OBJECTIVE To provide a reference for clinical pharmacists to participate in the treatment of rare and complex cases of CTLA-4 haploid deficiency combined with severe malnutrition. METHODS The clinical pharmacist participated in the diagnosis and treatment of a complex case of CTLA-4 haploid deficiency with severe malnutrition， type 1 diabetes， blood coagulation abnormalities with gastrointestinal bleeding and virus infection， assisted the doctor to develop an individualized parenteral nutrition program， and dynamically adjusted the ratio of glucose and insulin （from 3.9∶1 to 15.6∶1）. When patient had severe coagulation abnormalities and gastrointestinal bleeding， the clinical pharmacist recommended discontinuing fat emulsion and switching to glucose amino acid dual energy supply； when the patient had a high fever accompanied by a sudden drop in platelets， the clinical pharmacist recommended to improve the second-generation sequencing of plasma metagenomics. Based on positive results for both EB virus and cytomegalovirus， the clinical pharmacist recommended to discontinue meropenem and switch to ganciclovir for antiviral treatment； when the patient experienced systemic itching and mental excitement， the clinical pharmacist quickly diagnosed as an adverse reaction of ganciclovir and recommended to switch to acyclovir for antiviral treatment. The clinical pharmacist simultaneously carried out parenteral nutrition medication education， and standardized infusion speed， and continuously monitored bleeding-related indicators. RESULTS The physician adopted the advice of the clinical pharmacist. After comprehensive intervention， the patient’s body temperature returned to normal， gastrointestinal bleeding stopped， coagulation indicators significantly improved， blood sugar control reached the standard， and the condition improved and the patient was discharged. CONCLUSIONS Clinical pharmacists rely on comprehensive pharmaceutical services to balance the benefits and risks of treatment for rare and complex cases. They play a key role in individualized nutrition planning， refined blood glucose control， infection identification and anti-infection optimization， and identification and treatment of adverse drug reactions to ensure patient medication safety and efficacy.

OBJECTIVE: In Pakistan, traditional medicines are an important component of the medical system, with numerous varieties and great demands. However, due to the scattered resources and the lack of systematic collection and collation, adulteration of traditional Pakistani medicine (TPM) is common, which severely affects the safety of their medicinal use and the import and export trades. Therefore, it is urgent to systematically organize and unify the management of TPM and establish a set of standards and operable methods for the identification of TPM. METHODS: We collected and organized the information on 128 TPMs with regard to their medicinal parts, efficacy, usage, and genetic material, based on Pakistan Hamdard Pharmacopoeia of Eastern Medicine: Pharmaceutical Codex. The genetic information of TPM is summarized from national center for biotechnology information (NCBI) and global pharmacopoeia genome database (GPGD). Furthermore, we utilized bioinformatics technology to supplement the chloroplast genome (cp-genome) data of 12 TPMs. To build the web server, we used the Linux + Apache + MySQL + PHP (LAMP) system and constructed the webpage on a PHP: Hypertext Preprocessor (PHP) model view controller (MVC) framework. RESULTS: We constructed a new genomic database, the traditional Pakistani medicine genomic database (TPMGD). This database comprises five entries, namely homepage, medicinal species, species identification, basic local alignment search tool (BLAST), and download. Currently, TPMGD contains basic profiles of 128 TPMs and genetic information of 102 TPMs, including 140 cytochrome c oxidase subunit I (COI) sequences and 119 mitochondrial genome sequences from Bombyx mori, 1 396 internal transcribed spacer 2 (ITS2) sequences and 1 074 intergenic region (psbA-trnH) sequences specific to 92 and 83 plant species, respectively. Additionally, TPMGD includes 199 cp-genome sequences of 82 TPMs. CONCLUSION TPMGD is a multifunctional database that integrates species description, functional information inquiry, genetic information storage, molecular identification of TPM, etc. The database not only provides convenience for TPM information queries but also establishes the scientific basis for the medication safety, species identification, and resource protection of TPM.

Genetic transformation is a fundamental tool in molecular biology research of medicinal plants. Tailoring transgenic technologies to each distinct medicinal plant would necessitate a substantial investment of time and effort. Here, we present a simple hairy root transformation method that does not require sterile conditions, utilizing Agrobacterium rhizogenes strain K599 and the visible RUBY reporter system. Transgenic hairy roots were obtained for six tested medicinal plant species, roots or rhizomes of which have recognized medicinal value, spanning four botanical families and six genera (Platycodon grandiflorus, Atractylodes macrocephala, Scutellaria baicalensis, Codonopsis pilosula, Astragalus membranaceus, and Glycyrrhiza uralensis). Furthermore, two previously identified Glycyrrhiza uralensis UGTs that convert liquiritigenin into liquiritin in heterologous systems were studied in planta using the method. Our results indicate that overexpression of GuUGT1 but not GuUGT10 and Cas9-mediated knockout of GuUGT1 profoundly influenced the accumulation of liquiritin and isoliquiritin in licorice roots. Therefore, the method described here represents a simple, rapid and widely applicable hairy root transformation method that enables fast gene functional study in medicinal plants.

Objective:To explore the occurrence and clinical characteristics of nephrogenic systemic fibrosis (NSF) induced by gadolinium-based contrast agents (GBCA).Methods:CNKI, Wanfang, VIP and PubMed databases were searched (as of October 28, 2024) and case reports on GBCA-related NSF were collected; the following information was extracted, including the publication year of the literature, country, patient gender, age, basic kidney diseases and renal replacement therapy, variety of GBCA used, exposure frequency, time of occurrence or diagnosis of NSF, clinical manifestations, pathological examination, main intervention measures and outcomes. The data were analyzed by descriptive statistics.Results:A total of 45 case reports were collected, involving 97 patients. The literature were reported mainly from the United States and published mainly in 2006 and 2007. Number of the relevant literature decreased significantly after 2008, but there were still new cases reports in China in the following years (for example, in 2023). Among the 97 patients, 53 (54.6%) were male and 44 (45.4%) were female; the age ranged from 9 to 83 years with a median age of 53 years. One patient was with severe malnutrition, while the other 96 had severe basic kidney diseases, including chronic kidney disease in 85 (88.5%) patients and acute kidney injury in 11 (11.5%) patients. Variety of GBCA exposed was described in 76 patients, including gadodiamide in 67 (88.2%) patients. Exposure frequency of GBCA before NSF occurrence was described in 88 patients, 48 (54.5%) of which were exposed only once and 23 (26.1%) were exposed twice. Time from the first GBCA exposure to the occurrence of NSF was described in 92 patients, with the shortest time of 2 days and the longest time of more than 10 years; 70.7% (65/92) occurred within 3 months after GBCA exposure. All patients had typical skin symptoms of NSF, which were confirmed by pathological examination. Among them, 43 (44.3%) had joint disorders, 9 patients had eye involvement, a few patients had cardiac fibrosis, respiratory failure, metabolic acidosis, rhabdomyolysis, muscle necrosis, etc. Follow-up information was described in 82 patients with a range of 4 months to 11 years. Among them, 21 patients (25.6%) died, mainly due to the basic kidney diseases and complications; 11 (13.4%) were severely disabled; 7 (8.5%) were mildly disabled or slowly deteriorated; 43 (52.4%) had stable disease or slightly improved condition.Conclusion:NSF caused by GBCA mainly occurs in patients with severe basic renal diseases, mostly caused by gadodiamide. Severe skin damage is often accompanied by joint involvement or even disability, and the overall prognosis is poor.

Objective:To explore the occurrence and clinical characteristics of nephrogenic systemic fibrosis (NSF) induced by gadolinium-based contrast agents (GBCA).Methods:CNKI, Wanfang, VIP and PubMed databases were searched (as of October 28, 2024) and case reports on GBCA-related NSF were collected; the following information was extracted, including the publication year of the literature, country, patient gender, age, basic kidney diseases and renal replacement therapy, variety of GBCA used, exposure frequency, time of occurrence or diagnosis of NSF, clinical manifestations, pathological examination, main intervention measures and outcomes. The data were analyzed by descriptive statistics.Results:A total of 45 case reports were collected, involving 97 patients. The literature were reported mainly from the United States and published mainly in 2006 and 2007. Number of the relevant literature decreased significantly after 2008, but there were still new cases reports in China in the following years (for example, in 2023). Among the 97 patients, 53 (54.6%) were male and 44 (45.4%) were female; the age ranged from 9 to 83 years with a median age of 53 years. One patient was with severe malnutrition, while the other 96 had severe basic kidney diseases, including chronic kidney disease in 85 (88.5%) patients and acute kidney injury in 11 (11.5%) patients. Variety of GBCA exposed was described in 76 patients, including gadodiamide in 67 (88.2%) patients. Exposure frequency of GBCA before NSF occurrence was described in 88 patients, 48 (54.5%) of which were exposed only once and 23 (26.1%) were exposed twice. Time from the first GBCA exposure to the occurrence of NSF was described in 92 patients, with the shortest time of 2 days and the longest time of more than 10 years; 70.7% (65/92) occurred within 3 months after GBCA exposure. All patients had typical skin symptoms of NSF, which were confirmed by pathological examination. Among them, 43 (44.3%) had joint disorders, 9 patients had eye involvement, a few patients had cardiac fibrosis, respiratory failure, metabolic acidosis, rhabdomyolysis, muscle necrosis, etc. Follow-up information was described in 82 patients with a range of 4 months to 11 years. Among them, 21 patients (25.6%) died, mainly due to the basic kidney diseases and complications; 11 (13.4%) were severely disabled; 7 (8.5%) were mildly disabled or slowly deteriorated; 43 (52.4%) had stable disease or slightly improved condition.Conclusion:NSF caused by GBCA mainly occurs in patients with severe basic renal diseases, mostly caused by gadodiamide. Severe skin damage is often accompanied by joint involvement or even disability, and the overall prognosis is poor.

AIM To investigate the consistency of chemical constituents between formula granules and standard decoction of Coptidis Rhizoma.METHODS Eighteen batches of standard decoctions were prepared,after which the extraction rate and contents,transfer rates of magnolflorine,jatrorrhizine,columbamine,epiberberine,coptisine,palmatine,berberin were determined,HPLC characteristic chromatograms were established.RESULTS There were 11 common peaks in the characteristic chromatograms of 18 batches of standard decoctions and 24 batches of formula granules with the similarities of 0.861-1.000,which were clusterd into two categories.The formula granules and standard decoction demonstrated approximated extraction rate and contents,transfer rates of index constituents.CONCLUSION The chemical constituents between formula granules and standard decoction of Coptidis Rhizoma display good consistency,which can provide references for the quality control,process research and clinical application of the former.

AIM To evaluate the quality of Beidougen Formula Granules.METHODS Fifteen batches of standard decoctions and three batches of formula granules were prepared,after which paste rate and contents,transfer rates of magnoflorine,daurisoline,dauricine were determined.HPLC specific chromatograms were established,and cluster analysis was adopted in chemical pattern recognition.RESULTS For three batches of formula granules,the paste rates were 15.1%-16.6%,the contents of magnoflorine,daurisoline,dauricine were 18.93-19.39,9.42-9.60,6.79-6.85 mg/g with the transfer rates of 34.42%-35.25%,43.81%-44.65%,27.27%-27.51%from decoction pieces to formula granules,respectively,and there were seven characteristic peaks in the specific chromatograms with the similarities of more than 0.95,which demonstrated good consistence with those of standard decoctions and accorded with related limit requirements.Fifteen batches of standard decoctions were clustered into two types,and the medicinal materials produced from Jilin,Hebei,Shangdong could be used for the preparation of formula granules.CONCLUSION This reasonable and reliable method can provide references for the quality control and clinical application of Beidougen Formula Granules.

To identify the active constituents in vitro and blood-absorbed ingredients in vivo from Yin Chen Hao decoction provides scientific evidence for probing its prevention and treatment mechanism on acute liver injury. An ultrahigh performance liquid chromatography quadrupole-time of flight-mass spectrometry (UPLC-QTOF/MS) method was applied for analysis of Yin Chen Hao decoction and the serum samples of mice with con-A induced acute liver injury after preventive oral administration for 14 days (the use of all laboratory animals in this study was approved by the Ethics Committee of the Naval Medical University, 19YF1459400). A total of 90 chemical constituents were identified from Yin Chen Hao decoction, mainly were flavonoids, terpenoids, tannins, quinones. 5 prototype compounds were identified in the serum, including chrysophanol, deoxyrhapontin-8-O-gallate, mussaenosidic acid, herniarin, emodin. The established UPLC-QTOF/MS method could efficiently and sensitively identify the constituents in vitro and blood-absorbed ingredients of Yin Chen Hao decoction, primarily clarify the material basis of its hepatoprotective effect, and provided a scientific basis for the quality marker selection and the pharmacodynamic material basis research on the decoction.

UPLC-Q-TOF-MS combined with network pharmacology and experimental verification was used to explore the mechanism of acupoint sticking therapy(AST) in the intervention of bronchial asthma(BA). The chemical components of Sinapis Semen, Cory-dalis Rhizoma, Kansui Radix, Asari Radix et Rhizoma, and Zingiberis Rhizoma Recens were retrieved from TCMSP as self-built database. The active components in AST drugs were analyzed by UPLC-Q-TOF-MS, and the targets were screened out in TCMSP and Swiss-TargetPrediction. Targets of BA were collected from GeneCards, and the intersection of active components and targets was obtained by Venny 2.1.0. The potential targets were imported into STRING and DAVID for PPI, GO, and KEGG analyses. The asthma model induced by house dust mite(HDM) was established in mice. The mechanism of AST on asthmatic mice was explored by pulmonary function, Western blot, and flow cytometry. The results indicated that 54 active components were obtained by UPLC-Q-TOF-MS and 162 potential targets were obtained from the intersection. The first 53 targets were selected as key targets. PPI, GO, and KEGG analyses showed that AST presumedly acted on SRC, PIK3 CA, and other targets through active components such as sinoacutine, sinapic acid, dihydrocapsaicin, and 6-gingerol and regulated PI3 K-AKT, ErbB, chemokine, sphingolipid, and other signaling pathways to intervene in the pathological mechanism of BA. AST can improve lung function, down-regulate the expression of PI3 K and p-AKT proteins in lung tissues, enhance the expression of PETN protein, and reduce the level of type Ⅱ innate immune cells(ILC2 s) in lung tissues of asthmatic mice. In conclusion, AST may inhibit ILC2 s by down-regulating the PI3 K-AKT pathway to relieve asthmatic airway inflammation and reduce airway hyperresponsiveness.
Acupuncture Points ; Animals ; Asthma/drug therapy* ; Drugs, Chinese Herbal ; Immunity, Innate ; Lymphocytes ; Mice ; Network Pharmacology

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis and insulin resistance and there are currently no approved drugs for its treatment. Hyperactivation of mTOR complex 1 (mTORC1) and subsequent impairment of the transcription factor EB (TFEB)-mediated autophagy-lysosomal pathway (ALP) are implicated in the development of NAFLD. Accordingly, agents that augment hepatic TFEB transcriptional activity may have therapeutic potential against NAFLD. The objective of this study was to investigate the effects of nuciferine, a major active component from lotus leaf, on NAFLD and its underlying mechanism of action. Here we show that nuciferine activated ALP and alleviated steatosis, insulin resistance in the livers of NAFLD mice and palmitic acid-challenged hepatocytes in a TFEB-dependent manner. Mechanistic investigation revealed that nuciferine interacts with the Ragulator subunit hepatitis B X-interacting protein and impairs the interaction of the Ragulator complex with Rag GTPases, thereby suppressing lysosomal localization and activity of mTORC1, which activates TFEB-mediated ALP and further ameliorates hepatic steatosis and insulin resistance. Our present results indicate that nuciferine may be a potential agent for treating NAFLD and that regulation of the mTORC1-TFEB-ALP axis could represent a novel pharmacological strategy to combat NAFLD.