Sensorineural hearing loss induced by gefitinib: A CARE-compliant case report and literature reviews.

RATIONALE: Gefitinib is a potent and selective orally active growth factor receptor (EGFR)-tyrosine kinase inhibitor that is commonly used to treat advanced non-small cell lung cancer patients with activating EGFR mutations. Hearing impairment with gefitinib was sparsely reported. In this report, we describe a case of sensorineural deafness associated with the administration of gefitinib, with a Naranjo score of 7. PATIENT CONCERNS: An 81-year-old female was diagnosed with lung adenocarcinoma with bone metastasis and an EGFR-activating mutation. The patient was prescribed gefitinib tablets at a daily dose of 250 mg for lung adenocarcinoma treatment. However, the patient experienced moderate to severe bilateral sensorineural deafness, primarily in her right ear, after taking gefitinib. Following the cessation of gefitinib administration, the patient exhibited partial restoration of auditory function. Upon resuming the medication, she experienced a worsening of deafness. DIAGNOSES: The otoscopic audiogram and hearing test indicated moderate to severe bilateral sensorineural deafness. INTERVENTIONS: The otolaryngologist recommended bilateral hearing aids to enhance hearing function. OUTCOMES: Throughout our follow-up period, the patient did not receive a hearing aid implant. LESSONS: This article first reported the ototoxicity caused by gefitinib. While rare, our report highlights that gefitinib-induced sensorineural deafness is possible and its mechanisms are still unclear. This adverse reaction should be monitored closely during clinical application of gefitinib to improve patient outcomes.

Effects of tobacco smoking on cardiovascular disease in patients with systemic lupus erythematosus: A systematic review and meta-analysis.

Background: Patients with systemic lupus erythematosus (SLE) are at increased risk of cardiovascular disease (CVD) compared to the general population. However, little is known about the effects of tobacco smoking on CVD in patients with SLE. Objective: To systematically review and summarize the available literature regarding the effects of tobacco smoking on developing CVD in patients with SLE. Methods: We retrieved relevant studies from the following databases: PubMed, EMBASE, Web of Science and China National Knowledge Internet (CNKI) database. Two reviewers independently reviewed the eligible studies, assessed their validity, and extracted relevant data. Sensitivity and subgroup analyses were performed to distinguish sources of heterogeneity. Results: A total of 10 studies, which comprised 6984 participants, were included in the analysis. The overall quality of evidence was rated as moderate to low. The smoking prevalence among CVD patients was 39.28% (271/690), which was higher than 31.36% (1974/6294) among non-CVD patients. Compared with never-smokers, the risk of developing CVD in current smokers was 1.42 (95% CI: 1.21-1.66). No significant publication bias was found in our meta-analysis. Conclusions: In spite of the several negative results, this study found that current smokers with SLE have an increased risk of developing CVD, although most of the included studies were in low-to-moderate quality. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022338109.

The Effect of Cardiovascular Medications on Disease-Related Outcomes in Idiopathic Pulmonary Fibrosis: A Systematic Review and Meta-Analysis.

Background: Multiple studies have revealed that idiopathic pulmonary fibrosis (IPF) patients are more at risk for cardiovascular diseases and that many IPF patients receive cardiovascular medications like statins, angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), and anticoagulants. Existing studies have reported divergent findings on the link between cardiovascular medications and fibrotic disease processes. The aim of this study is to synthesize the evidence on the efficacy of cardiovascular medications in IPF. Methods: We searched studies reporting the effect of cardiovascular medications on IPF in the PubMed, Embase, Web of Science, Cochrane Library, and two Chinese databases (China National Knowledge Infrastructure database and China Wanfang database). We calculated survival data, forced vital capacity (FVC) decline, and IPF-related mortality to assess the efficacy of cardiovascular medications in IPF. We also estimated statistical heterogeneity by using I2 and Cochran Q tests, and publication bias was evaluated by risk of bias tools ROBINS-I. Results: A total of 12 studies were included in the analysis. The included studies had moderate-to-serious risk of bias. Statin use was associated with a reduction in mortality (hazard ratio (HR), 0.89; 95% CI 0.83-0.97). Meta-analysis did not demonstrate any significant relationship between statin use and the FVC decline (HR, 0.86; 95% CI 0.73-1.02), ACEI/ARB use, and survival data (HR, 0.92; 95% CI 0.73-1.15) as well as anticoagulant use and survival data (HR, 1.16; 95% CI 0.62-2.19). Conclusion: Our study suggested that there is a consistent relationship between statin therapy and survival data in IPF population. However, there is currently insufficient evidence to conclude the effect of ACEI, ARB, and anticoagulant therapy on IPF population especially to the disease-related outcomes in IPF.

Inhibition of Aspirin-Induced Gastrointestinal Injury: Systematic Review and Network Meta-Analysis.

Background: Administration of aspirin has the potential for significant side effects of gastrointestinal (GI) injury mainly caused by gastric acid stimulation, especially in long-term users or users with original gastrointestinal diseases. The debate on the optimal treatment of aspirin-induced gastrointestinal injury is ongoing. We aimed to compare and rank the different treatments for aspirin-induced gastrointestinal injury based on current evidence. Methods: We searched PubMed, EMBASE, Cochrane Library (Cochrane Central Register of Controlled Trials), and Chinese databases for published randomized controlled trials (RCTs) of different treatments for aspirin-induced gastrointestinal injury from inception to 1 May 2021. All of the direct and indirect evidence included was rated by network meta-analysis under a Bayesian framework. Results: A total of 10 RCTs, which comprised 503 participants, were included in the analysis. The overall quality of evidence was rated as moderate to high. Eleven different treatments, including omeprazole, lansoprazole, rabeprazole, famotidine, geranylgeranylacetone, misoprostol, ranitidine bismuth citrate, chili, phosphatidylcholine complex, omeprazole plus rebamipide, and placebo, were evaluated in terms of preventing gastrointestinal injury. It was suggested that omeprazole plus rebamipide outperformed other treatments, whereas geranylgeranylacetone and placebo were among the least treatments. Conclusion: This is the first systematic review and network meta-analysis of different treatments for aspirin-induced gastrointestinal injury. Our study suggested that omeprazole plus rebamipide might be considered the best option to treat aspirin-induced gastrointestinal injury. More multicenter, high quality, large sample size randomized controlled trials will confirm the advantages of these medicines in the treatment of aspirin-induced gastrointestinal injury in the future.

Combination of Xuesaitong and Aspirin Based on the Antiplatelet Effect and Gastrointestinal Injury: Study Protocol for a Randomized Controlled Noninferiority Trial.

BACKGROUND: Aspirin is the first-line medication for prevention and treatment of coronary heart disease (CHD). However, long-term use of aspirin resulting in gastrointestinal mucosal injury and bleeding limits the regularity of medication. Xuesaitong is a marketed Chinese medicine contained main active component in Panax notoginseng saponins (PNS), which can significantly inhibit platelet aggregation in patients with CHD. Our previous studies have already showed that PNS could reduce the gastrointestinal mucosal injury caused by aspirin in preclinical study. However, there is a need for further clinical studies to evaluate synergy and attenuation effect of the combination. METHODS: This trial is a prospectively planned, open-labeled, parallel-grouped, single-centered clinical trial. A total of eligible 480 participants will be randomly allocated into three groups: aspirin group, Xuesaitong group, and drug combination group at a ratio of 1 : 1 : 1. The primary outcome is the change of platelet aggregation rate and calprotectin activity. Secondary outcomes include PAC-1, P-selectin, P2Y12, I-FABP activity, and fecal occult blood. Discussion. The results of the study are expected to provide evidence of high methodological and reporting quality on the synergy function of Xuesaitong and aspirin upon the antiplatelet and anti-gastrointestinal injury effect for CHD. It also provides an experimental basis for clinical rational drug combination therapy. Trial Registration. This trial was registered in the Chinese Clinical Trail Registry, ChiCTR2000036311, on 22 August 2020, http://www.chictr.org.cn/edit.aspx?pid=58798&htm=4.

[Expert consensus on prescription comment of Chinese traditional patent medicine for promoting the rational use of drugs in Beijing].

With the growth of number of Chinese patent medicines and clinical use, the rational use of Chinese medicine is becoming more and more serious. Due to the complexity of Chinese medicine theory and the uncertainty of clinical application, the prescription review of Chinese patent medicine always relied on experience in their respective, leading to the uncontrolled of clinical rational use. According to the traditional Chinese medicine (TCM) theory and characteristics of the unique clinical therapeutics, based on the practice experience and expertise comments, our paper formed the expert consensus on the prescription review of Chinese traditional patent medicine for promoting the rational use of drugs in Beijing. The objective, methods and key points of prescription review of Chinese patent medicine, were included in this expert consensus, in order to regulate the behavior of prescription and promote rational drug use.

[Standardization of names in prescriptions of traditional Chinese medicines].

Chinese medicine prescriptions are a type of medical documents written by doctors after they understand the patients' conditions for syndrome differentiation. Chinese medicine prescriptions are also the basis for pharmacy personnel to dispense medicines and guide patients to use drugs. It has the legal, technical and economic significances. Chinese medicine prescriptions contain such information of names, quantity and usage. Whether the names of drugs in Chinese medicine prescriptions are standardized or not is directly related to the safety and efficacy of the drugs. At present, nonstandard clinical prescriptions are frequently seen. With "Chinese medicine prescription", "names of drug in Chinese medicine prescription" and "standards of Chinese medicine prescription" as key words, the author searched CNKI, Wanfang and other databases, and consulted nearly 100 literatures, so as to summarize current names of drugs in traditional Chinese medicine prescription, analyze the reasons, and give suggestions, in the expectation of standardizing the names of drugs used in traditional Chinese medicine prescriptions.

An improved association-mining research for exploring Chinese herbal property theory: based on data of the Shennong's Classic of Materia Medica.

Knowledge Discovery in Databases is gaining attention and raising new hopes for traditional Chinese medicine (TCM) researchers. It is a useful tool in understanding and deciphering TCM theories. Aiming for a better understanding of Chinese herbal property theory (CHPT), this paper performed an improved association rule learning to analyze semistructured text in the book entitled Shennong's Classic of Materia Medica. The text was firstly annotated and transformed to well-structured multidimensional data. Subsequently, an Apriori algorithm was employed for producing association rules after the sensitivity analysis of parameters. From the confirmed 120 resulting rules that described the intrinsic relationships between herbal property (qi, flavor and their combinations) and herbal efficacy, two novel fundamental principles underlying CHPT were acquired and further elucidated: (1) the many-to-one mapping of herbal efficacy to herbal property; (2) the nonrandom overlap between the related efficacy of qi and flavor. This work provided an innovative knowledge about CHPT, which would be helpful for its modern research.

[Study on effect of Curculiginis Rhizoma and its active ingredient on PXR-CYP3A of L02 cells in different states].

OBJECTIVE: To define the effect of Curculiginis Rhizoma and its active ingredient orcinol glucoside on PXR-CYP3A of L02 cells in normal and deficiency-cold states, in order to lay a foundation for studies on the mechanism of efficacy expression differentiation of Curculiginis Rhizoma in different states. METHOD: Serums of normal and deficiency-cold rats were adopted to culture L02 cells and induce cells in normal and deficiency-cold states. After aqueous extracts from Curculiginis Rhizoma and its active ingredient orcinol glucoside were used in cells in different states, PXR protain expression and CYP3A activity of L02 cells in normal and deficiency-cold states were observed. RESULT: MTT results showed that aqueous extracts from Curculiginis Rhizoma and orcinol glucoside could significantly enhance viability of L02 cells. Aqueous extracts from Curculiginis Rhizoma could significantly reduce PXR protein expression of L02 cells in normal state, while orcinol glucoside could significantly reduce CYP3A activity and PXR protein expression of L02 cells in normal state. Meanwhile, aqueous extracts from Curculiginis Rhizoma could significantly increase CYP3A activity and PXR protein expression of L02 cells in deficiency-cold state, while orcinol glucoside could significantly reduce CYP3A activity and increase PXR protein expression of L02 cells in deficiency-cold state. CONCLUSION: Curculiginis Rhizoma can activate PXR and induce CYP3A activity of L02 cells in deficiency-cold state, but with no effect or even counteraction on PXR and its induced CYP3A of L02 cells in normal state.

[A theoretical and experimental study on the Fuzzy evaluation model of biological performance of Chinese materia medica with an either cold or hot herbal property].

OBJECTIVE: The concepts of cold and hot herbal properties in traditional Chinese medicine (TCM), reflecting the efficacy trends of medicinal herbs, have the Fuzzy characteristics. It is suited for the application of Fuzzy mathematics in research of herbal properties. For a comprehensive evaluation of herbal properties, this work constructed and made a practice of the Fuzzy discrimination model regarding the biological performance of Chinese materia medica. METHODS: Firstly, TCM formulas of cold or hot property were employed for setting the reference values and calculating the membership functions of cold and hot Fuzzy sets with Fisher discriminant. Then the model parameters of cold performance function (CPF) and hot performance function (HPF) were acquired. Second, the experimental data from studies on changes in multisystem indicators of animals given the classical cold formula (Sanhuang Fang) and hot formula (Jiangfugui Fang) were collected to calculate CPF and HPF. Then an experiment of administration of hot property herbs, Rougui (Cortex Cinnamomi) and Xianmao (Rhizoma Curculiginis), and cold property herbs, Huangbai (Cortex Phellodendri) and Zhizi (Fructus Gardeniae) to normal animals and animals with glucocorticoid-induced yang-deficiency or yin-deficiency state was designed. The relative changes in animal states were analyzed by the evaluation model to find the way in which herbal properties are represented. RESULTS: The HPF values of biological performance were higher than the CPF values in administration of Rougui to animals of normal (0.528>0.221), yang-deficiency (0.203>-0.490) and yin-deficiency (1.750>-0.479) states, and in administration of Xianmao to animals of normal (0.474>-1.601) and yang-deficiency (0.288>-1.923) states, which represented the hot property. The HPF values of biological performance were lower than the CPF values in administration of Huangbai to animals of normal (-0.870<0.798) and yang-deficiency (-0.339<0.194) states, and in administration of Zhizi to animals of yin-deficiency (-1.802<0.354) state, which represented the cold property. CONCLUSION: The herbal properties and the biological performance characteristics of herbal formulas are ascertained by using the Fuzzy evaluation model. The personalities, as well as commonalities of herbal properties are key areas for focus because of the multi-approach biological performance of cold and hot property.

[A mathematical model for re-analysis of the relationship between essence of syndromes in traditional Chinese medicine and clinical biochemical indicators based on the residual-split method and its application].

Studying the essence of syndromes (Zheng) in traditional Chinese medicine (TCM) is a fundamental challenge in basic theoretical research of TCM. The relationship between any given syndrome and biochemical indicators is one of the important aspects of the study. As the indexes selected in each study are specific to a particular Western medical disease diagnosis, and the disease factor is inevitably introduced into the study, the effect of disease factor on the index changes cannot be assessed effectively by traditional data processing methods. This is known as "the same syndrome with different reasons", which has resulted in confusion in TCM research. This study aimed at providing a mathematical tool to address this issue. Based on information theory and the residual-split method, the syndrome information, which was covered in the index variation, was quantitatively calculated in this paper as an independent part of the disease factor. A mathematical model capable of objectively assessing and statistically testing the effect of the syndrome factor on the index changes was established. Applying this model to literature data of studies on the relationship between cyclic nucleotides and yang-deficiency syndrome showed following results. First, the values of yang-deficiency syndrome information were negative for cyclic adenosine monophosphate (cAMP) while positive for cyclic guanosine monophosphate (cGMP) in all included literature. This indicated that the group of yang-deficiency syndrome was correlated with an obvious trend of reduced cAMP levels and increased cGMP levels. Second, the statistical test results of yang-deficiency syndrome information of the two indexes were different among the literature included. The quality of original data was considered as a possible reason. Third, the significant differences between the yang-deficiency group of a specific disease and the normal group may, in some cases, be caused by a disease factor rather than a syndrome factor. The mathematical model provided a reasonable mathematical tool for the analysis of disease factor and syndrome factor in clinical research of TCM, suggesting that the mathematical model may give rise to innovative ideas and methods in the study of syndromes.

[Study of biological performance of Chinese materia medica with either a cold or hot property based on the three-element mathematical analysis model].

OBJECTIVE: The properties of Chinese materia medica are believed to be the summarization of the effects of biological performance on the various body states. Systemic discussion of chemical-factor elements, body-condition elements, biological-performance elements and their interrelationships is needed for research into the properties of Chinese materia medica. Following the practical characteristics of Chinese medicine, the three-element mathematical model was formed by introducing some mathematical concepts and methods and was used to study the cold or hot property of Chinese medicine, and to investigate the difference in biological performances of the two properties. METHODS: By using the concept of different functionality of Chinese medicine on abnormal states and the idea of interaction in mathematics, the effects of chemical-factor elements and body-condition elements were normalized to the amount of biological performance which was represented by some important indicators. The three-element mathematical model was formed with scatter plots through four steps, including effect separation, intensity calculation, frequency statistics and relevance analysis. A comparison pharmacology experiment of administration of hot property medicines, Fuzi (Radix Aconiti Lateralis Preparata) and Rougui (Cortex Cinnamomi), and cold property medicines, Huangbai (Cortex Phellodendri) and Zhizi (Fructus Gardeniae) on normal and glucocorticoid-induced yang-deficiency and yin-deficiency states was designed. The results were analyzed by the mathematical model. The scatter plots were the main output of model analysis. The expression of cold property and hot property was able to be quantified by frequency distribution of biological indexes of administrations on yang-deficiency and yin-deficiency states in the "efficacy zone" and "toxicity zone" of the plots and by the relevance analysis. RESULTS: The ratios of biological indicator frequency in the "efficacy zone" of administrations on yang-deficiency state and yin-deficiency state were 7:3 for Fuzi, 3:3 for Rougui, 4:4 for Huangbai and 1:5 for Zhizi. The sums of the biological indicator frequency in the "toxicity zone" of administration on the two states were 4 for Fuzi, 0 for Rougui, 2 for Huangbai and 4 for Zhizi. The relevance analysis showed that the order from Fuzi, Rougui, Huangbai to Zhizi was proportional to the change from "be true of yang-deficiency state" to "be true of yin-deficiency state". The extent of the hot property decreased while that of the cold property increased in the order of Fuzi, Rougui, Huangbai and Zhizi. The stronger the efficacy of above medicines is, the more obvious the toxicity displayed. CONCLUSION: The three-element mathematical model employed in this study is effectively capable of explaining the different biological expressions between hot property medicines and cold property medicines. This suggests that it may provide a mathematical tool and theoretical basis for the modern interpretation of cold property and hot property of Chinese medicine, and provide new ideas for further studing into the essence of Chinese medicine property theory.

[Classification of 365 Chinese medicines in Shennong's Materia Medica Classic based on a semi-supervised incremental clustering method].

Evidence of the pharmacological activity of traditional Chinese medicine (TCM) provides the basis for clinical prescription. Study of the classification of Chinese medicines according to these activities is key to understanding the general active tendencies of medicinal prescriptions, exploring their material basis, investigating their properties and searching for their alternatives. Taking the herbal classic Shennong's Materia Medica Classic (Shennong Bencao Jing) for the data source, this paper studied the classification of Chinese medicines based on semi-supervised incremental clustering algorithm using "micro-cluster" concept in order to investigate the complex similarity among Chinese medicines. The results showed that 253 Chinese medicines were reasonably classified into 14 types, such as invigoration, clearing heat, diuresis, dredging blockages in the channels, treating gynecological conditions and treating strange diseases caused by ghosts. The results also showed that the other 112 Chinese medicines were classified into 112 individual types and the same high similarity to different known types was the main reason for this. The semi-supervised incremental clustering algorithm employed in the study had a high quality and a good development for clustering which is suitable for classification of Chinese medicines. This study illustrated the diversity of Chinese medicines and their complex similarities, thus aiming to provide innovative ideas and methods for related research.