The National Essential Medicines System could protect public health and ensure access to essential medications.Although the current selection methods for China's National Essential Medicines Lists(NEMLs)are becoming more scientific and standardized,there are still problems such as much emphasis on expert experience and the lack of transparency of decision-making basis.To address these issues,it proposes an evidence-based decision-making pathway for NEMLs selection guided by clinical value.This approach ensures a strong integration of evidence and decision-making,offering valuable insights for improving the adjustment procedures and selection criteria of the NEMLs in China.

Objective:To detect adverse reaction risk signals of triazole antifungal agents and provide evidences for their safe use in clinic.Methods:Adverse reaction/event reports with fluconazole, itraconazole, voriconazole, posaconazole, or isavuconazonium as the primary suspect drug were collected from the data in National Adverse Drug Reaction Monitoring System of China reported by Shandong Province from January 2004 to June 2024 and the US Food and Drug Administration Adverse Event Reporting System (FAERS) database from the first quarter of 2004 to the second quarter of 2023. Adverse reaction/event terms were standardized using the preferred term (PT) and system organ class in Medical Dictionary for Regulatory Activities 24.0. Risk signals were detected using the reporting odds ratio (ROR) method and the Bayesian confidence propagation neural network (BCPNN) algorithm. A PT was defined as an adverse reaction risk signal if the number of reports was ≥3, the lower limit of the 95% confidence interval ( CI) for ROR was >2, and the lower limit of the 95% CI for the information component ( IC) was >0. Descriptive statistical analysis was performed. Results:A total of 3 988 reports with the above 5 antifungal drugs as the primary suspect drug were collected from data in National Adverse Drug Reaction Monitoring System of China reported by Shandong Province, 822 (20.6%) of which were serious cases. Voriconazole, fluconazole, itraconazole, posaconazole, and isavuconazonium was the primary suspect drug in 1 852, 1 395, 703, 27, and 11 cases among the 3 988 reports, and in 591 (31.9%), 149 (10.7%), 59 (8.4%), 18 (66.7%), and 5 (5/11) serious cases among the 822 serious case reports, respectively. A total of 20 066 reports with the above 5 drugs as the primary suspect drug were collected in FAERS database, 9 635 (48.0%) of which were serious cases. Voriconazole, fluconazole, itraconazole, posaconazole, and isavuconazonium was the primary suspect drug in 7 758, 6 180, 2 869, 1 796, and 1 463 cases among the 20 066 reports, and in 4 295 (55.4%), 2 806 (45.4%), 1 191 (41.5%), 828 (46.1%), and 515 (35.2%) serious cases among the 9 635 serious case reports, respectively. Based on the data reported by Shandong Province and in FAERS database, 18 and 207 risk signals of adverse reaction not mentioned in the labels were identified, respectively, and 5 of them were identified in both databases, including fluconazole-induced renal impairment and voriconazole-induced oliguria, delirium, psychiatric disorders, and rhabdomyolysis. In the data reported by Shandong Province and in FAERS database, 13 and 189 reports of muscle-related disorders (rhabdomyolysis, myopathy, and myositis) were identified respectively, involving voriconazole (in 8 and 62 cases), itraconazole (in 4 and 74 cases), and fluconazole (in 1 and 53 cases).Conclusions:Renal impairment induced by fluconazole and oliguria, delirium, psychiatric disorders, and rhabdomyolysis induced by voriconazole are risk signals of adverse reaction not mentioned in the labels for triazole antifungal agents. Voriconazole, itraconazole, and fluconazole may also cause muscle-related disorders, warranting vigilance in clinical practice.

Objective:To investigate the clinical and genetic characteristics of a family with cataplexy and epilepsy caused by KCNA1 gene mutations. Methods:The clinical data of a family with KCNA1 gene mutations leading to cataplexy and epilepsy who hospitalized in the Department of Pediatric Neurology at Anhui Children's Hospital in August 2022 were collected，and their clinical manifestations，imaging，electroencephalogram，gene testing results and treatment were analyzed. A total of 68 pathogenic or potentially pathogenic variants of the KCNA1 gene were identified by searching the database of CNKI，Wanfang Data Knowledge Service Platform, ClinVar, dbSNP and PubMed using the keyword‘KCNA1’between the establishment and August 2023. Results:The proband was a 9 years and 8 months old boy who initially presented with cataplexy induced by strenuous exercise or fatigue，followed by focal epilepsy. The whole exome sequencing detected heterozygous variation of exon 2 c.1006G>A（p.Gly336Arg）of KCNA1 gene，which was a missense mutation and was not reported in the country or abroad. Both the mother and brother of the proband detected heterozygous mutations at the same locus，and both had cataplexy induced by strenuous exercise or fatigue，but the type of seizure was generalized tonic-clonic seizure. The proband's grandmother，aunt，and brother all had seizures or cataplexy. Affected patients receiving different or the same anti-seizure drugs（sodium valproate，lamotrigine，phenytion sodium and carbamazepine）had varying degrees of relief，and those treated with sodium channel blockers had varying degrees of relief. A total of 68 mutation sites of KCNA1 gene were retrieved from domestic and foreign literature，mainly missense mutations，and most patients showed episodic ataxia type 1（EA1），and there was genetic heterogeneity between the genotype and phenotype of the variable patients. Conclusion:We have reported a heterozygous mutation in the KCNA1 gene c.1006G>A（p.Gly336Arg），which is a missense mutation and is easy to misdiagnose in patients with cataplexy and epilepsy as the main phenotypes. Patients with the KCNA1 mutation have different degrees of efficacy on sodium channel blockers.

OBJECTIVE To study the clinical efficacy of Professor Li Bingmao's Tongfu Xiere Quyu Shuli Prescription in the treatment of patients with functional dyspepsia(FD)of spleen and stomach damp-heat and qi stagnation and blood stasis type.METH-ODS A total of 206 patients with functional dyspepsia of spleen and stomach damp-heat and qi stagnation and blood stasis type diag-nosed by Hengshui People's Hospital were included in the study and randomly divided into a study group and a control group with 103 cases in each group.During the treatment,3 cases dropped out in each group.The control group adopted the conventional Western medicine treatment plan for functional dyspepsia(mosapride+rabeprazole),and the study group took Tongfu Xiere Quyu Shuli Pre-scription on the basis of the treatment of the control group.The treatment course of both groups was 4 weeks.The traditional Chinese medicine(TCM)syndrome scores,psychological status[self-rating anxiety scale(SAS),self-rating depression scale(SDS),and quality of life[Nepean dyspepsia life quality index(NDLQI)of the two groups of patients before and after treatment were observed and the clinical efficacy was evaluated;serum motilin(MTL),ghrelin,gastrin(GAS),corticotropin-releasing hormone(CRH)and pep-sinogen(PG Ⅰ,PG Ⅱ)were measured by enzyme-linked immunosorbent assay;changes in gastric motility indexes were analyzed by electrogastrogram analyzer;changes in intestinal flora were detected by instillation method.The occurrence of adverse reactions in the two groups of patients was monitored during treatment.RESULTS After treatment,the TCM syndrome scores of the two groups were significantly reduced(P<0.05,P<0.01),and the score in the study group was lower than that in the control group(P<0.01).The total effective rate of the study group was significantly higher than that in the control group(P<0.01).After treatment,the expression levels of MTL,Ghrelin,GAS,PG Ⅰ and PG Ⅱ in the two groups increased,and CRH decreased,and the improvement degree of the study group was better than that of the control group(P<0.01).After treatment,the main frequency and slow wave percentage of the electrogastrogram increased in the two groups,and the study group was better than that of the control group(P<0.01).After treat-ment,the number of bifidobacteria and lactobacilli in the two groups increased,and the number in the study group was greater than that in the control group,while the number of enterobacteria,enterococci and yeast decreased,and the number in the study group was less than that in the control group(P<0.01).There was no significant difference in adverse reactions between the two groups(P>0.05).CONCLUSION Tongfu Xiere Quyu Shuli Prescription is effective in the treatment of FD patients with spleen and stomach damp-heat syndrome,and can improve FD clinical symptoms,quality of life,anxiety and depression symptoms,regulate gastrointesti-nal hormone expression levels,gastric motility and intestinal flora expression,and does not increase adverse reactions,and is safe and reliable.

Objective:Severe fever with thrombocytopenia syndrome (SFTS), caused by the novel bunyavirus, is an emerging infectious disease with a high fatality rate. Co-infections with bacteria or fungi can exacerbate the disease. This study aimed to investigate the characteristics of co-infections in SFTS patients.Methods:A retrospective analysis was conducted on 143 SFTS patients admitted to Qilu Hospital of Shandong University and Juxian People’s Hospital from April 2021 to October 2024.Results:The result showed that 35.7% (51/143) of patients had co-infections, with 85.5% diagnosed within 48 hours of hospitalization. The co-infection group exhibited higher incidences of neurological and respiratory symptoms, lower median platelet counts, and significantly elevated levels of C-reactive protein (CRP), procalcitonin (PCT), blood urea nitrogen (BUN), creatinine (Cr), and ferritin ( P<0.01). Pathogen analysis revealed a predominance of lower respiratory tract Aspergillus infections. Co-infected patients had higher rates of ICU admission (31.4% vs 5.4%), mechanical ventilation (43.1% vs 6.5%), longer hospital stays, higher costs, and lower survival rates (74.5% vs 90.2%). The score within 6 days of disease onset (including age, neutrophil percentage, aspartate transaminase (AST), lactate dehydrogenase (LDH), and BUN) was a significant risk factor for co-infection. A predictive model combining CRP, BUN, and the composite score demonstrated superior performance (AUC=0.851). Conclusions:This study provides critical evidence for early diagnosis and identification of high-risk populations for co-infections in SFTS patients.

OBJECTIVE To study the clinical efficacy of Professor Li Bingmao's Tongfu Xiere Quyu Shuli Prescription in the treatment of patients with functional dyspepsia(FD)of spleen and stomach damp-heat and qi stagnation and blood stasis type.METH-ODS A total of 206 patients with functional dyspepsia of spleen and stomach damp-heat and qi stagnation and blood stasis type diag-nosed by Hengshui People's Hospital were included in the study and randomly divided into a study group and a control group with 103 cases in each group.During the treatment,3 cases dropped out in each group.The control group adopted the conventional Western medicine treatment plan for functional dyspepsia(mosapride+rabeprazole),and the study group took Tongfu Xiere Quyu Shuli Pre-scription on the basis of the treatment of the control group.The treatment course of both groups was 4 weeks.The traditional Chinese medicine(TCM)syndrome scores,psychological status[self-rating anxiety scale(SAS),self-rating depression scale(SDS),and quality of life[Nepean dyspepsia life quality index(NDLQI)of the two groups of patients before and after treatment were observed and the clinical efficacy was evaluated;serum motilin(MTL),ghrelin,gastrin(GAS),corticotropin-releasing hormone(CRH)and pep-sinogen(PG Ⅰ,PG Ⅱ)were measured by enzyme-linked immunosorbent assay;changes in gastric motility indexes were analyzed by electrogastrogram analyzer;changes in intestinal flora were detected by instillation method.The occurrence of adverse reactions in the two groups of patients was monitored during treatment.RESULTS After treatment,the TCM syndrome scores of the two groups were significantly reduced(P<0.05,P<0.01),and the score in the study group was lower than that in the control group(P<0.01).The total effective rate of the study group was significantly higher than that in the control group(P<0.01).After treatment,the expression levels of MTL,Ghrelin,GAS,PG Ⅰ and PG Ⅱ in the two groups increased,and CRH decreased,and the improvement degree of the study group was better than that of the control group(P<0.01).After treatment,the main frequency and slow wave percentage of the electrogastrogram increased in the two groups,and the study group was better than that of the control group(P<0.01).After treat-ment,the number of bifidobacteria and lactobacilli in the two groups increased,and the number in the study group was greater than that in the control group,while the number of enterobacteria,enterococci and yeast decreased,and the number in the study group was less than that in the control group(P<0.01).There was no significant difference in adverse reactions between the two groups(P>0.05).CONCLUSION Tongfu Xiere Quyu Shuli Prescription is effective in the treatment of FD patients with spleen and stomach damp-heat syndrome,and can improve FD clinical symptoms,quality of life,anxiety and depression symptoms,regulate gastrointesti-nal hormone expression levels,gastric motility and intestinal flora expression,and does not increase adverse reactions,and is safe and reliable.

The reverse phase nystagmus is not uncommon in clinical practice.Inadequate understanding brings great confusion to clinical diagnosis and treatment,which leads to misdiagnosis frequently and also increases the eco-nomic burden on patients.The purpose of this paper is to summarize and analyze the mechanism,characteristics and clinical significance of reverse phase nystagmus,to help clinicians better understand the significance of inversion nys-tagmus in benign paroxysmal positional vertigo,in order to achieve accurate and efficient diagnosis and treatment of these patients.

BACKGROUND:Preliminary clinical observations found that Jiawei Chunze Decoction is an effective formula for clinical treatment of urinary retention after spinal cord injury.Animal experiments have found that the phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway is closely related to the degree of bladder dysfunction. OBJECTIVE:To further investigate the effects of Jiawei Chunze Decoction on bladder function and PI3K/Akt signaling pathway in rats with urinary retention. METHODS:Sixty female Sprague-Dawley rats were randomly divided into sham operation group,model group,Jiawei Chunze Decoction low-dose group,Jiawei Chunze Decoction high-dose group and agonist group.In the sham operation group,the spinal cord was exposed but not transected.In the other groups,the modified Hassan Shaker spinal cord transection method was used to prepare the model of sacral medullary injury.At 24 hours after modeling,the sham operation group and model group were intragastrically given equal volume of normal saline,Jiawei Chunze Decoction low-dose and high-dose groups were given Jiawei Chunze Decoction granules containing 14.4 and 28.8 g/kg,respectively,via intragastric administration for 4 weeks,and the agonist group was treated with an intraperitoneal injection of PI3K/Akt signaling pathway agonist 740Y-P at a dose of 0.02 mg/kg.After 4 weeks of treatment,the maximum bladder capacity,leakage point pressure and bladder compliance of rats in each group were detected by urine flow dynamics.The minimum bladder contraction tension and frequency of rats in each group were detected by detrusor pull test.The pathological changes of the rat bladder in each group were observed by hematoxylin-eosin staining.The concentrations of GRP78,CHOP and Caspase-12 in serum were detected by ELISA,and the mRNA and protein expressions of PI3K,Akt,GRP78,CHOP and Caspase-12 in bladder tissues were detected by RT-PCR and western blot,respectively. RESULTS AND CONCLUSION:Compared with the sham operation group,the maximum bladder volume,bladder compliance and minimum systolic tension of rats in the model group were increased(P<0.05),and the leakage point pressure and bladder contraction frequency were decreased(P<0.05);serum GRP78,CHOP,and Caspase-12 levels were also increased(P<0.05).The arrangement of bladder epithelial cells in the model group was disordered,and there was monocyte infiltration between cells,tissue edema,and detrusor tract atrophy.The mRNA and protein expressions of PI3K and Akt in bladder tissues were significantly decreased in the model group compared with the sham operation group,while those of GRP78,CHOP and Caspase-12 were increased(P<0.05).Compared with the model group,the maximum bladder volume,bladder compliance and minimum systolic tension of rats were decreased in the Jiawei Chunze Decoction low-dose,high-dose and agonist groups after 4 weeks of intervention(P<0.05),while the leakage point pressure and bladder contraction frequency were increased(P<0.05);serum GRP78,CHOP,Caspase-12 levels were decreased(P<0.05).The bladder epithelial cells in the three intervention groups were distributed evenly,arranged neatly,with less inflammatory cell infiltration and fuller detrusor muscle bundle.Compared with the model group,the mRNA and protein expressions of PI3K and Akt were increased in the three intervention groups,while those of GRP78,CHOP and Caspase-12 were decreased(P<0.05).The Jiawei Chunze Decoction high-dose group was better than the Jiawei Chunze Decoction low-dose group and shared the similar results with the agonist group.To conclude,Jiawei Chunze Decoction can improve the bladder function of rats with urinary retention after spinal cord injury,and the mechanism may be related to reducing the occurrence of endoplasmic reticulum stress in bladder tissue through the PI3K/Akt signaling pathway,and then alleviating apoptosis.

BACKGROUND:Research has demonstrated a close association between ferroptosis and vascular dementia.Tongmai Kaiqiao Pill has a certain effect on improving the cognitive function of vascular dementia patients,but its mechanism is unclear. OBJECTIVE:To explore the interventional effects and molecular mechanisms of Tongmai Kaiqiao Pill for vascular dementia based on the regulation of ferroptosis by the nuclear factor erythroid-2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)/glutathione peroxidase 4(GPX4)signaling pathway. METHODS:Among eighty-four SD male rats,12 rats were used as the sham-operated group,and the rest of them were prepared as a model of vascular dementia by the modified 2-VO method,and then randomly divided into the model group,the Tongmai Kaiqiao Pills high-,moderate-,and low-dosage(27.6,13.8,and 6.9 g/kg)groups,the combined group(Tongmai Kaiqiao Pill high-dosage+ML385,20 mg/kg),and the donepezil hydrochloride group(0.45 mg/kg).The drug was given once a day by intragastric administration.The combined group was also intraperitoneally injected Nrf2 inhibitor ML385,once a day,for 4 weeks.Morris water maze was used to detect the learning memory ability of rats.Hematoxylin-eosin staining was used to observe the histopathological changes in the hippocampus of rats in each group.Colorimetric assay was used to detect the content of reduced glutathione,ferrous ion(Fe2+),and malondialdehyde in the serum of rats.Prussian blue staining was used to detect the iron deposition in the hippocampal tissue of rats.Transmission electron microscopy was used to observe the ultrastructural changes of mitochondria in rat hippocampal tissues.Western blot assay was used to detect the protein expression levels of Nrf2,HO-1,GPX4,XCT,and ferritin heavy chain 1(FTH1)in rat hippocampal tissues. RESULTS AND CONCLUSION:(1)In comparison to the sham operation,rats in the model group exhibited a significantly prolonged latency period(P<0.05)and a reduced number of platform crossings(P<0.05).Additionally,the hippocampal tissues of these rats displayed loosely organized structure,deeply stained cell nuclei,and solidified or lysed chromatin.Ferri ions aggregated in CA1 region.There were atrophied mitochondria with dissolved cristae and thickened mitochondrial membranes.Fe2+,malondialdehyde,and reduced glutathione levels in rat serum were found to be elevated(P<0.05).A significant reduction in the expression of GPX4,HO-1,XCT,Nrf2,and FTH1 proteins was detected in the hippocampus(P<0.05).(2)Compared to the model group,the average escape latency of the rats was significantly reduced following intervention with Tongmai Kaiqiao Pills and donepezil hydrochloride(P<0.05),with an increased number of platform crossings(P<0.05).Hippocampal neurons showed significant recovery.Notably,iron aggregation in the CA1 region was significantly reduced,and mitochondrial structure and function were improved.There were significant reductions in Fe2+and malondialdehyde levels,while the levels of GPX4,HO-1,XCT,Nrf2,and FTH1 in rat hippocampal tissues,and reduced glutathione in serum were significantly increased(P<0.05).(3)The high-dose Tongmai Kaiqiao Pills exhibited a treatment effect comparable to that of donepezil hydrochloride(P>0.05),with a significant prolongation of water maze escape latency(P<0.05),a reduced number of platform crossings(P<0.05),and insignificant neuronal pathological changes in the CA1 area.However,the combined group showed increased iron deposition,elevated malondialdehyde and Fe2+levels in blood serum(P<0.05),reduced glutathione content(P<0.05),hippocampal tissue mitochondrial atrophy,and reduced expression of Nrf2,XCT,HO-1,GPX4,and FTH1 proteins(P<0.05).Within a certain range,higher doses of Tongmai Kaiqiao Pills demonstrated a more pronounced effect,comparable to the efficacy of high-dose donepezil hydrochloride.(4)It is concluded that Tongmai Kaiqiao Pills have been shown to mitigate histopathological changes in the rat hippocampus and enhance cognitive function in rats with vascular dementia.The mechanism of action is likely associated with the suppression of ferroptosis through the activation of the Nrf2/HO-1/GPX4 signaling pathway.

OBJECTIVE To study the effects of peripheral blood-derived exosomes （Exo） intervened by Naozhenning （NZN） on injury of neuron cells HT22 induced by microglia BV-2 cells. METHODS Wistar rats were selected to prepare peripheral blood- derived Exo intervened by NZN （66.83 g/kg）， referred to as NZN-Exo； peripheral blood-derived Exo intervened by normal saline and piracetam （PLXT， 1.62 g/kg） were prepared using the same method， denoted as KB-Exo and PLXT-Exo respectively， and all Exo were subsequently identified. Meanwhile， BV-2 cells were stimulated with 1 μg/mL lipopolysaccharide （LPS） to prepare LPS- stimulated supernatant， and non-LPS-stimulated supernatant was prepared following the same protocol. HT22 cells were divided into four groups: KB-Exo group （treated with non-LPS-stimulated supernatant+KB-Exo）， model group （treated with LPS-stimulated supernatant+KB-Exo）， PLXT-Exo group （treated with LPS-stimulated supernatant+PLXT-Exo）， and NZN-Exo group （treated with LPS-stimulated supernatant+NZN-Exo）， with the concentration of the corresponding Exo in all groups being 50 μg/mL. After 24 hours of culture， the proliferation of HT22 cells was detected by the CCK-8 assay and EdU assay； the apoptosis of HT22 cells was detected； the microstructure of HT22 cells was observed； the contents of interleukin-1β （IL-1β）， IL-10， nuclear factor-κB （NF- κB）， and tumor necrosis factor-α （TNF-α） in HT22 cells were measured， as well as the expression levels of TNF-α， NOD-like receptor thermal protein domain associated protein 3 （NLRP3）， Caspase-1， B-cell lymphoma-2（ Bcl-2）， and Bcl-2-associated X protein （Bax）. RESULTS KB-Exo， PLXT-Exo and NZN-Exo were successfully prepared， and all Exo exhibited typical cup-shaped contours and membrane-enclosed characteristics. Compared with KB-Exo group， model group showed significantly decreased cell proliferation rates （detected by CCK-8 and EdU）， intracellular IL-10 levels， and Bcl-2 protein expression levels （P＜0.05）； while the cell apoptosis rate， intracellular levels of IL-1β， TNF-α， and NF-κB， as well as the expression levels of NLRP3， TNF-α， Caspase-1， and Bax proteins were significantly increased （P＜0.05）. Additionally， in the model group， the cells showed volume swelling， incomplete cell membrane， nucleolar rupture， significant swelling and deformation of mitochondria， and severe vacuolization. Compared with model group， the above quantitative indicators in the PLXT-Exo group and NZN-Exo group were significantly reversed （P＜0.05）， with large and round cell nuclei， intact nuclear membranes， and reduced mitochondrial vacuolization. CONCLUSIONS Peripheral blood-derived Exo intervened by naozhenning can alleviate the injury of neuronal cells HT22 by inhibiting inflammatory responses and cell apoptosis.