Association between chlamydia pneumoniae, mycoplasma infection and atherosclerosis / 公共卫生与预防医学

Objective To investigate the infection of Chlamydia pneumoniae and mycoplasma pneumoniae in adults and their association with atherosclerosis,and to provide theoretical guidance for the prevention of such diseases. Methods A case-control study was used to collect 362 patients who were diagnosed with atherosclerosis from January 2019 to December 2021 in Department of Sichuan Bazhong Central Hospital, and 370 cases who were admitted to the hospital during the same period of physical examination without any cardiovascular disease were selected as the control group, and whole blood samples of the two groups of study subjects were collected, and the infection of Chlamydia pneumoniae and mycoplasma pneumoniae was detected by PCR. Results The infection rate of Chlamydia pneumoniae was 35.49%, the infection rate of mycoplasma was 40.37%, and the co-infection rate was 11.37%；The infection rate of Chlamydia pneumoniae in the control group was 12.04%, the infection rate of mycoplasma was 15.83%, and the coinfection rate was 3.14%, and the difference between the two groups was statistically significant ( χ2=10.926, P=0.023). The effects of mycoplasma, chlamydia, and co-infection on atherosclerotic patients have sex differences, mainly manifested as higher infection rates in men; In addition, the effects of mycoplasma, chlamydia, and co-infection on atherosclerosis patients varied by age, mainly in the 55-70 years age group (P<0.05). Multivariate logistic regression results showed that Chlamydia pneumoniae infection was a risk factor for atherosclerosis (OR=1.303, 95%CI: 1.043-1.677) in the whole population, and chlamydia pneumoniae (OR=1.472, 95% CI: 1.037-1.556), mycoplasma (OR=2.003, 95%CI: 1.637-3.842) and co-infection in men (OR=1.937, 95%CI: 1.380-2.184) were risk factors for atherosclerosis, while co-infection in women (OR=1.699, 95%CI: 1.263-1.765) was a risk factor for atherosclerosis. Conclusion Chlamydia pneumoniae and mycoplasma infection are risk factors for atherosclerosis, and their impact on male groups is greater, and more attention needs to be paid to them.

Network pharmacology-based study on mechanism of Zhi-Huang-Zhi-Tong powder in rheumatoid arthritis treatment / 中国药理学通报

Aim To discover the potential active compounds and possible mechanisms in rheumatoid arthritis (RA) treatment with Zhi-Huang-Zhi-Tong powder (ZHZTP) by using network pharmacology and in vitro study. Methods The active ingredient targets and disease targets of Zhihuang Zhitong Powder were searched and screened by database; they intersected to get a common target; and the "drug-component-target" relationship network diagram was constructed for GO and KEGG enrichment analysis of the overlapping genes; then the core components were docked with the core targets. Finally, based on the inflammation model of HUVECs in vitro, the efficacy and mechanism of Zhihuang Zhitong powder were verified by MTT method, plate scratch test and Western blot. Results Active compounds involved in RA treatment were screened in the present study, and the top two were ursolic acid and emodin, all playing crucial roles in RA treatment with ZHZTP. Additionally, the key target was AKTA, TNF and IL-6. GO and KEGG enrichment analysis revealed that ZHZTP regulated BP, MF and CC, and also focused on regulating AKTA, TNF and IL-6 signaling pathway. Molecular docking showed that interactions between key active compounds and key targets were stable. In vitro ZHZTP significantly inhibited cell viability and migration of TNF-a-stimulated HUVECs, and the involved mechanism may be associated with PI3K/AKT/m-TOR signaling. Conclusions The present study reveals that the potential active compounds of ZHZTP are ursolic acid and emodin, and moreover, the involved mechanisms of ZHZTP for RA treatment are associated with PI3 K/AKT/m-TOR signaling.

IgG4-related hypertrophic pachymeningitis: a case report / 中华神经科杂志

A case of IgG4-related hypertrophic pachymeningitis was reported. The patient was an elderly female, with the course of disease more than 8 years. Clinical manifestations included recurrent headache, vision and hearing loss, exophthalmos and thyroid dysfunction. Finally, she was diagnosed as IgG4-related disease and IgG4-related hypertrophic pachymeningitis by PET-CT and dural biopsy. After treatment with methylprednisolone and mycophenolate mofetil, the patient′s clinical symptoms improved.

Prospective cohort study of frailty syndrome and its associated risk for adverse outcomes in elderly Chinese residents / 中华老年医学杂志

Objective:To explore the effects of frailty syndrome on activities of daily living and its associated risk for adverse outcomes among elderly residents in China.Methods:Using open data from "China Health and Retirement Longitudinal Survey", the 2011 baseline survey was conducted on general information, health risk factors, chronic disease, data obtained from various ability assessments and Fried frailty criteria assessments for community elderly aged 60 years and over.The follow-up data were used to analyze the adverse outcomes of frailty syndrome using a covariation-adjusted Logistic regression model.Results:Among the 5 630 people in the baseline population, 34.9%(1 963/5 630 cases)were non-frailty, 57.4%(3 236 cases)were pre-frailty, and 7.7%(431 cases)were frailty.The frailty group had higher rates of falls, hip fractures, hospitalizations, and death than the pre-frail and non-frail groups at the 3rd, 5th, and 8th years of follow-up.At follow up to 2015, the covariate-adjusted analysis of the study population showed that as compared with the non-frail group, the frail group had increased risks of falling( OR=1.738, 95% CI: 1.292-2.338, P<0.001), increased risks of hip fracture( OR=2.672, 95% CI: 1.365-5.233, P=0.004), increased risks of hospitalization( OR=1.670, 95% CI: 1.224-2.277, P=0.001), increased risk of death( OR=1.599, 95% CI: 1.256-2.035, P<0.001), increased risks of declined upper limb activity( OR=2.769, 95% CI: 2.101-3.650, P<0.001), of declined instrumental activity of daily living( OR=2.567, 95% CI: 1.941-3.395, P<0.001), and of declined basic activities of daily living( OR=2.790, 95% CI: 2.110-3.689, P<0.001). Conclusions:Frailty syndrome increases the risk of decreased ability to live, falls, hip fractures, hospitalization and death in older adults.Frailty screening is an effective tool for predicting the risk of adverse outcomes in elderly community populations.

Establishment and validation of prognosis prediction model for patients with gallbladder cancer based on albumin-bilirubin grade / 中华肝胆外科杂志

Objective:To establish and validate a prognosis prediction model of gall bladder cancer after surgery based on the albumin-bilirubin (ALBI) grade.Methods:The clinicopathological data of 161 patients with gallbladder cancer undergoing radical surgery in the First Hospital of Jiaxing between March 2011 to January 2020 were retrospectively analyzed, including 44 males and 117 females, aged (65±9) years old. The patients were grouped by the levels of ALBI score. The survival data were obtained through telephone or outpatient review. The Kaplan-Meier method was used to draw the survival curve. Multivariate analysis was performed using the Cox regression analysis model. The time-dependent receiver operating characteristic (ROC) curve was plotted to compare the prognostic value of the scoring system. A nomogram based on ALBI grade was established and its predictive performance was evaluated.Results:The 1, 3, 5 years overall survival (OS) rates of patients with gallbladder cancer were 76.7%, 52.5%, and 41.9%, respectively. The time-dependent ROC curves revealed that the area under the curve (AUC) values of ALBI grade were 0.659, 0.597 and 0.599 for 1, 2 and 3 years, showing a good prognostic performance. Multivariate regression analysis showed that poorer tumor differentiation ( HR=2.890, 95% CI: 1.816-4.600, P<0.001), TNM Ⅲ/Ⅳ stage ( HR=2.832, 95% CI: 1.781-4.503, P<0.001), ALBI grade 2 ( HR=1.595, 95% CI: 1.017-2.500, P=0.042), and ALBI grade 3 ( HR=3.938, 95% CI: 1.375-11.278, P=0.011) were independent risk factors for OS. The nomogram established with the independent risk factors such as ALBI grade showed a good predictive value for OS. The ROC curve results showed that the AUC values for 1, 3 and 5 years were 0.796, 0.806 and 0.799, respectively. The calibration plots and clinical decision curve analysis (DCA) showed the clinical feasibility of this nomogram. Conclusion:The nomogram model based on ALBI grading has a good predictive value for gallbladder cancer after surgery, which could guide the prognosis and individualized treatment decision-making.

Accuracy of bone age assessment system based on deep learning in children with abnormal growth and development / 中华放射学杂志

Objective:To explore the accuracy of artificial intelligence (AI) system based on deep learning in evaluating bone age of children with abnormal growth and development.Methods:The positive X-ray films of the left wrist of children with abnormal growth and development who were treated at the Affiliated Hospital of Guizhou Medical University from January 2020 to December 2021 were collected retrospectively. A total of 717 children were collected, including 266 males and 451 females, aged 2-18 (11±3) years. Based on Tanner Whitehouse 3 (TW 3)-RUS (radius, ulna, short bone) and TW3-Carpal (carpal bone) method, bone age was measured by 3 senior radiologists, and the mean value was taken as reference standard. The bone ages were independently evaluated by the AI system (Dr.Wise bone age prediction software) and two junior radiologists (physicians 1 and 2). The accuracy within 0.5 year, the accuracy within 1 year, the mean absolute error (MAE) and the root mean square error (RMSE) between the evaluation results and the reference standard were analyzed. Paired sample t-test was used to compare MAE between AI system and junior physicians. Intraclass correlation coefficient (ICC) was used to evaluate the consistency between AI system, junior physician and reference standard. The Bland-Altman diagram was drawn and the 95% consistency limit was calculated between AI system and reference standard. Results:For TW3-RUS bone age, compared with the reference standard, the accuracy within 0.5 year of AI system, physician 1 and physician 2 was 75.3% (540/717), 62.1% (445/717) and 66.2% (475/717), respectively. The accuracy within 1 year was 96.9% (695/717), 86.3% (619/717) and 89.1% (639/717), respectively. MAE was 0.360, 0.565 and 0.496 years, and RMSE was 0.469, 0.634 and 0.572 years, respectively. For TW3-Carpal bone age, compared with the reference standard, the accuracy within 0.5 year of AI system, physician 1 and physician 2 was 80.9% (580/717), 65.1% (467/717) and 71.7% (514/717), respectively. The accuracy within 1 year was 96.0% (688/717), 87.3% (626/717) and 90.4% (648/717), respectively. MAE was 0.330, 0.527 and 0.455 years, and RMSE was 0.458, 0.612, 0.538 years, respectively. Based on TW3-RUS and TW3-Carpal bone age, the MAE of AI system were lower than those of physician 1 and physician 2, and the differences were statistically significant ( P all<0.001). The evaluation results of AI, physician 1 and physician 2 were in good agreement with the reference standard (ICC all>0.950). The Bland-Altman analysis showed that the 95% agreement limits of AI system for assessing TW3-RUS and TW3-Carpal bone age were -0.75-1.02 years and-0.86-0.91 years, respectively. Conclusion:The accuracy of AI system in evaluating the bone age of children with abnormal growth and development is close to that of senior doctors, better than that of junior doctors, and in good agreement with senior doctors.

Pneumomediastinum secondary to diabetes ketoacidosis in high altitude: a case report / 中国综合临床

Diabetic ketoacidosis (DKA), a serious acute complication of diabetes mellitus, mainly manifests as hyperglycemia, ketosis, and acidosis. It is a metabolic syndrome resulting from insulin deficiency and increased insulin-antagonistic hormone levels. While type 2 diabetes mellitus complicated by DKA is relatively uncommon, secondary pneumomediastinum in DKA is extremely rare. Following alveolar rupture, air can travel through various routes to reach the hilum, causing anterior, middle, or posterior pneumomediastinum or even leading to intracranial epidural pneumatosis. The diagnosis of pneumomediastinum is mainly dependent on chest computed tomography findings. After the successful treatment of DKA, pneumomediastinum usually resolves spontaneously within 5-10 days with a good prognosis. One DKA patient admitted to Dege County People's Hospital developed Kussmaul respirations, followed by an increase in intra-alveolar pressure, an elevation in intra and extra-alveolar pressure difference, and protein decomposition in the alveolus wall, which promoted alveolar rupture and induced mediastinal emphysema. After rapid fluid replacement, blood glucose control with insulin, and maintenance of acid-base balance (correction DKA), the mediastinal emphysema was spontaneously absorbed. Through the analysis of the clinical data of this case, the purpose is to improve the clinicians' internal understanding of the relationship between mediastinal emphysema and DKA, avoid over-examination and over-treatment, and provide strategies for correct diagnosis and treatment.

Expression and significance of programmed death ligand 1 and programmed death 1 in colorectal cancer complicated by schistosomiasis / 中国基层医药

Objective:To investigate the expression and significance of programmed death ligand 1 (PD-L1) and programmed death 1 (PD-1) in colorectal cancer complicated by schistosomiasis.Methods:A total of 134 patients with colorectal cancer who received treatment in Xuancheng People's Hospital during 2014-2021 were included in this study. These patients consisted of 74 patients with colorectal cancer combined with schistosomiasis (patient group) and 60 patients with only colorectal cancer (control group). The expression of PD-L1 and PD-1 in colorectal cancer tissue was detected by an immunohistochemical method. The differences in PD-L1 and PD-1 expression were compared between the two groups. The relationships between PD-L1 and PD-1 expression and clinical pathological characteristics were determined.Results:The positive expression rates of PD-L1 and PD-1 in cancer cells and interstitial lymphocytes were 55.4% and 60.8% respectively in the patient group and they were 35.0% and 40.0% respectively in the control group. The positive expression rates of PD-L1 and PD-1 were significantly higher in the patient group than the control group ( χ2 = 5.55, 5.74, both P < 0.05). The expressions of PD-L1 and PD-1 in the patient group were correlated with lymph node metastasis and high tumor-node-metastasis stage ( P < 0.05). Conclusion:PD-L1 and PD-1 are highly expressed in colorectal cancer complicated by schistosomiasis and are related to their invasive behavior. PD-1/PD-L1 singaling pathway may be involved in the molecular mechanism underlying the occurrence and development of colorectal cancer complicated by schistosomiasis. Blocking PD-1/PD-L1 signaling pathway may be a new strategy for immunotherapy of colorectal cancer complicated by schistosomiasis.

Observation on the teaching effect of mind mapping on interns in nephrology department / 中华医学教育探索杂志

Objective:To improve the critical thinking ability of interns in nephrology department based on electronic "Spot" mind mapping teaching method.Methods:In the control group, the traditional clinical teaching method was adopted. Each kidney disease unit was divided into 3 courses. ①The clinical practice teacher dictated or demonstrated his/her experience to the student in the first class. ②Students could exchange questions and answers in the second class. ③In the third class, according to the homework situation, the teacher presided over the discussion, guided the students to express their difficulties and help them solve the problems. The research group adopted the electronic "Spot" mind mapping teaching method: ①Grouping: the students were divided into groups, 6 to 8 people in each group, a total of 16 groups. ②Preparation: each group established a WeChat group, and teachers guided them download the Mindmanager software and learn its mapping method. ③In class: each kidney disease unit was divided into 3 sessions. In the first class, based on what the instructor taught, the students summarized the contents and drew a mind map, and then explain their understanding according to the map. In the second class, "Spot" in the group was conducted based on standards, reading each other in the group, actively discussing with each other, further improving and reconstructing the core knowledge points of the chapter, and encouraging each student to actively participate in enhancing their subjective initiative in learning. In the third class, teachers evaluated students according to their learning situation, and students filled in the gaps according to their opinions, perfected their mind maps, and finally posted to the WeChat group. ④Review: the final versions were sent to the WeChat groups as review materials, which was convenient for learning together. SPSS 24.0 was used for Chi-square test.Results:There was no significant difference between the two groups before study ( P>0.005). After the research, the scores of theory test ( t=2.52, P=0.015), clinical skill test ( t=2.22, P=0.034) and total score ( t=3.53, P=0.003) in the experimental group were significantly higher than those in the control group ( P<0.05). There was no significant difference in the scores of critical thinking ability between the two groups before research ( P>0.05). Six months after research, the total scores of critical thinking ability in the experimental group were significantly higher than those in the control group ( P<0.05). Conclusion:The introduction of electronic "Spot" mind mapping teaching method into clinical practice teaching can realize the cross-linking of related knowledge points and systematize the knowledge. At the same time, it is interesting and can stimulate students' learning interest, and is helpful to cultivate the clinical critical thinking ability of students.

Novel insights into histone lysine methyltransferases in cancer therapy:From epigenetic regulation to selective drugs / 药物分析学报

The reversible and precise temporal and spatial regulation of histone lysine methyltransferases(KMTs)is essential for epigenome homeostasis.The dysregulation of KMTs is associated with tumor initiation,metastasis,chemoresistance,invasiveness,and the immune microenvironment.Therapeutically,their promising effects are being evaluated in diversified preclinical and clinical trials,demonstrating encouraging outcomes in multiple malignancies.In this review,we have updated recent understandings of KMTs'functions and the development of their targeted inhibitors.First,we provide an updated overview of the regulatory roles of several KMT activities in oncogenesis,tumor suppression,and im-mune regulation.In addition,we summarize the current targeting strategies in different cancer types and multiple ongoing clinical trials of combination therapies with KMT inhibitors.In summary,we endeavor to depict the regulation of KMT-mediated epigenetic landscape and provide potential epigenetic targets in the treatment of cancers.

Study on the value of Michigan nerve screening scale, pain and tactile temperature detection and vibration perception threshold in diagnosing diabetic peripheral neuropathy / 中国医师进修杂志

Objective:To analyze the diagnostic value of Michigan nerve screening Scale (MNSI), pain, touch and temperature detection combined with vibratory perception threshold (VPT) in diabetic peripheral neuropathy (DPN).Methods:A total of 500 patients with type 2 diabetes mellitus (T2DM) who received inpatient treatment in Xinhua Hospital Chongming Branch Affiliated of Shanghai Jiao Tong University School of Medicine from January to December 2018 were selected. Sixty four patients with DPN were enrolled in the DPN group, and the remaining 436 patients were enrolled in the no-DPN group. The clinical data and the results of MNSI scale, pain, touch and temperature detection thresholds and VPT of the two groups were compared. Receiver operating characteristic (ROC) curve was drawn to analyze the clinical value of single and combined examination indicators in the diagnosis of DPN.Results:MNSI symptom questionnaire score and MNSI physical examination score in DPN group were higher than those in no-DPN group: (3.00 ± 1.35) scores vs. (1.69 ± 0.52) scores, (1.57 ± 0.50) scores vs. (1.01 ± 0.24) scores; the proportion of touch regression, pain regression and temperature regression was significantly higher than that in no-DPN group; and the levels of VPT in the DPN group was higher than that in the no-DPN group: (26.34 ± 5.03) V vs. (17.97 ± 6.82) V, there were statistical differences ( P<0.01). When the single index was diagnosed, the area under the curve (AUC) value of VPT was the highest (0.825), and significantly higher than the pain, touch and temperature detection ( P<0.01). The AUC value of VPT + MNSI in combined diagnosis was the highest (0.738), and the sensitivity and specificity of DPN diagnosis were 51.56% and 96.10%, respectively. Conclusions:Compared with MNSI scale score, sensory detection such as pain, touch and temperature, VPT has the best diagnostic efficiency for DPN, while combined with MNSI, the specificity can be further improved, but the sensitivity decreases, which is worthy of clinical attention.

Efficacy of modified prostate tip separation technique combined with laparoscopic radical prostatectomy based on propensity score matching / 现代泌尿外科杂志

【Objective】 To explore the efficacy of modified prostate tip separation technique combined with laparoscopic radical prostatectomy based on propensity score matching (PSM) in the treatment of prostate cancer. 【Methods】 A total of 74 prostate cancer patients treated during Jan.2019 and Dec.2022 with modified prostate tip separation technique combined with laparoscopic radical prostatectomy were included in the combined group, and another 63 prostate cancer patients treated during the same period with laparoscopic radical prostatectomy were selected as the control group. Altogether 58 pairs of patients were matched with PSM. The perioperative indicators, incidence of complications, urinary control function and sexual function before and one month after surgery between the two groups after matching were compared. 【Results】 There were no statistically significant differences in general data between the two groups (P>0.05). One month after operation, the scores of the International Urinary Incontinence Questionnaire (ICIQ-SF) and International Erectile Function Questionnaire (IIEF-5) in both groups decreased, while the Expanded Prostate Cancer Index Composite (EPIC-UIN) and International Prostate Symptom Score (IPSS) in both groups increased (P<0.05). The scores of ICIQ-SF [(9.02±1.98) vs. (11.38±2.04)] and IPSS [(19.67±4.19) vs. (21.68±4.23)] were lower in the combined group than in the control group (P<0.05), while the scores of EPIC-UIN [(70.49±6.82) vs. (63.34±6.48)] and IIEF-5 [(18.17±1.73) vs. (16.72±1.58)] were higher in the combined group than in the control group (P<0.05). Compared with the control group, the combined group had shorter catheter retention time [(7.38±1.97) d vs. (5.11±1.82) d] and hospital stay [(13.18±2.23) d vs. (11.74±2.09) d], lower incidence of complications (22.41% vs. 6.90%), and higher positive rate of incision margin (8.62% vs. 20.69%) (P<0.05). 【Conclusion】 PSM can balance the differences between groups. The modified prostate tip separation technique combined with laparoscopic radical prostatectomy can improve the urinary control function, have little impact on sexual function, and cause fewer postoperative complications. However, the risk of positive incision margin is high, and further modification is needed to achieve the best therapeutic effects.

Development and validation of predictive model for cognitive impairment after stroke / 西安交通大学学报(医学版)

【Objective】 To construct and validate a risk prediction model for cognitive impairment after stroke based on demographic, clinical, and neuroimaging characteristics. 【Methods】 Through the medical record system, we collected all data of the patients. We finished cognitive function testing three months after the indexed stroke. The Mini-Mental State Examination Scale score≤26 was defined as cognitive dysfunction. Optimal subset regression analysis was used to screen variables, Logistic regression analysis was used to construct a predictive model for cognitive impairment, and C-index, calibration chart and clinical decision curve analyses were used to evaluate the discrimination, consistency, and clinical availability of the model. And nomograms were used to express the performance of the model. 【Results】 Seven variables were selected: cognitive function before stroke, age, years of education, National Institutes of Health Stroke Scale score at admission, history of ischemic heart disease, the number of old lacunar infarct lesions, and medial temporal lobe atrophy scale. The prediction model had a C-index of 0.845 (95% CI: 0.805-0.885). The clinical decision curve showed that the model had a positive net benefit when the threshold probability was 9.0%-90.0%. 【Conclusion】 The predictive model of cognitive impairment in stroke patients has good predictive efficiency and provides an effective assessment tool for screening high-risk cases of cognitive impairment in patients with stroke of various subtypes.

Correlation of extracellular enzymes activity of Candida glabrata clinical isolates with in vivo pathogenicity in Galleria mellonella larvae / 中华预防医学杂志

Objective: To explore the relationship between extracellular enzymes activity and virulence of Candida glabrata clinical isolates based on the infection model of Galleria mellonella larvae. Methods: Using experimental research methods, 71 strains of non-repetitive Candida glabrata were collected from Qinghai Provincial People's Hospital from June 2021 to January 2022. Bovine serum protein agar medium, egg yolk agar medium, sheep blood agar medium, Tween-80 agar medium and triglyceride agar medium were used to detect the aspartyl protease activity, phospholipase activity, hemolysis activity, esterase activity and lipase activity of Candida glabrata. Median lethal concentration (LC50) was calculated by using 1.25×108 CFU/ml,2.50×108 CFU/ml,3.75×108 CFU/ml,5.00×108 CFU/ml suspension of Candida glabrata ATCC2001 to infect Galleria mellonella larvae. Histopathological and etiological analysis was performed to determine whether the infection model was successfully established. The clinical isolates of Candida glabrata were configured to infect Galleria mellonella larvae with LC50 concentration to detect the pathogenicity of Galleria mellonella larvae.Spearman test or Pearson test were used to analyze the correlation between the extracellular enzyme activity of Candida glabrata clinical isolates and the pathogenicity of Galleria mellonella larvae. Results: 71 strains of Candida glabrata isolated clinically were detected to have low hemolytic activity after 2 days of culture. Aspartyl protease was detected after 4 days of culture, among which 7 strains (9.86%), 19 strains (26.76%) and 45 strains (63.38%) showed low, medium and high aspartyl protease activity. After 7 days of culture, 71 strains did not detect phospholipase, esterase and lipase activities. Candida glabrata on Galleria mellonella larvae of LC50=2.5×108 CFU/ml Fungal spore were found in the intestinal tissue pathological section of Galleria mellonella larvae in the experimental group, and Candida glabrata was identified by the microbial Mass Spectrometry after culture, while no fungi were found in the pathological section and culture of the control group. Spearman test shows that, there was a linear positive correlation between aspartyl protease activity and the survival rate of Galleria mellonella larvae (r = 0.73, P<0.01), the difference was statistically significant.Pearson test shows that, there was no significant linear relationship between hemolytic activity and survival rate of Galleria mellonella larvae (r = 0.16, P = 0.34), the difference was not statistically significant. Conclusion: The clinical isolates of Candida glabrata in this study had aspartyl protease activity and low hemolytic activity, but no phospholipase, esterase and lipase activity. The activity of aspartyl aspartyl protease of Candida glabrata was positively correlated with the pathogenicity of Galleria mellonella larvae.

Associations of genetic variations in pyroptosis related genes with acute adverse events in postoperative rectal cancer patients receiving concurrent chemoradiotherapy / 中华肿瘤杂志

Objective: This study aims to investigate the associations between genetic variations of pyroptosis pathway related key genes and adverse events (AEs) of postoperative chemoradiotherapy (CRT) in patients with rectal cancer. Methods: DNA was extracted from the peripheral blood which was collected from 347 patients before CRT. Sequenom MassARRAY was used to detect the genotypes of 43 haplotype-tagging single nucleotide polymorphisms (htSNPs) in eight pyroptosis genes, including absent in melanoma 2 (AIM2), caspase-1 (CASP1), caspase-4(CASP4), caspase-5 (CASP5), caspase-11 (CASP11), gasdermin D (GSDMD), gasdermin E (GSDME) and NLR family pyrin domain containing 3 (NLRP3). The associations between 43 htSNPs and AEs were evaluated by the odd ratios (ORs) and 95% confidence intervals (CIs) by unconditional logistic regression models, adjusted for sex, age, clinical stage, tumor grade, Karnofsky performance status (KPS), surgical procedure, and tumor location. Results: Among the 347 patients with rectal cancer underwent concurrent CRT with capecitabine after surgery, a total of 101(29.1%) occurred grade ≥ 2 leukopenia. rs11226565 (OR=0.41, 95% CI: 0.21-0.79, P=0.008), rs579408(OR=1.54, 95% CI: 1.03-2.29, P=0.034) and rs543923 (OR=0.63, 95% CI: 0.41-0.98, P=0.040) were significantly associated with the occurrence of grade ≥ 2 leukopenia. One hundred and fifty-six (45.0%) had grade ≥ 2 diarrhea, two SNPs were significantly associated with the occurrence of grade ≥ diarrhea, including CASP11 rs10880868 (OR=0.55, 95% CI: 0.33-0.91, P=0.020) and GSDME rs2954558 (OR=1.52, 95% CI: 1.01-2.31, P=0.050). In addition, sixty-six cases (19.0%) developed grade ≥2 dermatitis, three SNPs that significantly associated with the risk of grade ≥2 dermatitis included GSDME rs2237314 (OR=0.36, 95% CI: 0.16-0.83, P=0.017), GSDME rs12540919 (OR=0.52, 95% CI: 0.27-0.99, P=0.045) and NLRP3 rs3806268 (OR=1.51, 95% CI: 1.03-2.22, P=0.037). There was no significant difference in the association between other genetic variations and AEs of rectal cancer patients (all P>0.05). Surgical procedure and tumor location had great impacts on the occurrence of grade ≥2 diarrhea and dermatitis (all P<0.01). Conclusion: The genetic variants of CASP4, CASP11, GSDME and NLRP3 are associated with the occurrence of AEs in patients with rectal cancer who received postoperative CRT, suggesting they may be potential genetic markers in predicting the grade of AEs to achieve individualized treatment of rectal cancer.

CHD1 deletion stabilizes HIF1α to promote angiogenesis and glycolysis in prostate cancer / 亚洲男科学杂志(英文版)

Chromodomain-helicase-DNA-binding protein 1 (CHD1) deletion is among the most common mutations in prostate cancer (PCa), but its role remains unclear. In this study, RNA sequencing was conducted in PCa cells after clustered regularly interspaced palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9)-based CHD1 knockout. Gene set enrichment analysis (GSEA) indicated upregulation of hypoxia-related pathways. A subsequent study confirmed that CHD1 deletion significantly upregulated hypoxia-inducible factor 1α (HIF1α) expression. Mechanistic investigation revealed that CHD1 deletion upregulated HIF1α by transcriptionally downregulating prolyl hydroxylase domain protein 2 (PHD2), a prolyl hydroxylase catalyzing the hydroxylation of HIF1α and thus promoting its degradation by the E3 ligase von Hippel-Lindau tumor suppressor (VHL). Functional analysis showed that CHD1 deletion promoted angiogenesis and glycolysis, possibly through HIF1α target genes. Taken together, these findings indicate that CHD1 deletion enhances HIF1α expression through PHD2 downregulation and therefore promotes angiogenesis and metabolic reprogramming in PCa.

Research progress on the correlation between circadian rhythm and clock genes and the pathogenesis of diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

Diabetic retinopathy(DR)is the most common microvascular complication of patients with diabetes mellitus, and it has become one of the leading causes of visual impairment among working-age people worldwide. The pathogenesis of DR is complicated with multiple mechanisms. Plenty of studies have indicated that circadian rhythm and clock genes are closely related to the pathogenesis of DR. Circadian rhythm is a physiological process regulated by clock genes, which takes 24h as a cycle and is consistent with the changes of light and dark outside. Circadian rhythm regulates various physiological activities of the body. The disturbance of circadian rhythm induces DR by affecting the blood glucose level and the physiological homeostasis of the eye in patients with diabetes mellitus, and clock genes may be involved in the pathogenesis of DR by regulating oxidative stress response, inflammatory response, retinal autophagy rhythm, mitochondrial dysfunction and endothelial progenitor cell function. This paper will introduce the generation and regulation mechanism of circadian rhythm, as well as the internal circadian rhythm of retina, and further discuss the influence of circadian rhythm and clock genes on the occurrence and development of DR, aiming to provide a reference for the prevention and treatment of DR.

Syndrome Differentiation and Treatment of Obesity from "Orchids to Eliminate Stagnant Qi" / 中国实验方剂学杂志

Obesity is a chronic， recurrent， and progressive metabolic disorder characterized by the abnormal or excessive accumulation of body fat caused by multiple factors such as genetics， dietary structure， lifestyle and behavior， psychology， environment， and society， leading to an energy surplus. Obesity is a major risk factor that increases the risk of developing various chronic diseases， including type 2 diabetes， hypertension， cardiovascular diseases， stroke， and certain malignancies. The global incidence of obesity is increasing year by year. With the continuous improvement of people's living standards， more than half of adults in China are now overweight or obese， posing a serious threat to people's health and increasing the social and economic burden. It has become a pressing major public health issue that needs to be addressed urgently. The concept of obesity can be traced back to the Huangdi’s Internal Classic （Huang Di Nei Jing）， which describes it as "the problems in fat and affluent people are caused by excessive taking of rich food"， and suggests that ''frequent intake of rich and greasy foods can produce interior heat. Sweet flavor causes chest fullness. That is why its spleen-Qi flows upwards and changes into consumption-thirst disease. It can be treated by Eupatorii Herba which is used to remove stagnant Qi''. The stagnant qi is caused by the transformation failure of rich and greasy food and wine， so obesity is the disease of stagnant qi. Obesity is caused by indulging in rich and greasy food， wine， spicy and flavorful foods， raw and cold foods， and sweet and greasy foods， or overeating and leading a sedentary lifestyle， staying up late， or experiencing emotional imbalances such as excessive joy， anger， worry， pensiveness， and fear. It can also be caused by congenital abnormalities， leading to improper functioning of the spleen and stomach， dysregulation of the absorption and secretion of the small intestine， and the accumulation of stagnant Qi in the organs and muscles， resulting in a plump physique. The intake of food and drink depends on the functions of the stomach in receiving and decomposing， the small intestine in absorbing and secreting， and the spleen in transforming and transporting. The affected organs in obesity are the spleen， stomach， and small intestine. Orchids， specifically Eupatorii Herba and Lycopi Herba， are aromatic herbs that can regulate the smooth flow of Qi， eliminate stagnation， and cleanse impurities. In a broader sense， any aromatic and pungent substance that can invigorate the spleen， promote clarity， harmonize the stomach， reduce turbidity， and assist in the normal secretion and absorption functions of the small intestine， thereby eliminating excess， is referred to as orchid. Therefore， the treatment principle for obesity is to use ''orchids to eliminate stagnant Qi''， aiming to regulate the functions of the spleen， stomach， and small intestine using aromatic and pungent substances， gradually eliminating excessive dampness， phlegm， turbidity， and heat， and restore the balance of the middle energizer. This way， individuals who are obese can achieve a non-obese state.

The Clinical Observation of Inflammation Theory for Depression:The Initiative of the Formosa Long COVID Multicenter Study (FOCuS)

There is growing evidence that the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with increased risks of psychiatric sequelae. Depression, anxiety, cognitive impairments, sleep disturbance, and fatigue during and after the acute phase of COVID-19 are prevalent, long-lasting, and exerting negative consequences on well-being and imposing a huge burden on healthcare systems and society. This current review presented timely updates of clinical research findings, particularly focusing on the pathogenetic mechanisms underlying the neuropsychiatric sequelae, and identified potential key targets for developing effective treatment strategies for long COVID. In addition, we introduced the Formosa Long COVID Multicenter Study (FOCuS), which aims to apply the inflammation theory to the pathogenesis and the psychosocial and nutrition treatments of post-COVID depression and anxiety.

YAP regulates the liver size during the fasting-refeeding transition in mice

Liver is the central hub regulating energy metabolism during feeding-fasting transition. Evidence suggests that fasting and refeeding induce dynamic changes in liver size, but the underlying mechanisms remain unclear. Yes-associated protein (YAP) is a key regulator of organ size. This study aims to explore the role of YAP in fasting- and refeeding-induced changes in liver size. Here, fasting significantly reduced liver size, which was recovered to the normal level after refeeding. Moreover, hepatocyte size was decreased and hepatocyte proliferation was inhibited after fasting. Conversely, refeeding promoted hepatocyte enlargement and proliferation compared to fasted state. Mechanistically, fasting or refeeding regulated the expression of YAP and its downstream targets, as well as the proliferation-related protein cyclin D1 (CCND1). Furthermore, fasting significantly reduced the liver size in AAV-control mice, which was mitigated in AAV Yap (5SA) mice. Yap overexpression also prevented the effect of fasting on hepatocyte size and proliferation. Besides, the recovery of liver size after refeeding was delayed in AAV Yap shRNA mice. Yap knockdown attenuated refeeding-induced hepatocyte enlargement and proliferation. In summary, this study demonstrated that YAP plays an important role in dynamic changes of liver size during fasting-refeeding transition, which provides new evidence for YAP in regulating liver size under energy stress.