Background Atmospheric fine particulate matter (PM_2.5) can disrupt the metabolic homeostasis of the liver and accelerate the progression of liver diseases, but there are few studies on the effects of sub-chronic PM_2.5 exposure on the liver metabolome. Objectives To investigate the effects of sub-chronic exposure to concentrated PM_2.5 on hepatic metabolomics in mice by liquid chromatography-mass spectrometry (LC-MS), and to identify potentially affected metabolites and metabolic pathways. Methods Twelve male C57BL/6J (6 weeks old) mice were randomly divided into two groups: a concentrated PM_2.5 exposure group and a clean air exposure group. The mice were exposed to concentrated PM_2.5 using the "Shanghai Meteorological and Environmental Animal Exposure System" at Fudan University. The exposure duration was 8 h per day, 6 d per week, for a total of 8 weeks. The mice's liver tissues were collected 24 h after the completion of exposure. LC-MS was performed to assess changes in the hepatic metabolome. Orthogonal partial least squares discriminant analysis and t-test were employed to identify differentially regulated metabolites between the two groups under the conditions of variable important in projection (VIP)≥1.0 and P<0.05. Metabolic pathway enrichment analysis was performed using MetaboAnalyst 5.0 software and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Results A total of 297 differentially regulated metabolites were identified between the concentrated PM_2.5 exposure group and the clean air group. Among these metabolites, 142 were upregulated and 155 were downregulated. A total of 38 metabolic pathways were altered, with 7 pathways showing significant perturbation (P<0.05). These pathways involved amino acid metabolism, glucose metabolism, nucleotide metabolism, as well as cofactor and vitamin metabolism. The 7 significant metabolic pathways were pantothenic acid and coenzyme A biosynthesis; purine metabolism; amino sugar and nucleotide sugar metabolism; arginine biosynthesis; alanine, aspartate and glutamate metabolism; aminoacyl-tRNA biosynthesis; and fructose and mannose metabolism. Conclusion The results from metabolomics analysis suggest that sub-chronic exposure to PM_2.5 may disrupt hepatic energy metabolism and induce oxidative stress damage. Aspartic acid, succinic acid, ornithine, fumaric acid, as well as purine and xanthine derivatives, were identified as potential early biomarkers of hepatic response to sub-chronic PM_2.5 exposure.

ObjectiveBased on the network pharmacology system and quantitative spectroscopy of traditional Chinese medicine（TCM） compounds， a topological network analysis method with equilibrium constant as the core was established to further explore the interaction between allergenic components and their network targets in Shuanghuanglian injection（SHLI）， in order to provide new ideas and experimental basis for identifying and screening potential allergens of SHLI. MethodAfter one week of adaptive feeding， 72 SPF-grade SD male rats were randomly divided into blank group， SHLI standard group， Lonicerae Japonicae Flos（LJF） group， Scutellariae Radix（SR） group， Forsythiae Fructus（FF） group， and 7 groups of SHLI matching groups（groups 1-7）， with 6 rats in each group. Rats in each group were administered the drug intravenously and blood samples were taken after steady state， high performance liquid chromatography（HPLC） characterization profiles of the testing drugs and plasma components in each group were established， and the peak area changes of the drugs and plasma components in each group were calculated after the component groups were classified. Enzyme-linked immunosorbent assay（ELISA） was used to determine the changes of immunoglobulin E（IgE）， histamine（HIS）， tryptase（TPS）， total complement（CH50） and terminal complement complex（C5b-9） in animal blood samples. MATLAB R2020b v9.9.0 software was used to calculate the network balance constants of the component groups with the targets， and the eigenvalues of the matrices composed of network equilibrium constants were calculated and ranked according to their values. ResultELISA results showed that， compared with the blank group， groups 1-3 could significantly increase the IgE level， groups 1-2， groups 4-6 and SHLI standard group could significantly increase the HIS level， group 4 could significantly increase the CH50 level， groups 1， 3-4， LJF group and FF group could significantly increase the TPS level， SR group could significantly increase the C5b-9 level， and the differences were all statistically significant（P<0.05）. According to the retention time of chromatographic peaks， it was classified into 6 component groups from C1 to C6 by HPLC. The order of the network balance constants of each component group was C6>C4>C1>C5>C3>C2， indicating that C6 had the greatest effect on the allergic reaction， and was most likely to be the allergen. The sequence of eigenvalues was C2>C5b-9>C3>C1>CH50>C6>C5>IgE>TPS>C4>HIS， indicating that component group C2 had the greatest contribution to the whole network. ConclusionBased on the correlation analysis of SHLI component group and allergy-like target network， this study clarified that component group C6 may be a potential allergen in SHLI， and the component group C2 may be a key node in the mechanism of drug action， which can provide new strategies and methods for the screening of allergens in TCM injections.

Objective:To observe the anti-inflammatory and glycometabolic effects of glutathione(GSH)on macrophages in collagen induced arthritis(CIA)mice.Methods:①CIA model establishment and groups:A total of 14 female DBA/1J mice were ran-domly divided into:CIA+PBS group and CIA+GSH group.The mice were sacrificed on the 50th day,collecting serum and isolating bone marrow derived macrophages(BMDM),which were marked as BMDM1.②Trained immunity model establishment and groups:BMDM were isolated from normal DBA/1J mice,and were pretreated with histone H3K27 demethylases inhibitor(GSKJ1)or PBS for 2 h.Then,serum from CIA model mice in vivo was incubated for 24 h,and the samples were grouped as follows:(CIA+GSH)+PBS group,(CIA+GSH)+GSKJ1 group,(CIA+PBS)+PBS group,(CIA+PBS)+GSKJ1 group.Lipopolysaccharide(LPS)was adopted to stimulated cells on the 6th day,which were marked as BMDM2.③RNA sequencing was used to detect differentially expressed genes(DEGs)and their function in BMDM1 and BMDM2.q-PCR was adopted to estimate the mRNA levels of PFK and Idh3g.The culture supernatants were used to measure the protein levels of TNF-α and IL-6 by ELISA.Results:①Compared with CIA+PBS group,the mice in CIA+GSH group showed lighter of joint swelling(P<0.05),less arthritis index(P<0.05),HE staining suggested less inflam-matory cell infiltration,Safranin O-fast green staining showed more chondrocytes,TRAP staining indicated reduced osteoclasts.②In BMDM1,GO analysis showed that DEGs were mainly involved in glutathione derivative metabolic process,IL-6 production,inflammatory response,innate immune response,regulation of primary metabolic process and glycolipid binding,compared with CIA+GSH and CIA+PBS group.In CIA+GSH group,the mRNA level of PFK was significantly decreased(P<0.05),while Idh3g was also significantly up-regulated(P<0.05),and the expression of TNF-α,IL-6 were both reduced(P<0.05)compared with CIA+PBS group.③In BMDM2,GO analysis showed that DEGs were also involved in inflammatory response,activation of innate immune response,regulation of tumor necrosis factor production,positive regulation of IL-6 production,regulation of glycolytic process and 1,3-β-D-glucan binding between CIA+GSH and CIA+PBS group.Furthermore,in(CIA+GSH)+PBS group,PFK was decreased(P<0.05),Idh3g was up-regulated(P<0.05),and IL-6 was also significantly down-regulated(P<0.05)compared with(CIA+PBS)+PBS group.However,there was no significant difference in the expression of Idh3g and PFK,moreover,TNF-α and IL-6 were significantly up-regulated compared with(CIA+GSH)+GSKJ1 group and(CIA+GSH)+PBS group.Conclusion:GSH can regulate glycometabolism and inflammatory response of macrophages via demethylation of histone H3K27,and it can also alleviate CIA in mice.

Objective To analyze and summarize the clinical presentation of spontaneous and secondary intracranial hypotension syndrome(IHS).Methods Patients diagnosed with spontaneous or secondary IHS from September 2022 to May 2023 were retrospectively analyzed.The clinical data,imaging features,treatment methods and prognosis were collected.The correlation between intracranial pressure values and clinical characteristics of the patients was statistically analyzed.Results A total of 30 patients were enrolled,and the proportion of spontaneous and secondary IHS was 63%(19 cases)and 37%(11 cases),respectively.In terms of clinical features,orthostatic headache was the most common type(29 cases,96.7%)and most commonly involved occipital region(12 cases,40.0%),followed by frontoparietal region(9 cases,30.0%).Among the brain imaging features,dural enhancement was the most common(17 cases,56.7%).According to CT angiography of spinal cord findings,cerebrospinal fluid leakage is one of the most common location of cervical spine segments(10 cases),and on the thoracic segments(9 cases),followed by the thoracic segments(4 cases)and lumbar segments(4 cases).After conservative treatment and surgical treatment,the total effective rate was 90%.Conclusion Orthostatic headache and cranial MRI"dural enhancement"have strong indication on the definitive diagnosis of IHS.CT myelography is helpful to precisely localize the site of cerebrospinal fluid leakage.Targeted epidural blood patch therapy is an effective method to cure IHS when conservative treatment is ineffective.

Objective:To explore the clinical and genetic characteristics of patients with Ehlers-Danlos syndrome (EDS) and gastrointestinal involvement.Methods:We retrospectively collected the clinical data of patients with EDS and gastrointestinal involvement from the electronic medical records at Peking Union Medical College Hospital (PUMCH) from January 2003 to September 2023. Additionally, we conducted a systematic review by searching cases with EDS and gastrointestinal involvement in PubMed, Embase, Web of Science, and the Cochrane Library databases from January 2000 to September 2023.Results:Ninety-four patients with EDS and gastrointestinal involvement were retrieved, including five patients from PUMCH and 89 patients from 80 published articles. The average age of patients was (29±14) years. The most common manifestation of gastrointestinal involvement was gastrointestinal perforation ( n=46, 48.9%), followed by functional gastrointestinal symptoms ( n=33, 35.1%), and digestive arterial disorders ( n=10, 10.6%). The most common clinical subtype was vascular-EDS (vEDS) ( n=50, 53.2%) followed by hypermobile-EDS (hEDS) ( n=20, 21.3%). The most frequent genetic mutation occurred in the COL3A1 gene ( n=30, 31.9%). Among patients with vEDS, gastrointestinal manifestations included gastrointestinal perforation ( n=33, 66.0%), arterial lesions ( n=9, 18.0%), and functional gastrointestinal symptoms ( n=7, 14.0%). Among patients with hEDS, gastrointestinal manifestations included functional gastrointestinal symptoms ( n=18, 90.0%), visceral prolapse ( n=3, 15.0%) and intestinal volvulus ( n=1, 5.0%). Conclusions:The most common subtypes of gastrointestinal involvement in EDS were vEDS and hEDS. Patients with hEDS mainly presented with functional gastrointestinal symptoms, whereas those with vEDS primarily showed gastrointestinal perforation and digestive arterial disorders.

Objective:To analyze the rule of acupoint selection for acupuncture in relieving postoperative pain based on data mining technology.Methods:Articles about acupuncture for postoperative pain were retrieved from CNKI, SinoMed, VIP, Wanfang, PubMed, Embase and Web of Science databases from establishment to June 6, 2022. Excel 2019 and SPSS Modeler 18.0 software were used to establish acupoints database and conduct the data analysis.Results:Totally 308 articles were obtained, involving 317 acupuncture prescriptions and 173 acupoints. Acupoints of bladder meridian, stomach meridian, large intestine meridian and spleen meridian were used frequently. Zusanli (ST 36), Hegu (LI 4) and Neiguan (PC 6) were high-frequency acupoints with a frequency of ≥50 times. Five-shu acupoint was often selected in specific acupoints. The common sites for acupuncture to relieve postoperative pain were abdomen, perianal, lumbar back and knee. Zusanli (ST 36), Neiguan (PC 6) and other acupoints were commonly used for abdominal postoperative pain, and the most commonly used combination was "Zusanli (ST 36)-Neiguan (PC 6)"; Chengshan (BL 57), Changqiang (GV 1) and other acupoints were often used for perianal postoperative pain, and "Chengshan (BL 57)-Changqiang (GV 1)" was highly correlated combination; Shenshu (BL 23) and Huantiao (GB 30) were commonly used for postoperative pain in the lumbar and back region, and acupoints with high correlation were "Ashi acupoint-Huantiao (GB 30)" and "Shenshu (BL 23)-Huantiao (GB 30)"; Xuehai (SP10) and Liangqiu (ST 34) were commonly used for postoperative pain of knee, and their compatibility had a high correlation.Conclusion:Acupuncture therapy for relieving postoperative pain often selects Yang meridians acupoints, and follows the principle of distal-proximal points combination and acupoint selection along meridians, and pays attention to the use of specific acupoints.

Objective:To construct the evaluation index system of "early clinical contact" education of undergraduate medical students, and to provide guidance for the evaluation of "early clinical contact" education in medical teaching.Methods:The evaluation index system of "early clinical contact" education of undergraduate medical students was constructed by literature research, Delphi expert consultation and analytic hierarchy process, and the weight of each index was determined. Excel 2010 and SPSS 25.0 were used to make data entry and statistical analysis.Results:The enthusiasm of experts in the two rounds of expert consultation were 100.00%(26/26) and 96.15%(25/26) respectively, the expert authority coefficients were 0.900 and 0.920, and the coordination coefficients were 0.255 and 0.175 respectively ( P < 0.05). The evaluation index system included 4 first-class indexes, 12 second-class indexes and 47 third-class indexes. Conclusion:The index system has high scientificity and reliability. After further verification, it can be used as an evaluation tool for the teaching quality of "early clinical contact" education of undergraduate medical students.

OBJECTIVE: To assess the effect of tumor cell lysate (TCL) with low high-mobility group B1 (HMGB1) content for enhancing immune responses of dendritic cells (DCs) against lung cancer. METHODS: TCLs with low HMGB1 content (LH-TCL) and normal HMGB1 content (NH-TCL) were prepared using Lewis lung cancer (LLC) cells in which HMGB1 was inhibited with 30 nmol/L glycyrrhizic acid (GA) and using LLC cells without GA treatment, respectively. Cultured mouse DCs were exposed to different doses of NH-TCL and LH-TCL, using PBS as the control. Flow cytometry was used to detect the expressions of CD11b, CD11c and CD86 and apoptosis of the stimulated DCs, and IL-12 levels in the cell cultures were detected by ELISA. Mouse spleen cells were co-cultured with the stimulated DCs, and the activation of the spleen cells was assessed by detecting CD69 expression using flow cytometry; TNF-β production in the spleen cells was detected with ELISA. The spleen cells were then co-cultured with LLC cells at the effector: target ratios of 5:1, 10:1 and 20:1 to observe the tumor cell killing. In the animal experiment, C57/BL6 mouse models bearing subcutaneous LLC xenograft received multiple injections with the stimulated DCs, and the tumor growth was observed. RESULTS: The content of HMGB1 in the TCL prepared using GA-treated LLC cells was significantly reduced (P < 0.01). Compared with NH-TCL, LH-TCL showed a stronger ability to reduce apoptosis (P < 0.001) and promote activation and IL- 12 production in the DCs. Compared with those with NH-TCL stimulation, the DCs stimulated with LH-TCL more effectively induced activation of splenic lymphocytes and enhanced their anti-tumor immunity (P < 0.05). In the cell co-cultures, the spleen lymphocytes activated by LH-TCL-stimulated DCs showed significantly enhanced LLC cell killing activity (P < 0.01). In the tumor-bearing mice, injections of LH-TCL-stimulated DCs effectively activated host anti-tumor immunity and inhibited the growth of the tumor xenografts (P < 0.05). CONCLUSION Stimulation of the DCs with LH-TCL enhances the anti-tumor immune activity of the DCs and improve the efficacy of DCbased immunotherapy for LLC in mice.
Animals ; Humans ; Mice ; Apoptosis ; Dendritic Cells/immunology* ; Glycyrrhizic Acid/pharmacology* ; HMGB1 Protein ; Lung Neoplasms/immunology*

OBJECTIVE To excavate and evaluate β-blockers associated with acute renal failure（ARF）signal. METHODS Using the report odds ratio （ROR）method and Bayesian confidence interval progressive neural network （BCPNN）method，signal detection and analysis were performed for 4 kinds of β-blockers（metoprolol，bisoprolol，atenolol，nebivolol）associated with ARF Δ 基金项目：重庆市临床药学重点专科建设项目 （No.渝卫办发 in FDA adverse event reporting system （FAERS）from the two 〔2020〕68号）；重庆医科大学未来医学青年创新团队发展支持计划项 dimensions of Standard International Dictionary of Medical 目（No.W0081） Terms （MedDRA） analysis query （SMQ） term set and ＊药师，硕士研究生。研究方向：药物警戒。电话：023-68485161。 preferred term （PT） level terms. When the two methods E-mail：2020121624@stu.cqmu.edu.cn detected positive signals at the same time ，it indicated that # 通信作者：主任药师，硕士生导师。研究方向：临床药学、药物警 suspicious signals were detected. RESULTS Totally 14 328 戒。电话：023-63625666。E-mail：jiayuntaomail@hospital.cqmu.edu.cn ARF reports of 4 kinds of β-blockers were retrieved within the ·1380· China Pharmacy 2022Vol. 33 No. 11 中国药房 2022年第33卷第11期 narrow sense of “acute renal failure ”in SMQ term set ，of which men （6 964）were more than women （6 206）. The age of patients was mainly concentrated in the middle-aged and elderly （≥45 years old ），and serious adverse events accounted for 77.23％. The results of signal retrieval based on SMQ term set showed that ROR values and 95％ confidence intervals of metoprolol ，bisoprolol， atenolol and nebivolol detected by ROR method were 2.58（2.51，2.65），5.30（5.14，5.47），2.80（2.69，2.91）and 3.28（3.04， 3.53）respectively. The signal components （IC）detected by BCPNN method and the lower limit of IC were 1.29（1.25），2.26 （2.22），1.42（1.36）and 1.64（1.53）respectively，suggesting suspicious signals were detected in these four kinds of β-blockers associated ARF. The results of signal detection based on PT level terms showed that 37 positive signals were detected by ROR method，38 positive signals were detected by BCPNN method ，and 36 suspicious signals were detected by the two methods at the same time. For each drug ，12 suspicious signals of metoprolol were detected at the same time ，9 suspicious signals of bisoprolol and atenolol were detected at the same time ，and 6 suspicious signals of nebivolol were detected at the same time ；the number and type of signals were different among the 4 kinds of drug. CONCLUSIONS Four kinds of β-blockers may cause ARF. Compared with metoprolol and atenolol ，bisoprolol and nebivolol have strong statistical correlation with ARF ，suggesting that medical personnel should pay attention to the possible renal related adverse reactions of these drugs in the process of clinical use.

Objective:To explore the clinical and chest CT features of anti-interferon(IFN)-γ autoantibodies-positive talaromycosis marneffei (TSM) infection in human immune deficiency virus (HIV)-negative patients.Methods:Clinical data and chest CT findings including pulmonary manifestations, bronchial changes, pleural changes, and extrapulmonary manifestations in 54 HIV-negative patients with Talaromyces marneffei (TM) infection and positive anti-interferon-γ(IFN-γ) autoantibody in the First Affiliated Hospital of Guangxi Medical University from December 2012 to September 2019 were retrospectively analyzed. CT score was rated for the degree of lung involvement, and the difference of involvement at different regions of the lung were compared. Results:Of 54 patients, 46 cases had fever, 43 cases had cough and expectoration, 28 cases had cutaneous or subcutaneous lesion, and 19 cases had arthritis or arthralgia. Laboratory tests showed that the value of CD4/CD8 decreased in 29 cases and platelet count increased in 32 cases. Only one of 54 patients had no abnormal findings on chest CT. In the remaining patients, chest CT manifestations were diverse, mainly presenting as fibrous cord-like lesions (87.0%, 47/54), lymph node enlargement (75.9%, 41/54), sporadic nodules (74.1%, 40/54), patchy consolidation (72.2%, 39/54), pleural effusion (59.2%, 32/54), and consolidation lesions associated with air bronchogram (63.0%, 34/54). Most of the lesions showed bilateral distribution (77.8%, 46/54), and involved both peripheral and central regions in 38 cases (70.4%, 38/54). CT score showed that there was no significant difference in the degree of involvement at different regions of the lung.Conclusions:The clinical and imaging manifestations of anti-IFN-γ antibody-positive patients with TM infection are characteristic. Most TSM patients with positive anti-IFN-γ antibody have fever, cough and expectoration. The main features of chest CT are cord focus, nodules, consolidation and pleural effusion. Lymph node enlargement often coexists with the above signs, and most of the lesions are distributed bilaterally.