Prescription system to calculate precise doses of Chinese herbal medicine to avoid toxic effects.

Background and objectives: Traditional Chinese Medicine (TCM) is a therapeutic system which has been practiced for thousands of years. Although for much of its history the decoction of medicinal herbs was the most common method of consuming the herbal treatments, TCM prescriptions are now primarily prepared using concentrated Chinese herbal extracts (CCHE) in powder or granular form. However, determining the precise dose of each single Chinese herbal constituent within a prescription creates a challenge in clinical practice due to the potential risk of toxicity. To alleviate this, we invented the Chinese Intelligence Prescription System (CIPS) to calculate the exact dose of each single herb within an individual prescription. Methods: In this study, we applied CIPS in a real-world setting to analyze clinical prescriptions collected and prepared at the TCM Pharmacy of China Medical University Hospital (CMUH). Results: Our investigation revealed that 3% of all prescriptions filled in a 1-month period contained inexact dosages, suggesting that more than 170,000 prescriptions filled in Taiwan in a given month may contain potentially toxic components. We further analyzed the data to determine the excess dosages and outline the possible associated side effects. Conclusions: In conclusion, CIPS offers TCM practitioners the ability to prepare exact Chinese herbal medicine (CHM) prescriptions in order to avoid toxic effects, thereby ensuring patient safety.

Chinese Intelligence Prescription System improves prescription accuracy while decreasing labor and drug costs.

BACKGROUND AND AIM: The traditional method of taking Chinese Medicine involves creating a decoction by cooking medicinal Chinese herbs. However, this method has become less popular, being replaced by the more convenient method of consuming concentrated Chinese herbal extracts, which creates challenges related to the complexity of stacking multiple formulas. METHODS: We developed the Chinese Intelligence Prescription System (CIPS) to simplify the prescription process. In this study, we used data from our institutions pharmacy to calculate the number of reductions, average dispensing time, and resulting cost savings. RESULTS: The mean number of prescriptions was reduced from 8.19 ± 3.65 to 7.37 ± 3.34 ([Formula: see text]). The reduction in the number of prescriptions directly resulted in decreased dispensing time, reducing it from 1.79 ± 0.25 to 1.63 ± 0.66 min ([Formula: see text]). The reduced dispensing time totaled 3.75 h per month per pharmacist, equivalent to an annual labor cost savings of $15,488 NTD per pharmacist. In addition, drug loss was reduced during the prescription process, with a mean savings of $4,517 NTD per year. The combined savings adds up to a not insignificant $20,005 NTD per year per pharmacist. When taking all TCM clinics/hospitals in Taiwan into account, the total annual savings would be $77 million NTD. CONCLUSION: CIPS assists clinicians and pharmacists to formulate precise prescriptions in a clinical setting to simplify the dispensing process while reducing medical resource waste and labor costs.

Integrated Chinese herbal medicine and Western medicine successfully resolves spontaneous subcutaneous emphysema and pneumomediastinum in a patient with severe COVID-19 in Taiwan: A case report.

CASE: Serious complications of severe coronavirus disease 2019 (COVID-19) include subcutaneous emphysema (SE) and pneumomediastinum, which are complicated to treat with conventional Western medicine. We report how combining Chinese herbal medicine (CHM) with Western medicine quickly resolved a patient's COVID-19-associated pulmonary complications, shortened hospital stay and improved quality of life. CLINICAL FEATURES AND OUTCOME: A 59-year-old male with a history of smoking and tumors was diagnosed with COVID-19 in May 2021. At hospitalization, his oxygen saturation (SpO2) was 80%, he had a continuous severe cough, rapid shallow breathing, spontaneous SE and pneumomediastinum. By Day 4 of hospitalization, his condition was worsening despite standard care, so CHM was added. After 3-5 days, his coughing had lessened and supplementary oxygen therapy was de-escalated. Nine days after starting CHM, the SE had completely resolved and the patient avoided intubation. His WHO OS 10-point Scale score had fallen from 6 to 3 points and the modified Medical Research Council Dyspnea Scale score from 4 to 2 points. He was hospitalized for 19 days. At 1 week post-discharge, the patient could handle most of his daily activities and experienced minor shortness of breath only when performing labor-intensive tasks. At 1 month, his work output was restored to pre-COVID-19 levels. CONCLUSION: CHM combined with standard Western medicine improved pulmonary function, respiratory rate, blood oxygen saturation and shortened the hospital stay of a patient with severe COVID-19 complicated by SE and pneumomediastinum.

Evaluation of the Key Advantages between Two Modalities of Boronophenylalanine Administration for Clinical Boron Neutron Capture Therapy Using an Animal Model.

In clinical boron neutron capture therapy (BNCT), boronophenylalanine (BPA) administrations through one-step infusion (OSI) and two-step infusion (TSI) are the most widely used. This study compared the advantages of OSI and TSI using a human oral squamous cell carcinoma-bearing animal model. OSI was administered at a high-dose rate of 20 mg/kg/min for 20 min (total dose: 400 mg/kg) as the first step infusion. TSI was a prolonged infusion at a low-dose rate of 1.67 mg/kg/min for 15, 30, 45, and 60 min (total dose: 25, 50, 75, and 100 mg/kg) following the first step infusion. The sigmoid Emax model was used to evaluate the boron accumulation effect in the tumor. The advantages of TSI were observed to be greater than those of OSI. The observed advantages of TSI were as follows: a stable level of boron concentration in blood; tumor to blood boron ratio (T/B); tumor to muscle boron ratio (T/M); and skin to blood boron ratio (S/B). The boron accumulation effect in tumors increased to 68.98%. Thus, effective boron concentration in these tumor cells was achieved to enhance the lethal damage in BNCT treatment. Boron concentration in the blood was equal to that in the skin. Therefore, the equivalent dose was accurately estimated for the skin.

Application of Neural Network and Cluster Analyses to Differentiate TCM Patterns in Patients With Breast Cancer.

BACKGROUND AND PURPOSE: Pattern differentiation is a critical element of the prescription process for Traditional Chinese Medicine (TCM) practitioners. Application of advanced machine learning techniques will enhance the effectiveness of TCM in clinical practice. The aim of this study is to explore the relationships between clinical features and TCM patterns in breast cancer patients. METHODS: The dataset of breast cancer patients receiving TCM treatment was recruited from a single medical center. We utilized a neural network model to standardize terminologies and address TCM pattern differentiation in breast cancer cases. Cluster analysis was applied to classify the clinical features in the breast cancer patient dataset. To evaluate the performance of the proposed method, we further compared the TCM patterns to therapeutic principles of Chinese herbal medication in Taiwan. RESULTS: A total of 2,738 breast cancer cases were recruited and standardized. They were divided into 5 groups according to clinical features via cluster analysis. The pattern differentiation model revealed that liver-gallbladder dampness-heat was the primary TCM pattern identified in patients. The main therapeutic goals of the top 10 Chinese herbal medicines prescribed for breast cancer patients were to clear heat, drain dampness, and detoxify. These results demonstrated that the neural network successfully identified patterns from a dataset similar to the prescriptions of TCM clinical practitioners. CONCLUSION: This is the first study using machine-learning methodology to standardize and analyze TCM electronic medical records. The patterns revealed by the analyses were highly correlated with the therapeutic principles of TCM practitioners. Machine learning technology could assist TCM practitioners to comprehensively differentiate patterns and identify effective Chinese herbal medicine treatments in clinical practice.

Analysis of DNA Damage Responses After Boric Acid-mediated Boron Neutron Capture Therapy in Hepatocellular Carcinoma.

BACKGROUND: Boron neutron capture therapy (BNCT) selectively kills tumor cells while sparing adjacent normal cells. Boric acid (BA)-mediated BNCT showed therapeutic efficacy in treating hepatocellular carcinoma (HCC) in vivo. However, DNA damage and corresponding responses induced by BA-mediated BNCT remained unclear. This study aimed to investigate whether BA-mediated BNCT induced DNA double-strand breaks (DSBs) and to explore DNA damage responses in vitro. MATERIALS AND METHODS: Huh7 Human HCC cells were treated with BA and irradiated with neutrons during BA-BNCT. Cell survival and DNA DSBs were examined by clonogenic assay and expression of phosphorylated H2A histone family member X (γH2AX), respectively. The DNA damage response was explored by determining the expression levels of DNA repair- and apoptosis-associated proteins and conducting a cell-cycle analysis. RESULTS: DNA DSBs induced by BA-mediated BNCT were primarily repaired through the homologous recombination pathway. BA-mediated BNCT induced G2/M arrest and apoptosis in HCC. CONCLUSION: Our findings may enable the identification of radiosensitizers or adjuvant drugs for potentiating the therapeutic effectiveness of BA-mediated BNCT for HCC.

Selective Inhibition of PAR4 (Protease-Activated Receptor 4)-Mediated Platelet Activation by a Synthetic Nonanticoagulant Heparin Analog.

Objective- PAR4 (protease-activated receptor 4), one of the thrombin receptors in human platelets, has emerged as a promising target for the treatment of arterial thrombotic disease. Previous studies implied that thrombin exosite II, known as a binding site for heparin, may be involved in thrombin-induced PAR4 activation. In the present study, a heparin octasaccharide analog containing the thrombin exosite II-binding domain of heparin was chemically synthesized and investigated for anti-PAR4 effect. Approach and Results- PAR4-mediated platelet aggregation was examined using either thrombin in the presence of a PAR1 antagonist or γ-thrombin, which selectively activates PAR4. SCH-28 specifically inhibits PAR4-mediated platelet aggregation, as well as the signaling events downstream of PAR4 in response to thrombin. Moreover, SCH-28 prevents thrombin-induced ß-arrestin recruitment to PAR4 but not PAR1 in Chinese Hamster Ovary-K1 cells using a commercial enzymatic complementation assay. Compared with heparin, SCH-28 is more potent in inhibiting PAR4-mediated platelet aggregation but has no significant anticoagulant activity. In an in vitro thrombosis model, SCH-28 reduces thrombus formation under whole blood arterial flow conditions. Conclusions- SCH-28, a synthetic small-molecular and nonanticoagulant heparin analog, inhibits thrombin-induced PAR4 activation by interfering with thrombin exosite II, a mechanism of action distinct from other PAR4 inhibitors that target the receptor. The characteristics of SCH-28 provide a new strategy for targeting PAR4 with the potential for the treatment of arterial thrombosis.

Neural network analysis of Chinese herbal medicine prescriptions for patients with colorectal cancer.

Traditional Chinese Medicine (TCM) is an experiential form of medicine with a history dating back thousands of years. The present study aimed to utilize neural network analysis to examine specific prescriptions for colorectal cancer (CRC) in clinical practice to arrive at the most effective prescription strategy. The study analyzed the data of 261 CRC cases recruited from a total of 141,962 cases of renowned veteran TCM doctors collected from datasets of both the DeepMedic software and TCM cancer treatment books. The DeepMedic software was applied to normalize the symptoms/signs and Chinese herbal medicine (CHM) prescriptions using standardized terminologies. Over 20 percent of CRC patients demonstrated symptoms of poor appetite, fatigue, loose stool, and abdominal pain. By analyzing the prescription patterns of CHM, we found that Atractylodes macrocephala (Bai-zhu) and Poria (Fu-ling) were the most commonly prescribed single herbs identified through analysis of medical records, and supported by the neural network analysis; although there was a slight difference in the sequential order. The study revealed an 81.9% degree of similarity of CHM prescriptions between the medical records and the neural network suggestions. The patterns of nourishing Qi and eliminating dampness were the most common goals of clinical prescriptions, which corresponds with treatments of CRC patients in clinical practice. This is the first study to employ machine learning, specifically neural network analytics to support TCM clinical diagnoses and prescriptions. The DeepMedic software may be used to deliver accurate TCM diagnoses and suggest prescriptions to treat CRC.

Photoluminescence of monolayer transition metal dichalcogenides integrated with VO2.

Integrating a phase transition material with two-dimensional semiconductors can provide a route towards tunable opto-electronic metamaterials. Here, we integrate monolayer transition metal dichalcogenides with vanadium dioxide (VO2) thin films grown via molecular beam epitaxy to form a 2D/3D heterostructure. Vanadium dioxide undergoes an insulator-to-metal transition at 60-70 °C, which changes the band alignment between MoS2 and VO2 from a semiconductor-insulator junction to a semiconductor-metal junction. By switching VO2 between insulating and metallic phases, the modulation of photoluminescence emission in the 2D semiconductors was observed. This study demonstrates the feasibility to combine TMDs and functional oxides to create unconventional hybrid optoelectronic properties derived from 2D semiconductors that are linked to functional properties of oxides through proximity coupling.

Atomically thin heterostructures based on single-layer tungsten diselenide and graphene.

Heterogeneous engineering of two-dimensional layered materials, including metallic graphene and semiconducting transition metal dichalcogenides, presents an exciting opportunity to produce highly tunable electronic and optoelectronic systems. In order to engineer pristine layers and their interfaces, epitaxial growth of such heterostructures is required. We report the direct growth of crystalline, monolayer tungsten diselenide (WSe2) on epitaxial graphene (EG) grown from silicon carbide. Raman spectroscopy, photoluminescence, and scanning tunneling microscopy confirm high-quality WSe2 monolayers, whereas transmission electron microscopy shows an atomically sharp interface, and low energy electron diffraction confirms near perfect orientation between WSe2 and EG. Vertical transport measurements across the WSe2/EG heterostructure provides evidence that an additional barrier to carrier transport beyond the expected WSe2/EG band offset exists due to the interlayer gap, which is supported by theoretical local density of states (LDOS) calculations using self-consistent density functional theory (DFT) and nonequilibrium Green's function (NEGF).

Citral is renoprotective for focal segmental glomerulosclerosis by inhibiting oxidative stress and apoptosis and activating Nrf2 pathway in mice.

The pathogenesis of focal segmental glomerulosclerosis (FSGS) is considered to be associated with oxidative stress, mononuclear leukocyte recruitment and infiltration, and matrix production and/or matrix degradation, although the exact etiology and pathogenic pathways remain to be determined. Establishment of a pathogenesis-based therapeutic strategy for the disease is clinically warranted. Citral (3,7-dimethyl-2,6-octadienal), a major active compound in Litseacubeba, a traditional Chinese herbal medicine, can inhibit oxidant activity, macrophage and NF-κB activation. In the present study, first, we used a mouse model of FSGS with the features of glomerular epithelial hyperplasia lesions (EPHLs), a key histopathology index of progression of FSGS, peri-glomerular inflammation, and progressive glomerular hyalinosis/sclerosis. When treated with citral for 28 consecutive days at a daily dose of 200 mg/kg of body weight by gavage, the FSGS mice showed greatly reduced EPHLs, glomerular hyalinosis/sclerosis and peri-glomerular mononuclear leukocyte infiltration, suggesting that citral may be renoprotective for FSGS and act by inhibiting oxidative stress and apoptosis and early activating the Nrf2 pathway. Meanwhile, a macrophage model involved in anti-oxidative and anti-inflammatory activities was employed and confirmed the beneficial effects of citral on the FSGS model.

Evaluation of the antioxidant and melanogenesis inhibitory properties of pracparatum mungo (lu-do huang).

Pracparatum mungo (Lu-Do Huang) is a traditional Chinese functional medicine made from the natural fermentation of mung bean (Lǜ Dòu) mixed with other Chinese medicines. It has been recognized as having liver protecting and detoxifying effects. As mung beans have been verified to possess anti-inflammatory, antioxidant, antipyretic, and whitening actions, the present research utilized the in vitro, ex vivo, and in vivo experimental models to investigate the antioxidant and melanin inhibiting effects of P. mungo on the skin. The in vitro experiment revealed that P. mungo methanol extract (PMME) and P. mungo ethanol extract (PMEE) possess the capacity to clear α,α-diphenyl-2-picrylhydrazyl (DPPH) radicals and inhibit tyrosinase activity. The ex vivo experiment indicated that PMEE can promote the growth of MDCK cells and increase the enzymatic activities of superoxide dismutase (SOD) and catalase in MDCK cells. On the other hand, PMME and PMEE can suppress the proliferation of A375 cells, and PMEE can reduce the enzymatic activities of SOD and catalase in A375 cells. The in vivo results showed that P. mungo can enhance the enzymatic performance of SOD, Catalase, and glutathione peroxidase (GPx) in the liver. The results also showed that P. mungo has antioxidant characteristics and can inhibit tyrosinase activity, thereby promoting the growth of skin tissues and suppressing the proliferation of A375 cells, and thus enhancing the effects that the antioxidant enzymatic performance has on the liver. These results can be applied in the development of tyrosinase inhibitors or antioxidants used for the inhibition of melanin biosynthesis or for auto-oxidation in further industrial applications, particularly those relating to functional food or cosmetic compositions.

Therapeutic efficacy evaluation of curcumin on human oral squamous cell carcinoma xenograft using multimodalities of molecular imaging.

Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity; however the treatment approaches are still unsatisfactory. We used a luciferase-transfected animal model to evaluate the therapeutic effects of curcumin. Human oral squamous cell carcinoma SAS cell line was stably transfected with luc gene, named SAS/luc cells. For the in vivo study, they were inoculated subcutaneously to 6-week-old male NOD/SCID mice which were separated into four groups for intraperitoneal injection (i.p.) of curcumin: control, daily with 35 mg/kg, 70 mg/kg every 2 days, and 100 mg/kg every 3 days. We applied SAS/luc bearing animal model and bioluminescent imaging (BLI) to study the inhibition effect of curcumin on tumor growth. The cytotoxic effect of curcumin on SAS/luc cells was mainly at G2/M phase and a significant dose dependent increase of the apoptotic SAS/luc cells as represented by sub-G1 phase was shown. Therapeutic efficacy evaluated by both caliper assay and BLI showed a significant difference between curcumin-treated mice and the controls (p < 0.01). The significant inhibition effects of curcumin on the proliferation and the growth of human OSCC are observed both in vitro and in vivo. No significant body weight change (i.e. within 20%) was observed in all SAS/luc-bearing mice with or without curcumin treatment. This SAS/luc human OSCC bearing animal model combined with multimodalities of molecular imaging permits a sensitive and non-invasive approach to evaluate the therapeutic efficacy in vivo.