In this study， bibliometric methods were used to systematically investigate the name and origin， the evolution of prescription composition， dose evolution， origin and processing method， decoction method， ancient application， modified application， modern application and other information of Huoxiang Zhengqisan. After research， Huoxiang Zhengqisan， also known as Huoxiang Zhengqitang， was first recorded in Taiping Huimin Hejijufang. The original formula is composed of 41.3 g of Arecae Pericarpium， 41.3 g of Angelicae Dahuricae Radix， 41.3 g of Perilla frutescens（actually Perillae Folium）， 41.3 g of Poria， 82.6 g of Pinelliae Rhizoma， 82.6 g of Atractylodis Macrocephalae Rhizoma， 82.6 g of Citri Reticulatae Pericarpium（actually Citri Exocarpium Rubbum）， 82.6 g of Magnoliae Officinalis Cortex， 82.6 g of Platycodonis Radix， 123.9 g of Pogostemonis Herba， and 103.25 g of Glycyrrhizae Radix et Rhizoma. In this formula， Magnoliae Officinalis Cortex is processed according to the specifications for ginger-processed products， Glycyrrhizae Radix et Rhizoma is processed according to the specifications for stir-fried products， and other herbs are used in their raw products. The botanical sources of the herbs are consistent with the 2020 edition of Pharmacopoeia of the People's Republic of China. The above herbs are ground into a fine powder with a particle size passing through a No. 5 sieve. For each dose， take 8.26 g of the powdered formula， add 300 mL of water， along with 3 g of Zingiberis Rhizoma Recens and 3 g of Jujubae Fructus， and decoct until reduced to 140 mL. The decoction should be administered hot， with three times daily. To induce sweating， the patient should be kept warm under a quilt， and an additional dose should be prepared and taken if needed. This formula is traditionally used to relieve the exterior and resolve dampness， regulate Qi and harmonize the middle， which is mainly used to treat a series of diseases of digestive and respiratory systems. However， potential adverse reactions， including allergies， purpura and disulfiram-like reactions， should be considered during clinical use. Huoxiang Zhengqisan features a rational composition， extensive clinical application， and strong potential for further research and development.

In this study， bibliometric methods were used to systematically investigate the name and origin， the evolution of prescription composition， dose evolution， origin and processing method， decoction method， ancient application， modified application， modern application and other information of Huoxiang Zhengqisan. After research， Huoxiang Zhengqisan， also known as Huoxiang Zhengqitang， was first recorded in Taiping Huimin Hejijufang. The original formula is composed of 41.3 g of Arecae Pericarpium， 41.3 g of Angelicae Dahuricae Radix， 41.3 g of Perilla frutescens（actually Perillae Folium）， 41.3 g of Poria， 82.6 g of Pinelliae Rhizoma， 82.6 g of Atractylodis Macrocephalae Rhizoma， 82.6 g of Citri Reticulatae Pericarpium（actually Citri Exocarpium Rubbum）， 82.6 g of Magnoliae Officinalis Cortex， 82.6 g of Platycodonis Radix， 123.9 g of Pogostemonis Herba， and 103.25 g of Glycyrrhizae Radix et Rhizoma. In this formula， Magnoliae Officinalis Cortex is processed according to the specifications for ginger-processed products， Glycyrrhizae Radix et Rhizoma is processed according to the specifications for stir-fried products， and other herbs are used in their raw products. The botanical sources of the herbs are consistent with the 2020 edition of Pharmacopoeia of the People's Republic of China. The above herbs are ground into a fine powder with a particle size passing through a No. 5 sieve. For each dose， take 8.26 g of the powdered formula， add 300 mL of water， along with 3 g of Zingiberis Rhizoma Recens and 3 g of Jujubae Fructus， and decoct until reduced to 140 mL. The decoction should be administered hot， with three times daily. To induce sweating， the patient should be kept warm under a quilt， and an additional dose should be prepared and taken if needed. This formula is traditionally used to relieve the exterior and resolve dampness， regulate Qi and harmonize the middle， which is mainly used to treat a series of diseases of digestive and respiratory systems. However， potential adverse reactions， including allergies， purpura and disulfiram-like reactions， should be considered during clinical use. Huoxiang Zhengqisan features a rational composition， extensive clinical application， and strong potential for further research and development.

Sesquiterpenes are natural terpenes containing 15 carbon atoms. They are widely used in the perfume, pharmaceutical, and biofuel industries due to their remarkable biological activities. The traditional production of sesquiterpenes relies on chemical synthesis or plant extraction, which has the disadvantages of low yields and waste of resources. The construction of microbial cell factories for the efficient synthesis of sesquiterpenes by means of synthetic biology provides a new option. In recent years, with the development of metabolic engineering and synthetic biology, the heterologous synthesis of a variety of sesquiterpenes has been successfully achieved by metabolic engineering of the oleaginous yeast, Yarrowia lipolytica. In this paper, we review the research progress in the heterologous synthesis of different sesquiterpenes by Y. lipolytica, discuss the synthetic biology strategies commonly used in this field, and make an outlook on the research directions and engineering approaches to further enhance the sesquiterpene yield in this host. This paper provides a reference for strategies such as synergistic optimization of synthetic biology and metabolic engineering, enhanced precursors, and opens up new directions for the application of synthetic biology in green chemistry and sustainable production.
Yarrowia/genetics* ; Sesquiterpenes/metabolism* ; Metabolic Engineering/methods* ; Synthetic Biology/methods*

Objective This study aims to monitor the mRNA ratio of podocin to nephrin (PNR) in glomerular podocytes of early diabetic kidney disease (DKD) rat models. The feasibility of using PNR as an early diagnostic indicator for DKD was evaluated by comparing it with the urinary albumin-to-creatinine ratio (U-ACR). Additionally, the early intervention effects of valsartan and fosinopril sodium on DKD were compared. Methods The DKD rat model was established by caudal intravenous injection of streptozotocin (STZ) at a dosage of 60 mg/kg. The early changes in PNR and U-ACR were monitored and compared, followed by timely intervention with valsartan and fosinopril sodium. Hematoxylin and eosin staining (HE) was used to observe glomerular structure, while transmission electron microscopy examined the ultrastructure of glomerular podocytes. ResultsPNR reached the critical value(≥1) on day 9 after modeling, earlier than U-ACR, which reached the critical value(≥30 mg/g) on day 15. Intervention with valsartan and fosinopril sodium on day 9 after modeling significantly reduced U-ACR (P < 0.05), with low-dose valsartan showing better results than high-dose (P>0.05), while high-dose fosinopril sodium outperformed low-dose (P>0.05). Both low doses of valsartan and fosinopril sodium significantly reduced PNR (P<0.05), with no significant effect observed for high doses. The interventions with valsartan and fosinopril sodium improved and maintained glomerular structure and podocyte arrangement. ConclusionPNR changes earlier than U-ACR, indicating its potential as an early diagnostic marker for DKD in rats. Early intervention with valsartan and fosinopril sodium demonstrates a therapeutic effect on DKD in rats.

OBJECTIVE: To compare the clinical efficacy of micro steel plate and Kirschner needle oblique and transverse internal fixation of adjacent metacarpal bone in the treatment of metacarpal diaphyseal oblique fracture. METHODS: Fifty-nine patients with metacarpal diaphyseal oblique fractures admitted between January 2018 and September 2021 were selected as the study subjects and divided into the observation group (29 cases) and the control group (30 cases) based on different internal fixation methods. The observation group was treated with Kirschner wire oblique and transverse internal fixation of adjacent metacarpal bones, while the control group was treated with micro steel plate internal fixation. Postoperative complications, operation time, incision length, fracture healing time, treatment cost, and metacarpophalangeal function were compared between the two groups. RESULTS: No incision or Kirschner wire infections occurred in the 59 patients, except for one in the observation group. No fixation loosening, rupture, or loss of fracture reduction occurred in any of the patients. The operation time and incision length in the observation group were (20.5±4.2) min and (1.6±0.2) cm, respectively, which were significantly shorter than those in the control group (30.8±5.6) min and (4.3±0.8) cm (P<0.05). The treatment cost and fracture healing time in the observation group were (3 804.5±300.8) yuan and (7.2±1.1) weeks, respectively, which were significantly lower than those in the control group (9 906.9±860.6) yuan and (9.3±1.7) weeks (P<0.05). The excellent and good rate of metacarpophalangeal joint function in the observation group was significantly higher than that in the control group at 1, 2, and 3 months after operation (P<0.05), but there was no significant difference between the two groups at 6 months after operation (P>0.05). CONCLUSION Micro steel plate internal fixation and Kirschner wire oblique and transverse internal fixation of adjacent metacarpal bones are both viable surgical methods for treating metacarpal diaphyseal oblique fractures. However, the latter has the advantages of causing less surgical trauma, shorter operation time, better fracture healing, lower cost of fixation materials, and no need for secondary incision and removal of internal fixation.
Humans ; Metacarpal Bones/injuries* ; Fractures, Bone/surgery* ; Fracture Fixation, Internal/methods* ; Bone Wires ; Bone Plates ; Treatment Outcome

OBJECTIVE To investigate the effect of gene polymorphism on opioid-induced constipation. METHODS The target genes related to opioid-induced constipation were screened out through searching guidelines， databases and evidence-based medical data， and then 100 cancer pain patients who received opioid drugs for analgesia were included as the study subjects. According to whether there were adverse effects of constipation after medication or not， they were divided into test group and control group， with 50 cases in each group. The target gene was detected by PCR or fluorescence in situ hybridization. The SNPStats program was used to carry out Hardy-Weinberg balance test and correlation analysis between gene polymorphism and opioid-induced constipation. The multivariate Logistic regression analysis was used to explore the relevant predictive factors of opioid-induced constipation， and receiver operating characteristic （ROC） curve of subjects was drawn to analyze the effectiveness of each predictive factor in predicting opioid-induced constipation. RESULTS CYP2D6， CYP3A5*3， ABCB1 and OPRM1 were selected as target genes for detection. The results of genotype detection showed that the frequency distribution of CYP2D6 （rs1065852， rs1135822， rs16947， rs28371725， rs28371735）， CYP3A5*3 （058rs776746）， ABCB1 （062rs1045642）， OPRM1 （047rs1799971） alleles were consistent with Hardy-Weinbergbalance test. The correlation analysis results showed that the proportion of genotype GG and AG in CYP3A5*3 （058rs776746， 163.com A＞G） and genotype AA and AG in OPRM1 （047rs1799971， A＞G） of patients was significantly higher in test group than that in the control group （P＜0.05）. Multivariate Logistic regression analysis showed that medication duration， CYP3A5*3 and OPRM1 gene polymorphism could be used as predictors of opioid- induced constipation in patients （P＜0.05）. The ROC curve analysis results showed that the areas under the ROC curves for medication duration and CYP3A5*3， OPRM1 gene polymorphism were 0.648， 0.640 and 0.670， respectively， with the optimal cutoff values of 124.0， 0.5 and 0.5， respectively. CONCLUSIONS Genotype GG and AG in CYP3A5*3 （058rs776746，A＞G） and genotype AA and AG in OPRM1 （047rs1799971，A＞G） are associated with opioid-induced constipation， which are expected to become clinical predictors of opioid-induced constipation， and more attention should be paid to the occurrence of constipation in patients who have been taking opioids for a long time.

Fetal electrocardiogram (ECG) signals provide important clinical information for early diagnosis and intervention of fetal abnormalities. In this paper, we propose a new method for fetal ECG signal extraction and analysis. Firstly, an improved fast independent component analysis method and singular value decomposition algorithm are combined to extract high-quality fetal ECG signals and solve the waveform missing problem. Secondly, a novel convolutional neural network model is applied to identify the QRS complex waves of fetal ECG signals and effectively solve the waveform overlap problem. Finally, high quality extraction of fetal ECG signals and intelligent recognition of fetal QRS complex waves are achieved. The method proposed in this paper was validated with the data from the PhysioNet computing in cardiology challenge 2013 database of the Complex Physiological Signals Research Resource Network. The results show that the average sensitivity and positive prediction values of the extraction algorithm are 98.21% and 99.52%, respectively, and the average sensitivity and positive prediction values of the QRS complex waves recognition algorithm are 94.14% and 95.80%, respectively, which are better than those of other research results. In conclusion, the algorithm and model proposed in this paper have some practical significance and may provide a theoretical basis for clinical medical decision making in the future.
Algorithms ; Neural Networks, Computer ; Electrocardiography ; Databases, Factual ; Fetus

OBJECTIVE To conduct a c omprehensive clinical evaluation method of Chinese patent medicine ，and to provide reference for rational clinical drug use. METHODS Taking the top 10 Chinese patent medicine injections for promoting blood circulation and removing stasis in Shandong province from 2016 to 2020 collected by the National Rational Drug Use Monitoring Network as an example ，the method combining health technology assessment with objective judgement analysis is used to construct the comprehensive evaluation index system ；based on evidence-based medical evidence and pharmacoeconomic model ，the safety ， effectiveness and economy of the drug were evaluated comprehensively ，and the scores were quantified. RESULTS & CONCLUSIONS The final scores of the 10 kinds of Chinese patent medicine injections were between 26 and 37 scores. Safflower yellow for injection scored the highest score in the treatment of cerebral infarction and angina pectoris of coronary heart disease ， while Ginkgo diterpene lactone meglumine injection and Shuxuening injection had the highest scores in the treatment of coronary heart disease. The clinical comprehensive evaluation method of Chinese patent medicine based on evidence-based medical evidence and pharmacoeconomic model can clarify the comprehensive value of Chinese patent medicine in clinic ，promote rational drug use in clinic ，and provide basis for the next adjustment of medical insurance catalogue and essential medicine catalogue ，decision-making of centralized procurement of related drugs.

【Objective】 To explore and verify the mechanism of curcumin’s inhibition of the proliferation of renal clear cell carcinoma （RCCC） based on network pharmacology and bioinformatics. 【Methods】 We screened common target genes of RCCC and curcumin from PharmMapper and GeneCards databases. We used TCGA database data analysis to screen out common target genes which not only differentially expressed between RCCC tissue samples and normal tissue samples but also affected prognosis. We also used STRING platform to construct curcumin-RCCC targets interaction network， used R software to perform GO biological process analysis and KEGG pathway enrichment analysis based on the above-mentioned screening target proteins. After curcumin and/or active oxygen inhibitor N-acetyl-L-cysteine （NAC） were incubated in renal cancer 786-O and ACHN cells， CCK8 was used to detect the effects of different concentrations of curcumin on cell proliferation and cell viability. Reactive oxygen detection kit （DCFH-DA） was used to detect the level of intracellular reactive oxygen species， and malondialdehyde （MDA） determination kit （TBA method） to detect intracellular malondialdehyde changes. 【Results】 PharmMapper website and GeneCards database screened out 109 common targets of curcumin and RCCC. TCGA database data analysis screened out 37 differentially expressed genes （DEGs） that might affect the overall survival of patients. The core target proteins of curcumin screened out by protein-protein interaction （PPI） that inhibited the biological behavior of RCCC mainly involved CASP3， EGFR， CHEK1， HSP90AA1， and AR. GO enrichment analysis identified 213 items， mainly including reactive oxygen species metabolic process， response to steroid hormones， fibrinolysis and other biologically active processes. KEGG enrichment analysis identified 24 items， which were mainly related to pyruvate metabolism， glycolysis/gluconeogenesis， FoxO signaling pathway， colorectal cancer， tyrosine metabolism， IL-17 signaling pathway， apoptosis and other signaling pathways. Curcumin reduced the cell viability of 786-O and ACHN in a time- and dose-dependent manner （P<0.05）. After curcumin was incubated with kidney cancer cells， the level of reactive oxygen species and MDA increased significantly （P<0.05）. The addition of NAC reversed the effect of curcumin on the cell viability of 786-O and ACHN cells （P<0.05）. 【Conclusion】 Curcumin may participate in the oxidative stress pathway to inhibit the proliferation of renal cell carcinoma.

OBJECTIVE: To explore gender difference in the clinical manifestations of two children with Keishi-Bukuryo-Gan syndrome (KBGS). METHODS: Clinical manifestations of the two children were reviewed. Genetic testing was carried out through next generation sequencing (NGS). Treatment was summarized, and the prognosis was followed up. RESULTS: Both children showed particular appearance including megatooth, abnormal hair distribution, hands' abnormality and language development delay. NGS revealed that both children have carried pathogenic variants of the ANKRD11 gene (c.1903_1907del and c.4911delT), which resulted in shifting of amino acid sequences starting from the Lysine and Proline at positions 635 and 1638, respectively. The female patient exhibited central precocious puberty. Her height has increased by 13 cm, and sex characteristics has retracted after treatment with leuprorelin for 23 months and recombinant human growth hormone for 1 month. CONCLUSION Comparison of the two cases with different genders and summary of previously reported cases found that male KBGS patients have more obvious dysmorphisms such as triangular face, synophrys, ocular hypertelorism and vertebral body abnormality, with higher morbidity of epilepsy, mental retardation, autism, congenital heart disease, immune thrombocytopenia and other complications. KBGS is an autosomal dominant disease featuring more evident peculiar appearance and global development delay. Male patients often have multi-system involvement, and multidisciplinary cooperation is required for early recognition of particular features in order to improve the prognosis.
Abnormalities, Multiple ; Bone Diseases, Developmental ; Child ; Facies ; Female ; Humans ; Intellectual Disability ; Male ; Phenotype ; Repressor Proteins/genetics* ; Sex Characteristics ; Tooth Abnormalities