To investigate the protective effects and underlying mechanisms of Qin-Zhu-Liang-Xue decoction (QZLX) in atopic dermatitis (AD) and glucocorticoid resistance, we conducted a single-blinded, randomized controlled clinical trial to evaluate the efficacy and safety of this concoction. Network pharmacology analysis was performed and validated through clinical studies. The efficacy, safety, and mechanism of action of QZLX and glucocorticoid receptor (GR) α recombinant protein were assessed in AD mice induced by 2,4-dinitrofluorobenzene (DNFB). Correlation analysis was performed to determine the clinical relevance of GRα. The trial demonstrated that patients who received QZLX showed considerable improvements in their Scoring Atopic Dermatitis (SCORAD) and Dermatology Life Quality Index (DLQI) scores compared with those who received mizolastine at week 4. Network pharmacological analysis identified GRα as a key target for QZLX in AD treatment. QZLX administration increased the serum GRα expression in AD patients, alleviated AD symptoms in mice, decreased inflammatory cytokine expression, and increased GRα expression without affecting liver or kidney function. In addition, GRα recombinant protein improved AD-like skin lesions in DNFB-induced mice. A negative correlation was observed between GRα expression and clinical parameters, including SCORAD, DLQI, and serum IgE levels. QZLX alleviates AD symptoms through the upregulation of GRα and thus presents a novel therapeutic strategy for the prevention of glucocorticoid resistance in AD management.
Dermatitis, Atopic/drug therapy* ; Animals ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Mice ; Network Pharmacology ; Male ; Female ; Adult ; Receptors, Glucocorticoid/metabolism* ; Disease Models, Animal ; Single-Blind Method ; Middle Aged ; Young Adult

Objective:To investigate the longitudinal trajectory and influencing factors of cancer-related fatigue (CRF) in breast cancer patients during chemotherapy.Methods:From March 2019 to January 2020, breast cancer patients in Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine and Peking Union Medical College Hospital were selected as the research objects to conduct follow-up investigation. The survey tools included general information questionnaire, Cancer-related Fatigue Assessment Scale, International Physical Activity Questionnaire, and the Pittsburgh Sleep Quality Index Scale.Results:A total of 91 patients were included in the study. The incidence of severe CRF at each time point before chemotherapy, 3 weeks after chemotherapy and 6 weeks after chemotherapy were 1.1% (1/91), 8.8% (5/57) and 2.1% (1/48), respectively. The results of the generalized estimation equation showed that the trajectory of the total score CRF firstly increased and then decreased, reaching a peak at 3 weeks after chemotherapy (35.45±13.07), and mild CRF change showed statistical difference ( P<0.05). In addition, BMI and sleep and daytime dysfunction were the influencing factors of the total score of CRF. Disease stage, sleep disturbance and daytime dysfunction were the influencing factors of CRF with different severity. Conclusions:CRF is a prominent problem in breast cancer patients during chemotherapy. Attention should be paid to high-risk individuals with abnormal BMI and daytime function by medical staff.

Objective:To evaluate the differential expression of blood routine in different types of infection and the diagnostic value of C-reactive protein (CRP), procalcitonin (PT), ferritin (SF) and lactate dehydrogenase (LDH) in bacterial and mycoplasma pneumonia and their early warning value in severe cases.Method:A total of 627 patients, including 176 cases of bacterial pneumonia, 275 cases of mycoplasma pneumonia, 176 cases of viral infection and 180 cases of normal control were collected from May 2018 to December 2019 in children′s Hospital Affiliated to Capital Institute of Pediatrics. The mycoplasma pneumonia group was divided into mild group (151 cases) and severe group (124 cases) according to the results of lavage fluid RNA-examination. All patients received completed blood routine test at the first day of admission, patients in bacteria group and Mycoplasma group received the examination of four inflammatory indicators. The Kruskal-Wallis test was used to analyze the differences in blood routine results between different infection groups, and the differences of inflammatory indexes between bacterial group and Mycoplasma mild and severe group. The receiver operating characteristic (ROC)-curve method was used to analyze the predictive value of inflammatory indexes between different infection groups.Results:There were significant differences in leukocyte count, neutrophil, lymphocyte and monocyte percentage between bacterial pneumonia, mycoplasma pneumonia, viral infection and normal control group ( P<0.05). The differences of four inflammatory indexes in bacterial group, mild Mycoplasma group and severe group were statistically significant ( P<0.05). The rest of the index (CRP, PCT, LDH, SF and white blood cell count) were P<0.05 (CRP: area under curve [AUC] 0.799; PCT: AUC 0.579; LDH: AUC 0.651; SF: AUC 0.854), in mild and severe mycoplasma group, except WBC, by ROC-curves analysis. The AUC value of the area under the curve of CRP and SF is high, and the sensitivity and specificity at the diagnostic critical point are high, which has great diagnostic value (CRP: diagnostic critical point 12.55 mg/L, sensitivity 0.719, specificity 0.755; SF: diagnostic critical point 176.02 μg/L, sensitivity 0.765, specificity 0.960). ROC curve results also showed that of PCT, White blood cell and neutrophil percentage had the diagnostic value in bacterial infection and mycoplasma infection, P<0.05 (PCT: AUC 0.658; leukocyte: AUC 0.804; neutrophil: AUC 0.630). Leukocyte count is the best differential index (diagnostic critical point 9.585×10 9/L, sensitivity 0.778, specificity 0.698), PCT has higher sensitivity at the diagnostic critical point of 0.55 μg/L, but the specificity is slightly lower (diagnostic critical point of 0.55 μg/L, sensitivity 0.862, specificity 0.366). Conclusions:PCT and leukocyte count can be used as the preferred inflammatory indexes to distinguish bacterial and mycoplasma infection. CRP, LDH, PCT and SF can be used as early warning indexes to evaluate severe mycoplasma infection.

Objectives:To investigate the genetic characteristics of the blaNDM-1-carrying plasmid of the multidrug resistant Enterobacter hormaechei subsp. hoffmannii clinical isolate C37, and constructing a phylogenetic tree of the 66 publicly available genomes of the Enterobacter hormaechei subsp. hoffmannii to explore its global epidemic situation. Methods:Carbapenem-resistant Enterobacter cloacae complex (CRECC) strains isolated from the First Affiliated Hospital of Sun Yat-sen University from August 2014 to August 2021 were collected. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) and 16S rDNA Sanger sequencing were used for species identification. Micro broth dilution method was used for antibacterial susceptibility test. The polymerase chain reaction (PCR) was used to detect the β-lactamase resistance gene and plasmid-mediated quinolone resistance (PMQR) gene carried by the C37 strain. The conjugation experiment was used to confirm the conjugative metastasis of the resistance genes in C37 strain. Whole genome of the C37 strain was sequenced. Core genome was extracted and the phylogenetic analysis of 66 publicly available Enterobacter hormaechei subsp. hoffmannii was performed. Results:Enterobacter hormaechei subsp. hoffmannii C37 strain is resistant to third-generation cephalosporins, carbapenems, aminoglycosides and quinolones, and carries blaACT-5, blaNDM-1, qnrA1, aac(6′)-Ib-cr, oqxAB, fosA, dfrA15 and other resistance genes, as well as IncX3, IncX4, IncFIB and IncFII plasmids. Multilocus sequence typing (MLST) analysis showed that C37 strain belongs to the ST78 type of Enterobacter cloacae complex (ECC). Conclusions:ST78 type Enterobacter hormaechei subsp. hoffmannii is closely related to the spread of carbapenem resistance genes. It is a potential high-risk clone to spread carbapenem resistance genes. The prevalence and trends of ST78 type Enterobacter hormaechei subsp. Hoffmannii should be monitored.

Background: Brucella infection induces brucellosis, a zoonotic disease. The intracellular circulation process and virulence of Brucella mainly depend on its type IV secretion system (T4SS) expressing secretory effectors. Secreted protein BspJ is a nucleomodulin of Brucella that invades the host cell nucleus. BspJ mediates host energy synthesis and apoptosis through interaction with proteins. However, the mechanism of BspJ as it affects the intracellular survival of Brucella remains to be clarified. Objectives: To verify the functions of nucleomodulin BspJ in Brucella's intracellular infection cycles. Methods: Constructed Brucella abortus BspJ gene deletion strain (B. abortus ΔBspJ) and complement strain (B. abortus pBspJ) and studied their roles in the proliferation of Brucella both in vivo and in vitro. Results: BspJ gene deletion reduced the survival and intracellular proliferation of Brucellaat the replicating Brucella-containing vacuoles (rBCV) stage. Compared with the parent strain, the colonization ability of the bacteria in mice was significantly reduced, causing less inflammatory infiltration and pathological damage. We also found that the knockout of BspJ altered the secretion of cytokines (interleukin [IL]-6, IL-1β, IL-10, tumor necrosis factor-α, interferon-γ) in host cells and in mice to affect the intracellular survival of Brucella. Conclusions BspJ is extremely important for the circulatory proliferation of Brucella in the host, and it may be involved in a previously unknown mechanism of Brucella's intracellular survival.

Objective:To investigate the predictive value of peritoneal protein clearance (Pcl) for cardiovascular events and cardiovascular mortality in peritoneal dialysis (PD) patients.Methods:Eligible PD patients were prospectively enrolled from January 2014 to April 2015 in the PD Center of Renji Hospital, School of Medicine, Shanghai Jiao Tong University. All patients were followed up until death, withdrawing from PD, transferring to other centers, or the end of study period (October 1, 2018). The patients were divided into high Pcl group and low Pcl group by the median Pcl, and the differences of related indicators between the two groups were compared. A multiple linear regression model was used to analyze the influencing factors of Pcl. The Kaplan-Meier method and Log-rank test were used to compare the cumulative survival rates of patients between the two groups. A multivariate Cox regression model was used to estimate the risk of cardiovascular events and cardiovascular mortality in relation to Pcl in PD patients.Results:A total of 271 patients were enrolled, with 135 males (49.8%), age of (56.92±0.84) years old and a median PD duration of 38.77(19.00, 63.10) months. There were 70 patients (25.8%) comorbiding with diabetes and 81 patients (29.9%) with cardiovascular diseases (CVD). The median Pcl of this cohort was 67.93(52.31, 88.36) ml/d. Compared with the low Pcl group (Pcl<67.93 ml/d), the high Pcl group (Pcl≥67.93 ml/d) had older age, and greater proportion of CVD, body mass index (BMI), pulse pressure, brain natriuretic peptide, mass transfer area coefficient of creatinine (MTACcr), and lower serum albumin (all P<0.05). There was no significant difference in gender, dialysis duration, proportion of diabetes, proportion of angiotensin converting enzyme inhibitor and angiotensin receptor blocker, proportion of continuous ambulatory PD, high sensitivity C reactive protein, fluid removal including 24 h urine volume and 24 h ultrafiltration, and residual renal function between the two groups (all P>0.05). Multiple linear regression analysis showed that serum albumin ( β=-0.388, P<0.001), BMI ( β=0.189, P<0.001), and MTACcr ( β=0.247, P<0.001) were independently related to lg(Pcl). During the study period, 55 patients experienced one or more cardiovascular events and 39 patients had cardiovascular mortality. According to Kaplan-Meier analysis, cardiovascular mortality in the high Pcl group was higher than that of low Pcl group (Log-rank χ2=6.902, P=0.009). Multivariate Cox regression analysis showed that, high lg(Pcl) was an independent influencing factor of cardiovascular events in PD patients ( HR=7.654, 95% CI 1.676-34.945, P=0.009). Conclusions:Serum albumin, BMI and MTACcr are independently associated with Pcl, and Pcl is an independent predictor of cardiovascular events in PD patients.

Background: Androgenetic alopecia (AGA) leads to thinning of scalp hair and affects 60%~70% of the adult population worldwide. Developing more effective treatments and studying its mechanism are of great significance. Previous clinical studies have revealed that hair growth is stimulated by 650-nm red light. Objective: This study aimed to explore the effect and mechanism of 650-nm red light on the treatment of AGA by using ex vivo hair follicle culture. Methods: Human hair follicles were obtained from hair transplant patients with AGA. Hair follicles were cultured in Williams E medium and treated with or without 650-nm red light.Real-time RT-PCR and immunofluorescence staining were used to detect the expression level of genes and proteins in hair follicles, respectively. RNA-sequencing analysis was carried out to reveal the distinct gene signatures upon 650 nm treatment. Results: Low-level 650 nm red light promoted the proliferation of human hair follicles in the experimental cultured-tissue model. Consistently, 650 nm red light significantly delayed the transition of hair cycle from anagen to catagen in vitro. RNA-seq analysis and gene clustering for the differentially expressed genes suggests that leukocyte transendothelial migration, metabolism, adherens junction and other biological process maybe involved in stimulation of hair follicles by 650-nm red light treatment. Conclusion The effect of 650-nm red light on ex vivo hair follicles and the transcriptome set which implicates the role of red light in promoting hair growth and reversing of miniaturization process of AGA were identified.

Objective:To evaluate the influencing factors of carotid-femoral pulse wave velocity (CF-PWV) and its value to predict outcomes in peritoneal dialysis (PD) patients.Methods:Eligible patients undergoing PD in Renji Hospital of Shanghai Jiao Tong University between August 2016 and July 2018 were recruited and prospectively followed up until death, PD cessation, or to the end of the study. CF-PWV was measured by an arterial pulse wave velocity meter to assess arterial stiffness (July 31, 2020). Overhydration was measured by bioimpedance spectroscopy. The patients were divided into CF-PWV≤10 m/s group and CF-PWV>10 m/s group according to the measured value of CF-PWV. The influencing factors of elevated CF-PWV were analyzed by multivariate logistic regression. Survival curves were generated using the Kaplan-Meier method and multivariate Cox proportional hazards models were used to analyze the difference for all-cause mortality and cardiovascular disease (CVD) mortality between the two groups.Results:A total of 224 PD patients were enrolled, including 133 males (59.4%). The age was (55.2±13.4) years old, and median PD vintage was 22.3(6.5, 59.3) months. Among them, 47(21.0%) patients were comorbid with diabetes, and 37(16.5%) patients had CVD history. The median CF-PWV was 9.6(8.4, 11.4) m/s for the cohort, and 105(46.9%) participants had CF-PWV over 10 m/s. Compared with CF-PWV≤10 m/s group, CF-PWV>10 m/s group patients had older age, increased percentage of diabetes and CVD (all P<0.05). Multivariate logistic analysis showed that increased age ( OR=1.070, 95% CI 1.043-1.099, P<0.001), diabetes ( OR=3.693, 95% CI 1.646-8.287, P=0.002) and higher overhydration ( OR=1.238, 95% CI 1.034-1.483, P=0.020) were independent influencing factors for elevated CF-PWV in PD patients. After followed up for 37.4(25.6, 41.7) months, 24 patients died, including 19 cases of CVD-related deaths. Kaplan-Meier survival analysis showed that all-cause mortality and CVD mortality were significantly higher in the CF-PWV>10 m/s group than those in CF-PWV≤10 m/s group (Log-rank χ2=6.423, P=0.011; Log-rank χ2=6.243, P=0.012, respectively). Multivariate Cox proportional hazards models showed that increased age was an independent influencing factor for both all-cause mortality and CVD mortality ( HR=1.057, 95% CI 1.010-1.107, P=0.018; HR=1.062, 95% CI 1.009-1.118, P=0.022). Conclusions:Increased arterial stiffness is relatively common in PD patients. Higher CF-PWV in PD patients is associated with increased age, diabetes and higher overhydration, and it is probably a valuable predictor of outcome in PD patients.

Objective:To study the clinical application effect of modified nasopharyngeal swab sampling for 2019 novel coronavirus nucleic acid detection.Methods:This study covered the period from January 14 to March 1, 2020.The supine position method and the protective face screen were used to collect nasopharyngeal swabs from February 24 onwards, before which, the nasopharyngeal swabs were collected by sitting position method. All the patients who were diagnosed with suspected/confirmed 2019 novel coronavirus infection were admitted from February 19 with the nasopharyngeal swabs collected outside the hospital before admission. (1) Thirty-four swabbing operators meeting the inclusion criteria of the study were recruited in this retrospective cohort study. They were grouped according to the collection method of nasopharyngeal swabs. Sixteen operators of Wuhan Taikang Tongji Hospital who applied the supine position method and the protective face screen were included in supine position method+ protective face screen group (15 males and 1 female, aged 34-49 years); 18 operators (12 from the First Affiliated Hospital of Army Medical University (the Third Military Medical University), 1 from Wuhan Jiangxia Mobile Cabin Hospital, 5 from the East District of People′s Hospital of Wuhan University) who applied the traditional sitting position method were included in sitting position method group (2 males and 16 females, aged 25-49 years). In supine position method+ protective face screen group, when collecting sample, the patient lay flat and wore a special protective face screen for nasopharyngeal swab sampling, with neck slightly extending and face turning to the opposite side of the operator about 10°. The self-designed questionnaire was used to investigate the cooperation, the incidence of nausea, coughing, sneezing, and struggling of patients evaluated by the operators, the operation time for a single swab sample, the fear of operation and the perceived exposure risk of operators in the two groups. (2) Sixty-five patients (22 males and 43 females, aged 25-91 years) admitted to Wuhan Taikang Tongji Hospital who successively received the sitting position method and supine position method+ protective face screen for nasopharyngeal swabs sampling and with complete nucleic acid detection results were included. The positive rates of nucleic acid detection by the two sampling methods of nasopharyngeal swabs of the patients were statistically analyzed. (3) Forty-one patients who could express their feelings accurately were selected out of those 65 patients (12 males and 29 females, aged 27-83 years). The comfort of patients in the process of sampling by the two methods was investigated. (4) Thirty-four patients (10 males and 24 females, aged 25-83 years) with two or more consecutive negative results of nucleic acid detection of nasopharyngeal swabs by sitting position method were selected from the above 65 patients. The positive rate of nucleic acid detection of nasopharyngeal swab of patients by supine position method+ protective face screen, i. e. negative to positive rate was statistically analyzed. Data were statistically analyzed with t test, Wilcoxon signed rank test, and chi-square test. Results:(1) Compared with those of sitting position method group, the cooperation score of patients evaluated by the operators in supine position method+ protective face screen group was significantly higher ( Z=-4.928, P<0.01), the incidence of nausea, choking cough, sneezing, and struggling of patients evaluated by the operators, and the fear of operation score and the perceived exposure risk score of operators in supine position method+ protective face screen group were significantly lower ( Z=-5.071, -5.046, -4.095, -4.397, -4.174, -5.049, P<0.01), and the operation time for a single swab sample in supine position method+ protective face screen group was significantly longer ( t=223.17, P<0.01). (2) The positive rate of nucleic acid detection of nasopharyngeal swabs by supine position method+ protective face screen was 60.00% (39/65), which was obviously higher than 41.54% (27/65) by sitting position method ( χ2=4.432, P<0.05). (3) The comfort score of the 41 patients during nasopharyngeal swabs sampling by supine position method+ protective face screen was significantly higher than that by sitting position method ( Z=-5.319, P<0.01). (4) Of the 34 patients with two or more consecutive negative results of nucleic acid detection of nasopharyngeal swabs by sitting position method, the rate of negative to positive of nucleic acid detection was 26.47% (9/34) after sampling by supine position method+ protective face screen. Conclusions:Compared with the traditional sitting position method, detection of 2019 novel coronavirus nucleic acids of nasopharyngeal swabs collected by supine method combined with protective face screen is worth promoting, because of its better comfort of patients, low exposure risk for operators, in addition to reducing in the false negative result to some extent, which may help reduce false recurrence of discharged patients.