Objective To investigate the role of cytochrome P450 2E1 (CYP2E1) in trichloroethylene (TCE)-induced skin sensitization and liver damage in guinea pigs, using diallyl sulfide (DAS), a CYP2E1 inhibitor, as an intervention. Methods Specific pathogen-free female guinea pigs were randomly divided into blank control group, solvent control group, positive control (2,4-dinitrochlorobenzene) group, TCE-exposure group, and DAS-intervention group. Skin sensitization experiments were conducted using the guinea pig TCE maximal dose-skin sensitization test. Urinary trichloroacetic acid levels were determined following TCE induction and challenge. At 48 hours after the final challenge, serum liver function markers and inflammatory cytokines levels were detected. Histopathological examination on skin and liver tissues was performed, and hepatic CYP2E1 protein expression and oxidative stress indicators were assessed. Results The sensitization rates of guinea pigs were 100.0%, 75.0%, and 33.3% in the positive control, TCE-exposure, and DAS-intervention groups, respectively, while the blank control and solvent control groups were both 0.0%. Compared with the guinea pigs in TCE-exposure group, those in the DAS-intervention group had lower urinary trichloroacetic acid levels at intradermal induction, local induction, first challenge, and 24 hours after the final challenge time point (all P<0.05). Histopathology of guinea pigs showed dermal inflammatory infiltration and basal keratinocyte necrosis in the TCE-exposure group, whereas only mild dermal inflammation was observed in the DAS-intervention group. The guinea pigs in TCE-exposure group exhibited diffuse hepatocellular necrosis, while hepatic damage in the DAS-intervention group was alleviated, characterized by only mild hepatocellular steatosis and hepatocyte swelling around the central vein. The skin sensitization rate of guinea pigs in the TCE-exposure group increased (all P<0.01), the serum alanine aminotransferase (ALT )activity, the levels of interleukin (IL)-2, IL-17, and tumor necrosis factor-α (TNF- α) increased (all P<0.05), the relative expression of CYP2E1 protein, the activity of superoxide dismutase (SOD), and the level of malondialdehyde in liver tissue increased (all P<0.05), while the activity of catalase decreased (P<0.05), compared with the blank control and solvent control groups. The serum ALT activity and the levels of IL-2, IL-17, and TNF-α of guinea pigs in DAS-intervention group reduced (all P<0.05), as well as CYP2E1 protein expression, SOD activity, and malondialdehyde level in liver tissue reduced (all P<0.05), compared with the TCE-exposure group. Conclusion TCE can induce hepatic CYP2E1 expression, thereby promoting oxidative stress and inflammatory responses, which contributes to skin sensitization and liver damage. DAS alleviates TCE-induced toxic effects on skin and liver by inhibiting CYP2E1 expression.

ObjectiveBased on the integrated strategy of "empirical prescriptions in ancient books-medical cases by prestigious doctors-computational analysis"， this study aims to explore and analyze the prescriptions and medical cases for treating tremors in traditional Chinese medicine （TCM）， predict their efficacy， and obtain the core prescriptions for treating tremors in TCM， providing references for clinical application and new drug development. MethodThe Chinese Medicine Prescription Database and the China National Knowledge Infrastructure （CNKI） were searched for relevant prescriptions and medical cases for treating tremors in TCM to establish a database of prescriptions for tremors. The Traditional Chinese Medicine Inheritance Computer System （V3.0） was used to analyze and explore the medication rules including drug frequency， properties， flavor， meridian tropism， and pharmacological effects， as well as core drugs and formula associations. A multi-target drug efficacy prediction platform based on network robustness was used to evaluate the predicted efficacy of the core prescriptions obtained. Based on the integration of ancient prescriptions， prestigious doctors' medical cases， and network analysis results， the priority level of the developed prescriptions was determined through comprehensive evaluation. ResultA total of 81 ancient prescriptions were screened， involving 246 drugs， and 171 prescriptions were screened from prestigious doctors' medical cases， involving 278 drugs. The frequently used TCM drugs were mostly warm in nature and sweet in flavor， mainly acting on the liver， spleen， and kidney meridians. In terms of efficacy， they were mainly effective in tonifying deficiency， soothing liver and extinguishing wind， activating blood and resolving blood stasis， clearing heat， and resolving exterior. Through association rules and K-means clustering， the core prescriptions were composed of high-frequency drugs such as Glycyrrhizae Radix et Rhizoma， Ginseng Radix et Rhizoma， Astragali Radix， Atractylodis Macrocephalae Rhizoma， Angelicae Sinensis Radix， Poria， Gastrodiae Rhizoma， and Uncariae Ramulus Cum Uncis. Drug combinations mainly focused on tonifying Qi and nourishing blood， with the additional functions of calming wind and dredging collaterals. Clustering analysis of core prescriptions from ancient prescriptions and prestigious doctors' medical cases， as well as multi-target drug efficacy prediction， showed that Combination 1 had the highest disturbance score on the disease network. Furthermore， comparative analysis revealed consistent results with both the analysis of ancient prescriptions and prestigious doctors' medical cases， indicating its optimal development potential based on theoretical inheritance and empirical practice. In comparison， Combinations 3， 2， and 4 were less utilized in contemporary clinical practice， with lower rankings in network disturbance scores， suggesting that their development value still warranted further exploration. ConclusionTCM clinical treatment of tremors emphasizes the regulation of the liver， spleen， and kidney. In line of syndrome differentiation， drugs potent in soothing liver， extinguishing wind， activating blood， and resolving blood stasis are added based on deficiency-tonifying drugs. The core prescriptions based on Glycyrrhizae Radix et Rhizoma， Angelicae Sinensis Radix， Paeoniae Radix Alba， Astragali Radix， Poria， and Atractylodis Macrocephalae Rhizoma （combination 1） have the highest potential development value. The integrated strategy "empirical prescriptions in ancient books-medical cases by prestigious doctors-computational analysis" can be used for the screening of candidate prescriptions for new TCM drugs.

Objective:To analyze the clinical characteristics and outcomes of patients with invasive fungal sinusitis (invasive fungal rhinosinusitis, IFR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and explored the risk factors for IFR after allo-HSCT.Methods:Nineteen patients with IFR after allo-HSCT at Peking University People’s Hospital from January 2012 to December 2021 were selected as the study group, and 95 patients without IFR after allo-HSCT during this period were randomly selected as the control group (1:5 ratio) .Results:Nineteen patients, including 10 males and 9 females, had IFR after allo-HSCT. The median age was 36 (10–59) years. The median IFR onset time was 68 (9–880) days after allo-HSCT. There were seven patients with acute myeloid leukemia, five with acute lymphoblastic leukemia, two with myelodysplastic syndrome, two with chronic myeloid leukemia, one with acute mixed-cell leukemia, one with multiple myeloma, and one with T-lymphoblastic lymph node tumor. There were 13 confirmed cases and 6 clinically diagnosed cases. The responsible fungus was Mucor in two cases, Rhizopus in four, Aspergillus in four, and Candida in three. Five patients received combined treatment comprising amphotericin B and posaconazole, one patient received combined treatment comprising voriconazole and posaconazole, nine patients received voriconazole, and four patients received amphotericin B. In addition to antifungal treatment, 10 patients underwent surgery. After antifungal treatment and surgery, 15 patients achieved a response, including 13 patients with a complete response and 2 patients with a partial response. Multivariate analysis revealed that neutropenia before transplantation ( P=0.021) , hemorrhagic cystitis after transplantation ( P=0.012) , delayed platelet engraftment ( P=0.008) , and lower transplant mononuclear cell count ( P=0.012) were independent risk factors for IFR after allo-HSCT. The 5-year overall survival rates in the IFR and control groups after transplantation were 29.00%±0.12% and 91.00%±0.03%, respectively ( P<0.01) . Conclusion:Although IFR is rare, it is associated with poor outcomes in patients undergoing allo-HSCT. The combination of antifungal treatment and surgery might be effective.

Objective:To summarize the clinical features associated with respiratory syncytial virus (RSV) infection in patients following the hematopoietic stem cell transplant (HSCT) and exploring the risk factors for death.Methods:Patients who had RSV infection after undergoing HSCT from October 2023 to January 2024 in the hematology department of Peking University People’s Hospital were enrolled in the study. The clinical characteristics of the participating patients were summarized. The clinical characteristics of the surviving and the dying patients were compared, and the risk factors of death were analyzed by binary logistic regression.Results:Among the 43 RSV-positive HSCT patients, 20 (46.5%) were hypoxemic, six (14.0%) were admitted to the ICU for further treatment, four (9.3%) required tracheal intubation assisted ventilation, and seven patients (16.3%) died. A comparison of the clinical features of the surviving patients and the deceased patients demonstrated that the deceased patients had a lower PLT when infected with RSV [74.5 (8.0-348.0) ×10 9/L vs 15.0 (10.0-62.0) ×10 9/L, P=0.003], a higher incidence of simultaneous bacterial infections (85.7% vs 41.7%, P=0.046), and a higher rate of hematological recurrence (71.4% vs 13.9%, P=0.004). Hematological recurrence ( OR=15.500, 95% CI 2.336-102.848, P=0.005), influenza A viral infection ( OR=14.000, 95% CI 1.064-184.182, P=0.045), and low PLT at the time of RSV infection ( OR=0.945, 95% CI 0.894-0.999, P=0.048) were the factors associated with death following HSCT. Conclusion:Patients infected with RSV after undergoing HSCT have a poor prognosis, and active prevention and treatment of RSV in the autumn and winter requires urgent attention.

Objective To investigate the effects of long-term exposure to three new types of light emitting diode (LED) sources on the behavior, learning, and memory of rats. Methods A total of 160 specific pathogen-free SD rats were divided into eight groups as followed, trichromatic fluorescent lamps color temperature control group, violet-chip full-spectrum white LED group, blue-chip white LED group, and blue-chip full-spectrum white LED group based on the light sources types, with color temperature of 4 000 K and 6 500 K groups in each group using the 4×2 factorial design. There were 20 rats in each group, with half of the rats were males and half females. Rats were exposed to artificial lighting, and the illumination was set at 750 lx. The rats in each group were exposed to different lighting environments for 12 hours per day for 24 weeks. The open-field and step-down tests were conducted in rats after 24 weeks exposure, followed by sacrifice of rats and measurement of organ coefficients. Differences in body weight, organ coefficients, and neurobehavioral indexes of rats in different groups were compared. Results The spleen coefficient of female rats decreased in blue-chip white LED of 6 500 K color temperature group, and the liver coefficient of male rats decreased in the violet-chip full-spectrum white LED of 4 000 K color temperature, blue-chip full-spectrum white LED of 4 000 K color temperature, and blue-chip full-spectrum white LED of 6 500 K color temperature groups, compared with the same-sex rats in trichromatic fluorescent lamps with same-color temperature control group (all P<0.05). The result of different types of light sources compared in the open-field test showed that the index of total distance and movement speed of female rats in the blue-chip full-spectrum white LED group were lower than those in the other three groups, and the time cost to the central area was longer than that in the blue-chip white LED group and the violet-chip full-spectrum white LED group (all P<0.05). The total distance and movement speed of male rats in the blue-chip full-spectrum white LED group were longer or higher than those in the violet-chip full-spectrum white LED group (all P<0.05). Based on the comparison of color temperature, the time and total distance of male rats in 6 500 K color temperature group were lower than that in the 4 000 K color temperature group (both P<0.05). In the step-down test, both male and female rats in the blue-chip full-spectrum white LED group made more errors compared with other three groups with the same gender (all P<0.05). Conclusion Based on the experimental conditions of this study, the blue-chip full-spectrum white light LED affects behavior, learning and memory of the rats, and trichromatic fluorescent lamp has the lowest effect on neurobehavior. The color temperature also affects behavior of the rats, and high color temperature has higher risk.

Objective:To explore the TCM syndromes and risk factors of patients with anxiety and/or depression after coronary revascularization through real-world data mining based on the national pilot project of Chinese and Western medicine clinical collaboration for major difficult diseases; To provide clinical evidence and guide practice for the diagnosis and treatment of bicardiac diseases after coronary revascularization.Methods:A retrospective multi-center clinical study was conducted. From September 2018 to December 2019, 577 patients who underwent successful percutaneous coronary intervention in the Department of Cardiovascular Medicine of Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Department of Cardiovascular Medicine of the People's Hospital of Liaoning Province were enrolled using the collaborative platform system of TCM and Western Medicine Diagnosis and follow-up for coronary disease. Clinical data database was established. Baseline data, TCM syndrome types and elements, coronary angiography and stent implantation status, relevant disease history, Hamilton Anxiety and Depression Scale, etc. were collected. A combination of postoperative phone calls and outpatient visits was performed, with follow-up every 3 months for a total of 1 year. The TCM treatment patterns and risk factors of patients with anxiety and depression after coronary artery revascularization surgery were analyzed and explored.Results:A total of 577 patients were enrolled and 561 patients were followed up. Age distribution: The age of males and females undergoing coronary revascularization due to ACS was (61.80±11.00) years and (68.37±10.13) years, with no statistical significance between groups ( P>0.05), but the age of onset in males tended to be earlier than in females. The distribution pattern of TCM syndrome elements showed that the most deficiency syndrome elements were qi deficiency (61.75%, 176/285), followed by yin deficiency (28.77%, 82/285). The most common excessive symptom was blood stasis (39.13%, 108/276), and the other syndromes were phlegm turbidity (36.23%, 100/276) and qi depression (20.29%, 56/276), etc. The distribution of TCM syndrome types was as follows: in the population with anxiety and depression state of coronary revascularization, the TCM syndrome types with frequency higher than 10% were successively phlegm and blood stasis with depression syndrome, qi deficiency and blood stasis syndrome, heart, gallbladder and qi deficiency and qi-yin deficiency with blood stasis syndrome. Among the people without anxiety and depression, the TCM syndromes with a frequency higher than 10% were heart blood stasis syndrome and qi deficiency and blood stasis syndrome, with statistical significance ( χ2=12.07, P<0.01). Correlation analysis showed that the number of stents, and LDL-C were positive correlated with anxiety and depression( r values were 0.107, 0.118,respectively, P<0.05), and the uric acid was negative correlation ( r=-0.127, P=0.011). Multivariate Cox proportional hazards regression showed the age [ RR (95% CI)=1.052 (1.012-1.094), P=0.010] and diabetes mellitus [ RR (95% CI)=4.561 (1.028-20.238), P=0.046] at the sixth month of treatment. Conclusions:The age of acute coronary syndrome and coronary revascularization is mainly concentrated in patients aged 60-70 years, and male patients tend to have earlier onset than female patients, and the risk of coronary heart disease is relatively high. Qi-deficiency syndrome accounts for the highest proportion, and the most excessive syndrome is blood stasis syndrome. The TCM syndromes with high frequency of anxiety and depression are phlegm and blood stasis with depression syndrome and qi-yin deficiency with blood stasis syndrome. The number of stents implanted and low density lipoprotein cholesterol are positively correlated with postoperative anxiety and depression. Age and diabetes history are independent risk factors for end-point events at about 6 months after treatment.

Objective:To investigate the effect of maintenance hemodialysis (MHD) combined with levocarnitine on vascular sclerosis and vascular endothelial function in patients with chronic renal failure.Methods:Patients with chronic renal failure receiving MHD treatment admitted to Shanxian Central Hospital of Shandong Province from June 2019 to May 2020 were selected as the research object and they were divided into the observation group (53 cases) and the control group (49 cases) by the random number table method. The patients in the control group were treated with maintenance hemodialysis and the patients in the observation group were treated with combined levocarnitine on the basis of the control group. The levels of serum creatinine (SCr), blood urea nitrogen (BUN) and other renal function indicators were determined before and 6 months after the treatment. The levels of nuclear factor kappa B (NF-κB), tumor necrosis factor (TNF-α) and other microinflammatory indexes, and advanced oxidation protein products (AOPP), malondialdehyde (MDA), glutathione peroxidase (GSH-Px) and other oxidative response indexes were determined. The levels of endothelin-1 (ET-1), von Willebrand factor (vWF) and vascular reactive hyperemia index (RHI) were measured. Common carotid atherosclerosis β and pulse wave conduction velocity (PWV) were measured by color Doppler ultrasonography.Results:The levels of SCr, BUN in the two groups after treatment had no significant differences ( P>0.05). The levels of TNF-α and NF-κB in the observation group after treatment were lower than those in the control group: (20.22 ± 7.15) μg/L vs.(26.14 ± 5.96) μg/L, (6.10 ± 0.80) mg/L vs. (6.55 ± 1.10) mg/L, there were statistical differences ( P<0.05). The levels of AOPP, MDA in the observation group after treatment were lower than those in the control group and the level of GSH-PX was higher than that in the control group: (78.52 ± 17.41)μmol/L vs.(97.96 ± 18.29) μmol/L, (4.44 ± 1.02) μmol/L vs. (6.07 ± 1.26) μmol/L, (110.14 ± 22.17) mg/L vs.(90.63 ± 19.28) mg/L, there were statistical differences ( P<0.05). The levels of PWV, ET-1 and vWF in the observation group after treatment were lower than those in the control group and the RHI was higher than that in the control group: (7.29 ± 0.59) m/s vs. (7.89 ± 0.63) m/s, (44.15 ± 10.27) ng/L vs. (52.41 ± 12.74) ng/L, (30.26 ± 7.45) U/L vs. (35.71 ± 6.23) U/L, 1.54 ± 0.25 vs. 1.45 ± 0.20, there were statistical differences ( P<0.05). Conclusions:The combination of levocarnitine in the treatment of MHD can alleviate microinflammation, oxidative stress response and improve vascular endothelial function and arteriosclerosis.

Objective:To summarize the clinical features of intestinal Beh?et′s disease, so as to provide reference for the diagnosis of the disease.Methods:From April 1 2014 to January 31 2019, the clinical data of 47 patients diagnosed as intestinal Beh?et′s disease at the Second Hospital of Hebei Medical University were retrospectively analyzed, which included initial symptoms, gastrointestinal symptoms, complications, erythrocyte sedimentation rate (ESR), the levels of C reactive protein (CRP), hemoglobin, serum albumin, results of acupuncture test, gastrointestinal involved site and ulcer shape. At the same time, gender differences of clinical manifestations were compared. Chi-square test was used for statistical analysis.Results:Among 47 patients with intestinal Beh?et′s disease, the initial symptoms of 26 (55.3%) cases were gastrointestinal symptoms. Abdominal pain was the most common symptom, the others were diarrhea, anorexia, abdominal distension and perianal abscess, and the incidence rate was 80.9%(38/47), 46.8% (22/47), 42.6% (20/47), 36.2% (17/47) and 2.1% (1/47), respectively. The main complications were gastrointestinal bleeding, perforation and obstruction, and the incidence rates was 40.4% (19/47), 4.3% (2/47) and 4.3% (2/47), respectively. Thirty-seven (78.7%) patients had different degrees of hypoalbuminemia (serum albumin<35 g/L). The CRP level of 36(76.6%) patients increased. The ESR of 36 (76.6%) patients increased. Twenty-two (46.8%) patients had mild anemia (hemoglobin<90 g/L). The acupuncture test was positive in 25 (53.2%) patients. The involved sites of gastrointestinal tract were terminal ileum and ileocecal junction, colon, esophagus, duodenum and jejunum, stomach, and rectum, the proportion was 57.4% (27/47), 27.2% (13/47), 23.4% (11/47), 23.4% (11/47), 17.0% (8/47) and 8.5% (4/47), respectively. All 47 (100.0%) patients had oral ulcers. 62.1%(18/29) patients presented with multiple ulcers under endoscope. The shape of ulcer was round ulcer, irregular ulcer, and longitudinal ulcer, the proportion was 48.3% (14/29), 34.5% (10/29) and 17.2 (5/29), respectively. The incidence rate of genital ulcer of female patients with intestinal Beh?et′s disease was higher than that of male patients with intestinal Beh?et′s disease (85.7%, 18/21 vs. 30.8%, 8/26), and the difference was statistically significant ( χ2=14.189, P<0.01). There were no significant differences between the female group and the male group in the incidence rate of oral ulcer, abdominal pain, diarrhea, and positive rate of acupuncture test (100.0%, 21/21 vs. 100.0%, 26/26; 85.7%, 18/21 vs. 76.9%, 20/26; 42.9%, 9/21 vs. 50.0%, 13/26; 52.4%, 11/21 vs. 58.3%, 14/26, all P>0.05). Conclusions:The common clinical symptoms of intestinal Beh?et′s disease are oral ulcers, abdominal pain, diarrhea and genital ulcer. Female patients with intestinal Beh?et′s disease are more likely to develop genital ulcer than male patients with intestinal Beh?et′s disease. Multiple ulcers are more common under endoscopy, which are round ulcer, irregular ulcer and longitudinal ulcer. The most common sites are the terminal ileum and ileocecal junction, followed by colon, esophagus and other parts.

Objective:To investigate the value of minimal residual disease (MRD) in prediction of prognosis in acute lymphoblastic leukemia (ALL) patients with or above complete remission 2 (CR2) underwent.Methods:A retrospective analysis was performed on 201 ALL patients who received allogeneic stem cell transplantation (allo-SCT) and pretransplant disease status ≥CR2 in Peking University People′s Hospital from January 2009 to December 2018. MRD was measured by multi-parameter flow cytometry at 1 month before transplantation and 1 month, 2 months, 3 months, 4 months, 6 months, 9 months or 12 months after transplantation. To investigate the influence of dynamic changes of MRD before and after transplantation on prognosis.Results:201 ALL patients, including 126 males and 75 females, with a median age of 18 years. The 3-year cumulative incidence of relapse (CIR), non-relapse mortality (NRM), leukemia-free survival (LFS) and overall survival (OS) of all cases were 34%, 16%, 50%, and 56%, respectively. Positive pre-SCT MRD patients with higher 3-year CIR (47% vs 26%, P=0.003), lower 3-year LFS (40% vs 55%, P=0.047) and OS (42% vs 60%, P=0.065) than those with negative one. Subjects with positive post-MRD had higher 3-year CIR (73% vs 22%, P<0.001) and lower 3-year LFS (28% vs 56%, P=0.005) and OS (32% vs 60%, P=0.040) compared with those with negative one. Multivariate analysis showed that both pre-MRD and post-MRD were associated with higher CIR ( HR=1.823, P=0.018; HR=3.474, P<0.001), lower LFS ( HR=1.779, P=0.007; HR=2.185, P=0.001) and OS ( HR=1.609, P=0.034; HR=1.970, P=0.001). Negative pre-and post-SCT MRD group had lower 3-year CIR (17%, 42%, 82%; P<0.001) and higher 3-year LFS (61%, 44%, 18%; P<0.001) and OS (63%, 47%, 27%; P<0.001) compared with those unrisen post-SCT MRD group, and increased post-SCT MRD group. Multivariate analysis showed that pre-and post-SCT MRD dynamics were associated with CIR, LFS and OS ( P<0.01 for all) independently. The pre-and post-SCT MRD dynamics could better distinguish CIR (C=0.669) from that of pre-SCT MRD (C=0.587) and post-SCT MRD (C=0.629). Conclusion:Our data suggest that pre-SCT MRD, post-SCT MRD and the dynamic peri-SCT MRD could be used to predict transplant outcome of ALLpatients with or above CR2 who underwent allo-SCT.

Objective　To study the association between neutrophil to lymphocyte ratio (NLR) or platelet to lymphocyte ratio (PLR) in patients with vestibular neuritis (VN).Methods　A total of 137 patients who were finally diagnosed as VN were selected as the study group and 192 healthy volunteers without a history of dizziness or vertigo were selected as the control group in Hwa Mei Hospital and Ningbo Women and Children’s Hospital from January 2016 to December 2020.The general information,complete blood counts,NLR and PLR were obtained and analyzed.Results　There were no significant differences in the age distribution,sex ratio,body mass index,comorbidities,hemoglobin,lymphocyte and platelet values between the study group and control group.White blood cell and neutrophil count were significantly higher in the study group and control group (P<0.001).NLR and PLR were significantly higher in the study group as well (2.5 vs 1.9,Z=-5.74,P<0.001;124.2 vs 109.5,Z=-2.727,P=0.003).Conclusion　The elevations of NLR and PLR in patients with VN indicate that inflammation is involved in the pathogenesis of VN.