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Background and Objective: The nature of Narrative version of Islamic medicine (NIM) is based on Quran and hadith, exclusive attention to Islamic narrative references and rejection of the strategies of other medical schools. This study was conducted to criticize NIM. Methods: In this qualitative study of content analysis, after collecting the opinions of 6 prominent scholars of NIM, the criticisms of these opinions were presented and categorized by three doctors specialized in Persian medicine, a cleric in the field of Islamic jurisprudence and a methodologist by holding expert panel meetings. Findings: Criticisms were raised based on three points of view. The intra-religious area including the routine of Ahl al-Bayt (The holy family of the Prophet Muhammad) in illness and the role of physicians, the place of reason and experience in Islamic sciences, differences in geographical areas, not mentioning the full history of patients and newly occurring diseases was brought up. From a medical point of view, the important points include lack of a research method to check the effectiveness of a medical narrative, lack of diagnostic aspects and an approach to screening. From the viewpoint of religious and social consequences, religious trauma resulting from lack of response to treatment attributed to Ahl al-Bayt, approach to other manifestations of Western civilization, ethical issue of producing, prescribing and selling drugs by a group and loss of life and money due to waste of time in cases with definitive or relative treatment was raised in other medical schools. Conclusion: Based on the results of this research, the introduction of this theory to society without sufficient investigations in the seminaries and universities of medical sciences may cause physical, mental and religious trauma at the individual and social level.

Background: Renal disorders including renal failure are common complications which affect the whole body system. The treatment methods in modern medicine seem to be inadequate in a large number of cases. Regarding the increasing interest of the community towards traditional and complementary medicine, the potential of Persian medicine (PM) in management of renal diseases, could be put to test in research programs in order to find possible effective treatment. Objective: The aim of this study is to introduce materia medica which are commonly used in PM for the purpose of protection and functional empowerment of the kidneys against destructive factors. Methods: This research is a literature-based study on effective material medica used in the treatment of two significant renal disorders; renal weakness and renal atrophy (Hozal). Six pharmaceutical references of Persian medicine from different historical periods were searched by certain keywords related to renal weakness and renal atrophy. Results: Fourteen materia medica related to the prevention or treatment of renal weakness and fifteen for renal atrophy were found. Poppy (Papaver somniferum), Amber and shellac are the most repeated medicines in the treatment of renal weakness; whereas fig (ficus carica), banana (musa sapientum) and hazelnut (corynus avelana) are mostly repeated for either prevention or treatment of renal atrophy. Conclusion: Medicinal plants represented by Persian medicine references could be a basis for experimental and clinical researches for drug development in the field of prevention or even treatment of acute or chronic renal failure.

BACKGROUND AND OBJECTIVE: Nowadays, heart failure is one of the most common diseases and is the cause of death in a high percentage of the population. Despite all the progress made, researches continue for achieving a better understanding of its causes. The present study aims to evaluate the causes of heart failure from Persian medicine (PM) point of view. METHODS: In this review article, first PM books with references to causes of heart failure and weakness such as Al Qanun Fi Al-Tibb (The Canon of Medicine) and Exir-e-azam were reviewed and compared with modern medical findings in Braunwald's Heart Disease, Harrison's Principles of Internal Medicine and Cecil medicine books as well as online databases including PubMed, Science direct, Scopus and Google scholar. FINDINGS: Reviewing the documentation revealed that, according to definitions and symptoms, heart failure is the equivalent of the term “heart weakness” in PM. Accordingly, results of the study demonstrated that according to PM, causes such as Sue-e-Mizaj, obstruction, tissue detachment, mental disorders, direct and indirect excessive disposal of body essential materials may underlie the heart’s inability to meet the needs of the organs. CONCLUSION: Several factors are mentioned as the cause of heart failure or heart weakness in PM, only a few of which are considered in modern medicine. However, some of these less considered theories can be used as new assumptions to prevent and control this disease

BACKGROUND AND OBJECTIVE: Persian (Iranian) medicine is one of the oldest traditional medical science with more than 1000 years of history. Scientometrics studies on the current research achievement of Persian medicine in academic communities are lacking. The purpose of this study is assessment and analysis of scientific attainment of Persian medicine in international research publication and provides overview of research efforts in the field of Persian traditional medicine until 2015. METHODS: Documents were collected from Pub Med database with these keywords: “Iranian medicine”, “Persian medicine”, “Iranian traditional medicine” and “Persian traditional medicine”. All data were classified based on type of manuscript, field of study, kind of research, journal type and publication year. FINDINGS: 502 Articles were found up to the end of 2015; 54.3% original articles, 26% review, 13.7% letter to editor, 29% biographical and historical articles. Pharmacological and phytochemical studies were the most published articles (14/7%). Between 139 journals which published these articles, 59% have Impact factor (IF) and highest IF belonged to the Lancet neurol J (23/46). More than one citation was reported in 43.7% of articles and the most citation belong to the one of the published article in year 2012 (23 citation). H-Index of all collected articles was 12. CONCLUSION: The number of published articles in Persian (Iranian) Medicine had significant growth in the last years. But usage of several keywords for Persian traditional medicine, by authors, inhibits aggregation and availability to these. However proposed unique full or abbreviate name be used in all published research document.

BACKGROUND AND OBJECTIVE: Maple syrup urine disease is a rare inborn metabolic inherited disorder caused by deficiency of branched chain α-keto acid dehydrogenase complex and leading to accumulation of branched chain amino acids in body fluid. The incidence of MSUD is higher in populations with high consanguineous marriage. BCKD is a mitochondrial complex which is encoded by four nuclear genes (BCKDHA, BCKDHB, DBT, and DLD) and MSUD can be caused by mutation within any of these four genes. Accumulation of metabolic is associated with impairment of energy metabolism, provoke apoptosis, dysfunctional neurotransmitter synthesis and neuropathological defects such as seizure, psychomotor delay and coma. In the present study, we investigated the incidence of MSUD in Iran, compiled previously reported mutations in Iranian population and also explained molecular pathomechanisms underlying MSUD. METHODS: To compile MSUD mutations, we systematically reviewed PubMed and magiran databases to find related articles in English and Persian language, respectively. The key words "MSUD" and "Iran" was used as query. FINDINGS: Until 9th December 2018, twenty four MSUD mutations were collected from Iranian population of which 18 mutations have been only identified in Iran and were not reported in other populations yet. Likewise, because of high consanguineous marriages, the incidence of MSUD were higher than worldwide average in different provinces. CONCLUSION: Identification and compiling of MSUD mutations in Iranian population can be useful for prenatal genetic diagnosis in at risk families and play crucial role in early diagnosis and also treatment before starting neurological symptoms in newborns.

Ethnopharmacological Relevance: Pistacia atlantica Desf. (Baneh) is a native tree in many areas of Iran such as Zagros mountains and Sistan va Baluchestan Province. It is famous mostly due to its oleo-gum resin and there are many studies on its effects on gastrointestinal disorders and musculoskeletal problems. However, the oil from its fruits is also of use in local communities as a part of their food and for therapeutic purposes such as analgesic effects on joint pains., Aim of the Study: Osteoarthritis is a widespread form of joint pain in older adults. This double-blinded randomized clinical trial aimed to compare the effects of Baneh fruit oil on knee osteoarthritis with topical diclofenac., Material and Methods: Ninety-two patients with primary knee osteoarthritis were randomly divided into two groups and asked to rub a fingertip of Baneh ointment or diclofenac on their knee 3 times a day for four weeks. The Knee Injury and Osteoarthritis Outcome Score (KOOS) and Visual Analog Scale (VAS) were completed at the beginning, fourth and eighth weeks. The data was analyzed in SPSS software and intention to treat (ITT) analysis was performed. A P-value less than 0.05 was considered statistically significant., Results: After 4 weeks, all parameters improved significantly in both groups but the pain (based on VAS and KOOS), activity, and quality-of-life showed statistically more improvement in the Baneh group (P = 0.001, P < 0.001, and P = 0.009, respectively). Four weeks after stopping the interventions, all parameters in both groups were still significantly better than the baseline (P ≤ 0.05). However, improvement in pain (VAS and KOOS) and activity was stayed better in the Baneh group (P = 0.028, P = 0.001, and P = 018, respectively). Only one case of temporary itching was reported., Conclusion: This study revealed that Baneh oil had a positive effect on relieving the symptoms of knee osteoarthritis, however, more clinical trials with longer duration of treatment and larger sample sizes are recommended., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Background: Introduction: Mizaj is the basis of attention to individual differences in Persian Medicine (PM). Regarding the importance of Mizaj for health preservation and treating diseases, it is necessary to achieve a standard tool for Mizaj identification. The purpose of this study was to design a standard self-reporting Mizaj identification questionnaire for elders., Methods: In this exploratory sequential study, criteria of Mizaj identification were extracted by reviewing PM literatures and interview with PM experts and elders. The primary questionnaire was designed and its validity and reliability were assessed, using weighted Kappa statistics, Pearson correlation coefficient (PCC) assessment, receiver operating characteristic (ROC) curve and determining the specificity and sensitivity of cut-off points., Results: Among the 101 items in the primary questionnaire, 73 items had acceptable reliability. The final 20-item questionnaire was obtained after the criterion validity and PCC assessment. The sensitivity and specificity of this questionnaire were 83% and 88% for warmness, 49% and 80% for moderate in warmness-coldness, 72% and 91% for coldness, 57% and 78% for wetness, 30% and 79% for moderate in wetness-dryness, and 81% and 67% for dryness, respectively., Conclusion: The standard Mizaj identification is recommended as a supplementary diagnostic tool for clinicians and researchers in PM. Also, the people with age over 60 can use it to identify their own Mizaj and then, choose the suitable PM or Unani medicine lifestyle recommendations based on their Mizaj., Competing Interests: The authors declare that they have no conflict of interest., (© The Author(s).)

Gastrointestinal (GI) disorders characterized by persistent and recurrence gastrointestinal symptoms are prevalent. The genus Pistacia is widely emphasized as the relief of gastrointestinal diseases in traditional medicine. This review aimed to investigate the latest evidence on the effect of the Pistacia genus on GI tract disorders. The systematic search was performed following to PRISMA guidelines. The databases PubMed and Scopus were searched from 1980 to 2022 with restrictions to the original studies. Electronic databases were searched in title/abstract, using the keywords relevant to GI tract disorders. Forty-eight studies were included in this review following the inclusion criteria. Fifteen and 22 studies were clinical and animal studies, respectively, of which 6 clinical and 13 animal studies were on Inflammatory Bowel diseases. Seven clinical studies were on functional GI disorders. The most pieces of evidence from animal and clinical studies were on the intestinal inflammation and peptic ulcer affecting the inflammation as well as oxidative stress through different mechanistic pathways. The most referred active phytochemicals seem to be terpenoid compounds. Various in vitro studies have also shown the inhibitory activity of the different plant parts of Pistacia herbs on several GI tract cancer cells. Available scientific evidence supports the effects of various components of Pistacia genus plants in the field of GI tract diseases, especially digestive inflammations. Further studies are required to systematically evaluate the natural products of the genus Pistacia, particularly in the context of digestive disorders., Competing Interests: Declaration of competing interest There is no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Numerous herbal products have been the subject of research regarding their potential role in cancer prevention or adjuvant therapy. Pistacia atlantica and its main phytochemicals have garnered significant attention for their potential anti-cancer effects. The study aimed to assess the growth inhibitory effects of P. atlantica essential oil (PAEO) on MKN-45 and AGS cells. This study quantified the volatile compounds in PAEO using Gas Chromatography-Mass Spectrometry (GC-MS). Subsequently, MKN-45 and AGS cells were treated with varying concentrations of PAEO (5%, 2.5%, 1.25%, 0.625%, 0.3125%, 0.156%, 0.0781%, 0.0391%, 0.0195%) for 24 h. Cell viability was evaluated through the MTT assay. The impact of PAEO on gene expression was investigated by quantifying the mRNA levels of Bax and Bcl2 in the various experimental groups using quantitative Real-Time PCR (qRT-PCR) analysis. Additionally, flow cytometry was utilized to evaluate apoptosis in the treated cells. The analysis of PAEO revealed that α-pinene was the predominant monoterpene, constituting 87.9% of the oil composition. The cytotoxic effects of PAEO were evaluated, and it was found that the oil significantly reduced the viability of MKN-45 and AGS cells. The IC 50 for MKN-45 cells was determined to be 1.94 × 10 -3 % after 24 h of treatment, while for AGS cells the IC 50 was 2.8 × 10 -3 % after 24 h. Additionally, the research revealed that PAEO triggered a notable rise in apoptotic cells in both AGS and MKN-45 cell lines. Moreover, at the molecular level, the findings indicated an increase in Bax expression and a decrease in Bcl2 mRNA expression, providing further evidence of the induction of apoptosis in both MKN-45 and AGS cell lines following PAEO treatment. The findings of this study offer evidence supporting the cytotoxic effects of PAEO on gastric cancer cell lines by promoting apoptosis. The findings suggest that PAEO may offer potential as a therapeutic candidate in managing and treating gastric cancer., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Ethnopharmacological Relevance: Different parts of the alfalfa plant (Medicago sativa L.), especially its seeds, have been introduced as a semen quality enhancer in the folk medicine of different regions of Iran as well as in the traditional Persian medicine (PM) books. The seeds of this plant are also used in many combined medicines to treat male infertility in PM., Aim of the Study: This study was designed to investigate the effect of M. sativa seed powder plus vitamin E vs. vitamin E alone on semen analysis of men with idiopathic infertility., Materials and Methods: In this randomized clinical trial, 60 participants were randomly divided into two groups and then received M. sativa seed powder (6 g daily) or placebo for three months, as add-on to vitamin E (100 U). Results of semen analysis (sperm total count, motility, and morphology as well as semen volume) of these two groups and their changes were compared before and after treatment as the primary outcome. The number of pregnancies after one month and probable side effects were also assessed., Results: After 12 weeks, sperm total count changed from 36.2 ± 21.8 × 10 6 /ml to 48.5 ± 19.1 × 10 6 /ml in M. sativa and from 39.5 ± 23.5 × 10 6 /ml to 41.2 ± 20.9 × 10 6 /ml in placebo, percentage of normal morphology changed from 1.8 ± 0.8% to 2.6 ± 1.2 % in M. sativa and from 2.0 ± 0.9% to 2.6 ± 1.2% in placebo and percentage of motile sperm changed from 36.5 ± 11.8 % to 39.7 ± 12.0% in M. sativa and from 39.3 ± 10.1 % to 38.1 ± 12.1% in placebo. The improvements in M. sativa group are significantly better than placebo group (P = 0.00, 0.01 and 0.04, respectively). However, semen volume decreased in both groups, but its changes were not significant. The number of pregnancies was four in the intervention and zero in placebo group. One case with abdominal bloating and one with respiratory allergy withdrew from the intervention group. No other adverse effect was reported., Conclusions: In this study, significant improvement was detected in sperm parameters (except semen volume) of men with idiopathic infertility in M. sativa plus vitamin E group in compare to vitamin E alone after 12 weeks. These findings suggest that the M. sativa, as a complementary therapy, may have a beneficial effect on semen quality. More clinical trials with larger sample size are needed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Mizaj (Temperament) is a concept to express individual differences in Persian medicine and according to this theory, there is a relationship between Mizaj type and the abilities of different body organs. This cross-sectional study aimed to investigate the relationship between the type of Mizaj and the memory score (Quotient)., Methods: The target population was the 18 to 38 years old students of Babol University of Medical Sciences. Mojahedi's Mizaj questionnaire (MMQ) was used for determining the whole Mizaj. The physical Persian version of Wechsler Memory Scale III (WMS III) was used to assess memory score. The collected data were analyzed by SPSS Version 22 and the chi square (x2) and t-test were run and p- value 0.05 was considered as significant difference., Results: Forty-two of participants were females and 18 were males. The average age of them was 23.6 (21-27). The average of Memory Quotient (MQ) was 122.1 ± 5.7. The average of MQ in warm Mizaj was 125.46 ± 1.2 and in cold Mizaj was 118.79 ± 6.5. The difference between two groups is statistically significant (p< 0.001). The average of MQ in dry Mizaj was 124.16 ± 2.67 and in wet Mizaj was 118.40 ± 7.64. The difference between two groups is statistically significant (P= 0.005)., Conclusion: The results showed there are significant relationship between memory score and warm/cold Mizaj and dry /wet Mizaj. It means students with warm or dry Mizaj had better memory score than students with cold or wet Mizaj. This relation was also detected between subtypes of memory and Mizaj expect between working memory and dry/wet Mizaj. These results are in accordance with theories in PM which indicate people with warm Mizaj and dry Mizaj have better memory and people with cold Mizaj and wet Mizaj have weaker memory and are more at risk of memory dysfunction., Competing Interests: no conflict of interest., (© The Author(s).)

Pomegranate is widely used to preserve human health and help prevent many kinds of diseases. This study aims to review and assess the effects of pomegranate on women's health during and after menopause. PubMed, Web of science, Cochrane, Scopus, and Google Scholar were searched up to the end of 2022 with no language or study type restriction. All types of clinical research studies (randomized clinical trial [RCT], pre-post, case report, and case series) were included. The Cochrane RoB 2.0 tool was used for quality assessment of RCTs. A summary of intervention's effects for each study was provided by calculating standardized mean differences and accompanying 95% confidence interval using random effect model. Weighted mean differences and heterogeneity between studies were assessed using Hedges's method and Cochran's Q test, respectively. Pomegranate can significantly improve hot flashes severity and menopause symptoms and decrease FSH. It significantly improves high-density lipoprotein but not low-density lipoprotein, body mass index, and weight. Most of our results are inconclusive, and the small sample sizes and the lack of blinding and randomization have led to an increased risk of bias. Pomegranate can decrease menopause symptoms, but more well-designed studies, with bigger sample sizes are needed to establish its other clinical benefits for menopausal women., (© 2023 John Wiley & Sons Ltd.)

Background: One of the principles of Persian medicine (PM) is the individualized approach that is presented with the concept of Mizaj. In this viewpoint, on the whole body, Mizaj is determined for every person based on 10 criteria, which is a result of the Mizaj of the main organs, including the brain, liver, and heart. There is no standard diagnostic tool for Mizaj assessment yet. The purpose of this study is to explain the method of Mizaj assessment and data analysis in the elderly in one of the biggest health and aging projects in Iran. The second phase of the Amirkola health and aging project (AHAP) evaluated more than 1,700 clinical and laboratory examinations of 2135 elderly people., Methods: In this study, a novel Mizaj assessment method in two phases is presented. In the first phase, 1541 elderly were assessed by a PM expert and typical diagnoses (the high confidence of expert's proficiency) were determined. At the second phase, an expert panel including 5 PM experts evaluated the cases. The data of the elderly whose Mizaj agreed in the expert panel was used to assess its correlation with Mizaj. Also, the Mizaj of the main organs of these cases was evaluated this way., Conclusion: In the lack of valid and reliable questionnaires to assess the personalized viewpoint of PM, a new expert-based method has been introduced that can be used in similar studies. The result of the Mizaj assessment in this way will be used to obtain objective values for the Mizaj assessment., Competing Interests: There is no competing interest.

Background: Gastric disorders are one of the most common human ailments, which impose a huge economic burden on countries. In Persian Medicine (PM), it is possible to predict the susceptibility to gastric diseases with diagnosis of gastric Mizajes (temperaments) and dystemperaments. The semiology of gastric dystemperaments has been investigated in PM textbooks, although the value of each sign and symptom is not mentioned. Consequently, this research is designed to determine the major and minor criteria for classifying gastric dystemperaments on the basis of valid manuscripts and with the help of PM specialists in the present era., Methods: This was a consensus-based study consisting of four phases. In the first phase, reference PM textbooks were studied. Symptoms and signs of gastric dystemperaments were collected and listed in four groups. In the second phase, semi-structured interviews with a sample of PM experts were carried out. Phase three included a focused group discussion with experts. Eventually, findings were integrated from the three study phases in a two-day meeting in Sari City., Results: Selected criteria included eight major and eight minor criteria for hot-cold dystemperament, as well as six major and eight minor criteria for wet-dry gastric dystemperament., Conclusion: Modern lifestyles and the interfering factors are responsible for some changes in diagnostic signs and symptoms according to PM. This was the first step to coordinate PM diagnostic criteria for gastric dystemperaments. Further studies are recommended to reach a unique protocol in the field of PM diagnostics. The next step includes design and validation of national diagnostic tools., Competing Interests: None declared.

Background/objectives: Neonatal abstinence syndrome (NAS) incidence continues to rise in the United States due to increasing opioid use disorder in pregnancy. While cutaneous excoriations have been noted in NAS, there is a paucity of literature regarding abnormal nail findings in NAS., Methods: A retrospective, observational case series was conducted of twelve patients with NAS and abnormal nail findings who were admitted to the neonatal intensive care unit between January 1, 2018, and May 1, 2020., Results: Twelve neonates (10 male, 2 female, mean gestational age at birth 38.1 weeks) with NAS diagnosis and abnormal nail findings were identified between January 1, 2018, and May 1, 2020. NAS was diagnosed by elevated Modified Finnegan Neonatal Abstinence Syndrome Tool (M-FNAST) scores. All patients required pharmacologic treatment for NAS with seven (58.3%) requiring phenobarbital in addition to first-line morphine. Common nail findings included periungual erythema, yellow crusting, desquamation of the proximal and/or distal lateral nail folds and sheared distal nail edges. Two patients (16.7%) required antibiotic treatment for paronychia. Peak M-FNAST scores were positively correlated with number of abnormal nail findings (r = .58, P = .047)., Conclusions: Twelve neonates with severe NAS demonstrated similar nail abnormalities, likely secondary to NAS agitation and motor hyperactivity. Nail exams, therefore, are important in the setting of suspected or confirmed NAS to limit continued nail trauma and infection. Our findings also introduce an association between NAS severity and abnormal nail findings, which will require larger studies for further confirmation., (© 2021 Wiley Periodicals LLC.)

Background: Complementary and Alternative Medicine (CAM) have recently become more popular and accepted worldwide. One principal step to identify the status and organize strategies of CAM is evaluating the manner and the prevalence of its usage among people. This study aimed to investigate the prevalence of CAM modalities usage by the people of Babol, a central city in the North of Iran, in 2018., Methods: Using the original International CAM Questionnaire (I-CAM-Q), a questionnaire was redesigned in Persian (Farsi) with some changes such as adding special modalities in Iran and its validity and reliability were assessed. Six hundred households were evaluated using a cluster sampling method in 2018 spring by 12 trained interviewers., Results: Finally, 1770 questionnaires were correctly completed. A total of 110 participants (6.21% of the completed questionnaires) had visited CAM therapists in the last year, 109 persons (6.15%) had received prescriptions from physicians and paramedics to use CAM, and a total of 1032 people (58.30%) used herbs and herbal medicines in the last 12 months. Also, 1265 individuals (71.46%) had used CAM throughout their lives. The most popular methods were herbal medicine (65.76%), Persian Medicine (13.78%), water therapy (10.45%) and music therapy (8.36%). The use of CAM was more popular among women., Conclusions: The general use of CAM in Babol was similar to other studies, but there were fewer visits by CAM therapists and less frequent adoption of common methods including homeopathy, acupuncture, and energy therapy. It was found that CAM was mostly used for non-serious diseases such as cold and transient gastrointestinal disorders, a pattern that is different from other studies in this field.

Attention to diet was considered important issues in improvement of men infertility in Persian Medicine (PM). The purpose of this study was to extract herbal foodstuffs introduced by Avicenna, one of the greatest PM physicians to improve the semen production and to provide evidence of their impact on the basis of current studies."Canon of Medicine", the most important Avecinna's book, was searched with keywords equivalent to semen, fertility and infertility, main herbal foodstuffs were extracted and was searched with keywords sperm, semen, infertility, and fertility in Google scholar, PubMed and Scopus databases. Manuscripts from 1950 up to December 2019 were selected and reviewed. Almond, Onion, Chickpea, Garlic, Coconut, Palm date, Sesame, Fenugreek, Carrot, Fig, Grapes, Pistachio, Hazelnut and Walnut are among main foodstuffs which recommended by Avicenna and there is also evidence that they have positive effects on testosterone production and improvement of various sperm parameters, including count, motility and morphology. Containing large amount of different macro and micronutrients such as vitamins including vit B, C, A and E, minerals such as Mg, Se, Zn, Cu and Fe, important unsaturated fatty acids such as linoleic and oleic acids, amino acids such as lysine and arginine and phytochemicals such as polyphenols, flavonoids, triterpenes and steroids can be considered as a main factor in the effectiveness of these foodstuffs. Designing a diet based on the fruits, vegetables, nuts and seeds that Avicenna has recommended, may be effective in treating male infertility but further studies are needed to clarify this issue. Research on the effectiveness of his other recommended foodsuffs may also offer new treatments and supplements for this purpose., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

The tendency to use herbs to manage menopausal symptoms has increased in recent years. The purpose of this study was to evaluate the effect of Silybum marianum (L.) compared with placebo in women with hot flashes. Eighty women were randomly allocated into two equal groups (S. marianum extract [400 mg/d] or placebo capsules). Hot flashes frequency and severity were evaluated in 12 weeks with the Greene Climacteric Scale (GCS) and the Hot Flash Related Daily Interference Scale (HFRDIS). The data were analyzed in SPSS software using t-test, Mann-Whitney, chi-square test and repeated measure analysis. Hot flashes frequency and severity decreased from 4.32 ± 0.20/day to 1.31 ± 0.15/day and from 5.25 ± 0.22 to 1.62 ± 0.08, respectively, during the study in test group (p < .001) which were significantly better than effects of placebo in all steps of study (p < .001). Significant decreases in GCS and HFRDIS scores were also detected in S. marianum group compared with placebo after 4, 8 and 12 weeks (p < .001). The results showed that S. marianum can decrease frequency and severity of hot flashes significantly. Considering the safety and high consumption of this herbal medicine worldwide, its use in women with menopausal symptoms can be helpful., (© 2020 John Wiley & Sons, Ltd.)

Introduction Mizaj or temperament is a main concept in Persian Medicine (PM), which the process of diagnosis, treatment and preventive prescriptions are developed based on it. In this study, the articles written on the concept of Mizaj were reviewed. Method Credited electronic resources, including Pubmed, Scopus, Cochrane Library and web-of-science were searched using keywords Temperament, Mizaj, Mizadj, Midzaj and Mezaj (with the concept of Mizaj in Persian and/or Greek medicine). Search results were limited to English articles, published in 1995-2017. The articles in which temperament had the psychoanalytic aspect or was based on Ayurveda or Chinese/Korean medicine were removed. A team of four PM experts evaluated the method and the results. Results Among the total of 32 articles were published in this field, 14 were review articles, 2 were on animal subject, 14 were on human subject and 2 were surveys for designing questionnaire for people's Mizaj assessment. Most of review studies were just new versions of ancient Persian texts translated into English and the innovations on the subject were few. Studies on animal subject and developing questionnaires were also limited. In some human studies, use of standard questionnaires and homogenous methodology in Mizaj assessment was not considered. Conclusions It seems that studies on temperaments have increased in the past few years but are still at the forefront. In human studies a homogenous method for evaluating temperament has not been used and some of them failed to address the main concept of Mizaj in PM. Therefore, it is necessary to use the original category of Mizaj and to design standard method.

Background: COVID-19 caused a global pandemic problem. No confident management is introduced for it yet. This study aimed to propose a dietary protocol for hospitalized patients with the diagnosis of acute respiratory infectious disease caused by COVID-19 based on Persian Medicine., Methods: This study was conducted in three phases. In the first phase, any diseases that could be matched with the clinical features of infection with COVID-19 were searched in selected PM references. In the second phase, medicinal herbs and foods that were available and could be used in the hospital diet were extracted and summarized. In the third phase, the new documentation of these pharmaceutical and food items was conducted., Results: The signs and symptoms of infectious respiratory disease caused by COVID-19 can be categorized in the field of Zato al-rieh that can mainly be matched with pneumonia. Based on the described criteria, some nutrients and medicinal materia medica have been introduced for acute respiratory infection including Cydonia oblonga, Honey, Citrus sinensis, Malus domestica, Citrus medica, Crocus sativus, Raisin, Rosa Damas Cena, D.Carota, Camellia Sinensis, Anethum graveolens dhi, Punica granatum, Petroselinum Crispum, Coriandrum sativum, Urtica dioica, Allium sativum, Sesamum indicum., Conclusion: Most materia medica has documents in current articles including anti-cough suppressants, antiviral properties, anti-bacterial, anti-inflammatory, antioxidant, immunomodulatory etc. A protocol of hospital diet for patients with infectious respiratory syndrome caused by COVID-19 has been introduced in this manuscript.

Introduction: Vulvovaginal candidiasis is the second most common cause of vulvovaginal infections. The aim of this study is to evaluate the effectiveness of vaginal cream of Achillea millefolium extract in women with vulvovaginal candidiasis in comparison with vaginal clotrimazole., Materials and Methods: This double-blind randomized clinical trial study was conducted on 80 women diagnosed with vulvovaginal candidiasis clinically and by laboratory test; 40 women received vaginal cream clotrimazole 1 % and 40 received vaginal cream containing the aqueous extract of A. millefolium for 7 days. Clinical and laboratory assessments were performed before and after the intervention. Minimum inhibitory concentration of the extract was evaluated with Broth micro-dilution procedure., Results: The Dermatology life quality index score showed significant reduction in both groups after treatment, but it was significantly more reduced in control group (p < 0.05). Improvement in vulvar erythema was observed in both groups with no statistically difference (p = 0.1). Vaginal culture was negative in term of Candida in 28(77 %) patients of control group and in 18(53 %) patient of experimental group (p < 0.05). The Minimum inhibitory concentration of the extract was 37.5 mg/mL for the standard strain., Discussion and Conclusion: Study results showed that vaginal cream containing A. millefolium could reduce the complaints of vulvovaginal candidiasis. But, future studies with a larger sample size and different dosages are recommended to assess the outcomes of this new treatment., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: Developing a new medicine is a costly and time-consuming process. This study presents a novel method to collate a new materia medica from previously documented traditional Persian medicine (TPM) references. A well-documented materia medica will facilitate a quick and easy process to find traditional medicine for specific symptoms or diseases. Materials and methods: A nine-step algorithm is proposed to collate a new materia medica by searching and matching descriptions and references stated in various traditional Persian literature: (1) finding the equivalent of traditional description of symptoms or diseases; (2) determining the keywords to search in the references of TPM, including The Canon of Medicine (Book by Avicenna); (3) determining the best references of TPM for the aim of the study; (4) weighing up the references (a) based on the prominence of the author's prominence (b) determining whether the references are the author's own clinical findings or has citation from other scholars been used, (c) the popularity of the book that the references feature in, among other later scholars of TPM, the geographical and historical span across which the book has been distributed; (5) searching the references using keywords of symptoms or diseases; (6) finding the synonyms of terminologies in the various materia medicas and categorizing the findings; (7) revision (of references found) to ensure that nothing is neglected; (8) scoring the findings based on the defined criteria; (9) prioritization: sorting the materia medica based on the total scores. Some important economic, cultural or historical factors cannot be included in the main process of prioritization during the initial searching of the TPM materia medica. Therefore, it is necessary to take these factors into account after discovering the medicine and before using in practice to ascertain that they are a good match of a specific treatment, disease or symptom. Conclusion: A process to compile a new materia medica has been proposed which will enable the quick and easy selection of herbal treatments for various signs and symptoms of illnesses.

The gut-brain axis is a bidirectional communication system that exists between the brain and gut. Several studies claimed that some types of headaches are associated with various gastrointestinal (GI) disorders. In Persian medicine (PM), physicians believed that gastric disturbances could stimulate headache and introduced some herbs for boosting gastric function as a therapeutic remedy for headache. Here we review the current evidence for the gastroprotective and antiheadache effects of herbs used in PM. Herbs used for their gastrotonic effects in PM were identified from selected Persian medical and pharmaceutical textbooks. PubMed, Scopus and Google Scholar were used to search for contemporary scientific evidence relating to the gastric and neurologic effects of these plants. A total of 24 plants were recorded from the selected sources included in this review, most of which belonged to the Rosaceae family. Phyllanthus emblica, Zingiber officinale, Boswellias errata, Punica granatum and Hypericum perforatum had the most recent studies related to GI disorder and headache, while current research about quince, rose, apple, hawthorn and pear was limited. Reducing Helicobacter pylori growth, gastritis, erosion of the stomach lining, hemorrhage and perforation, improving gastric mucosal resistance, antisecretary, antiulcer, antipyretic, analgesic, sedative, anxiolytic, anti-inflammatory, anticonvulsant, neuroprotective and antioxidant effects as well as improvement in memory scores were some of the gastrotonic and neuroprotective mechanisms described in the current research. These results confirmed that medicinal plants prescribed in PM may improve headache in patients through the management of GI abnormalities. However, further studies are recommended to investigate the efficacy and safety of the mentioned medicinal plants., (Copyright © 2019 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.)

Neuroprotective agents are able to defend the central nervous system against acute or chronic neuronal injuries. Even with the progress made over the last decades, most of the medications prescribed for the management of neurodegenerative diseases can only reduce their symptoms and slow down their progression. Based on natural product research, there are potential effective medicinal plants and phytochemicals for modulating neuronal functions and protecting against neurodegeneration. Plants in the genus Pistacia are also among valuable natural resources for neuroprotection research based on experiences in traditional medicine. Studies have supported the value of bioactive compounds of the genus Pistacia for central nervous system disorders such as Alzheimer's, Parkinson's, multiple sclerosis, cerebral ischemia, depression, and anxiety. Related literature has also revealed that most of the evidence on neuroprotection in the genus Pistacia is in the form of preliminary studies, mainly including models of behavior, motor function, and memory impairments in animals, neural toxicity, cerebral ischemia and seizure models, evaluation of their effects on antioxidant and inflammatory biomarkers, amyloid β aggregation, and acetylcholinesterase as well as investigations into some cellular pathways. Along with the phytonutrients in kernels such as pistachios, various phytochemicals, mostly terpenes, and phenolic compounds have also been identified in different plant parts, in particular their oleoresins, of species in the genus Pistacia . In this review, the pharmacology of neurological effects and related molecular mechanisms of the plants belonging to the genus Pistacia and its active constituents, as well as pharmacokinetics aspects, are discussed., Competing Interests: The authors declare that they have no conflict of interest., (Georg Thieme Verlag KG Stuttgart · New York.)

Gastrointestinal (GI) cancers are major causes of cancer-related mortality worldwide and include malignancies of the GI tract such as the stomach, liver, pancreas, small intestine, colon, and rectum. Promising and selective anticancer effects of pharmacologically active components of saffron (Crocus sativus L.) have been shown in preclinical in vitro and in vivo studies. Saffron and its active components including crocin, crocetin, and safranal exert their anticancer effects through different mechanisms, including induction of apoptosis, influence on the cell cycle, and regulation of host immune response and anti-inflammatory activities. This review summarizes the recent literature on the chemopreventive properties of saffron in GI cancers to have a better understanding of the potential underlying mechanisms and hence the appropriate management of these malignancies., (© 2019 Wiley Periodicals, Inc.)

Introduction: Since the treatment of gastroesophageal reflux disease (GERD) symptoms in children is of the utmost importance, the current study is aimed to evaluating the efficacy of quince syrup and ranitidine in the management of pediatric patients with symptomatic GERD., Methods and Materials: This double-blind, randomized clinical trial was performed on 96 children suspected of suffering from GERD. The patients referred to the gastrointestinal clinic of Ghaem Hospital, Iran, during 2017. The participants were randomly categorized into two groups (ranitidine and ranitidine plus quince syrup). The GERD symptoms, including the severity and frequency of vomiting, refusal of eating, difficulty in swallowing, choking at the time of eating, burping or belching, and abdominal or belly pain, were gathered before and after the intervention (4 weeks) using standardized Global Severity Questionnaire (GSQ-YC)., Results: The comparison of two groups in terms of vomiting, refusal of eating, burping or belching, and abdominal or belly pain showed a significant difference 4 and 6 weeks after the intervention (P< 0.05). However, the comparison of difficulty in swallowing and choking at the time of eating between the two groups showed that there was no significant difference after 2, 4, and 6 weeks of the intervention (P > 0.05). The comparison of the total scores between the two groups showed that there was a significant difference 2 (17.8 ± 2.6 vs 23.4 ± 4.0; P < 0.05), 4 (11.5 ± 2.3 vs 18.8 ± 3.6; P< 0.05), and 6 (12.2 ± 2.3 vs 21.1 ± 4.1; P<  0.05) weeks after the intervention., Conclusion: The results showed that the administration of ranitidine plus quince syrup was useful to improve pediatric GERD. However, it is recommended to conduct the future studies with a larger sample size and different dosage., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Functional gastrointestinal diseases are common in general populations and comprise more than 40% visits to gastroenterologists . Treatment options of gastrointestinal diseases have been limited. There are a few medications for functional gastrointestinal diseases and some of medications are not available in the market or in the place where the patient lives. Traditional Persian medicine (TPM) is a branch of alternative and traditional medicine based on individual viewpoint and humoral theory, focuses on lifestyle modification and uses natural products to manage the patients., Methods: In this study, a set of compound drugs known as digesters (jawarishes) and other applications are described based on main TPM text books., Results: Jawarishes have different formulations containing various medicinal herbs used for better food digestion and improved gastric functions and also used for other disorders including reinforcing the brain, heart, liver and some therapeutic approaches., Conclusions: By reviewing medieval Persian pharmaceutical manuscripts, we can conclude that many herbs are effective in different systems of the body and improve gastric functions. Zingiber officinalis and Piper nigrum are mixed together to get various formulations. The variety of jawarishes formulations and their different clinical applications can indicate continuity of their use., Competing Interests: Authors did not have any conflict of interest.

Skin melanoma represents one of the most common and lethal solid tumor. It usually develops on the skin but it can occur in any tissues with melanine- containing-cells (extracutaneous malignant melanoma). Only 4-5% of malignant melanomas originate in extracutaneous tissues, and they have an extremely lethal behavior (1). These non-skin malignant melanomas are rare but extremely aggressive. Primary melanoma of the genitourinary tract accounts for less than 0.2% of all melanomas. To date only 28 cases of primary bladder melanoma (PMM) are described. We report a rare case of PMM of the bladder in a 72 years old man treated with radical cystectomy and immunotherapy with Nivolumab.

Exploring relationships between admission variables and outcome using regression models has been the focus of Traumatic Brain Injury (TBI) research. Although practical and well established, these approaches do not evaluate interactions between predictors. We therefore applied a set-theoretic logical analysis to the Corticosteroid Randomization after Significant Head Injury (CRASH) trial database. Complete data analysis of 6945 patients demonstrated 9 different configurations of admission variables were sufficient for favorable outcome in 87.5% of all cases and explained 57% of favorable outcomes (moderate disability or good outcome). We also evaluated the contrasting configurations for unfavorable versus favorable outcome. Results are largely in line with findings of previous studies however the influence of age fell behind GCS components, which is unexpected. Specifying a combination of admission parameters that are likely to translate into a given clinical outcome is appealing from a clinician's perspective therefore our results have considerable translational value.

The spleen has been one of the least understood major organs for centuries. Its significance is relatively well-known today but it seems that all aspects of its activities are not fully understood. Persian medicine (PM) has special views on the function of spleen; many side effects were reported in PM due to spleen dysfunction. On the other hand nowadays splenectomy as a treatment strategy is recommended for some disorders and increasing risk of infections is considered as the most important long term side effect of that. In this study, we hypothesize that splenectomy may have more side effects than currently proven. According to PM, spleen is in close connection with liver, cardiovascular system, stomach, bone, brain and skin, and that is why any kind of spleen dysfunction leads to change in blood viscosity, appetite and bone strength, liver dysfunction, mood and skin disorders, cancer formation and fever. Considering this viewpoint it can be hypothesized such side effects may also occur after splenectomy. Proven complications of splenectomy include hypercoagulated state, cardiovascular events and infectious diseases but there is also some evidence about increased risk of cancer, skin disease like systemic lupus erythematosus, mood disorder such as depression, defective bone formation and impairment of immunity which can be considered as different levels of evidence to confirm the hypothesis. But for some others such as changes in appetite, there are no studies let alone convincing evidence. Future research about theses possible complications may lead to novel results., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

An increase in the prevalence of Alzheimer's disease (AD) as a multifactorial neurodegenerative disorder is an almost obvious issue in the world. Researches on natural products for finding effective drugs to prevent the disease are in progress. There is special attention to the three types of nuts including almond, hazelnut and walnut in manuscripts of traditional Persian medicine (PM) as the preventive agents against brainatrophy and memory loss. The purpose of this study is a pharmacological review of their bioactive constituents and introducing the value of these nuts as the effective supplements and natural medicinal foods in AD patients. Databases including PubMed and ScienceDirect were searched in title, abstract and keywords from year 2000 to present for AD-related researches on these tree nuts, their major phytochemicals and their mechanisms of action. As result, almond, hazelnut and walnut provide macronutrients, micronutrients, and phytochemicals which affect several pathways in AD pathogenesis such as amyloidogenesis, tau phosphorylation, oxidative stress, cholinergic pathways, and some non-target mechanisms including cholesterol lowering and anti-inflammatory properties, as well as effect on neurogenesis. These nuts are recommended in PM for their brain-protective activity and particularly reversing brain atrophy in case of hazelnut. The therapeutical statements of PM scholars mentioned in their books are based on their clinical observations with support of a long history of experiences. Beyond the molecular activities attributed to the phytochemicals, the use of these tree nuts could be more considered in scientific researches as the effective nutrients for prevention or even management of AD., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Thrombosis is one of the major causes of morbidity and mortality in a wide range of vessels diseases. Due to the high prevalence of thromboembolic disorders investigations are being carried out on new antithrombotic agents with limited adverse side effects in which herbal medicines are considered as alternative remedies. Persian medicine (PM) as a traditional medicine has a good potential for pharmacotherapy based on its own principles and development of drugs via investigating PM literature. In PM manuscripts there are some concepts that express the management of blood clots and antithrombotic properties. This study reviewed the pharmacological effects of medicinal plants mentioned in PM literature for blood clot management in light of current knowledge. Plants mentioned in PM for management of blood clot belong to 12 families in which Apiaceae, Lamiaceae and Compositae were the most repeated ones. Among the proposed plants Allium sativum, Rosmarinus officinalis, Boswellia serrata, Sesamum indicum, Matricaria chamomilla and Carthamus tinctorius have been the most researched plants in modern antithrombotic studies while for some plants such as Helichrysum stoechas, Dracocephalum kotschi, Carum carvi, Bunium persicum and Lagoecia cuminoides no evidence could be found. One of the interesting notes in clot management in PM texts was introducing the target organ for some of the recommended herbs like Carum carvi and Bunium persicum for dissolving blood clot in stomach and Commiphora mukul for thrombosed hemorrhoid. It seems review of PM recommendations can help to design future researches for antithrombotic drugs discovering with more effectiveness and safety.

Background: The club cell 10-kDa protein (CC10) is a homeostatic protein that is produced in the lung, diffuses into the blood, and is then excreted into the urine and stool. CC10 is known to have anti-inflammatory properties and to have lower endogenous production in preterm infants., Objectives: As recombinant human CC10 (rhCC10) is being studied in preterm infants to reduce lung injury, understanding CC10 levels in term infants with normal lungs is needed to establish appropriate target dosing ranges., Methods: Serum, urine, and stool samples were collected from 24 healthy full-term infants, and CC10 levels were measured. Levels in term infants were then compared to those in preterm infants who were examined in our previous studies., Results: The mean gestational age and birth weight of the term infants were 38.8 ±1.1 weeks and 3,257 ± 513 g, respectively. The mean gestational age of the preterm infants was 26.8 ± 1.4 weeks. The median serum [CC10] levels with minimum and maximum values in term infants (214.2 ng/mL [34.1, 428.1]) were >7-fold higher than in preterm infants (27.5 ng/mL [8.0, 760.0]; p < 0.05). A significant correlation was found between [CC10] in urine and stool as well as between gestational age and stool [CC10] (p < 0.05)., Conclusions: CC10 is detectable in serum, urine, and stool in healthy term infants, with levels significantly higher than in preterm infants. This provides important data for ongoing therapeutic intervention trials with rhCC10 in high-risk preterm infants., (© 2016 S. Karger AG, Basel.)

Background: Due to negligence, Persian (Iranian) traditional medicine has had a weak presence in the world of research for a long time. However, in recent years, a variety of activates by research and faculty centers have created awareness and a platform to introduce and promote Persian medicine to the world. The aim of this study is to present and analyze scientific achievements of Persian medicine in the world of research., Methods: Articles were collected from PubMed database using keywords such as "Persian medicine", "Persian traditional medicine", "Iranian medicine", and "Iranian traditional medicine". All data were classified based on the type of research (review, intervention, case reports, etc.), the field of study (neurology, cardiovascular, metabolic, historical studies, etc.), publication year, and journal type., Results: A total of 501 articles were identified until the end of 2015, comprising of 222 reviews and 219 interventional (108 animal, 57 clinical and 54 cellular). Most studies were on neurology (20.1%), gastroenterology (14.5%), and cardiovascular diseases (10.4%). The publications in 2015 and 2014 had the highest hit rate with 139 and 132 articles, respectively, with 1:2 publication ratio between foreign and Iranian journals. The most published articles, both foreign and Iranian, were in "Evidence-Based Complementary and Alternative Medicine" and "Iranian Red Crescent Medicine" journals. The contribution of foreign authors was 5%. The primary focus of the articles was on "Basic concepts of Persian medicine", "Healthy lifestyle according to Persian medicine", and "Historical aspects", by 3.1%, 2.9%, and 6.7%, respectively., Conclusion: During the last 2 years, the number of articles published in Persian (Iranian) medicine, particularly clinical studies had significant growth in comparison with the years before. The tendency of foreign researchers to use the keywords "Iranian" or "Persian" medicine is notable. This research was only based on the designated keyword and other keywords were omitted. It is recommended that additional keywords be used in a broader investigation.

Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease of the skeletal system without definitive treatment. Nowadays, the aim of therapeutic interventions is preventing disease progression, but eventually many patients have different degrees of decreased range of motion, especially in the spine accompanied by pain and fatigue., Methods: A 44-year-old man with AS from 22 years ago was treated with NSAIDs and sulfasalazine. He visited for developed pain and stiffness in spine from 7 years ago. He did not confer with the rheumatologist from 2012 due to the lack of treatment satisfaction and maintained his treatment with 75 mg indomethacin daily. The patient was assessed in the Iranian traditional medicine clinic and other problems were chronic fatigue, interrupted sleep, and extreme dry skin. Diagnosis was general dryness and treatment started with oral and tropical moisture and nutritional advice., Results: In the third month of treatment, joint pain, morning stiffness and sleep disturbance improved. After 8 months, in addition to complete improvement of skin dryness, sleep disturbance and joint pain, range of motion in cervical and lumbar spine were increased. In cervical rotation, distance from the chin to acromion decreased from 24 to 15 cm in right rotation and 20 to 13 cm in left rotation. Additionally, in cervical flexion distance from the chin to sternal notch decreased from 16 to 8 cm after treatment. In the lumbar spine, an increased Schober's index was seen., Conclusion: The use of Persian traditional medicine's viewpoints and treatment strategies can be effective in improving Ankylosing spondylitis prognosis and proposed for future clinical research.