Combined with elastic network model (ENM), the perturbation response scanning (PRS) has emerged as a robust technique for pinpointing allosteric interactions within proteins. Here, we proposed the PRS analysis of drug-target networks (DTNs), which could provide a promising avenue in network medicine. We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework, for drug repurposing of multiple sclerosis (MS). First, the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes. Then, based on topological analysis and functional annotation, the neurotransmission module was identified as the "therapeutic module" of MS. Further, perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis, giving a list of repurposable drugs for MS. Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of serotonin 2B receptor (HTR2B). Finally, we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex. These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS. As a useful systematic method, our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

Chinese patent medicines(CPMs) are unique therapeutic drugs in China. Establishing and improving the evaluation criteria is an important measure to promote the high-quality development of CPMs. Based on the "evaluation criteria of high-grade CPMs with quality as the core index" established by our group in 2018, the "high-quality evaluation criteria for CPMs based on whole process control" was proposed in the present study in 2022. The scope of application and basic principles of the new criteria were clarified. A quality evaluation scoring table was established in the new criteria, including five parts: raw material selection, production process, quality control, efficacy evaluation, and brand building. The technical evaluation indexes involved have increased from 20% in the original criteria to 70% in the new criteria, and efficacy evaluation has been added in the new criteria. The subjective evaluation indicators account for a large proportion in the original criteria, which is prone to bias. The improved criteria overcome this shortcoming. It is expected that the new criteria as a basis can play a better role in the selection of high-quality products of CPMs, guide enterprises and institutions to participate actively in the evaluation and research of high-quality CPMs, and promote the high-quality development of CPMs.
Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use* ; Nonprescription Drugs ; Chlorobenzenes ; China

Objective: To identify the main metals involved in cognitive impairment in the Chinese oldest old, and explore the association between these metal exposures and cognitive impairment. Methods: A cross-sectional study was conducted on 1 568 participants aged 80 years and older from Healthy Aging and Biomarkers Cohort Study (2017 to 2018). Fasting venous blood was collected to measure the levels of nine metals (selenium, lead, cadmium, arsenic, antimony, chromium, manganese, mercury, and nickel). The cognitive function of these participants was evaluated by using the Chinese version of the Mini-Mental State Examination (CMMSE). The random forest (RF) was applied to independently identify the main metals that affected cognitive impairment. The multivariate logistic regression model and restricted cubic splines (RCS) model were used to further verify the association of the main metals with cognitive impairment. Results: The age of 1 568 study subjects was (91.8±7.6) years old, including 912 females (58.2%) and 465 individuals (29.7%) with cognitive function impairment. Based on the RF model (the out-of-bag error rate was 22.9%), the importance ranking of variables was conducted and the feature screening of five times ten-fold cross-validation was carried out. It was found that selenium was the metal that affected cognitive function impairment, and the other eight metals were not included in the model. After adjusting for covariates, the multivariate logistic regression model showed that with every increase of 10 μg/L of blood selenium levels, the risk of cognitive impairment decreased (OR=0.921, 95%CI: 0.889-0.954). Compared with the lowest quartile(Q₁) of blood selenium, the ORs (95%CI) of Q₃ and Q₄ blood selenium were 0.452 (0.304-0.669) and 0.419 (0.281-0.622) respectively. The RCS showed a linear dose-response relationship between blood selenium and cognitive impairment (P_nonlinear>0.05). Conclusion: Blood selenium is negatively associated with cognitive impairment in the Chinese oldest old.
Aged, 80 and over ; Female ; Humans ; Selenium ; Cohort Studies ; Cross-Sectional Studies ; Metals/analysis* ; Cognitive Dysfunction/epidemiology* ; China/epidemiology*

Objective: To compare the efficacy of two induction regimens, namely, idarubicin combined with cytarabine (IA) versus the combination of homoharringtonine, daunorubicin, and cytarabine (HAD) , in adult patients with newly diagnosed de novo acute myeloid leukemia (AML) . Methods: From May 2014 to November 2019, 199 patients diagnosed with AML receiving either the IA or HAD regimens were assessed for overall survival (OS) , relapse-free survival (RFS) , as well as the CR rate and the MRD negative rate after induction therapy. The differences in prognosis between the two induction therapy groups was assessed according to factors, including age, white blood cell (WBC) count, NPM1 mutation, FLT3-ITD mutation, 2017 ELN risk stratification, CR(1) transplantation, and the use of high-dose cytarabine during consolidation therapy, etc. Results: Among the 199 patients, there were 104 males and 95 females, with a median age of 37 (15-61) years. Ninety patients received the IA regimen, and 109 received the HAD regimen. Comparing the efficacy of the IA and HAD regimens, the CR rates after the first induction therapy were 71.1% and 63.3%, respectively (P=0.245) , and the MRD negative rates after the first induction therapy were 53.3% and 48.6%, respectively (P=0.509) . One patient in the IA group and two in the HAD group died within 60 days after induction. The two-year OS was 61.5% and 70.6%, respectively (P=0.835) , and the two-year RFS was 51.6% and 57.8%, respectively (P=0.291) . There were no statistically significant differences between the two groups. Multivariate analysis showed that the ELN risk stratification was an independent risk factor in both induction groups; CR(1) HSCT was an independent prognostic factor for OS and RFS in the IA patients and for RFS in the HAD patients but not for OS in the HAD patients. Age, WBC level, NPM1 mutation, and FLT3-ITD mutation had no independent prognostic significance. Conclusion: The IA and HAD regimens were both effective induction regimens for AML patients.
Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Cytarabine/therapeutic use* ; Daunorubicin/therapeutic use* ; Female ; Homoharringtonine/therapeutic use* ; Humans ; Induction Chemotherapy ; Leukemia, Myeloid, Acute/genetics* ; Male ; Middle Aged ; Nuclear Proteins ; Prognosis ; Remission Induction ; Retrospective Studies ; Young Adult

Objective: To investigate the incidence and treatment of perioperative anemia in patients with gastrointestinal neoplasms in Hubei Province. Methods: The clinicopathological data of 7 474 patients with gastrointestinal neoplasms in 62 hospitals in 15 cities (state) of Hubei Province in 2019 were collected in the form of network database. There were 4 749 males and 2 725 females. The median age of the patients was 62 years (range: 17 to 96 years). The hemoglobin value of the first time in hospital and the first day after operation was used as the criterion of preoperative anemia and postoperative anemia. Anemia was defined as male hemoglobin <120 g/L and female hemoglobin <110.0 g/L, mild anemia as 90 to normal, moderate anemia as 60 to <90 g/L, severe anemia as <60 g/L. The t test and χ² test were used for inter-group comparison. Results: The overall incidence of preoperative anemia was 38.60%(2 885/7 474), and the incidences of mild anemia, moderate anemia and severe anemia were 25.09%(1 875/7 474), 11.37%(850/7 474) and 2.14%(160/7 474), respectively. The overall incidence of postoperative anemia was 61.40%(4 589/7 474). The incidence of mild anemia, moderate anemia and severe anemia were 48.73%(3 642/7 474), 12.20%(912/7 474) and 0.47%(35/7 474), respectively. The proportion of preoperative anemia patients receiving treatment was 26.86% (775/2 885), and the proportion of postoperative anemia patients receiving treatment was 14.93% (685/4 589). The proportions of preoperative anemia patients in grade ⅢA, grade ⅢB, and grade ⅡA hospitals receiving treatment were 26.12% (649/2 485), 32.32% (85/263), and 29.93% (41/137), and the proportions of postoperative anemia patients receiving treatment were 14.61% (592/4 052), 22.05% (73/331), and 9.71% (20/206). The proportion of intraoperative blood transfusion (16.74% (483/2 885) vs. 3.05% (140/4 589), χ²=434.555, P<0.01) and the incidence of postoperative complications (17.78% (513/2 885) vs. 14.08% (646/4 589), χ²=18.553, P<0.01) in the preoperative anemia group were higher than those in the non-anemia group, and the postoperative hospital stay in the preoperative anemia group was longer than that in the non-anemia group ((14.1±7.3) days vs. (13.3±6.2) days, t=5.202, P<0.01). Conclusions: The incidence of perioperative anemia in patients with gastrointestinal neoplasms is high. Preoperative anemia can increase the demand for intraoperative blood transfusion and affect the short-term prognosis of patients. At present, the concept of standardized treatment of perioperative anemia among gastrointestinal surgeons in Hubei Province needs to be improved.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anemia/epidemiology* ; Blood Transfusion ; Female ; Gastrointestinal Neoplasms/surgery* ; Humans ; Length of Stay ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Young Adult

The saliva secreted from submandibular gland (SMG) accounts for 60%-65%. It plays an important role in maintaining the human function of swallow, digestion, testing, speech, protection of oral mucosa, and prevention from dental carries. The SMG is frequently resected during the treatment for various kinds of oral and maxillofacial diseases, resulting in xerostomia and decreased quality of life. During the past 15 years, Research Center of Salivary Gland Diseases in Peking University School and Hospital of Stomatology conducted a series of studies on new techniques for preservation of SMG and achieved remarkable results. The clinicopathologic and imaging characteristics of IgG4-related sialadenitis (IgG4-RS) were clarified based on systematic studies. The results of studies on the pathogenesis of IgG4-RS showed that unbalance of inflammatory factors mediated the abnormality of secretion of SMG. IL-4 participates in occurring and development of glandular fibrosis of SMG. Regulation of tumor necrosis factor α (TNF-α) and cleaning of senescent cells might be taken as the targets for treatment of IgG4-RS. The combination of glucocorticoid and steroid-sparing agents showed effective results for treating IgG4-RS, clinical remission was achieved in all the patients, serum IgG4 levels decreased, and salivary gland secretion significantly increased. Sialoendoscopy-assisted sialolithectomy was applied in the treatment of about 1 000 cases with submandibular hilar calculi with a success rate of more than 90%. Transfer of SMG was used for prevention from radiation-induced xerostomia in the patients with head and neck carcinoma. SMG was transferred to the submental region before radiotherapy and was kept away from the ra-diation field. The results of prospective clinical controlled study showed this technique could effectively preserve the function of SMG and prevent from xerostomia. Based on the micro-anatomical study on the blood vessels and ducts of SMG, partial sialoadenectomy was applied for treatment of benign tumors in the SMG. A clinical controlled study confirmed its safety for control of the tumors and its advantage of preservation of SMG function. The studies on the involvement of SMG in oral squamous cell carcinoma (OSCC) provided the anatomical and histopathological basis for preservation of SMG during neck dissection for early cases with OSCC. A innovated surgical modality "four preservations including SMG" was used during the neck dissection for the early cases with OSCC. A prospective randomized clinical controlled study confirmed its safety, feasibility, effectiveness for control of the carcinoma, and advantages of preservation of SMG function.
Humans ; Carcinoma, Squamous Cell/pathology* ; Glucocorticoids ; Immunoglobulin G ; Interleukin-4 ; Mouth Neoplasms/pathology* ; Prospective Studies ; Quality of Life ; Sialadenitis/surgery* ; Submandibular Gland/surgery* ; Tumor Necrosis Factor-alpha ; Xerostomia/prevention & control* ; Randomized Controlled Trials as Topic

Objective To investigate the effects of dexmedetomidine (DEX) on the nuclear factor-KB inhibitor protein kinase (IKK)/nuclear factor-KB inhibitor protein a (IKB(X)/nuclear factor-KB (N F - K B) pathway and cognitive dysfunction in rats with post-traumatic stress disorder (PTSD) . Methods Rats were randomly divided into control group, model group, positive group and DEX group. Except for the control group, the PTSD model was constructed by single prolonged stress method (SPS), and the corresponding drugs were given after the completion the model. Open field test and Morris water maze method were used to detect the autonomous activity, learning and memory ability of rats; HE staining was used to observe the morphological characteristics of cerebral cortex and hippocampus; ELISA and Western blotting were used to detect the contents of interleukin (IL)-1(3, IL-6, tumor necrosis factor a (TNF-a) and the expression levels of IKK, IKB(X, purinergic ligand-gated ion channel 7 receptor (P2X7R), leucine-rich repeat domain protein 3(NALP3) in hippocampus; the NF-KB activity was assessed by electrophoretic mobility shift assay (EMSA). Results Compared with the control group, the cerebral cortex and hippocampal CA1 region of model group were in structural disorders, nuclear pyysis and other pathological changes happend, learning and memory ability of rats decreased (P < 0. 05), contents of IL-lp, IL-6 and TNF-a, expression levels of IKK, IKB(X, P2X7R and NALP3, NF-KB activity in hippocampus increased (P<0. 05); Compared with the model group, the pathological phenomena in cerebral cortex and hippocampal CA1 area of rats in positive group and DEX group were in alleviated, and the changes of the above indexes were opposite to those of model group (P<0. 05) . Conclusion DEX can significantly improve the autonomous activity ability and learning and memory ability in PTSD rats, reduce inflammatory reaction in hippocampus and improve cognitive dysfunction, which may be related to the down-regulation of IKK/TKBQ!/NF-KB pathway.

The big brand of Chinese patent medicine, Fufang Danshen Prescription(FDP), effective in promoting blood circulation, resolving blood stasis, regulating qi, and relieving pain, is wide in clinical application and diverse in dosage forms and products, but its quality and price are uneven, which causes problems for doctors and patients. To clarify the key links and weakness of quality control leading to the quality difference of FDP products, the present study carried out a comprehensive evaluation of the whole production cycle of FDP based on the "high-quality Chinese patent medicine evaluation criteria" and analyzed the advantages and disadvantages of production and quality of different FDP products according to scores. The results showed that the scores of various products in the "raw materials selection" varied greatly. The highest score(S1) and the lowest score(S2) differed by more than 3 times, indicating that different manufacturers had inconsistent requirements for the selection of raw materials, leading to fundamental differences in the quality of raw materials. The scores in the "production process" varied slightly, with an average score of 66.8%. The manufacturer S8 obtained the highest score(84.0%), which indicated the emergence of intelligent manufacturing production. The scores(with the average score of 44.0%) in the "quality control" were lower than those of the previous two items, which was attributed to the fact that most FDP products only met the "qualified" benchmark required by the 2020 edition of Chinese Pharmacopoeia, and their consistency and high quality were both uncontrollable. The scores in the "post-marketing research" were the lowest(with an average score of 28.5%), and most manufacturers were scored 0, which reflected little attention paid. Only a few brand manufacturers were scored acceptably and they were willing to carry out relevant research on post-marketing evaluation. The evaluation results demonstrated the key links and weakness leading to the production and quality differences of FDP from different manufacturers. It is expected to improve the quality of FDP, promote the formation of the "high quality and good price" mechanism, and provide information for the centralized procurement of governments.
China ; Drugs, Chinese Herbal/analysis* ; Humans ; Medicine, Chinese Traditional ; Nonprescription Drugs ; Prescriptions

Objective: To investigate the clinical and pathological features of salivary secretory carcinoma (SSC). Methods: Ten cases of SSC confirmed in the Department of Pathology,Capital Medical University School of Stomatology from January 2014 to December 2021 were retrospectively included, including 5 males and 5 females, with a median age of 46.5 years. The microscopic morphology, immunophenotype, special staining and clinical follow-up of 10 cases of salivary secretory carcinoma were observed. Ten patients were tested with S-100, vimentin, mammaglobin, Dog-1, p63 and Ki-67, 9 cases with cytokeratin (CK) 8/18, 8 with CK7, 6 with calponin, 5 with smooth muscle actin (SMA) and GCDFP15, 4 with CK5/6 and 1 with SOX10. The ETV6-NTRK3 fusion gene was detected by fluorescence in situ hybridization. Results: Seven of the 10 SSC were located in the parotid gland and 3 were located in the cheeks. Histomorphology showed solid, papillary-cystic, follicular, microcystic, and macrocystic types. In 7 cases, tumor cells were dominated by single arrangement type, while certain mixed arrangements existed in some areas. The cytoplasm of the tumor cells was rich in eosinophilic, fine granular or vacuolar shapes, and clear cytoplasm was seen in 2 cases. The nuclei were mostly oval-shaped vesicular nuclei, with nucleoli in the center. Immunohistochemistry showed CK7 (8/8) positive, CK8/18 (9/9) positive, S-100 (10/10) positive, vimentin (5/10) positive, (4/10) partially positive and (1/10) less partially positive, mammaglobin (7/10) positive, (1/10) partially positive and (2/10) some individual cells positive, Dog-1 (10/10) negative, CK5/6 (4/4) negative, p63 (7/10) negative and (3/10) partially positive, SMA (5/5) negative, calponin (6/6) negative, and Ki-67 index was 5%-20%. Secretions of 5 cases showed periodic acid-Schiff (PAS) and PAS with diastase (PAS-D) staining positive. All 10 cases showed ETV6-NTRK3 fusion positive. Six cases were successfully followed up for 32-91 months, of which 2 cases recurred after 28 and 74 months and underwent surgical resection again. All cases followed up are alive and disease-free. Conclusions: The salivary secretory carcinoma is a rare low-grade malignant tumor. In certain cases, morphology is atypical and mammaglobin is immunohistochemically positive in only individual tumor cells. Therefore, the diagnosis should be supported with morphology, immunohistochemical staining, and molecular feature preferably.
Female ; Male ; Biomarkers, Tumor ; Carcinoma/pathology* ; In Situ Hybridization, Fluorescence ; Ki-67 Antigen/genetics* ; Neoplasm Recurrence, Local ; Retrospective Studies ; S100 Proteins ; Salivary Gland Neoplasms/pathology* ; Vimentin