To develop the Pharmacovigilance Guidelines for Clinical Application of Chinese Patent Medicines for Mucosal Administration in response to common problems， including insufficient safety information in package inserts， amplified medication risks in special populations， and non-standard clinical practices， thus establishing a risk management system tailored to the characteristics of Chinese patent medicines for mucosal administration. An approach combining qualitative and quantitative methods was adopted. In accordance with the Drug Administration Law of the People's Republic of China （2019 revision） and the GB/T 1.1—2020 standard， a systematic search was performed in the Chinese Pharmacopoeia （2020 edition）， the Catalog of Medicines Covered by Medical Insurance （2022 edition）， Chinese databases ［China Network of Knowledge Infrastructure （CNKI）， Wanfang Data （Wanfang）， and VIP journal resource integration service platform （VIP）］， and international databases （Cochrane Library， PubMed， and EMbase）. Guideline outlines were developed through questionnaire surveys， expert interviews， and the nominal group technique. The content of each item was formulated with full consideration of traditional Chinese medicine （TCM） incompatibility， as well as the conceptual connotations and extensions of pharmacovigilance. The results included 54 Chinese patent medicines for mucosal administration from the Chinese Pharmacopoeia （2020 edition） and 58 from the Catalog of Medicines Covered by Medical Insurance （2022 edition）. Safety-related items in the corresponding package inserts were collected， and 27 relevant publications were retrieved. Thirty experts from 24 institutions were mobilized for the drafting， and opinions from 61 external experts were solicited. A pharmacovigilance framework was established， covering the full chain of "monitoring， identification， assessment， and control". Based on seven anatomical sites， including nasal， ocular， and oral mucosa， a stratified monitoring system was constructed. The guideline proposed key recommendations on improving package insert sections such as "Adverse Reactions"， "Contraindications"， and "Precautions"， clinical procedure standardization in healthcare institutions， risk control， and dynamic pharmacovigilance. The Guideline provides evidence-based support tailored to the risk profile of Chinese patent medicines for mucosal administration， filling the current gap in international pharmacovigilance standards in this field， while offering technical support for safety management across the full life cycle of medicines for mucosal administration.

To develop the Pharmacovigilance Guidelines for Clinical Application of Chinese Patent Medicines for Mucosal Administration in response to common problems， including insufficient safety information in package inserts， amplified medication risks in special populations， and non-standard clinical practices， thus establishing a risk management system tailored to the characteristics of Chinese patent medicines for mucosal administration. An approach combining qualitative and quantitative methods was adopted. In accordance with the Drug Administration Law of the People's Republic of China （2019 revision） and the GB/T 1.1—2020 standard， a systematic search was performed in the Chinese Pharmacopoeia （2020 edition）， the Catalog of Medicines Covered by Medical Insurance （2022 edition）， Chinese databases ［China Network of Knowledge Infrastructure （CNKI）， Wanfang Data （Wanfang）， and VIP journal resource integration service platform （VIP）］， and international databases （Cochrane Library， PubMed， and EMbase）. Guideline outlines were developed through questionnaire surveys， expert interviews， and the nominal group technique. The content of each item was formulated with full consideration of traditional Chinese medicine （TCM） incompatibility， as well as the conceptual connotations and extensions of pharmacovigilance. The results included 54 Chinese patent medicines for mucosal administration from the Chinese Pharmacopoeia （2020 edition） and 58 from the Catalog of Medicines Covered by Medical Insurance （2022 edition）. Safety-related items in the corresponding package inserts were collected， and 27 relevant publications were retrieved. Thirty experts from 24 institutions were mobilized for the drafting， and opinions from 61 external experts were solicited. A pharmacovigilance framework was established， covering the full chain of "monitoring， identification， assessment， and control". Based on seven anatomical sites， including nasal， ocular， and oral mucosa， a stratified monitoring system was constructed. The guideline proposed key recommendations on improving package insert sections such as "Adverse Reactions"， "Contraindications"， and "Precautions"， clinical procedure standardization in healthcare institutions， risk control， and dynamic pharmacovigilance. The Guideline provides evidence-based support tailored to the risk profile of Chinese patent medicines for mucosal administration， filling the current gap in international pharmacovigilance standards in this field， while offering technical support for safety management across the full life cycle of medicines for mucosal administration.

Objective:To analyze the results of lymphocyte subsets and 12 plasma cytokines in patients with tuberculosis by flow cytometry and to evaluate their diagnostic efficacy in these patients.Methods:This is a retrospective case-control study. A total of 128 patients with evidence of tuberculosis disease or clinically confirmed tuberculosis who were admitted to the 8th Medical Center of PLA General Hospital from January 2022 to December 2023 were included. According to the location of mycobacterium tuberculosis infection, the patients were divided into the pulmonary tuberculosis group (83 cases) and the extrapulmonary tuberculosis group (45 cases), and 100 healthy age-and sex matched people who underwent health check up during the study period were selected as the control group. Flow cytometry was used to detect peripheral blood lymphocyte subsets and 12 plasma cytokines [including 10 pro-inflammatory factors: interleukin (IL)-5, interferon (IFN)-α, IL-2, IL-6, IL-1β, IFN-γ, IL-8, IL-17, IL-12P70, Tumor necrosis factor (TNF)-α, and two anti-inflammatory factors: IL-4, IL-10] in participants of all groups. Spearman correlation method was used to analyze the correlation between lymphocyte subsets and cytokines, binary Logistic regression was used to screen the TB related factors, and receiver operating curve (ROC) was used to evaluate the diagnostic efficacy of TB related factors.Results:Compared with the control group, the absolute number of CD3 +T lymphocytes, CD3 +CD8 +T lymphocytes, CD3 +CD4 +T lymphocytes, NK cells and B cells were lower in pulmonary tuberculosis group and extrapulmonary tuberculosis group (all P<0.05). Except for IL-1β, the levels of other 11 cytokines are all significantly higher in the pulmonary tuberculosis group (all P<0.01), and the levels of IL-6, IFN-γ, IL-17, TNF-α, IL-4 and IL-10 were significantly higher in extrapulmonary tuberculosis group (all P<0.05). Compared with extrapulmonary tuberculosis group, the level of IL-8 was higher in pulmonary tuberculosis group ( P=0.026). Spearman correlation analysis showed that IL-6, IFN-γ and IL-8 were negatively correlated with the absolute numbers of CD3 +T lymphocytes, CD3 +CD8 +T lymphocytes, CD3 +CD4 +T lymphocytes, NK cells and B cells (IL-6: R2=-0.30, -0.28, -0.32, -0.26, -0.28; IFN-γ: R2=-0.36, -0.31, -0.37, -0.25, -0.36; IL-8: R2=-0.14, -0.13, -0.16, -0.14, -0.22; all P<0.05), IL-10 was negatively correlated with the absolute number of CD3 +CD4 +T lymphocytes, NK cells and B cells ( R 2=-0.14, -0.19, -0.21, all P<0.05); Binary Logistic regression analysis showed that IL-6, IFN-γ, IL-8 and IL-10 were the related factors of tuberculosis ( OR=1.809, 1.136, 0.910, 2.218, all P<0.05), ROC curve analysis showed that the AUC of IL-6, IFN-γ, IL-8 and IL-10 in the joint diagnosis of tuberculosis was 0.845, the sensitivity was 0.766, and the specificity was 0.820. Conclusion:The lower absolute number of lymphocyte subsets and cytokine levels in patients with pulmonary tuberculosis and extrapulmonary tuberculosis indicate that their immune function is in a low state, and the higher levels of pro-inflammatory factors (IL-6, IFN-γ, IL-8) and anti-inflammatory factor (IL-10) indicates the higher inflammatory status, and evaluation of these 4 cytokines has satisfactory diagnostic efficacy for tuberculosis.

This study reported a 50-year-old female patient who was diagnosed with anti-IgLON family member 5 (anti-IgLON5) antibody-related encephalopathy, presented with cognitive and sleep disorders, autonomic dysfunction and seizures, positive serum IgLON5 antibody but negative cerebrospinal fluid IgLON5 antibody, negative human leukocyte antigen (HLA) by genetic testing, and was diagnosed as anti-IgLON5 antibody-related encephalopathy. After hospital admission, the patient was given intravenous methylprednisolone combined with immunoglobulin immunotherapy, donepezil for improvement of cognition, sodium valproate and oxcarbazepine for prevention and treatment of epileptic seizures, and finally her symptoms improved significantly.

Humans ; Stomach Neoplasms/pathology* ; Neoadjuvant Therapy ; Chemotherapy, Adjuvant ; Gastrectomy ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Neoplasm Staging

Metabolic reprogramming, a newly recognized trait of tumor biology, is an intensively studied prospect for oncology medicines. For numerous tumors and cancer cell subpopulations, oxidative phosphorylation (OXPHOS) is essential for their biosynthetic and bioenergetic functions. Cancer cells with mutations in isocitrate dehydrogenase 1 (IDH1) exhibit differentiation arrest, epigenetic and transcriptional reprogramming, and sensitivity to mitochondrial OXPHOS inhibitors. In this study, we report that berberine, which is widely used in China to treat intestinal infections, acted solely at the mitochondrial electron transport chain (ETC) complex I, and that its association with IDH1 mutant inhibitor (IDH1^mi) AG-120 decreased mitochondrial activity and enhanced antileukemic effect in vitro andin vivo. Our study gives a scientific rationale for the therapy of IDH1 mutant acute myeloid leukemia (AML) patients using combinatory mitochondrial targeted medicines, particularly those who are resistant to or relapsing from IDH1^mi.
Humans ; Oxidative Phosphorylation ; Berberine ; Electron Transport ; Mitochondria ; Leukemia, Myeloid, Acute ; Isocitrate Dehydrogenase

It is an urgent demand worldwide to control the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The 3-chymotrypsin-like protease (3CL^pro) and papain-like protease (PL^pro) are key targets to discover SARS-CoV-2 inhibitors. After screening 12 Chinese herbal medicines and 125 compounds from licorice, we found that a popular natural product schaftoside inhibited 3CL^pro and PL^pro with IC₅₀ values of 1.73 ± 0.22 and 3.91 ± 0.19 μmol/L, respectively, and inhibited SARS-CoV-2 virus in Vero E6 cells with EC₅₀ of 11.83 ± 3.23 μmol/L. Hydrogen-deuterium exchange mass spectrometry analysis, quantum mechanics/molecular mechanics calculations, together with site-directed mutagenesis indicated the antiviral activities of schaftoside were related with non-covalent interactions with H41, G143 and R188 of 3CL^pro, and K157, E167 and A246 of PL^pro. Moreover, proteomics analysis and cytokine assay revealed that schaftoside also regulated immune response and inflammation of the host cells. The anti-inflammatory activities of schaftoside were confirmed on lipopolysaccharide-induced acute lung injury mice. Schaftoside showed good safety and pharmacokinetic property, and could be a promising drug candidate for the prevention and treatment of COVID-19.

Image-guided radiation therapy using magnetic resonance imaging (MRI) is a new technology that has been widely studied and developed in recent years. The technology combines the advantages of MRI imaging, and can offer online real-time tracking of tumor and adjacent organs at risk, as well as real-time optimization of radiotherapy plan. In order to provide a comprehensive understanding of this technology, and to grasp the international development and trends in this field, this paper reviews and summarizes related researches, so as to make the researchers and clinical personnel in this field to understand recent status of this technology, and carry out corresponding researches. This paper summarizes the advantages of MRI and the research progress of MRI linear accelerator (MR-Linac), online guidance, adaptive optimization, and dosimetry-related research. Possible development direction of these technologies in the future is also discussed. It is expected that this review can provide a certain reference value for clinician and related researchers to understand the research progress in the field.
Magnetic Resonance Imaging ; Particle Accelerators ; Radiometry ; Radiotherapy Planning, Computer-Assisted ; Radiotherapy, Image-Guided

Objective:To compare the short-term clinical effect between laparoscopic distal pancreatectomy (LDP) and open distal pancreatectomy (ODP).Methods:We performed a retrospective study on 161 patients who underwent pancreatectomy between September 2017 to December 2018 in the Department of Pancreatic and Gastric Surgery, Cancer Hospital of Chinese Academy of Medical Sciences. According to the mode of operation, the patients were divided into the LDP group ( n=43) and the ODP group ( n=118). To compare the short-term clinical effect and safety between the LDP group and the ODP group, the preoperative clinical data, intraoperative related index, postoperative complication, postoperative recovery index, preoperative and postoperative inflammatory index were analyzed. Results:The preoperative clinical characteristics between the LDP group and the ODP group were not statistically different ( P>0.05). The intraoperative blood loss in LDP group was (194.19±241.83) ml, significantly less than (315.17±295.94) ml in ODP group ( P<0.05), and the postoperative exhaust time in LDP group was (3.00±0.72) days, significantly shorter than (4.05±0.97) days in OPD group ( P<0.001). The time to get out of bed in LDP group was (3.14±1.01) days, significantly shorter than (3.55±1.05) days in OPD group ( P<0.05). The postoperative eating time in LDP group was (3.88±1.61) days, significantly shorter than (5.11±1.56) days in ODP group ( P<0.001). The time of the drainage tube removal in LDP group was (8.44±1.93) days, significantly shorter than (9.82±3.70) days in ODP group ( P<0.05). The postoperative hospital stay in LDP group was (9.65±3.57) days, significantly shorter than (11.99±6.57) days in ODP group ( P<0.05). The mean operation time in LDP group was (168.65±55.45) min, shorter than (171.23±65.61) min in ODP group, but without significant difference ( P>0.05). The incidences of non-pancreatic fistula-related complications in LDP group and ODP group were 16.3% and 11.0%, respectively, without statistical significance ( P>0.05). The incidences of pancreatic fistula in LDP group and ODP group were 16.3% and 19.5%, respectively, without statistical significance ( P>0.05). The total incidences of complications in LDP group and ODP group were 32.6% and 30.5%, respectively, without statistical significance ( P>0.05). The preoperative and postoperative inflammatory indexes between these two groups were not statistically different ( P>0.05). Conclusions:Compared with ODP, LDP has the advantages of less intraoperative blood loss, faster postoperative recovery, shorter postoperative hospital stays, without increased postoperative complications and prolonged operation time. LDP is a safe and feasible operation method, and its short-term clinical effect is better than that of ODP.

Objective:To compare the short-term clinical effect between laparoscopic distal pancreatectomy (LDP) and open distal pancreatectomy (ODP).Methods:We performed a retrospective study on 161 patients who underwent pancreatectomy between September 2017 to December 2018 in the Department of Pancreatic and Gastric Surgery, Cancer Hospital of Chinese Academy of Medical Sciences. According to the mode of operation, the patients were divided into the LDP group ( n=43) and the ODP group ( n=118). To compare the short-term clinical effect and safety between the LDP group and the ODP group, the preoperative clinical data, intraoperative related index, postoperative complication, postoperative recovery index, preoperative and postoperative inflammatory index were analyzed. Results:The preoperative clinical characteristics between the LDP group and the ODP group were not statistically different ( P>0.05). The intraoperative blood loss in LDP group was (194.19±241.83) ml, significantly less than (315.17±295.94) ml in ODP group ( P<0.05), and the postoperative exhaust time in LDP group was (3.00±0.72) days, significantly shorter than (4.05±0.97) days in OPD group ( P<0.001). The time to get out of bed in LDP group was (3.14±1.01) days, significantly shorter than (3.55±1.05) days in OPD group ( P<0.05). The postoperative eating time in LDP group was (3.88±1.61) days, significantly shorter than (5.11±1.56) days in ODP group ( P<0.001). The time of the drainage tube removal in LDP group was (8.44±1.93) days, significantly shorter than (9.82±3.70) days in ODP group ( P<0.05). The postoperative hospital stay in LDP group was (9.65±3.57) days, significantly shorter than (11.99±6.57) days in ODP group ( P<0.05). The mean operation time in LDP group was (168.65±55.45) min, shorter than (171.23±65.61) min in ODP group, but without significant difference ( P>0.05). The incidences of non-pancreatic fistula-related complications in LDP group and ODP group were 16.3% and 11.0%, respectively, without statistical significance ( P>0.05). The incidences of pancreatic fistula in LDP group and ODP group were 16.3% and 19.5%, respectively, without statistical significance ( P>0.05). The total incidences of complications in LDP group and ODP group were 32.6% and 30.5%, respectively, without statistical significance ( P>0.05). The preoperative and postoperative inflammatory indexes between these two groups were not statistically different ( P>0.05). Conclusions:Compared with ODP, LDP has the advantages of less intraoperative blood loss, faster postoperative recovery, shorter postoperative hospital stays, without increased postoperative complications and prolonged operation time. LDP is a safe and feasible operation method, and its short-term clinical effect is better than that of ODP.