Background Salidroside (SAL) has a protective effect on multiple organ systems. Exposure to fine particulate matter (PM_2.5) in the atmosphere may lead to disruptions in gut microbiota and impact intestinal health. The regulatory effect of SAL on the gut microbiota of mice exposed to PM_2.5 requires further investigation. Objective To evaluate gut microbiota disruption in mice after being exposed to PM_2.5 and the potential effect of SAL. Methods Forty male C57BL/6 mice, aged 6 to 8 weeks, were randomly divided into four groups: a control group, an SAL group, a PM_2.5 group, and an SAL+PM_2.5 group, each containing 10 mice. In the SAL group and the SAL+PM_2.5 group, the mice were administered SAL (60 mg·kg⁻¹) by gavage, while in the control group and the PM_2.5 group, sterile saline (10 mL·kg⁻¹) was administered by gavage. In the PM_2.5 group and the SAL+PM_2.5 group, PM_2.5 suspension (8 mg·kg⁻¹) was intratracheally instilled, and in the control group and SAL group, sterile saline (1.5 mL·kg⁻¹) was intratracheally administered. Each experiment cycle spanned 2 d, with a total of 10 cycles conducted over 20 d. Histopathological changes in the ileum tissue of the mice were observed after HE staining. Colon contents were collected for gut microbiota sequencing and short-chain fatty acids (SCFAs) measurements. Results The PM_2.5 group showed infiltration of inflammatory cells in the ileum tissue, while the SAL+PM_2.5 group exhibited only a small amount of inflammatory cell infiltration. Compared to the control group, the PM_2.5 group showed decreased Shannon index (P<0.05) and increased Simpson index (P<0.05), indicating that the diversity of gut microbiota in this group was decreased; the SAL+PM_2.5 group showed increased Shannon index compared to the PM_2.5 group (P<0.05) and decreased Simpson index (P<0.05), indicating that the diversity of gut microbiota in mice intervened with SAL was increased. The principal coordinates analysis (PCoA) revealed a significant separation between the PM_2.5 group and the control group, while the separation trend was less evident among the control group, the SAL group, and the SAL+PM_2.5 group. The unweighted pair-group method with arithmetic means (UPGMA) clustering tree results showed that the control group and the SAL group clustered together first, followed by clustering with the SAL+PM_2.5 group, and finally, the three groups clustered with the PM_2.5 group. The PCoA and UPGMA clustering results indicated that the uniformity and similarity of the microbiota in the PM_2.5 group were significantly decreased. Compared to the control group, the PM_2.5 group showed decreased abundance of phylum Bacteroidetes and Candidatus_Saccharimonas (P<0.05) and increased abundance of phylum Proteobacteria, genus Escherichia, genus Bacteroides, genus Prevotella, genus Enterococcus, and genus Proteus (P<0.05). Compared to the PM_2.5 group, the SAL+PM_2.5 group showed decreased abundance of phylum Proteobacteria, phylum Actinobacteria, genus Prevotella, and genus Proteus (P<0.05), and increased abundance of Candidatus_Saccharimonas (P<0.05). The PM_2.5 group showed reduced levels of propionic acid, valeric acid, and hexanoic acid compared to the control group (P<0.05), while the SAL+PM_2.5 group showed increased levels of propionic acid, isobutyric acid, butyric acid, valeric acid, and hexanoic acid compared to the PM_2.5 group (P<0.05). Conclusion Exposure to PM_2.5 can cause pathological alterations, microbial dysbiosis, and disturbing production of SCFAs in intestinal tissue in mice. However, SAL can provide a certain degree of protective effect against these changes.

OBJECTIVE To design and synthesize novel α-naphthylthiol amino acid ester lysine specific demethylase 1(LSD1) inhibitors, evaluate their inhibitory activity with selectivity against LSD1, and explore their binding mechanism through molecular docking and dynamics simulation. METHODS Based on the binding mode of hit compound 3a with LSD1, the α- naphthyl mercapto amino acid ethyl ester small molecule compound were designed by fixing the planar hydrophobic naphthyl ring in the structure, while introducing hydrophilic amino fragment, and they were prepared through a multi-component one-pot cascade reaction. All the compounds were evaluated for their inhibitory activity against LSD1 at concentrations of 5.0 and 1.0 μmol·L–1 using the LSD1 screening platform of research group. The most potent compound was tested for its IC50 value and enzyme selectivity over MAO-A and MAO-B, and its binding mode was investigated through molecular docking and dynamics simulation. RESULTS A total of 13 compounds were obtained, all of which exhibited significant inhibitory effects on LSD1. Among them, nine compounds showed an inhibitory rate of over 50.0% against LSD1 at a concentration of 1.0 μmol·L–1, while compound 3l displaying the best activity with an IC50 value of 0.17 μmol·L–1, 174 times higher than the positive control. It also showed excellent selectivity towards MAO-A and MAO-B. Molecular docking and dynamics simulations indicated that compound 3l inhibited the activity of LSD1 through multiple interactions. CONCLUSION The structures of α-naphthylthiol amino acid ester can serve as lead compounds or active fragments, laying a solid foundation for the subsequent design of LSD1 inhibitors based on structure-oriented drug design.

Objective:To explore the effect of "Internet +" combined with multidisciplinary out of hospital management in hospital-home transitional period management of patients after lumbar internal fixation.Methods:From October 2021 to September 2022, convenience sampling was used to select 176 patients who underwent lumbar internal fixation at the Department of Orthopedics of the First Affiliated Hospital of Zhengzhou University. According to the admission time, patients enrolled from October 2021 to March 2022 were included in the control group, and patients enrolled from April to September 2022 were included in the observation group, with 88 cases in each group. The control group implemented routine out of hospital follow-up management, while the observation group implemented "Internet +" combined with multidisciplinary out of hospital management. After three months of intervention, the recovery of lumbar and back function [Oswestry Disability Index (ODI) and Macnab score], surgical efficacy (NaKa grading), nursing satisfaction, and readmission rate were compared between the two groups.Results:After three months, the ODI score of the observation group was lower than that of the control group, and the Macnab score was higher than that of the control group, the NaKa grading was better than that of the control group, with statistically significant differences ( P<0.05). In the observation group and control group, the total effective rate of surgery, nursing satisfaction, and readmission rate were 88.64% (78/88) vs. 67.05% (59/88), 94.32% (83/88) vs. 78.41% (69/88), 4.55% (4/88) vs. 17.05% (15/88), respectively. The total effective rate and nursing satisfaction of the observation group were higher than those of the control group, and the readmission rate was lower than that of the control group, with statistical differences ( P<0.05) . Conclusions:"Internet +" combined with multidisciplinary out of hospital management can effectively improve the recovery of lumbar function in hospital-home transitional period management of patients after lumbar internal fixation, enhance the surgical efficacy and nursing satisfaction, and reduce the readmission rate.

Objective To explore the current status of post-traumatic stress disorder(PTSD)symptoms among military officers at high altitude,determine the effects of childhood trauma experiences on the symptoms,and investigate the role of parent-child alienation in the process.Methods A cross-section study was conducted on 238 male military officers at high altitude subjected with cluster sampling.All of them were surveyed with childhood trauma question(CTQ),inventor of alienation toward parents(IAP),and Post-traumatic Stress Disorder Checklist(PCL-C)in October 2021.Then the mediating effect of parent-child alienation on childhood trauma and PTSD symptoms was investigated.Results ①The prevalence of PTSD-positive symptoms was 8.5％among the military officers at high altitude.②The prevalence of PTSD-positive symptoms was 15.6％for the military officers with childhood trauma,which was significantly higher than that of those without childhood trauma(5.1％,Chi-square=7.27,P＜0.01).③ PTSD symptoms,childhood trauma experiences and parent-child alienation were significantly positively correlated with each other(r=0.35～0.76,P＜0.01).④ Both childhood physical abuse(β=1.05,P＜0.001)and parent-child alienation(β=0.39,P＜0.01)could positively predict the severity of PTSD symptoms for them.⑤Parent-child alienation played a partial mediating role in the association between physical abuse and PTSD symptoms(β=1.16,95％CI:0.54～1.75).Conclusion Military officers at high altitude with childhood trauma have a higher prevalence of PTSD-positive symptoms and more severe symptoms.Childhood physical abuse can not only directly affect PTSD symptoms,but also indirectly affect its severity through parent-child alienation.

ObjectiveTo establish a quantitative analysis multi-components by single marker method （QAMS） for five main components （aucubin， geniposidic acid， chlorogenic acid， asperuloside and rutin） in Eucommiae Folium， to verify its feasibility and applicability in the determination of Eucommiae Folium， so as to provide a scientific basis for the development of quality standard of this herb. MethodHigh performance liquid chromatography was performed on a Welch Boltmatetm™ C₁₈ column （4.6 mm×100 mm， 2.7 μm） with methanol （A）-0.2% phosphoric acid aqueous solution （B） as the mobile phase for gradient elution （0-8 min， 3%A； 8-10 min， 3%-11%A； 10-26 min， 11%A； 26-27 min， 11%-25%A； 27-60 min， 25%-32%A）， the column temperature was set at 30 ℃， the flow rate was 0.6 mL·min^-1， the detection wavelengths were at 210 nm and 254 nm. Chlorogenic acid was used as an internal reference to establish the relative correction factors （f） between it and the other four components， and the contents of the five components in 14 batches of Eucommiae Folium were determined by QAMS and external standard method （ESM）， respectively. ResultThe f values of chlorogenic acid to aucubin， geniposidic acid， asperuloside and rutin were 3.13， 1.45， 2.64 and 0.56， respectively. Repeatability was good under different experimental conditions， relative standard deviation （RSD） was <5.0%. The contents of aucubin， geniposidic acid， chlorogenic acid， asperuloside and rutin in 14 batches of Eucommiae Folium were 1.340-28.975， 0.252-36.086， 10.016-27.443， 1.396-8.646， 0.533-1.766 mg·g^-1， respectively. There were no significant difference between content results of QAMS and that of ESM （RSD<5.0%）. ConclusionQAMS established with chlorogenic acid as the internal reference can be used to determine the contents of five components in Eucommiae Folium， and this method is simple and accurate. After comprehensive evaluation， the quality standard of Eucommiae Folium in subsequent editions of Chinese Pharmacopoeia is suggested that three main active components， chlorogenic acid， aucubin and geniposidic acid， are selected as quality markers， and their content limits are recommended not less than 1.5%， 1.0% and 1.0%， respectively. This quality standard draft can avoid the potential quality risk due to poor specificity and low content limit of the index component （chlorogenic acid） in the previous editions of Chinese Pharmacopoeia.

Objective:To screen and diagnose cervical lesions in middle-aged and elderly postmenopausal women and analyze the characteristics of cervical lesions in middle-aged and elderly women.Methods:A retrospective analysis was conducted on the screening data of 1 337 postmenopausal women aged between 50 and 86 years who visited the outpatient clinics of the gynecology department of Beijing Hospital between January, 2015 and December, 2019.Participants were divided into groups based on age, with 787 in the 50-59 years old group, 483 in the 60-69 years old group, 60 in the 70-79 years old group, and 7 in the 80-89 years old group.Exfoliated cervical cells were collected, and high-risk human papillomavirus(HPV)detection and liquid-based cervical cytology examination were performed to confirm the diagnosis based on the pathological results of cervical biopsy.Cervical lesions were analyzed.Results:53.0%(708)of the 1 337 enrolled patients made their hospital visits because of symptoms.There were 666 patients(49.8%)with cervical lesions, including 357 with low-grade squamous intraepithelial lesions(LSIL), 252 with high-grade squamous intraepithelial lesions(HSIL)and 57(4.3%)with cervical cancer.The 70-79 group showed the highest incidence of HSIL at 30.0%(18/60), while the 50~59 group had the highest incidence of LSIL at 30.6%(241/787), and there were significant differences in different types of cervical lesions between different age groups( χ2=28.919, P<0.01). Liquid-based cervical cytology examination revealed a positive rate of 51.6%(166/322)for LSIL, a positive rate of 70.8%(143/202)for HSIL, and a rate of 71.4%(25/35)for cervical cancer.There were significant differences in LSIL, HSIL and other above-mentioned positive rates of lesions( P<0.05). In the cervical malignancy group, cytological high-grade squamous epithelial lesions made up 51.4%(18/35). Intraepithelial lesions or cancerous lesions represented 29.2%(59/202)in the HSIL group.The rate of intraepithelial lesions or cancerous lesions in the LSIL group was 48.4%(156/322), with statistically significance in these differences( χ2=118.806, P<0.01). Chronic cervicitis was found in 52.9%(109)of 206 patients with atypical squamous cells and positive HPV, and in 76.2%(16)of 21 patients without HPV.HPV examination was completed in 1 301 patients, with 69.4%(903)having infections by one HPV strain and 30.6%(398)having infections by mixed HPV strains.Biopsy results showed that the rates of HPV infections in LSIL, HSIL and cancer patients were 84.6%(302/357), 95.9(185/193)and 100%(54/54), respectively, and the differences in these pathological results were statistically significant( P<0.01). HPV16 was the most common subtype in single HPV strain infections.The most common subtypes of HPV infections in cervical lesions with HSIL and above were HPV16 and HPV18.The agreement rate was 52.4%(187/357)for LSIL, 60.7%(153/252)for HSIL, and 64.9%(37/57)for cervical cancer between diagnoses based on cervical biopsy and those based on colposcopy.As the severity of lesions increased, the accuracy of colposcopy also increased.Differences between colposcopic diagnosis and pathological diagnosis on different types of cervical lesions were statistically significant( χ2=550.382, P<0.01).1 310 patients underwent endocervical curettage, identifying 120 cases of HSIL and 39 cases of cervical cancer, with a detection rate of 55.8%(159/285). Conclusions:The incidence of cervical cancer is high in elderly women.The incidences of high-grade lesions and cervical cancer in patients with atypical squamous cells plus HPV infections in the cervix are also high.Postmenopausal patients with cervical lesions are mainly infected by a single HPV subtype, with subtype 16 being the most common one.With increasing severity of lesions, the accuracy of colposcopy-based diagnosis increases and the rate of missed diagnosis decreases.Cervical curettage is an important means to reduce missed diagnosis with colposcopy.

Objective:To systematically review the profile of lymph node dissection (LND) for patients with intrahepatic cholangiocarcinoma (ICC) in China.Methods:Using the key words "intrahepatic cholangiocarcinoma" "intrahepatic cholangiocellular carcinoma" "lymph node dissection" "lymphadenec-tomy" "lymph node metastasis", the databases including China Zhiwang, Wanfang, Weipu, Sinomed, PubMed, Embase, Web of Science, Scopus, Cochrane Library were systematically searched. Cohort studies or randomized controlled clinical trials with intraoperative LND documentation and with analysis on the clinicopathologic characteristics or prognostic influences on patients with ICC were included into this meta-analysis from the date of database creation to April 20, 2022. The risk of bias in non-randomized controlled trials was evaluated using the Newcastle-Ottawa scale. A meta-analysis of preoperative imaging lymph node enlargement rates, LND rates, and pathological lymph node metastasis rates were performed using R software.Results:Thirty-three relevant studies that met the systematic evaluation criteria were included, all of which were retrospective cohort studies. All these publications were of medium to high quality. Patients’ enrollment ranged from 1993 to 2020. Patients were enrolled from 20 provinces/autonomous regions/municipalities with a total of 39 medical centers and 4 278 patients. The meta-analysis indicated that the LND rate, preoperative imaging lymph node enlargement rate, pathological lymph node metastasis rate were 47.8%(95% CI: 41.3%-54.3%), 18.5%(95% CI: 7.5%-29.6%) and 51.2%(95% CI: 43.8%-58.6%), respectively. Subgroup analysis showed the LND rate was 36.0%(95% CI: 27.0%-45.0%) in studies with a median year of enrollment before 2010, 48.3% (95% CI: 38.1%-58.6%) in studies from 2010 to 2017, and 53.3%(95% CI: 43.3%-63.2%) in studies after 2017. The LND rates were statistically different in the studies in the different periods of patient enrollment ( P=0.032). Conclusion:The meta-analysis indicated that the overall LND rate for ICC in China was not high but showed an increasing tendency.

Chimeric antigen receptor T cell (CAR-T) is a kind of adoptive cell immunotherapy, in which T cells are genetically modified to exert targeted killing effect on tumors. CAR-T cell therapy has shown remarkable antitumor efficacy for the treatment of tumors, especially for hematological malignancies, but is less effective in solid tumors. Single-target CAR-T is prone to off-target effect during application, and there is a risk of relapse or more refractory treatment. The development of double-target or multi-target CAR-T is expected to extend the antigen coverage of target cells, effectively avoids antigen escape and prevents tumor recurrence, and prolongs the survival time of patients. This article reviews the advances of multi-target chimeric antigen receptor T cell, and discusses the prospect of its development.

Objective:To develop an air particulate protective mask filter test device that can simulate the dynamics process of human breathing.Methods:The new device used two air pumps working alternately to simulate the dynamics process of human breathing. On March 4th to 17th, 2017, the new device and the traditional one-way airflow mask filtration test device were used to measure the internal and external particle levels of 39 masks of 13 models of 6 brands, and then the filtration efficiency of the mask was calculated and the test results were compared.Results:For the mask without breathing valve, there was no statistically significant difference between the filter efficiency test results of the new device and the traditional unidirectional airflow filter performance test device ( P>0.05) . For masks with breathing valves, the new device detected that three of them had lower filtration efficiency (99.50% vs 98.63%, P<0.01) . After sealing the mask breathing valve with glue, the filtering efficiency of the mask with a breathing valve detected by the new device significantly improved (98.63% vs 99.50%, P<0.01) . Conclusion:This new device can simulate the dynamic process of human exhalation and inhalation, and measure the filtration efficiency of the mask. For masks with breathing valves, the new device makes it easier to detect the decrease in the filtering efficiency of the mask caused by the breathing valve.

Objective: To determine the effect of gut microbiota on a rat model of post-traumatic stress disorder(PTSD)and explore the correlation of gut microbiota with behavior and neurotransmitters.Methods: We established a single prolonged stress(SPS)model to examine the pathogenesis of PTSD on rat behavior,gut microbiota,and neurotransmitter levels.Rats were separated into control and model groups,and neurotransmitter levels were measured using enzyme linked immunosorbent assay.Then,16 S rRNA sequencing was used to compare the gut microbiota between the control and model groups.Results: Compared with those in the control group,freezing time significantly increased,while number of standing upright,crossing frequency,time spent in the central arena,and total distance traveled were significantly reduced in the model group after exposure to SPS(all P<.05).Meanwhile,serotonin,or 5-hydroxytryptamine,levels in the brain in the model group were significantly lower than those the control group(P=.0332).In addition,changes were observed in the gut microbiota diversity and relative abundances of bacterial phyla,orders,families,and genera in the model group.Especially,changes in Firmicutes,Bacteroidetes,Cyanobacteria,and Proteobacteria levels were most pronounced after SPS exposure.Correlation analysis showed that the strongest positive correlation was found between Bac-teroidaceae and 5-HT(P =.0009).Moreover,RF32 abundance was the most negatively related to 5-HT(P=.0009),crossing frequency(P=.0007),and total distance(P=.0003).Conclusion: Our results suggest that SPS model rats showed differences in behavior,neurotransmitter levels,and gut microbiota with control rats.Moreover,Firmicutes,Bacteroidetes,Cyanobacteria,and Proteobacteria were most relevant to the exhibited fear-like and anxiety-like behaviors and significant serotonin content reduction in SPS model rats.