3N0 (P=0.010). The dual-staining immunohistochemistry analysis of breast cancer tissues showed M1 macrophage density (median) of 62.0 and 38.0 cells/mm(2) for stage T1N3 and T3N0, respectively. The difference was statistically significant (P=0.002). Conclusion: The density of M1 macrophages is notably higher in stage T1N3 patients and is associated with lymph node metastasis.

Effects of Yinqi Sanhuang Jiedu Decoction （茵芪三黄解毒汤） on Liver Hardness and Epithelial Mesenchymal Transition in Hepatic Fibrosis Model Mice / 中医杂志

ObjectiveTo investigate the possible mechanism of compound Yinqi Sanhuang Jiedu Decoction （茵芪三黄解毒汤， YSJD） against the progression of hepatic fibrosis （HF）. MethodsThirty-eight C57BL/6J mice were randomly divided into blank group， model group， silybin group and low-， medium- and high-dose YSJD groups， with eight mice in the model group and six mice each in other groups. Except for the blank group， all mice were injected intraperitoneally with 10% carbon tetrachloride （CCl4） to establish a HF model， twice a week for 8 weeks. The drug intervention started one week after the first modeling； the low-， medium- and high-dose YSJD groups were given 8.325， 16.65 and 33.3 g/（kg·d） of YSJD suspension by gavage， respectively， while the silybin group was given 55 mg/（kg·d） of silybin suspension by gavage， and the blank group and the model group were given 0.2 ml normal saline by gavage， all for 8 weeks. The liver hardness of living mice was observed using a small animal ultrasound detector， and grey-scale ultrasound was recorded. The liver tissue was observed by Sirius scarlet staining， and the proportion of collagen fiber deposition was calculated. Liver function indicators including alanine aminotransferase （ALT） and aspartate aminotransferase （AST）， and serum laminin （LN）， hyaluronic acid （HA）， pre-collagen type III （PCIII） and collagen type IV （CIV） were also detected. The protein expression of transforming growth factor β1 （TGF-β1）， Vimentin， E-cadherin， α smooth muscle actin （α-SMA） in liver tissue were detected. ResultsCompared to the blank group， the model group showed increased gray value， collagen deposition，serum ALT， AST， HA， LN and PCIII levels， decreased expression of E-cadherin， and increased expression of N-cadherin，α-SMA，Vimentin and TGF-β1 in liver tissues （P＜0.05）. Compared to the model group， the ultrasonic gray value and the proportion of collagen fiber deposition in liver of silybin group and YSJD medium- and high-dose groups decreased， and the serum ALT， AST， LN， HA and PCⅢ levels decreased. Compared to the model group， the expression of E-cadherin in liver tissues of silybin group and all three YSJD groups increased， while the expressions of N-cadherin， Vimentin， TGF-β1 and α-SMA decreased （P＜0.05）， and among them， most improvements were seen in the medium-dose YSJD group （P＜0.05）. ConclusionThe effect of YSJD on significantly reducing the extent of HF in mice caused by CCl4 may be related to its ability to regulate liver hardness and inhibit the occurrence of epithelial mesenchymal transition in mice.

Chinese expert consensus on clinical treatment of adult patients with severe traumatic brain injury complicated by corona virus disease 2019 (version 2023) / 中华创伤杂志

The condition of patients with severe traumatic brain injury (sTBI) complicated by corona virus 2019 disease (COVID-19) is complex. sTBI can significantly increase the probability of COVID-19 developing into severe or critical stage, while COVID-19 can also increase the surgical risk of sTBI and the severity of postoperative lung lesions. There are many contradictions in the treatment process, which brings difficulties to the clinical treatment of such patients. Up to now, there are few clinical studies and therapeutic norms relevant to sTBI complicated by COVID-19. In order to standardize the clinical treatment of such patients, Critical Care Medicine Branch of China International Exchange and Promotive Association for Medical and Healthcare and Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Chinese expert consensus on clinical treatment of adult patients with severe traumatic brain injury complicated by corona virus infection 2019 ( version 2023) based on the joint prevention and control mechanism scheme of the State Council and domestic and foreign literatures on sTBI and COVID-19 in the past 3 years of the international epidemic. Fifteen recommendations focused on emergency treatment, emergency surgery and comprehensive management were put forward to provide a guidance for the diagnosis and treatment of sTBI complicated by COVID-19.

Double versus triple D-J ureteral stents in management of benign secondary ureteral stricture / 现代泌尿外科杂志

【Objective】 To compare the clinical efficacy of double and triple D-J ureteral stents in the treatment of benign secondary ureteral stricture. 【Methods】 Clinical data of 58 patients with benign secondary ureteral stricture treated at our hospital during Dec.2018 and Aug.2021 were retrospectively analyzed. According to the number of D-J ureteral stents, the patients were divided into the double group (n=29) and triple group (n=29). The clinical efficacy, complications during catheterization, and fluctuations of serum creatinine and hydronephrosis volume were compared and analyzed between the two groups. 【Results】 There were no significant differences in the general data, catheter duration and follow-up between the two groups (P>0.05). The triple group had more reduction of hydronephrosis than the double group [-22.8(32) cm3vs. -7.4(12) cm3, P=0.001] . There were no significant differences in the change of serum creatinine [-8.0(15)μmol·L-1 vs. -4.0(15) μmol·L-1, P =0.657] and incidence of complications (34.4% vs. 41.4%, P=0.588) between the two groups. The triple group had higher total effective rate than the double group (93.1% vs. 86.2%), but the difference was not statistically significant (P=0.666). There was no significant difference in the efficacy of balloon dilatation between the two groups (100.0% vs. 90.9%, P=0.407). 【Conclusion】 Both double and triple D-J ureteral stents are safe and effective in the treatment of benign secondary ureteral stenosis, but three D-J ureteral stents can better reduce hydronephrosis. Clinicians can choose appropriate indwelling scheme according to patients’ condition.

Clinical efficacy of flexible ureteroscopic lithotripsy under local anesthesia and risk factors of perioperative pain / 现代泌尿外科杂志

【Objective】 To explore the efficacy of flexible ureteroscopic lithotripsy (FURL) under local anesthesia (LA) in the treatment of upper urinary tract calculi, and to analyze the risk factors of pain. 【Methods】 Clinical data of 255 patients treated during Apr.2022 and Sep.2022 were reviewed, including visual analogue score (VAS) of pain during ureteroscopy, sheath placement, holmium laser lithotripsy, 1 hour and 8 hours after operation. VAS ≥5 was defined as significant pain. Clinical and follow-up data of the significant pain group and non-significant pain group were analyzed with logistic regression to analyze the risk factors of pain in FURL under LA. 【Results】 Altogether 198 patients (77.6%) successfully completed the operation, and the stone-free rate (SFR) was 89.9% (178/198). The VAS of ureteroscopy was the highest (4.49±1.08), and 73 patients (28.6%) experienced significant pain. Univariate analysis showed that significant pain was associated with gender, previous surgical history, age, body mass index (BMI), education level, and ASA classification (P<0.05). Multivariate analysis showed that male (OR=2.896, 95%CI:1.413-5.933, P=0.040) and BMI≥28 (OR=7.776, 95%CI:2.268-26.657, P=0.001) were independent risk factors of significant pain, while age ≥65 years (OR=0.237, 95%CI:0.083-0.672, P=0.007) and previous surgical history (OR=0.156, 95%CI:0.032-0.754, P=0.021) were the protective factors. 【Conclusion】 It is feasible and effective to treat upper urinary tract calculi with FURL under LA. The presence of significant pain is associated with factors such as gender, age, BMI and previous surgical history.

Study on risk factors of recurrent Henoch-Schonlein purpura recurrence in children based on Cox regression analysis / 西安交通大学学报(医学版)

【Objective】 To explore the relevant risk factors of Henoch-Schonlein purpura (HSP) recurrence so as to provide some theoretical basis for early identification of children prone to recurrence. 【Methods】 The clinical data of 417 children with HSP hospitalized in Department of Pediatrics, The First Affiliated Hospital of Xi’an Jiaotong University, in the past five years were collected and followed up. They were divided into recurrent group and non-recurrent group. Cox regression analysis was used for univariate and multivariate analysis, and finally the independent risk factors for HSP recurrence were screened. 【Results】 A total of 417 children with initial onset of HSP were included in the study. During the follow-up period of 14 to 60 months, 78 cases recurred, and the recurrence rate was 18.7%. 94.9% of the children had relapse within 1 year. The results of univariate Cox regression analysis showed that age >7 years old at the time of onset, history of infection, history of strenuous exercise, duration of rashes more than 4 weeks, high level of neutrophil-to-lymphocyte ratio (NLR), and high level of platelet-to-lymphocyte ratio (PLR) were all risk factors for HSP recurrence (P7 years old at the time of onset, history of infection, history of strenuous exercise, duration of rashes for more than 4 weeks at the first onset, and high PLR level were independent risk factors for HSP recurrence (P 7 years at the time of onset, with a history of infection, vigorous exercise, rashes lasting more than 4 weeks, and high PLR level, nursing should be strengthened after discharge to avoid infection and vigorous exercise and increase the frequency of follow-up.

Regulatory role of mechanical forces in the formation of liver organoids / 临床肝胆病杂志

In recent years， the continuous advances in material sciences and techniques have helped with the establishment and development of liver organoids that can simulate the structure and function of organs in vivo. In addition to the research on traditional biological factors， the construction of microenvironments with different mechanical cues to investigate the influence of mechanical stimulation on the growth of liver organoids has also become a research focus. This article first discusses the development of liver organoids and then reviews the influence of mechanical forces of different properties on the formation of liver organoids， so as to lay a foundation for the construction of more complex and ordered liver organoids in vitro and provide ideal research models for understanding the interaction between biological and mechanical factors in the formation of liver organoids.

In-silico annotation of the chemical composition of Tibetan tea and its mechanism on antioxidant and lipidlowering in mice

BACKGROUND/OBJECTIVES@#Tibetan tea is a kind of dark tea, due to the inherent complexity of natural products, the chemical composition and beneficial effects of Tibetan tea are not fully understood. The objective of this study was to unravel the composition of Tibetan tea using knowledge-guided multilayer network (KGMN) techniques and explore its potential antioxidant and hypolipidemic mechanisms in mice.MATERIALS/METHODS: The C57BL/6J mice were continuously gavaged with Tibetan tea extract (T group), green tea extract (G group) and ddH 2 O (H group) for 15 days. The activity of total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) in mice was detected.Transcriptome sequencing technology was used to investigate the molecular mechanisms underlying the antioxidant and lipid-lowering effects of Tibetan tea in mice. Furthermore, the expression levels of liver antioxidant and lipid metabolism related genes in various groups were detected by the real-time quantitative polymerase chain reaction (qPCR) method. @*RESULTS@#The results showed that a total of 42 flavonoids are provisionally annotated in Tibetan tea using KGMN strategies. Tibetan tea significantly reduced body weight gain and increased T-AOC and SOD activities in mice compared with the H group. Based on the results of transcriptome and qPCR, it was confirmed that Tibetan tea could play a key role in antioxidant and lipid lowering by regulating oxidative stress and lipid metabolism related pathways such as insulin resistance, P53 signaling pathway, insulin signaling pathway, fatty acid elongation and fatty acid metabolism. @*CONCLUSIONS@#This study was the first to use computational tools to deeply explore the composition of Tibetan tea and revealed its potential antioxidant and hypolipidemic mechanisms, and it provides new insights into the composition and bioactivity of Tibetan tea.

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.

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.

Analysis of the effect of one-stage transurethral prostatectomy for benign prostatic hyperplasia accompanied by non-neurogenic detrusor acontractility / 中华泌尿外科杂志

Objective:To investigate the safety and efficacy of one-stage transurethral prostatectomy for prostatic hyperplasia accompanied by non-neurogenic detrusor acontractility.Methods:The clinical data of 35 patients with benign prostatic hyperplasia accompanied by non-neurogenic detrusor acontractility admitted to The Second Affiliated Hospital of Zhengzhou University from January 2015 to Octorber 2021 were analyzed.The average age was (74.0±7.9) years old. The average volume of prostate was (77.8±44.5)cm 3. The average total prostate specific antigen(tPSA)was(8.9±8.7)ng/ml. The preoperative international prostate symptom score(IPSS) was (19.1±4.3) and the preoperative quality of life score(QOL)was 5(5, 5). All the patients were treated with one-stage transurethral prostatectomy and suprapubic cystostomy. After removing the cystostomy tube, the post-void resident volume(PVR), the maximum urine flow rate(Q max), IPSS, QOL were recorded, and complications were followed up. Successful treatment is defined as the removal of the cystostomy tube without worsening of upper urinary tract hydronephrosis. Results:All the operations were successfully completed. The success rate of treatment was 85.7%(30/35), and the median time to resume spontaneous urination was 4.0(3.3, 4.5) weeks. The average postoperative Q max was (12.6±2.3)ml/s, and the average PVR was(27.7±9.5)ml. The postoperative IPSS was (5.5±2.4), which was significantly improved compared to preoperative( P<0.001). The postoperative QOL score was 1(1, 2) points, which was significantly lower than preoperative( P<0.001). The patients voiding spontaneously were followed up for 3-69 months, and no complications such as urinary retention, recurrent urinary tract infection and hydronephrosis occurred. Conclusions:One-stage transurethral prostatectomy for patients with benign prostatic hyperplasia accompanied by non-neurogenic detrusor acontractility has a high success rate and few complications, which greatly improves the quality of life of patients.

Predictive model of fecal or urinary incontinence among older adults in China / 中华老年医学杂志

Objective:To construct and validate a predictive model of fecal/urinary incontinence among older adults in China.Methods:Data was obtained from the Seventh Chinese Longitudinal Healthy Longevity Survey in 2018.In the questionnaire, "Are you able to control your bowel and urine" , was regarded as the main effect indicator.Receiver operating curves(ROC)were used to find the best cut-off values of calf circumference for predicting fecal/urinary incontinence, and univariate Logistic model method was used to explore the potential factors associated with fecal/urinary incontinence among community-living older adults in China.A random sampling method was used to extract 70% of the survey data as the training set, and the remaining 30% of the survey data as the test set.A multivariate Logistic regression analysis was conducted in the training set to build a prediction model that encompassed all predictors, and a nomogram was plotted.Results:Logistic regression analysis showed that age, small calf circumference(male <28.5 cm, female <26.5 cm), inability to walk 1 km continuously, inability to lift 5 kg items, inability to do three consecutive squats, limited daily activities, and a history of urinary system disorders, nervous system disorders, and cerebrovascular disorders were all risk factors for fecal/urinary incontinence for older adults in China.Female, better socioeconomic status, and normal body mass index were protective factors for fecal/urinary incontinence.The Logistic regression model for predicting fecal/urinary incontinence among Chinese older adults was constructed using the above twelve factors.The consistency index(C-index)value of the model was 0.907, indicating that the model had good predictive ability.The area under the ROC curve(AUC)of the overall sample, training set and test set were 0.906(95% CI: 0.896-0.917), 0.907(95 % CI: 0.894-0.921)and 0.910(95% CI: 0.892-0.928), respectively, indicating that the model had high prediction ability and good discrimination. Conclusions:Age, sex, calf circumference, ability to walk 1 km continuously, ability to lift 5 kg items, ability to do three consecutive squats, daily activities, history of urinary system disorders, nervous system disorders and cerebrovascular disorders, socioeconomic status, and body mass index were independent predictors for fecal/urinary incontinence among older adults in China.The nomogram based on the above indicators has a good predictive effect on fecal/urinary incontinence for older adults.

Construction of a Prognostic Model of Multiple Myeloma Based on Metabolism-Related Genes / 中国实验血液学杂志

OBJECTIVE@#To screen the prognostic biomarkers of metabolic genes in patients with multiple myeloma (MM), and construct a prognostic model of metabolic genes.@*METHODS@#The histological database related to MM patients was searched. Data from MM patients and healthy controls with complete clinical information were selected for analysis.The second generation sequencing data and clinical information of bone marrow tissue of MM patients and healthy controls were collected from human protein atlas (HPA) and multiple myeloma research foundation (MMRF) databases. The gene set of metabolism-related pathways was extracted from Molecular Signatures Database (MSigDB) by Perl language. The biomarkers related to MM metabolism were screened by difference analysis, univariate Cox risk regression analysis and LASSO regression analysis, and the risk prognostic model and Nomogram were constructed. Risk curve and survival curve were used to verify the grouping effect of the model. Gene set enrichment analysis (GSEA) was used to study the difference of biological pathway enrichment between high risk group and low risk group. Multivariate Cox risk regression analysis was used to verify the independent prognostic ability of risk score.@*RESULTS@#A total of 8 mRNAs which were significantly related to the survival and prognosis of MM patients were obtained (P<0.01). As molecular markers, MM patients could be divided into high-risk group and low-risk group. Survival curve and risk curve showed that the overall survival time of patients in the low-risk group was significantly better than that in the high risk group (P<0.001). GSEA results showed that signal pathways related to basic metabolism, cell differentiation and cell cycle were significantly enriched in the high-risk group, while ribosome and N polysaccharide biosynthesis signaling pathway were more enriched in the low-risk group. Multivariate Cox regression analysis showed that the risk score composed of the eight metabolism-related genes could be used as an independent risk factor for the prognosis of MM patients, and receiver operating characteristic curve (ROC) showed that the molecular signatures of metabolism-related genes had the best predictive effect.@*CONCLUSION@#Metabolism-related pathways play an important role in the pathogenesis and prognosis of patients with MM. The clinical significance of the risk assessment model for patients with MM constructed based on eight metabolism-related core genes needs to be confirmed by further clinical studies.

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.

Diagnosis and Treatment of Klebsiella Pneumoniae Combined with Enterobacter Cloacae in Lumbar Intervertebral Space Infection / 中山大学学报(医学科学版)

ObjectiveTo explore the clinical diagnosis and treatment of rare primary lumbar intervertebral space infection with Klebsiella pneumoniae and Enterobacter cloacae， and provide clinical experience for the diagnosis and treatment of this rare spinal infection. MethodsAn elderly male patient with low back pain and numbness in the left lower extremity for more than 7 months， which aggravated for more than 1 week， was diagnosed with lumbar disc herniation after laboratory and imaging examinations. After admission， the symptoms became acutely aggravated， and re-examination of lumbar enhanced MRI showed local enhancement at the posterior edge of the L3/4 intervertebral space. The VAS score was 9 points， and the lumbar JOA score was 6 points. A posterior lumbar interbody fusion of L3-L5 was performed， and L3/4 intervertebral disc specimens were collected during the operation for bacterial culture. ResultsBacterial culture results showed Klebsiella pneumoniae and Enterobacter cloacae infection. The patient was treated with sensitive antibiotics for 6 weeks after the operation， and the patient was cured during the follow-up of half a year after the operation. ConclusionFor middle-aged and elderly patients with clinical manifestations of acute severe low back pain or lower extremity pain， the possibility of spinal infection should be considered when routine laboratory and imaging examinations suggest lumbar degenerative diseases.