[Research and development strategy of new traditional Chinese medicine drugs for syndromes based on human use experience].

Chinese drug registration laws and regulations have always reserved a place for the new traditional Chinese medicine(TCM) drugs for syndromes, but so far no such new drugs have been approved for registration. This paper expounded on the relevant policies, regulations, and technologies of new TCM drugs for syndromes in China and pointed out that the application of the animal model of TCM syndromes to carry out pharmacodynamics research and clinical efficacy evaluation criteria of TCM syndromes were the main technical difficulties in the research and development of new TCM drugs for syndromes. Not all syndromes are suitable for developing new drugs, and the indications for new TCM drugs should be constant syndromes. Among the three research and development models of simple syndrome, syndrome-unified disease, and combined disease and syndrome, the research and development model of combined disease and syndrome is recommended. Clinical positioning is the key to new TCM drugs for syndromes. It is encouraged to conduct high-quality human use experience studies to determine the clinical positioning of new TCM drugs for syndromes, as well as the target population, dose, course of treatment, and initial therapeutic and safety, and apply for exemption from non-clinical effectiveness studies. Clinical trials of new TCM drugs for syndromes should take the target symptoms or signs as the main efficacy index and the efficacy of TCM syndromes as the secondary efficacy index. Clinical research program design should implement the "patient-centered" concept and introduce clinical outcome evaluation indicators. In the clinical safety evaluation, special conditions such as characteristic syndromes and changes should be considered. With the construction of the human use experience technology system and the promotion of the TCM registration and evaluation evidence system featuring the "combination of TCM theory, human use experience, and clinical trials", it is believed that many high-quality new TCM drugs for syndromes will be developed in the future.

[Methods for traditional Chinese medicine syndrome-based efficacy evaluation: a review].

Traditional Chinese medicine(TCM) syndrome-based efficacy is an evaluation index which is unique to TCM and can reflect the advantages of TCM. The development of the methods and measurement tools for evaluating TCM syndrome-based efficacy can provide objective and quantitative evidence for the clinical efficacy evaluation of TCM and the development of new Chinese medicine preparations, being the exploration direction of innovative methods and technologies for evaluating TCM efficacy. The conventional evaluation methods are subjective and limited to the mitigation of symptoms and the improvement of physical signs, which make it difficult to form a unified evaluation standard. In addition, the evaluation methods lack unity, objectivity, and quantitative research. The scientific connotation, evaluation ideas and methods, and key technologies of the evaluation for the therapeutic effect on syndromes remain unclear, which leads to diverse evaluation modes, methods, and indexes. The syndrome-based efficacy scale provides a new idea for the objective quantification and standardization of TCM syndromes. This review systematically summarizes the methods and problems, introduces the research progress in the evaluation scales, and puts forward some thoughts on the characteristics of TCM syndrome-based efficacy evaluation, aiming to provide insights for the research in this field.

[Transcriptome data mining combined with clinical and animal experiments for identification of syndrome element marker genes during entire course of steroid-induced osteonecrosis of femoral head].

A research strategy combining transcriptome data mining and experimental verification was adopted to identify the marker genes characterizing the syndrome elements of phlegm, stasis, and deficiency in steroid-induced osteonecrosis of the femoral head(SONFH). Firstly, the common differentially expressed gene sets of SONFH with the syndromes of phlegm-stasis obstructing collaterals, vessel obstruction, and liver-kidney deficiency were obtained from the clinical transcriptomic analysis of a previous study. The differential expression trend analysis and functional gene mining were then employed to predict the candidate marker gene sets representing phlegm, stasis, and deficiency. The whole blood samples from SONFH patients, whole blood samples from SONFH rats, and affected femoral head tissue samples were collected for qPCR, which aimed to determine the expression levels of the candidate marker genes mentioned above. Furthermore, the receiver operating characteristic curve(ROC) was established to objectively evaluate the syndrome differentiation effectiveness of the candidate marker genes mentioned above. The transcriptome data analysis results showed that the candidate marker genes for phlegm was ELOVL fatty acid elongase 6(ELOVL6), and those for stasis were ankyrin 1(ANK1), glycophorin A/B(GYPA/B), and Rh-associated glycoprotein(RHAG). The candidate marker genes for deficiency were solute carrier family 2 member 1(SLC2A1) and stomatin(STOM). The qPCR results showed that compared with that in the non-SONFH group, ELOVL6 had the lowest expression level in the peripheral blood of the SONFH patients with the syndrome of phlegm-stasis obstructing collaterals(P<0.05). Compared with that in the normal control group, ELOVL6 had the lowest expression level in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 4 weeks(P<0.01), and it showed better syndrome differentiation effectiveness of rats modeled for 4 weeks(AUC=0.850, P=0.006) than at other modeling time points(8, 12, 16, and 21 weeks, AUC of 0.689, 0.766, 0.588, and 0.662, respectively). Compared with that in the non-SONFH group, the expression levels of ANK1, GYPA, and RHAG were the lowest in the peripheral blood of SONFH patients with the vessel obstruction syndrome(P<0.05). The expression levels of the three genes were the lowest in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 12 weeks(P<0.05, P<0.01), and their syndrome differentiation effectiveness in the rats modeled for 12 weeks(GYPA: AUC=0.861, P=0.012; ANK1: AUC=0.855, P=0.006; RHAG: AUC=0.854, P=0.009) was superior to that for 4, 8, 16, and 21 weeks(GYPA: AUC=0.646, 0.573, 0.691, and 0.617, respectively; ANK: AUC1=0.630, 0.658, 0.657, and 0.585, respectively; RHAG: AUC=0.592, 0.511, 0.515, and 0.536, respectively). Compared with the non-SONFH group, both SLC2A1 and STOM had the lowest expression levels in the peripheral blood of patients with the syndrome of liver and kidney deficiency(P<0.05). Compared with the normal control group, their expression levels were the lowest in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 21 weeks(P<0.05, except STOM in the peripheral blood of rats). Moreover, the syndrome differentiation effectiveness of SLC2A1 in the rats modeled for 21 weeks(AUC=0.806, P=0.009) was superior to that for 4, 8, 12, and 16 weeks(AUC=0.520, 0.580, 0.741, 0.774, respectively), and STOM was meaningless in syndrome differentiation. In summary, the candidate marker gene for phlegm in SONFH is ELOVL6; the candidate marker genes for stasis are GYPA, RHAG, and ANK1; the candidate marker gene for deficiency is SLC2A1. The results help to reveal the biological connotations of phlegm, stasis, and deficiency in SONFH at the genetic level.

[Retrospective cross-sectional survey of clinical characteristics and syndrome elements distribution at different stages of coronary heart disease].

The clinical data of coronary heart disease(CHD) patients treated in the First Affiliated Hospital of Guangzhou University of Chinese Medicine and Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine from January 2022 to March 2023 were retrospectively collected. This study involved the descriptive analysis of demographic characteristics, clinical symptoms, and tongue and pulse features. The χ~2 test was conducted to analyze the distribution of syndrome elements and their combinations at diffe-rent stages of CHD, so as to reveal the clinical characteristics and syndrome patterns at various pathological stages of CHD. This study extracted 28 symptom entries, 10 tongue manifestation entries, and 7 pulse manifestation entries, summarized the 5 main disease locations of the heart, lung, liver, spleen, and kidney, and the 8 main disease natures of blood stasis, phlegm turbidity, Qi stagnation, heat(fire), fluid retention, Qi deficiency, Yin deficiency, and Yang deficiency and 8 combinations of disease natures. The χ~2 test showed significant differences in the distribution of syndrome elements including the lung, liver, spleen, kidney, blood stasis, heat(fire), Qi stagnation, heat syndrome, water retention, Qi deficiency, Yin deficiency, and Yang deficiency between different disease stages. Specifically, the liver, blood stasis, heat(fire), and Qi stagnation accounted for the highest proportion during unstable stage, and the lung, spleen, kidney, water retention, Qi deficiency, Yin deficiency, and Yang deficiency accounted for the highest proportion at the end stage. The distribution of Qi deficiency varied in the different time periods after percutaneous coronary intervention(PCI). As shown by the χ~2 test of the syndrome elements combination, the distribution of single disease location, multiple disease locations, single disease nature, double disease natures, multiple natures, excess syndrome, and mixture of deficiency and excess varied significantly at different stages of CHD. Specifically, single disease location, single disease nature, and excess syndrome accounted for the highest proportion during the stable stage, and double disease natures accounted for the highest proportion during the unstable stage. Multiple disease locations, multiple disease natures, and mixture of deficiency and excess accounted for the highest proportion during the end stage. In conclusion, phlegm turbidity and blood stasis were equally serious during the stable stage, and a pathological mechanism caused by blood stasis and toxin existed during the unstable stage. The overall Qi deficiency worsened after PCI, and the end stage was accompanied by the Yin and Yang damage and the aggravation of water retention. There were significant differences in the distribution of clinical characteristics and syndrome elements at different stages of CHD. The pathological process of CHD witnessed the growth and decline of deficiency and excess and the combination of phlegm turbidity and blood stasis, which constituted the basic pathogenesis.

[Analysis of clinical research features and outcome indexes of traditional Chinese medicine intervention in septic kidney injury].

This study aims to systematically review the clinical features and outcome indicators in randomized controlled trial(RCT) of traditional Chinese medicine(TCM) intervention in septic kidney injury and provide a reference for optimizing clinical study design and building the core outcome set(COS) of TCM treatment of septic kidney injury. Computer searches were conducted on PubMed, Cochrane Library, EMbase, Web of Science, CNKI, Wanfang, VIP, and SinoMed to find published RCT of TCM intervention in septic kidney injury in the past five years, extract the basic characteristics, intervention measures, outcome indicators, and other data of included studies, and conduct descriptive analysis. 53 RCTs were included, and the sample size was mostly concentrated in 60-80 cases, with abdominal infection being the most common(15 articles, 83.3%) and the TCM syndrome of blood stasis being the most frequent(9 articles, 50.0%). The frequency of intervention methods from high to low were TCM decoction(28 articles, 52.8%), Chinese patent medicine(22 articles, 41.5%), and combined TCM therapy(3 articles, 7.5%); the intervention time of the trial was more than 7 d(34 articles, 69.4%). The risk of bias in included studies was unclear. A total of 84 outcome indicators were involved, which were divided into 9 fields, including 63 physical and chemical tests(305 times, 72.2%), 4 kinds of disease degree(48 times, 11.6%), 4 kinds of clinical effective rate(15 times, 3.6%), 1 kind of quality of life(1 time, 0.2%), 2 kinds of economic evaluation(14 times, 3.3%), 1 kind of TCM disease(9 times, 2.1%), 2 kinds of long-term prognosis(16 times, 3.8%), 2 kinds of safety events(6 times, 1.4%), and 5 other indicators(8 times, 0.7%). The cumulative frequency was 422 times, among which the outcome indicators with higher frequency were inflammatory factors(42 articles, 79.2%) and markers of renal function and kidney injury(40 articles, 75.5%). Only 1(1.9%) of the included articles mentioned primary and secondary outcome indicators, and 6 articles(11.3%) mentioned safety events, 13 articles(24.5%) mentioned economic assessment. The RCT quality of TCM intervention in septic renal injury was generally low, and the reference standards for sepsis, kidney injury, and TCM syndrome diagnosis were not uniform. There are some problems in outcome indicators, such as unclear distinction between primary and secondary indicators, neglect of endpoint indicators, lack of application of TCM characteristic indicators, and insufficient attention to safety events and economic assessment. It is suggested that the quality of clinical research methodology should be improved in the future, and the COS should be constructed to provide high-level evidence-based evidence for TCM intervention in septic kidney injury.

Visual snow syndrome: recent advances in understanding the pathophysiology and potential treatment approaches.

PURPOSE OF REVIEW: Visual snow syndrome (VSS) is a disorder characterized by persistent visual disturbances, including the visual snow phenomenon, palinopsia, heightened perception of entoptic phenomena, impaired night vision, and photophobia. The purpose of this review is to provide an update on recent findings over the past 18 months in VSS research and to summarize the current state of treatment approaches. RECENT FINDINGS: Electrophysiological studies have revealed cortical hyperresponsivity in visual brain areas, imaging studies demonstrated microstructural and functional connectivity alterations in multiple cortical and thalamic regions and investigated glutamatergic and serotoninergic neurotransmission. These findings suggest that VSS might be a network disorder.Only few treatment studies are currently available demonstrating limited response to medication and even worsening or triggering of visual symptoms by certain antidepressants. Promising nonpharmacological treatments include mindfulness-based cognitive therapy, the use of chromatic filters, and research on visual noise adaption and neuro-optometric visual rehabilitation therapy (NORT). However, the level of evidence is still low and further research is needed including larger trials and involving objective measures of individual dysfunction. SUMMARY: Although there has been recent progress, we still have not fully understood the nature of VSS. Further research is needed on a clinical and pathophysiological level to successfully treat the condition.

Observation of the efficacy of elongated needle therapy in treating patients with â ¢B prostatitis of stagnant dampness-heat syndrome. / 芒针治疗湿热瘀阻证⠢Båž‹å‰åˆ—è ºç‚Žæ‚£è€ çš„ç–—æ•ˆè§‚å¯Ÿ.

OBJECTIVES: To observe the clinical efficacy in patients with ⅢB prostatitis of stagnant dampness-heat syndrome treated with elongated needle therapy. METHODS: A total of 90 patients with ⅢB prostatitis of stagnant dampness-heat syndrome were selected and randomly divided into a treatment group(45 cases, 2 dropped out) and a control group(45 cases, 1 dropped out) using a random number table method. The control group was treated with oral administration of Qianlie Shutong Capsule, 3 capsules per dose, 3 times a day for a total of 4 weeks. The treatment group received elongated needle therapy at Qihai(CV6), Zhongji(CV3), bilateral Zhibian(BL54) and Shuidao(ST28), with one treatment per day for 4 weeks. Before and after treatment, the traditional Chinese medicine syndrome score, National Institutes of Health Chronic Prostatitis Symptom Index(NIH-CPSI) score were compared between the two groups, and the clinical efficacy was compared after treatment. RESULTS: Compared with that before treatment, the control group showed significant decrease in traditional Chinese medicine syndrome score, testicular pain, urinary frequency, unending remnants of urine, scrotal wetness, yellowish urine, urinary symptoms, and quality of life scores after treatment(P<0.05)；the treatment group showed significant decrease in traditional Chinese medicine syndrome score, and perineal pain, groin pain, pelvic pain, testicular pain, scrotal wetness, yellowish urine scores, NIH-CPSI total score, pain symptoms, urinary symptoms, and quality of life scores after treatment(P<0.05). After treatment, the treatment group showed significantly lower traditional Chinese medicine syndrome score, and perineal pain, groin pain, pelvic pain, testicular pain scores, NIH-CPSI total score, pain symptoms, and quality of life scores than those of the control group(P<0.05). The effective rate in the treatment group (63.64%, 28/43) was significantly higher than that in the control group (88.37%, 38/44, P<0.05). CONCLUSIONS: Elongated needle therapy can significantly improve the traditional Chinese medicine syndrome score, NIH-CPSI total score, and pain symptom scores in patients with ⅢB prostatitis of stagnant dampness-heat syndrome. It can significantly improve the cure rate in these patients and is particularly effective in relieving pain.

Exploring the Efficacy of the Paula Method of Muscle Exercises in Managing Low Anterior Resection Syndrome Using an Integrative Approach: A Preliminary Study.

Background: Low anterior resection syndrome (LARS) is a post-proctectomy consequence characterized by variable and unpredictable bowel function, including clustering, urgency, and incontinence, which significantly impacts the quality of life. Currently, there is no established gold-standard therapy for LARS. Primary Study Objective: This study aimed to evaluate the effectiveness of the Paula method of exercise as part of an integrative treatment approach for patients with LARS. Design: This preliminary study utilized a single-arm pretest-posttest design. Setting: The study was conducted at a tertiary care medical center. Participants: Five patients diagnosed with LARS completed the study. Intervention: Participants underwent twelve weeks of individualized Paula method exercise sessions. Two questionnaires were employed to assess the severity of LARS and quality of life. Primary Outcome Measures: (1) Low Anterior Resection Syndrome (LARS) Score; (2) Memorial Sloan Kettering Cancer Bowel Function Instrument (MSK-BFI); (3) Global Quality-of-Life (QOLS) Score . Results: All participants completing the 12-week Paula exercise regimen reported no difficulty in engaging with the exercises. Statistically significant improvements were observed in both the LARS score and MSK-BFI (P = .039 and P = .043, respectively, Wilcoxon Rank Sum test). While there were improvements in the global quality-of-life score and functional scales of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, these improvements did not reach statistical significance. Conclusions: This preliminary study suggests that patients with LARS can successfully complete a 12-week exercise program using the Paula method, resulting in improved LARS scores. However, further investigation through larger, multicenter, randomized controlled trials is necessary to establish the efficacy of these exercises as a treatment for LARS.

TCMSSD: A comprehensive database focused on syndrome standardization.

BACKGROUD: Quantitative and standardized research on syndrome differentiation has always been at the forefront of modernizing Traditional Chinese Medicine (TCM) theory. However, the majority of existing databases primarily concentrate on the network pharmacology of herbal prescriptions, and there are limited databases specifically dedicated to TCM syndrome differentiation. PURPOSE: In response to this gap, we have developed the Traditional Chinese Medical Syndrome Standardization Database (TCMSSD, http://tcmssd.ratcm.cn). METHODS: TCMSSD is a comprehensive database that gathers data from various sources, including TCM literature such as TCM Syndrome Studies (Zhong Yi Zheng Hou Xue) and TCM Internal Medicine (Zhong Yi Nei Ke Xue) and various public databases such as TCMID and ETCM. In our study, we employ a deep learning approach to construct the knowledge graph and utilize the BM25 algorithm for syndrome prediction. RESULTS: The TCMSSD integrates the essence of TCM with the modern medical system, providing a comprehensive collection of information related to TCM. It includes 624 syndromes, 133,518 prescriptions, 8,073 diseases (including 1,843 TCM-specific diseases), 8,259 Chinese herbal medicines, 43,413 ingredients, 17,602 targets, and 8,182 drugs. By analyzing input data and comparing it with the patterns and characteristics recorded in the database, the syndrome prediction tool generates predictions based on established correlations and patterns. CONCLUSION: The TCMSSD fills the gap in existing databases by providing a comprehensive resource for quantitative and standardized research on TCM syndrome differentiation and laid the foundation for research on the biological basis of syndromes.

Historical and contemporary applications of moxibustion at Gaohuang (BL 43). / 膏肓灸古今应用探析.

The relevant passages on moxibustion at Gaohuang (BL 43) in the Chinese Medical Code (fifth edition), and relevant literature on moxibustion at Gaohuang (BL 43) published up to January 17th, 2023 in the CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, EMbase and Scopus were searched. The localization and selection methods of Gaohuang (BL 43), types of moxibustion at Gaohuang (BL 43), moxibustion quantity, and the main clinical indications were analyzed. As a result, a total of 227 ancient passages were included, with 51 related to moxibustion quantity and 171 related to clinical indications, encompassing 33 different diseases. A total of 50 modern articles were reviewed, covering 26 different diseases. The key of selection methods of Gaohuang (BL 43) is exploring sensitivity around the scapula, with direct moxibustion as a preferred technique; the optimal moxibustion dose is detenuined by arrival and withdrawal of deqi, and primary indications were related to syndrome of heart and lung deficiencies.

PGAP2-Related Hyperphosphatasia-Mental Retardation Syndrome: Report of a Novel Patient, Toward a Broadening of Phenotypic Spectrum and Therapeutic Perspectives.

PGAP2 gene has been known to be the cause of "hyperphosphatasia, mental retardation syndrome-3" (HPMRS3). To date, 14 pathogenic variants in PGAP2 have been identified as the cause of this syndrome in 24 patients described in single-case reports or small clinical series with pan-ethnic distribution. We aim to present a pediatric PGAP2-mutated case, intending to further expand the clinical phenotype of the syndrome and to report our experience on a therapeutic approach to drug-resistant epilepsy.We present the clinical, neuroradiological, and genetic characterization of a Caucasian pediatric subject with biallelic pathogenic variants in the PGAP2 gene revealed by next generation sequencing analysis.We identified a subject who presented with global developmental delay and visual impairment. Brain magnetic resonance imaging showed mild hypoplasia of the inferior cerebellar vermis and corpus callosum and mild white matter reduction. Laboratory investigations detected an increase in alkaline phosphatase. At the age of 13 months, he began to present epileptic focal seizures with impaired awareness, which did not respond to various antiseizure medications. Electroencephalogram (EEG) showed progressive background activity disorganization and multifocal epileptic abnormalities. Treatment with high-dose pyridoxine showed partial benefit, but the persistence of seizures and the lack of EEG amelioration prompted us to introduce ketogenic diet treatment.Our case provides a further phenotypical expansion of HPMRS3 to include developmental and epileptic encephalopathy. Due to the limited number of patients reported so far, the full delineation of the clinical spectrum of HPMRS3 and indications for precision medicine would benefit from the description of new cases and their follow-up evaluations.

The curative efficacy of auricular comprehensive therapy on menstrual migraine and its effect on serum prostaglandin. / è€³ç©´ç»¼åˆç–—æ³•æ²»ç–—æœˆç»æ€§åå¤´ç—›æ‚£è€ ä¸´åºŠç–—æ•ˆåŠå¯¹è¡€æ¸ å‰åˆ—è ºç´ çš„å½±å“.

OBJECTIVES: To observe the curative efficacy of auricular comprehensive therapy on menstrual migraine(MM) and its effect on serum prostaglandin F2α(PGF2α), prostaglandin E2(PGE2) contents and ratio, so as to explore its possible mechanism. METHODS: A total of 66 patients with MM of liver-fire syndrome were randomly divided into observation group (33 cases, 2 cases dropped off) and control group (33 cases, 2 cases dropped off), and 20 healthy women were included in the normal group. Patients in the control group were given flunarizine hydrochloride capsules orally, twice a day, for 3 consecutive weeks. Patients in the observation group were treated with auricular comprehensive therapy, starting 2-5 days before menstrual cramps, once a week, for a total of 3 weeks. The visual analogue scale (VAS) and migraine score were evaluated before and after treatment, and follow-up for 1 and 2 menstrual cycles. Serum PGF2α and PGE2 contents were measured before and after treatment, and the PGF2α/PGE2 ratio was calculated. The clinical effective rates in the two groups were calculated. RESULTS: After treatment and follow-up for 1 and 2 menstrual cycles, the VAS scores, headache degree, the frequency and duration of headache attacks, as well as accompanying symptoms of the observation and control groups were lower than those before treatment(P<0.05), and those of the observation group was lower than those of the control group(P<0.05). Before treatment, the PGF2α contents in the observation and control group were significantly higher(P<0.05), while the PGE2 contents lower(P<0.05) and PGF2α/PGE2 ratio higher(P<0.05) than those in the normal group. After treatment, the serum PGF2α contents in the observation and control group were significantly reduced compared with which before treatment(P<0.05), and were lower in the observation group than that in the control group (P<0.05). The serum PGE2 contents in the observation and control groups were significantly increased after treatment compared with which before treatment(P<0.05), with the contents in the observation group higher than that in the control group(P<0.05). The serum PGF2α/PGE2 ratio in the observation and control group was significantly reduced after treatment compared with which before treatment(P<0.05), with the control group higher than the normal group(P<0.05), and the observation group lower than the control group(P<0.05). The clinical effective rate of the observation group was 93.5% (29/31), and that of the control group was 77.4% (24/31). The effective rate of the observation group was significantly higher than that of the control group(P<0.05). CONCLUSIONS: The curative efficacy of auricular comprehensive therapy on MM with liver-fire syndrome is significantly better than that of oral flunarizine hydrochloride capsules, especially in relieving hea-daches, reducing the frequency and duration of headache attacks, as well as accompanying symptoms. Its mechanism may be related to regulating the abnormal PGF2α and PGE2 contents of patients and reducing the ratio of PGF2α/PGE2.

Effective Treatment of Solitary Rectal Ulcer Syndrome by Using Photobiomodulation Therapy: A Case Report.

Objective: To investigate the efficacy of Photobiomodulation therapy (PBMT) for the treatment of solitary rectal ulcer syndrome (SRUS). Background: SRUS is a benign disease, diagnosed by symptoms, clinical, and histological findings. PBMT has been reported for the treatment of various inflammation-based diseases including aphthous ulcer, but still no such study on the treatment of SRUS is published. Materials and methods: A 29-year Asian women, diagnosed for SRUS of 0.57 cm diameter, was treated by a laser at 635 nm through seven sessions. Laser fluence of 85 J/cm2 was delivered to ulcer lesion during each session for 10 min. Clinical results were valued by physician with sigmoid probe throughout PBMT sessions and no medicines were prescribed to the patient. Results: After seven sessions, the lesion was completely healed with 100% clinical response. In follow-up, patient did not respond to any additional/recurring abnormality, and no side effects were observed. Conclusions: In conclusion, PBMT by using laser at 635 nm is an effective treatment for SRUS without any side effects and patient remained comfortable throughout treatment sessions. Patient registration No. H-744/23.

Exploration of the methods and rules of syndrome/pattern differentiation and treatment of headache from the acupuncture-moxibustion prescriptions of ancient literature based on the data mining technology. / 基于数据挖掘技术探析古代头痛针灸方的辨治方法与规律.

The study aims to identifying and exploring the methods and rules of the syndrome/pattern differentiation and treatment of headache through collating acupuncture-moxibustion prescriptions recorded earliest in ancient literature. Using Excel2016 software, the structural data table was prepared with "name of disease", "location of disease", "etiology and pathogenesis", "complicated symptoms", "sites for acupuncture and moxibustion" and "techniques of acupuncture and moxibustion" included. The normative approach was conduced on "name of disease", "etiology and pathogenesis", "complicated symptoms" and "nomenclature of acupoint". Using conventional literature statistical method, combined with Apriori algorithm of association rule, the implicit multi-dimensional correlation rules were explored among various elements of syndrome/pattern differentiation of headache and corresponding therapeutic methods. Based on the findings of the study, the regularity was distinct regarding the treatment at "distal acupoints along the affected meridian and the local acupoints at the affected area" after identifying the location of headache; the strong association was presented between "etiology and pathogenesis" and "acupoint selection", and between "etiology and pathogenesis" and "therapeutic methods", including 9 and 12 rules, respectively. Guanyuan (CV 4) selected in treatment of headache was associated with kidney deficiency, the combination of Zhongwan (CV 12) and Zusanli (ST 36) was with phlegm, Fengfu (GV 16), Fengchi (GB 20), Xinghui (GV 22) and Baihui (GV 20) was with wind, and Hegu (LI 4) was with cold. Moxibustion was dominant in treatment if headache was caused by pathogenic cold or related to deficiency syndrome; acupuncture was used specially for the case caused by phlegm, or interaction of wind and phlegm or wind and heat. For heat syndrome, either acupuncture or moxibustion was applicable, in general, acupuncture was more commonly used in comparison with moxibustion for headache. There were 6 association rules regarding the acupoint selection and the techniques of acupuncture and moxibustion. Moxibustion was generally applied to Xinghui (GV 22), Shangxing (GV 23) and Baihui (GV 20) ; and acupuncture was to Fengfu (GV 16), Hegu (LI 4) and Zusanli (ST 36). There were few association rules between the complicated symptoms and acupoint selection. Among nearly 100 complications, there were only 3 feature associations. Zhongwan (CV 12) was selected for the case with poor appetite, Chengjiang (CV 24) was with neck stiffness, and Fengchic (GB 20) combined with Fenglong (ST 40) or Jiexi (ST 41) was used if vertigo was present. In the ancient time, regarding the treatment of headache, acupuncture and moxibustion are delivered based on the three aspects, i.e. the location of illness, the etiology and pathogenesis, and the complicated symptoms. For acupoint selection, in line with the courses of affected meridians, the adjacent and distal acupoints are combined according to the location of headache. The acupoint prescription is composed in terms of the etiology and pathogenesis. The techniques of acupuncture and moxibustion are optimized in consideration of the sites where acupuncture and moxibustion are operated.

Efficacy and safety of traditional Chinese medicine in the treatment of menopause-like syndrome for breast cancer survivors: a systematic review and meta-analysis.

BACKGROUND: In recent years, breast cancer (BC) incidence and mortality have been the highest in females. Menopause-like syndrome (MLS), arising from hypoestrogenism caused by endocrine therapy, significantly affects the quality of life for females. Traditional Chinese Medicine (TCM) has advantages in ameliorating MLS, but the efficacy of TCM in patients with BC has not been systematically evaluated. METHODS: A comprehensive search was performed on PubMed, Web of Science, Embase, Ovid, Cochrane Library, China National Knowledge Infrastructure, Wanfang database, Chinese Scientific Journals Database, and Clinical Trial Registry from inception to September 4, 2023. The Cochrane Risk of Bias assessment tool was used for the quality evaluation of the randomized controlled trials (RCTs). Review Manager 5.4 software was used for statistical analysis, and the Grading of Recommendations Assessment, Development, and Evaluation was used for quality evaluation of the synthesized evidence. RESULTS: This review included 42 studies involving 3112 female patients with BC. The results showed that the TCM group was better at decreasing the Kupperman Menopausal Index (KMI) scores (standardized MD, SMD = - 1.84, 95% confidence interval, CI [- 2.21--1.46], Z = 9.63, P < 0.00001). Regarding the main symptoms of MLS, the TCM groups could significantly decrease the scores of hot flashes and night sweats (SMD = - 0.68, 95% CI [- 1.1--0.27], Z = 3.24, P = 0.001), paraesthesia (SMD = - 0.48, 95% CI [- 0.74--0.21], Z = 3.53, P = 0.0004), osteoarthralgia (SMD = - 0.41, 95% CI [- 0.6-0.21], Z = 4.09, P < 0.0001), anxiety (MD = - 0.85, 95% CI [- 1.13, - 0.58], Z = 6.08, P < 0.00001) and insomnia (MD = - 0.61, 95% CI [- 0.8, - 0.43], Z = 6.51, P < 0.00001). TCM can effectively improve the symptoms of MLS in patients with BC. Moreover, TCM could improve the objective response rate (ORR) by 50% (RR = 1.5, 95% CI [1.37-1.64], Z = 9.01, P < 0.00001). Follicle-stimulating hormone (FSH) and oestradiol (E2) had no significant difference compared with the control group (p = 0.81 and p = 0.87), and luteinizing hormone (LH) in the TCM group decreased significantly (MD = - 0.99, 95% CI [- 1.38, - 0.5], Z = 5.01, P < 0.00001). This means that the use of TCM does not negatively affect endocrine therapy and may even have a synergistic effect. The incidence of adverse events (AEs) was lower in the TCM groups than in the control groups. CONCLUSIONS: The meta-analysis stated that TCM could better improve the MLS of patients, alleviate related symptoms, and did not increase adverse drug reactions in BC survivors. This review brings more attention to MLS, and the present findings shed light on the potential applications of TCM in the treatment of MLS in BC survivors.

Diagnosis and Management of Pollen Food Allergy Syndrome to Nuts.

Oral allergy syndrome or pollen food allergy syndrome (PFAS) represents a common clinical conundrum when the reported trigger food is a tree nut (usually almond or hazelnut) or peanut. The PFAS may give rise to uncertainty about the potential severity of the future reactions, indications for prescribing epinephrine, and the extent of the necessary dietary avoidance. As a food allergy, secondary to cross-reactivity with airborne pollen, PFAS usually manifests toward the end of the first decade of life as contact urticaria of the oropharyngeal mucous membranes. Molecular allergology facilitates diagnosis and risk stratification by establishing the profile of sensitization. Exclusive sensitization to pathogenesis-related proteins family 10 (PR10) and profilins indicates that signs and symptoms are due to PFAS, whereas sensitization to seed storage proteins with or without sensitization to PR10 and profilins may indicate a more severe primary nut allergy phenotype. Management relies on avoidance of the specific nut trigger, advice on the likelihood of more severe local or systemic symptoms, and treatment of reactions according to the severity. Future studies are needed to better delineate the risk of systemic reactions in individuals with nut PFAS and to establish the role of food or pollen allergen immunotherapy for the prevention or moderation of this condition.

Identification of AIRE pathogenic variants ends diagnostic odyssey for Saudi child with infantile-onset keratoconjunctivitis as an early sign of autoimmune polyglandular syndrome type1; a case report.

PURPOSE: Chronic keratoconjunctivitis is a rare presentation of autoimmune polyglandular syndrome type 1 (APS-1) during the first year of life. Herein, We report a case of a 10-month-old baby girl with chronic bilateral keratoconjunctivitis, corneal scarring and neovascularization that was treated initially with topical immunosuppressants. METHODS: Detailed ophthalmological assessment followed by molecular testing using whole exome sequencing. RESULTS: In addition to the severe chronic bilateral keratoconjunctivitis, corneal scarring and neovascularization, patient weight was found to be low than 10th percentile. Further genetic testing revealed autoimmune regulator (AIRE) gene variant that was only reported once in the literature confirming the diagnosis of APS-1. Further workup detected hypoparathyroidism that was treated with calcium supplementation. CONCLUSION: Our case represents the importance of multidisciplinary services and highlights the role of genetic testing in diagnosing such syndromic cases. We reviewed previous reports and found that available treatment for ocular involvement is usually nonsatisfactory; however, early detection and referral by ophthalmologists could result in treating previously undetected endocrine disorders that can be life threatening if left untreated.

Hepatocyte nuclear factor 1B deletion, but not intragenic mutation, might be more susceptible to hypomagnesemia.

AIMS: HNF1B syndrome is caused by defects in the hepatocyte nuclear factor 1B (HNF1B) gene, which leads to maturity-onset diabetes of the young type 5 and congenital organ malformations. This study aimed to identify a gene defect in a patient presenting with diabetes and severe diarrhea, while also analyzing the prevalence of hypomagnesemia and its correlation with the HNF1B genotype. MATERIALS AND METHODS: Whole exome sequencing was used to identify responsible point mutations and small indels in the proband and their family members. Multiplex ligation-dependent probe amplification was carried out to identify HNF1B deletions. Furthermore, an analysis of published data on 539 cumulative HNF1B cases, from 29 literature sources, was carried out to determine the correlation between the HNF1B genotype and the phenotype of serum magnesium status. RESULTS: Using multiplex ligation-dependent probe amplification, we identified a de novo heterozygous HNF1B deletion in the patient, who showed dorsal pancreas agenesis and multiple kidney cysts, as detected by magnetic resonance imaging. Magnesium supplementation effectively alleviated the symptoms of diarrhea. Hypomagnesemia was highly prevalent in 192 out of 354 (54.2%) patients with HNF1B syndrome. Compared with patients with intragenic mutations, those with HNF1B deletions were more likely to suffer from hypomagnesemia, with an odds ratio of 3.1 (95% confidence interval 1.8-5.4). CONCLUSIONS: Hypomagnesemia is highly prevalent in individuals with HNF1B syndrome, and those with HNF1B deletion are more susceptible to developing hypomagnesemia compared with those with intragenic mutations. The genotype-phenotype associations in HNF1B syndrome have significant implications for endocrinologists in terms of genotype detection, treatment decisions and prognosis assessment.