Curbing COVID-19 progression and mortality with traditional Chinese medicine among hospitalized patients with COVID-19: A propensity score-matched analysis.

BACKGROUND: Viral- and host-targeted traditional Chinese medicine (TCM) formulae NRICM101 and NRICM102 were administered to hospitalized patients with COVID-19 during the mid-2021 outbreak in Taiwan. We report the outcomes by measuring the risks of intubation or admission to intensive care unit (ICU) for patients requiring no oxygen support, and death for those requiring oxygen therapy. METHODS: This multicenter retrospective study retrieved data of 840 patients admitted to 9 hospitals between May 1 and July 26, 2021. After propensity score matching, 302 patients (151 received NRICM101 and 151 did not) and 246 patients (123 received NRICM102 and 123 did not) were included in the analysis to assess relative risks. RESULTS: During the 30-day observation period, no endpoint occurred in the patients receiving NRICM101 plus usual care while 14 (9.27%) in the group receiving only usual care were intubated or admitted to ICU. The numbers of deceased patients were 7 (5.69%) in the group receiving NRICM102 plus usual care and 27 (21.95%) in the usual care group. No patients receiving NRICM101 transitioned to a more severe status; NRICM102 users were 74.07% less likely to die than non-users (relative risk= 25.93%, 95% confidence interval 11.73%-57.29%). CONCLUSION: NRICM101 and NRICM102 were significantly associated with a lower risk of intubation/ICU admission or death among patients with mild-to-severe COVID-19. This study provides real-world evidence of adopting broad-spectrum oral therapeutics and shortening the gap between outbreak and effective response. It offers a new vision in our preparation for future pandemics.

Efficacy and Safety of a Low-Level Light Therapy for Androgenetic Alopecia: A 24-Week, Randomized, Double-Blind, Self-Comparison, Sham Device-Controlled Trial.

BACKGROUND: Previous studies have reported the benefits of low-level/light laser therapy (LLLT) for the promotion of hair regrowth. However, the effectiveness of LLLT for the treatment of androgenetic alopecia (AGA) is still a topic of debate. OBJECTIVE: To investigate the efficacy and safety of LLLT on hair regrowth in patients with AGA. METHODS: This 24-week, randomized, double-blind, self-comparison, sham device-controlled trial enrolled 100 patients with AGA. All participants were randomly assigned to receive the investigational LLLT on one side of the head and sham light treatment on the contralateral side, 3 times weekly for 30 minutes each, over a 24-week period. Global scalp photography, phototrichogram assessment, the investigator's global assessment (IGA) of hair regrowth, and the subject's assessment of the treatment satisfaction were used for evaluation. RESULTS: After 24 weeks of treatment, the LLLT-treated scalp exhibited significantly greater hair coverage than the sham light-treated side (14.2% vs. 11.8%, p < .001). A significantly greater improvement from baseline in hair thickness, hair count, hair coverage, and IGA were also observed in the LLLT-treated side than in the sham light-treated side at the 12- and 24-week visits. No serious adverse events were observed. CONCLUSION: The use of LLLT might be an effective, safe, well-tolerated treatment for AGA.

The status of Her2 amplification and Kras mutations in mucinous ovarian carcinoma.

Jayson GC et al. remarked in Lancet that nearly 100% of mucinous ovarian cancer cases have Kras mutation as well as a high frequency of Her2 amplification. Using the Abbott PathVysion Her2 DNA Probe Kit and Kras mutant-enriched PCR Kits (FemtoPath®), 21 samples of primary ovarian mucinous cystadenocarcinomas from Taiwanese patients were examined to determine the status of Her2 amplification and Kras mutations. Our results showed the Her2 amplification rates were 33.33%, while the Kras mutation rates were 61.90%. We present here our results in order to enlighten the readership that the ~100% Kras mutant frequency and the high Her2 amplification rate reported by Jayson et al. may be too exaggerated to be applicable into all populations. Additionally, we report another 2 novel Kras mutations (A11V, V14I).

Regression analysis of multivariate current status data with dependent censoring: application to ankylosing spondylitis data.

Multivariate current-status failure time data consist of several possibly related event times of interest, in which the status of each event is determined at a single examination time. If the examination time is intrinsically related to the event times, the examination is referred to as dependent censoring and needs to be taken into account. Such data often occur in clinical studies and animal carcinogenicity experiments. To accommodate for possible dependent censoring, this paper proposes a joint frailty model for event times and dependent censoring time. We develop a likelihood approach using Gaussian quadrature techniques for obtaining maximum likelihood estimates. We conduct extensive simulation studies for investigating finite-sample properties of the proposed method. We illustrate the proposed method with an analysis of patients with ankylosing spondylitis, where the examination time may be dependent on the event times of interest.

HER2 mutations in advanced cervical neuroendocrine carcinoma: implications for trastuzumab deruxtecan therapy.

Recent clinical evidence shows that the antibody-drug conjugate (ADC) trastuzumab deruxtecan (T-DXd) can successfully treat patients with advanced HER2-mutant non-small cell lung cancer (NSCLC). We aimed to characterize HER2 mutations in cervical neuroendocrine carcinoma (NEC) among Taiwanese women to provide the rationale for exploring T-DXd as a tumor-agnostic targeted therapy option. We analyzed 12 archived primary cervical NEC samples from Taiwanese patients. Tumor-rich areas were marked for microdissection on 10 µm unstained sections. DNA was extracted, and HER2 hotspots were sequenced using a targeted panel on the Illumina MiSeq. HER2 missense mutations were identified in 5 of 12 cases (41.7%). Of the 5 cases with mutations, 2 patients (40%) had a single mutation, while 3 patients (60%) had double mutations. We detected 4 substitutions outside the tyrosine kinase domain (non-TKD), which were p.P1170A, p.S305C, p.I655V, and a novel T328K alteration. No mutations were found within the tyrosine kinase domain (TKD). The 41.7% HER2 mutation rate warrants expanded screening and future clinical investigation of the T-DXd targeting HER2 mutations in cervical NEC patients. Overall, this study contributes to the molecular understanding of cervical NEC and lays the groundwork for developing more effective treatment strategies.

Testing of the factor structure of the Sexual Health Knowledge Measure with young adolescent Taiwanese girls.

Knowledge of sexual health is an important indicator of the development of healthy adolescent sexuality. An evaluation instrument in nursing school practice, whose results can lead to improved sexual health in adolescents, is needed. We conducted this study to undertake rigorous testing of the Sexual Health Knowledge Scale (SHKS) as a means to ensure a reliable and valid quantitative measure of sexual health knowledge among young adolescent females. A panel of experts assessed the content validity of the 40-item measure. Initial testing involved 481 female adolescents (12-14 years old), using principal component factor analysis with varimax rotation and the determination of Cronbach's alpha coefficients. Confirmatory factor analysis (CFA) was conducted using data from an additional sample of 234 female adolescents (12-14 years old). Principal component factor analysis yielded a four-factor solution with eigenvalues greater than 1 that explained 43.40% of the variance. As a result of the analysis of the scale, 22 items were deleted, resulting in an 18-item scale. The CFA identified a second-order factor termed "sexual health knowledge." Goodness-of-fit indices showed an acceptable fit overall with the full model (χ(2)/df (131) = 1.69, RMSEA = 0.054, RMR = 0.013, CFI = 0.92, and GFI = 0.99). We determined that the SHKS is a reliable and valid measure, with good composite reliabilities and goodness-of-fit indices.

Borane-induced dehydration of silica and the ensuing water-catalyzed grafting of B(C6F5)3 to give a supported, single-site Lewis acid, ≡SiOB(C6F5)2.

A supported, single-site Lewis acid, ≡SiOB(C(6)F(5))(2), was prepared by water-catalyzed grafting of B(C(6)F(5))(3) onto the surface of amorphous silica, and its subsequent use as a cocatalyst for heterogeneous olefin polymerization was explored. Although B(C(6)F(5))(3) has been reported to be unreactive toward silica in the absence of a Brønsted base, we find that it can be grafted even at room temperature, albeit slowly. The mechanism was investigated by (1)H and (19)F NMR, in both the solution and solid states. In the presence of a trace amount of H(2)O, either added intentionally or formed in situ by borane-induced dehydration of silanol pairs, the adduct (C(6)F(5))(3)B·OH(2) hydrolyzes to afford C(6)F(5)H and (C(6)F(5))(2)BOH. The latter reacts with the surface hydroxyl groups of silica to yield ≡SiOB(C(6)F(5))(2) sites and regenerate H(2)O. When B(C(6)F(5))(3) is present in excess, the resulting grafted boranes appear to be completely dry, due to the eventual formation of [(C(6)F(5))(2)B](2)O. The immobilized, tri-coordinate Lewis acid sites were characterized by solid-state (11)B and (19)F NMR, IR, elemental analysis, and C(5)H(5)N-TPD. Their ability to activate two molecular C(2)H(4) polymerization catalysts, Cp(2)ZrMe(2) and an (α-iminocarboxamidato)nickel(II) complex, was explored.

Diagnostic performance of serum interleukin-6 and interleukin-10 levels and clinical predictors in children with rotavirus and norovirus gastroenteritis.

OBJECTIVES: Rotavirus and norovirus are the two most common causes of acute viral gastroenteritis in children. This study aimed to explore the association of serum interleukin-6 (IL-6) and interleukin-10 (IL-10) levels and the clinical features in children with rotavirus and norovirus gastroenteritis. METHODS: This prospective study enrolled 168 acute gastroenteritis patients admitted to a tertiary care center. Peripheral blood samples were collected for IL-6 and IL-10 assays within the first 72 h of illness. The diagnostic performance of clinical tests was estimated using the receiver operating characteristic (ROC) analysis. Binary logistic regression modeling was performed to examine the predictive variables. RESULTS: Serum IL-6 and IL-10 were measured in children with rotavirus infection (n=30), norovirus infection (n=25), Salmonella infection (n=26), and in 11 healthy controls. There were significant higher degrees of severity of illness and levels of IL-10 in the rotavirus group as compared to the norovirus group. The binary logistic regression analysis revealed that both the ANC and maximum body temperature (BT) were significant clinical predictors for discriminating rotavirus and norovirus gastroenteritis. The ROC curve to evaluate the accuracy of logistic regression model had an AUC of 0.847 (95% CI: 0.741-0.952, p<0.001). CONCLUSIONS: IL-10 shows a significant discriminating ability between rotavirus and norovirus infection. A model incorporating maximum BT and ANC can help pediatricians to distinguish between rotavirus and norovirus in children with a suspected viral gastroenteritis.

Autocrine CCL2 promotes cell migration and invasion via PKC activation and tyrosine phosphorylation of paxillin in bladder cancer cells.

The amount of monocyte chemoattractant protein-1 (MCP-1/CCL2) produced by a transitional cell carcinoma is directly correlated with high recurrence and poor prognosis in bladder cancer. However, the mechanisms underlying the effects of CCL2 on tumor progression remain unexplored. To investigate the role played by CCL2, we examined cell migration in various bladder cancer cell lines. We found that high-grade cancer cells expressing high levels of CCL2 showed more migration activity than low-grade bladder cancer cells expressing low levels of the chemokine. Although the activation of CCL2/CCR2 signals did not appreciably affect cell growth, it mediated cell migration and invasion via the activation of protein kinase C and phosphorylation of tyrosine in paxillin. Blocking CCL2 and CCR2 with small hairpin RNA (shCCL2) or a specific inhibitor reduced CCL2/CCR2-mediated cell migration. The antagonist of CCR2 promoted the survival of mice bearing MBT2 bladder cancer cells, and CCL2-depleted cells showed low tumorigenicity compared with shGFP cells. In addition to observing high-levels of CCL2 in high-grade human bladder cancer cells, we showed that the CCL2/CCR2 signaling pathway mediated migratory and invasive activity, whereas blocking the pathway decreased migration and invasion. In conclusion, high levels of CCL2 expressed in bladder cancer mediates tumor invasion and is involved with advanced tumorigenesis. Our findings suggest that this CCL2/CCR2 pathway is a potential candidate for the attenuation of bladder cancer metastases.

A randomized, double-blind, placebo-controlled study to evaluate the efficacy and tolerability of Fufang Danshen (Salvia miltiorrhiza) as add-on antihypertensive therapy in Taiwanese patients with uncontrolled hypertension.

Hypertension generally requires the use of a combination therapy to achieve the satisfactory control of blood pressure. A traditional Chinese herb, Danshen (Salvia miltiorrhiza), has been shown to have cardioprotective effects in animals and humans. The study investigated the add-on effect of Fufang Danshen extract capsule in Taiwanese hypertensive patients with uncontrolled blood pressure. This was a double-blind, placebo-controlled, randomized, single-center study clinical trial. Fifty-five patients with uncontrolled mild to moderate hypertension were enrolled under current conventional antihypertensive treatment, randomized equally to receive a Fufang Danshen capsule (formula mixture) 1000 mg twice-daily or a placebo capsule for 12 weeks. Primary endpoints were the control rate and the response rate. By ITT analysis at week 12, the control rates were 25.5% in the Fufang Danshen group and 7.3% in the control group (p = 0.016). The response rates were 45.6% in the Fufang Danshen group and 38.2% in the placebo group (p = 0.946). A significant reduction of systolic blood pressure at week 12 was noted in the Fufang Danshen group compared with the placebo group (13.8 vs 4.2 mmHg, p = 0.005). A decrease of pulse rate was also noted in the Fufang Danshen group (- 3.2 vs +2.7/min, p = 0.027). Adverse events were not statistically different between the two groups. It was concluded that Fufang Danshen (Salvia miltiorrhiza) extract reduced systolic blood pressure and pulse rate, and was well tolerated in patients with hypertension.

Comparing the 2017 ASCO/CAP guideline for gastroesophageal adenocarcinoma surgical specimen to the 2018 ASCO/CAP guideline for breast cancer in assessing the HER2 status in primary mucinous ovarian carcinoma.

The successful experiences of HER2 inhibitors in patients with HER2 ( +) breast cancer (BC) and advanced gastroesophageal adenocarcinoma (GEA) have encouraged us to continuously explore the HER2 status and its potential as a therapeutic target in primary mucinous ovarian carcinoma (mOC). Using 49 primary mOC samples, we compared the assay characteristics of HER2 status between both 2017 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) for GEA and 2018 ASCO/CAP for BC guideline recommendations. We demonstrated moderate to strong agreement between their HER2 IHC results (Weighted Kappa = 0.78) and perfect agreement between their HER2 FISH results (Kappa = 1.00). The overall concordance of non-equivocal HER2 IHC and HER2 FISH results was 97.56% (kappa = 0.93) by 2017 ASCO/CAP for GEA criteria and 100% (kappa = 1.00) by 2018 ASCO/CAP for BC criteria. The number (n = 8; 16.32%) of HER2 IHC equivocal (score + 2) by 2017 ASCO/CAP for GEA criteria was twofold higher than that (n = 4; 8.16%) by 2018 ASCO/CAP for BC criteria. Additionally, we identified one false-positive (FP) case (n = 1; 2.04%) that was HER2 IHC positive (score + 3), but HER2 FISH non-amplified result by the 2017 ASCO/CAP for GEA criteria. In conclusion, owing to the absence of FP/ FN and fewer equivocal cases of HER2 IHC, we recommend that the 2018 ASCO/CAP for BC are more appropriate than 2017 ASCO/CAP for GEA criteria in appraising the HER2 status in mOC and justifying the inclusion of eligible subjects for basket clinical trials of the newly developmental anti-HER2 treatments.

Identification of the coexisting HER2 gene amplification and novel mutations in the HER2 protein-overexpressed mucinous epithelial ovarian cancer.

BACKGROUND: Although overexpression, amplification, and somatic mutation of the HER2 gene have been noted in various types of human cancers, we report here for the first time that novel mutations and amplification of the HER2 gene occurred concomitantly in mucinous epithelial ovarian cancer (EOC). METHODS: Twenty-seven tissue microarray samples from EOC patients were analyzed by immunohistochemistry (IHC) with Dako c-erb-B2 antibody and subsequently were examined by fluorescence in situ hybridization (FISH) with the Abbott PathVysion HER2 DNA Probe Kit. HER2 gene, exon 18-24, encoding a tyrosine kinase domain, was analyzed by polymerase chain reaction (PCR) and direct sequencing. RESULTS: The FISH-IHC paired results confirmed 19 concordant negative results and 3 concordant positive results. Moreover, all 4 HER2-amplified cases were of the mucinous type, whereas the remaining 23 HER2-nonamplified cases were of the nonmucinous type. The 4 mucinous EOC cases with HER2 gene amplification were selected and further analyzed for HER2 gene mutations. Data revealed that somatic mutations were present in 2 cases (R970W and E971G), but absent in the other 2 cases. CONCLUSIONS: HER2 protein overexpression correlated significantly with HER2 gene amplification in EOC (P = 0.027). It is surprising that all 4 cases of mucinous EOC showed HER2 gene amplification confirmed by FISH testing. However, we suppose that increasing the number of cases would possibly modify the results. This study also showed that both HER2 gene amplification and somatic mutations are not mutually exclusive in mucinous EOC. Further studies are warranted to investigate the potential role of anti-HER2 therapy.

Quantitative investigation of a hybrid Ziegler-Natta catalyst support prepared by grafting di(n-butyl)magnesium onto partially dehydroxylated silica.

MgCl(2)-modified silica is an important component of some Ziegler-Natta catalysts used in the manufacture of polyethylene. Information about the structure of the dispersed magnesium sites formed by the reaction of di-n-butylmagnesium (nBu(2)Mg) with silica was sought to provide a basis for understanding their subsequent interactions with transition-metal or co-catalyst components. From infrared spectra and elemental analysis, we deduced that nBu(2)Mg reacts with porous silica in two ways: about half (47%, 0.99 mmol g(-1)) is grafted through protonolysis by surface hydroxyl groups (≡SiOH), whereas the other half (53%, 1.11 mmol g(-1)) reacts directly with siloxane bonds (≡SiOSi≡). In the (29)Si and (13)C CP/MAS NMR spectra of Sylopol-2100 silica pretreated at 500 °C then modified with nBu(2)Mg at room temperature, both alkylsilicon and alkylmagnesium sites are evident. The alkylmagnesium-modified silica surface is proposed to contain dimers and/or tetramers with the empirical formula [≡SiOMg(nBu)](n). Upon exposure of nBu(2)Mg-modified silica to anhydrous HCl, alkanes are liberated, hydroxyl groups are regenerated, and water is formed. The appearance of water suggests condensation of hydroxyl group pairs, induced by the coordinatively unsaturated nanoclusters (MgCl(2))(n) that arise by ligand exchange on the silica-supported n-butylmagnesium oligomers.

Assessing the impact of polysomy-17 on HER2 status and the correlations of HER2 status with prognostic variables (ER, PR, p53, Ki-67) in epithelial ovarian cancer: a tissue microarray study using immunohistochemistry and fluorescent in situ hybridization.

Although HER2 overexpression and Her2 amplification have been noted in breast and a variety of human cancers, we report here for the first time the impact of polysomy-17 on HER2 status and the correlations between HER2 status and other prognostic factors in patients with epithelial ovarian cancers (EOC).We analyzed HER2, estrogen receptor (ER), progesterone receptor (PR), p53, and Ki-67 protein overexpressions by immunohistochemistry (IHC) and determined Her2 gene amplification by fluorescence in situ hybridization (FISH) in 27 tissue microarray samples from EOC patients.We achieved 100% positive concordance (3/3) and 100% negative concordance (19/19) between HER2 testing by IHC and FISH. Both the total Her2 gene copies and FISH scores increased significantly in a stepwise order through the negative, equivocal, and positive HER2 IHC result categories in all 27 cases (P=0.001, P=0.001), and still increased significantly in 18 nonpolysomy-17 cases (P=0.007 and 0.013) after the exclusion of 9 polysomy-17 cases. HER2 protein expression is inversely correlated with both ER (P=0.002) and PR expressions (P=0.046). Her2 gene amplification is inversely correlated with ER expression (P=0.007) but not with PR expression (P=0.106).This study showed extremely high positive and negative concordances between Her2 FISH and HER2 IHC assays. Polysomy-17 is insufficient for causing a significant impact on the relationship between HER2 testing by IHC and FISH in EOC. ER and PR expressions were inversely correlated with HER2 protein expression. In addition, ER but not PR expression is inversely correlated with Her2 gene amplification.

The HER2 gene copies per tumor cell either before or after correction for chromosome-17 correlated significantly with HER2 IHC results in epithelial ovarian cancer in a tissue microarray study.

BACKGROUND: HER2 gene amplification and HER2 protein overexpression are important factors in predicting clinical sensitivity to anti-HER2 monoclonal antibody therapy in breast cancer patients. The purpose of this study is to evaluate the correlation between HER2 protein expressions and the HER2 gene copies per tumor cell either before or after chromosome-17 correction in epithelial ovarian cancer (EOC). METHODS: Adopting 2007 ASCO/CAP guideline recommendations for HER2 testing, 27 tissue microarray (TMA) samples from EOC patients were analyzed by immunohistochemistry (IHC) using Dako, c-erb-B2 antibody and subsequently examined by fluorescence in situ hybridization (FISH) using Abbott/Vysis, PathVysion HER2 DNA Probe Kit. RESULTS: The overall concordance revealed 81.5% between HER2 IHC and HER2 FISH results. Additionally, HER2 gene copies prior to chromosome-17 correction increased significantly in a stepwise order through the negative, equivocal, and positive IHC result categories (P = 0.026), as did the HER2 gene copies after chromosome-17 correction (P = 0.028). On the other hand, HER2 IHC results correlated significantly with both chromosome-17 uncorrected HER2 gene copy numbers (ρ = 0.430, P = 0.025) and chromosome-17 corrected HER2 gene copy numbers (ρ = 0.524, P = 0.027). CONCLUSION: We demonstrated that both chromosome-17 corrected and uncorrected HER2 gene copies correlated significantly with HER2 IHC result categories; and tests for the HER2 gene copies per tumor cell either before or after correction for chromosome-17 can be applied as a potentially valuable tool in analyzing the HER2 status in EOC.

High frequency of BRAF mutations in primary mucinous ovarian carcinoma of Taiwanese patients.

OBJECTIVE: Considering the clinical evidence of BRAF inhibitors that can treat melanoma patients successfully, we aimed to investigate the status of BRAF mutations of primary mucinous ovarian carcinomas (MOC) in Taiwanese women, and apply the emerging paradigm classification of BRAF mutation groups. MATERIALS AND METHODS: 20 archived primary MOC samples were analyzed. The BRAF mutations of activation segment (exon 15), CR3 (conserved regions 3), kinase domain of the BRAF gene were analyzed using the highly sensitive BRAF mutant enriched kit (FemtoPath®) with Sanger sequencing method. Additionally, we extended our prior reported data of HER2 aberrations and KRAS mutation into this study in order to compare with the status of BRAF mutation. RESULTS: Of them (n = 20), 16 (80%) harbored BRAF missense mutations. Their mutation profile and case number (n) were categorized as (1) class I: V600E (n=1), V600M (n = 1); (2) class II: A598V (n = 1), T599I (n = 10); (3) class III: none (n = 0); and (4) unclassified variants: S602F (n = 2), T599I/S602F (n = 1). The BRAF S602F is novel. The prevalence of BRAF mutation is significantly higher than either HER2 mutation (80% vs. 35%; p = 0.022) or HER2 amplification (80% vs. 35%; p = 0.022). However, the mutation rates of BRAF and KRAS were not significantly different (80% vs. 60%; p = 0.289). CONCLUSION: Activating BRAF mutation, HER2 amplification, HER2 mutation and KRAS mutation were not mutually exclusive. However, they may even have a synergistic effect in tumorigenesis. BRAF mutation is not uncommon in primary MOC of Taiwanese. The BRAF mutant (T599I) stands the majority. We suggested that there was a lower potential response to the existing V600 BRAF inhibitors, but may be responsive to dual BRAF plus MEK inhibitors or single MEK inhibitor. Further studies are warranted to investigate the clinical benefits of newly targeted therapy in recurrent or advanced stage primary MOC patients carrying different classes of BRAF mutation.

A traditional Chinese medicine formula NRICM101 to target COVID-19 through multiple pathways: A bedside-to-bench study.

COVID-19 is a global pandemic, with over 50 million confirmed cases and 1.2 million deaths as of November 11, 2020. No therapies or vaccines so far are recommended to treat or prevent the new coronavirus. A novel traditional Chinese medicine formula, Taiwan Chingguan Yihau (NRICM101), has been administered to patients with COVID-19 in Taiwan since April 2020. Its clinical outcomes and pharmacology have been evaluated. Among 33 patients with confirmed COVID-19 admitted in two medical centers, those (n = 12) who were older, sicker, with more co-existing conditions and showing no improvement after 21 days of hospitalization were given NRICM101. They achieved 3 consecutive negative results within a median of 9 days and reported no adverse events. Pharmacological assays demonstrated the effects of the formula in inhibiting the spike protein/ACE2 interaction, 3CL protease activity, viral plaque formation, and production of cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α. This bedside-to-bench study suggests that NRICM101 may disrupt disease progression through its antiviral and anti-inflammatory properties, offering promise as a multi-target agent for the prevention and treatment of COVID-19.