POEMS syndrome is a rare condition associated with plasma cell disorders， and it often involves multiple systems and has diverse clinical manifestations. This article reports two cases of POEMS syndrome with hepatosplenomegaly as the initial manifestation. During the course of the disease， the patients presented with lower limb weakness， hepatosplenomegaly， lymph node enlargement， ascites， hypothyroidism， positive M protein， and skin hyperpigmentation， and ¹⁸F-FDG PET-CT imaging revealed bone lesions mainly characterized by osteolytic changes and plasma cell tumors. There was an increase in the serum level of vascular endothelial growth factor. The patients were finally diagnosed with POEMS syndrome， and the symptoms were relieved after immunomodulatory treatment.

Objective To evaluate tolerability,safety and pharmacokinetics of JS026 and JS026-JS016 single dose intravenous infusion in healthy adults.Methods This phase 1,randomized,double-blind,placebo-controlled,dose-escalation study totally included 48 participants:32 healthy subjects were enrolled in JS026 single intravenous infusion groups and 16 healthy subjects were enrolled in JS026-JS016 groups.JS026 was sequentially administered from low dose to high dose(30-1 000 mg),with intravenous infusion of JS026 or placebo in JS026 single-dose groups,and intravenous infusion of JS026-JS016 or placebo in the combination drug groups.Blood was collected according to the time point designed for trial.Serum concentrations of JS026 and JS016 were determined by enzyme linked immunosorbnent assay(ELISA),and pharmacokinetics parameters were calculated by WinNonlin 8.2.The power model method was used to evaluate the linear analysis of dose and drug exposure.Results 47 subjects completed trial and 1 subject lost to follow-up.After a single intravenous injection of JS026 of 30 mg,100 mg,300 mg,600 mg,and 1 000 mg,mean Cmax were(9.47±1.53),(33.20±4.95),(96.10±13.70),(177.00±22.20)and(353.00±56.70)μg·mL-1,respectively;mean AUC0-∞ were(4 225.00±607.00),(1.78 × 104±3 268.00),(5.83 × 104±1 038.00),(1.07 × 105±152.00),(1.66 × 105±327.00)μg·h·mL-1,respectively;mean t1/2 of JS026 were 563-709 h.The Cmax and AUC0-∞ of JS026 were basically similar alone or in combination with JS016.The results of Power model showed that Cmax and AUC0-∞ increased approximately linearly with the increasing dose of JS026.Treatment emergent adverse event was not increasing when dose increased and most of adverse event associated with drugs were abnormal on laboratory tests and haematuria,thus JS026 and JS016 was well tolerated in all groups.Conclusion The single intravenous infusion of JS026 can almost be thought to be a linear relationship between the doses and drug serum exposure.JS016 had no significant effect on serum concentration of JS026 and JS026 was well tolerated and safe in healthy subjects within 30-1 000 mg.

Objective To investigate the distribution of traditional Chinese medicine(TCM)constitution in pregnant women with iron deficiency anemia(IDA)and its related influencing factors,so as to provide a reference for the TCM prevention and treatment of IDA in pregnancy.Methods A total of 109 eligible patients with IDA during pregnancy were included in the study.The general data of pregnant women,the TCM constitution types and relevant laboratory indicators including serum ferritin(Fer),hemoglobin(Hb)and mean corpuscular volume(MCV)were collected.Statistical analyses were conducted on the distribution of TCM constitution types of IDA pregnant women and its related influencing factors as well as the pregnancy outcomes.Results(1)The 109 IDA pregnant women were predominated by biased constitution types,accounted for 60 cases(55.05％).The distribution of the constitution types of 109 IDA pregnant women was as follows:balanced constitution(49 cases,44.95％)>damp-heat constitution(13 cases,11.93％)>yang deficiency constitution(12 cases,11.01％)>yin deficiency constitution(11 cases,10.09％)>qi deficiency constitution(10 cases,9.17％)>qi stagnation constitution(9 cases,8.26％)>blood stasis constitution(3 cases,2.75％)>phlegm-damp constitution(2 cases,1.83％).(2)Comparison of Hb and MCV levels in IDA pregnant women with various constitution types showed no statistically significant differences(P>0.05),but Fer level in IDA pregnant women with damp-heat constitution was significantly higher than that in IDA pregnant women with balanced constitution(P<0.01),and the probability of occurrence of amniotic opacity in IDA pregnant women with damp-heat constitution was significantly higher than that in IDA pregnant women with balanced constitution and other biased constitution types(P<0.05).Conclusion Damp-heat constitution is the most common TCM constitution type in pregnant women with IDA,followed by yang deficiency constitution,yin deficiency constitution and qi deficiency constitution.The damp-heat constitution may be the susceptible constitution of pregnant women with IDA,and IDA pregnant women with damp-heat constitution have significantly higher Fer level than those with balanced constitution,and also have the higher probability of occurrence of amniotic opacity than those with balanced constitution and other biased constitution types.

Objective:To investigate the clinical characteristics of non-perinatal adult patients with Listeria monocytogenes (LM) infection. Methods:Twenty-five non-perinatal adult patients who were etiologically confirmed as listeriosis in Tangdu Hospital, Fourth Military Medical University during January 2010 and July 2023 were enrolled in this study. The characteristics of demographic data, underlying diseases, clinical manifestations, laboratory indicators, cranial imaging examination, anti-microbial therapeutic schemes and clinical outcomes were retrospectively analyzed. The clinical characteristics were compared between patients with Listeria septicemia and Listerial meningoencephalitis, as well as between survival and death patients. Independent samples t test and Mann-Whitney U test were used for statistical analysis. Results:The age of enrolled patients was (52.84±12.17) years. Eighteen patients were male, and seven patients were female. The major clinical manifestations included fever (23/25(92%)), headache (15/25 (60%)), disorder of consciousness (12/25(48%)) and vomiting (8/25(32%)). Thirteen (52%) patients had underlying diseases (including hematological diseases, autoimmune disorders, solid neoplasms, and liver cirrhosis, etc). There were no significant differences in blood routine test, aminotransferase, protein levels, renal function, electrolyte, blood glucose, and inflammatory indicators between patients with Listeria septicemia and Listerial meningoencephalitis (all P>0.05). The platelet count in the death group was significantly higher than that in the recovery group ((243.10±92.96)×10 9/L vs (157.80±75.55)×10 9/L, t=2.45, P=0.022). There were also no significant differences in blood biochemical index and inflammatory indicators between these two groups (all P>0.05). Cranial imaging examination of patients with Listerial meningoencephalitis manifested as intracranial infection, cerebral edema/hydrocephalus or cerebral hernia. All nineteen patients with Listerial meningoencephalitis had elevated cerebrospinal fluid (CSF) pressure (220.0(130.0, 290.0) mmH 2O (1 mmH 2O=0.009 8 kPa)), elevated CSF total cell count (522.0(350.0, 783.0)×10 6/L), elevated CSF white blood cell count (356.0(266.0, 668.0)×10 6/L), and CSF protein level (1 817.0(822.5, 6 000.0) mg/L). Fifteen patients had reduced CSF chloride level ((111.70±8.51) mmol/L). Ten patients had decreased CSF glucose level (3.71(1.45, 7.11) mmol/L). The drug sensitivity results of blood and CSF cultures revealed that LM was sensitive to ampicillin. One case was resistance to penicillin, three cases were resistance to meropenem, while three cases were resistance to trimethoprim-sulfonamide. Thirteen cases out of seventeen recovery patients were administered with ampicillin or penicillin-based therapy. Conclusions:When patients with underlying diseases or immune dysfunction suffered with clinical symptoms such as high fever, central nervous system infection, they should be alert to the possibility of listeriosis. Early administration of ampicillin-based therapeutic strategy is beneficial for clinical recovery of the patients.

The National Medical Products Administration have become an official applicant of the Pharmaceutical Inspection Co-operation Scheme(PIC/S)in 2023,and the good manufacturing practice appendix and inspection memorandum are key documents of PIC/S.Based on the analysis of the history,framework and main contents of the appendix and inspection memorandum of PIC/S investigational medicinal products,this paper discusses the key contents of the appendix and inspection memorandum of PIC/S clinical trial drugs,and provides reference for the inspection work.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Objective:To explore the mechanism of Honghua Xiaoyao Tablets in the treatment of premature ovarian failure (POF) using network pharmacology and molecular docking technology; To conduct further experimental verification.Methods:The active components and related targets of Honghua Xiaoyao Tablets were obtained using TCMSP and PubChem databases, and the related targets of POF were obtained by using GeneCards database. The Venn online tool was used to screen the intersection genes, and the STRING database was used to construct the PPI network. Then, GO function enrichment analysis and KEGG pathway enrichment analysis were performed on the intersecting genes through the Metescape database, and Cytoscape 3.7.1 software was used to construct the "active component-target" network and "Chinese materia medica-active component-target-key pathway-disease" network. Finally, molecular docking verification was carried out. Mice were divided into blank group, model group, and Honghua Xiaoyao Tablets group using a random number table method, with 8 mice in each group. Except for the blank group, mice in each group were treated with zona pellucida polypeptide 3 (ZP3) and Freund's Complete Adjuvant (FCA) to establish a mouse model of immune POF. Mice in the Honghua Xiaoyao Tablets group received Honghua Xiaoyao Tablets solution 0.56 g/kg for gavage, and the blank control group and the model group received saline for gavage for consecutive 4 weeks. The histopathological changes of the mouse ovary were observed by HE staining. Immunohistochemical staining was used to observe the expression of ESR1, and Western blot was used to detect the expressions of Akt and p-Akt.Results:A total of 80 intersection targets between Honghua Xiaoyao Tablets and POF were obtained, and the PPI network contained 44 core targets. The top 5 compounds in the topological analysis were formononetin, quercetin, Betulinic acid, Hydroxysafflor Yellow A and Baicalin, and the top 5 targets were PPARG, ESR1, AR, AKT1 and IL6. The molecular function of core genes was mainly receptor ligand activity, and its biological process mainly involved the positive regulation of cell migration. The cellular components mainly included membrane rafts, which were involved in signaling pathways such as cancer signaling pathway, proteoglycans in cancer, PI3K-Akt signaling pathway, and HIF-1 signaling pathway. "Chinese materia medica-component-target-pathway-disease" network showed that 8 kinds of Chinese materia medica in the Honghua Xiaoyao Tablets had important core components, among which Glycyrrhizae Radix et Rhizoma and Carthami Flos involved the most important core components. Molecular docking results showed that the active components had a good affinity with the core target. The experimental verification confirmed that Honghua Xiaoyao Tablets promoted follicular development, increased the expression of ESR1 in ovarian tissues and up-regulated the expression level of the key factor of Akt phosphorylation in the PI3K-Akt signaling pathway.Conclusions:The various active components of Honghua Xiaoyao Tablets may act on PPARG, ESR1 and other targets through multiple signaling pathways such as PI3K-Akt and HIF-1 to treat POF. The potential active components are mainly formononetin, quercetin, etc.

Objective To observe the efficacy of Asini Corii Colla for the treatment of women with pregnancy anemia induced by β-thalassemia and its effect on the expression of early growth response 2(EGR2).Methods Transcriptome sequencing(RNA-seq)was performed firstly.Twenty pregnant women with β-thalassemia were randomly assigned to the treatment group and the control group at the proportion of 3:1.There were 15 cases allocated to the treatment group,one case fell off during the trial,and eventually 14 cases were included.The control group had 5 cases.The treatment group was given Asini Corii Colla powder orally,and the control group had no intervention.The course of treatment covered 4 weeks.The peripheral blood of the two groups of pregnant women was sampled before and after treatment for RNA-seq analysis,and then the candidate targets were defined.Subsequently,a prospective clinical randomized controlled trial(RCT)was conducted.A total of 41 pregnant women with β-thalassemia were randomly assigned to the treatment group(24 cases)and the control group(17 cases)at the proportion of 3:2.The treatment group was treated with Asini Corii Colla powder orally,and the control group was treated with the simulant of Asini Corii Colla Powder orally.The course of treatment covered 4 weeks.The hematological parameters of the two groups of pregnant women were detected before and after treatment,and the mRNA and protein expression levels of candidate targets were detected by real-time polymerase chain reaction(real-time PCR)and western blotting respectively.Results(1)The results of RNA-seq analysis showed that EGR2 expression of patients with genotype βCD41-42(-TTCT)/βN in the treatment group was significantly up-regulated after treatment(log2 FC=1.915;Padj=9.84E-03),and EGR2 was named as the candidate target.(2)The results of RCT showed that after treatment,there was no significant difference in the average hemoglobin(Hb)concentration between the two groups of pregnant women with β-thalassemia(P＞0.05),but the average Hb of the patients with genotypeβCD41-42(-TTCT)/βN in the treatment group increased by(6.54±4.74)g/L,which was significantly higher than that of other genotypes of pregnant women with β-thalassemia(P＜0.05).The expression levels of EGR2 Mrna and protein in peripheral blood of the patients with genotypeβCD41-42(-TTCT)/Βn in the treatment group were significantly increased after treatment(P＜0.05).The pre-and post-treatment difference of Hb concentration in the two groups of pregnant women withβ-thalassemia was positively correlated with pre-and post-treatment difference of EGR2 Mrna level and EGR2 protein level,and the correlation coefficients were 0.701 and 0.683,respectively(P＜0.001).Conclusion The pregnant women with thalassemia of genotype Βcd41-42(-TTCT)/Βn can achieve satisfactory efficacy after oral administration of Asini Corii Colla.Its curative effect for improving anemia may be related to the transcriptional regulation of globin genes through up-regulating EGR2 expression,activating RNA polymerase Ⅱ promoter,and promoting nucleic acid binding.

Objective To investigate the clinical efficacy of therapy of clearing heat,percolating dampness and lowering turbidity combined with Silibin Meglumine Tablets in the treatment of non-alcoholic steatohepatitis(NASH)patients with abnormal alanine aminotransferase(ALT)level of damp-heat accumulation type.Methods A retrospective study was conducted.According to the medication,80 patients with NASH with abnormal ALT level of damp-heat accumulation type were divided into control group and observation group,with 40 cases in each group.The control group was treated with Silibin Meglumine Tablets,and the observation group was treated with therapy of clearing heat,percolating dampness and lowering turbidity on the basis of treatment for the control group.The course of treatment covered 12 weeks.The changes of liver function indicators of ALT,aspartate aminotransferase(AST),and gamma glutamyl transpeptidase(GGT),blood lipid indicators of total cholesterol(CHOL)and triglyceride(TRIG),and the degree of hepatic steatosis in the two groups were observed before and after treatment.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)After 12 weeks of treatment,the total effective rate of the observation group was 95.00%(38/40),and that of the control group was 77.50%(31/40).The curative effect of the observation group was significantly superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the levels of ALT,AST and GGT in the two groups were significantly lower than those before treatment(P＜0.05),and the decrease of ALT,AST and GGT in the observation group was significantly superior to that in the control group(P＜0.05).(3)After treatment,the levels of CHOL and TRIG in the two groups were significantly lower than those before treatment(P＜0.05),and the decrease of CHOL and TRIG in the observation group was significantly superior to that in the control group(P＜0.05).(4)After treatment,the degree of hepatic steatosis in the two groups was significantly lower than that before treatment(P＜0.05),and the decrease of the degree of hepatic steatosis in the observation group was significantly superior to that in the control group(P＜0.05).(5)During the treatment,no obvious adverse reactions occurred in the two groups,indicating high safety.Conclusion The therapy of clearing heat,percolating dampness and lowering turbidity combined with Silibin Meglumine Tablets exerts certain effect in the treatment of NASH patients with abnormal ALT level of damp-heat accumulation type,and the therapy can significantly enhance the clinical efficacy of Silibin Meglumine Tablets alone for NASH.

Refractory prolactinoma is the most common pituitary neuroendocrine tumor.Dopamine receptor agonists(DA)are the primary choice for drug treatment.Most patients with prolactinomas respond well to DA.However,a minority of prolactinomas patients still show resistance to DA.Although drug-resistant and refractory prolactinomas are rare in clinical practice,their treatment is extremely challenging.Even a combination of drug therapy,multiple surgeries,and radiotherapy may not yield satisfactory outcomes.Therefore,standardizing the diagnosis and treatment process and pathway for refractory prolactionmas and exploring more effective multidisciplinary collaborative treatment strategies are urgent problems to be solved.In the clinical management of refractory prolactinomas,it is often necessary to consider the patient's condition comprehensively,replace other types of DA,or consider surgery,radiotherapy,and immunotherapy,which requires multidisciplinary diagnosis and treatment.This review synthesizes the latest literature at home and abroad to systematically discuss the latest advances in drug therapy,surgery,and radiotherapy treatments for refractory prolactionmas,aiming to provide new ideas for basic research,clinical diagnosis and treatment.