Qijiao Shengbai Capsule alleviated leukopenia by interfering leukotriene pathway: Integrated network study of multi-omics.

BACKGROUND: Leukopenia could be induced by chemotherapy, which leads to bone marrow suppression and even affects the therapeutic progression of cancer. Qijiao Shengbai Capsule (QSC) has been used for the treatment of leukopenia in clinic, but its bioactive components and mechanisms have not yet been elucidated clearly. PURPOSE: This study aimed to elucidate the molecular mechanisms of QSC in treating leukopenia. STUDY DESIGN: Serum pharmacochemistry, multi-omics, network pharmacology, and validation experiment were combined to study the effect of QSC in murine leukopenia model. METHODS: First, UPLC-QTOF-MS was used to clarify the absorbed components of QSC. Then, cyclophosphamide (CTX) was used to induce mice model with leukopenia, and the therapeutic efficacy of QSC was assessed by an integrative approach of multi-omics and network pharmacology strategy. Finally, molecular mechanisms and potential therapeutic targets were identified by validated experiments. RESULTS: 121 compounds absorbed in vivo were identified. QSC significantly increase the count of white blood cells (WBCs) in peripheral blood of leukopenia mice with 15 days treatment. Multi-omics and network pharmacology revealed that leukotriene pathway and MAPK signaling pathway played crucial roles during the treatment of leukopenia with QSC. Six targets (ALOX5, LTB4R, CYSLTR1, FOS, JUN, IL-1ß) and 13 prototype compounds were supposed to be the key targets and potential active components, respectively. The validation experiment further confirmed that QSC could effectively inhibit the inflammatory response induced by leukopenia. The inhibitors of ALOX5 activity can significantly increase the number of WBCs in leukopenia mice. Molecular docking of ALOX5 suggested that calycosin, daidzein, and medicarpin were the potentially active compounds of QSC. CONCLUSION: Leukotriene pathway was found for the first time to be a key role in the development of leukopenia, and ALOX5 was conformed as the potential target. QSC may inhibit the inflammatory response and interfere the leukotriene pathway, it is able to improve hematopoiesis and achieve therapeutic effects in the mice with leukopenia.

Adjuvant treatment with Cordyceps sinensis for lung cancer: A systematic review and meta-analysis of randomized controlled trials.

ETHNOPHARMACOLOGICAL RELEVANCE: Cordyceps sinensis (CS) is a fungus parasitic on lepidopteran larvae which is often used to treat lung diseases and regulate immune function. AIM OF THE STUDY: This review aimed to evaluate the efficacy of CS in the adjuvant treatment of lung cancer. MATERIALS AND METHODS: As of June 2022, the electronic database search was conducted in PubMed, EMBASE, Cochrane Library, China Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Wanfang Database and China Science Journal Database (VIP database). Randomized clinical trials (RCTs) that evaluated the efficacy of CS as an adjuvant treatment for lung cancer were included. After the quality evaluation, meta-analysis was performed with Stata 16.0 software. RESULTS: A total of 12 RCTs with 928 patients were identified for this meta-analysis, which showed that as an adjuvant treatment, CS has the following advantages in the treatment of lung cancer: (1) Improved tumor response rate (TRR) (RR: 1.17， 95%CI: 1.05-1.29，P = 0.00); (2) improved immune function, including increased CD4 (MD: 4.98, 95%CI: 1.49-8.47, P = 0.01), CD8 (MD: 1.60, 95%CI: 0.40-2.81, P = 0.01, I2 = 0.00%), NK (MD: 4.17, 95%CI: 2.26-6.08, P = 0.00), IgA (MD: 1.29, 95%CI: 0.35-2.24, P = 0.01), IgG (MD: 3.95, 95%CI: 0.98-6.92, P = 0.01) and IgM (MD: 6.44, 95%CI: 0.63-12.26, P = 0.03); (3) improved patients' quality of life based on the mean ± SD of Karnofsky Performance Status (KPS) (MD: 8.20, 95%CI: 6.87-9.53, P = 0.00); (4) reduced the incidence of adverse drug reactions (ADRs), including the incidence of myelosuppression (RR: 0.38, 95%CI: 0.19-0.75, P = 0.01), leukopenia (RR: 0.76, 95%CI: 0.63-0.92, P = 0.00), and thrombocytopenia (RR: 0.52, 95%CI: 0.31-0.86, P = 0.01) (5) reduced the incidence of radiation pneumonitis (RR: 0.74, 95%CI: 0.62-0.88, P = 0.00). However, the number of improved patients based on KPS (RR: 1.47, 95%CI: 0.98-2.20, P = 0.06) were similar between two groups, liver and renal damage (RR: 0.32, 95%CI: 0.09-1.10, P = 0.07) and gastrointestinal adverse reactions (RR: 0.80, 95%CI: 0.47-1.37, P = 0.42) as well. Subgroup analysis showed that CS could increase the TRR in the treatment with 6 g/d and 21 days/3-4 cycles. CONCLUSION: Compared with conventional treatment, adjuvant treatment with CS of lung cancer not only improve TRR, QOL and immune function, but also reduce the incidence of ADRs and radiation pneumonitis. The optimal usage may be 6 g/d and 21 days/3 to 4 cycles. PROSPERO REGISTRATION NO: CRD42022333681.

Bojungikgi-tang for Chemotherapy-induced Leukopenia: A Systematic Review and Meta-Analysis.

Chemotherapy-induced leukopenia is a common side effect of cytotoxic anticancer drugs. It can deprive patients of treatment opportunities, resulting in the delay, reduction, or discontinuation of chemotherapy or other anticancer drug administration. Two researchers searched English, Chinese, Japanese, and Korean electronic databases, without limiting the time period and language, using search terms such as "Bojungikgi," "WBC," "leuko," and "neutrop." Among the human randomized controlled studies in which Bojungikgi-tang was administered to patients who underwent chemotherapy, studies reporting leukopenia-related outcomes were selected, and data extraction, bias risk assessment, and meta-analysis were performed on the selected papers. Ten studies were selected, and a systematic review with meta-analysis was conducted. Nine papers were published in China and the total number of participants was 715. As a result of administering Bojungikgi-tang to these patients, the number of patients with chemotherapy-induced leukopenia significantly decreased (OR: 0.41, 95% CI: 0.27-0.61, P = .0001, I2 = 35%). Further, white blood cell counts were compared with that of the control group, and it showed an effect on prevention (MD: 0.64, 95% CI: 0.46-0.83, P < .00001, I2 = 90%). A pronounced effect was observed, especially when administered after a diagnosis based on the pattern identification, such as Qi deficiency. (OR: 0.32, 95% CI: 0.18-0.58, P = .0002, I2 = 0%). However, all studies had a high risk of bias due to non-blinding, and most studies had a high or uncertain risk of bias in creating random assignment orders and concealing them. Bojungikgi-tang has an effect on the prevention and treatment of chemotherapy-induced leukopenia. The effect rate can be increased when administered after proper diagnosis, and the possibility of adverse reactions and side effects is lower than that of Granulocyte-Colony Stimulating Factor (G-CSF) injection. Bojungikgi-tang appears to be useful in the treatment and prevention of leukopenia caused by cytotoxic anticancer drugs. However, it is necessary to conduct high-quality clinical studies in the future, considering the possibility of local and language bias, heterogeneity of carcinoma and intervention, and the risk of bias.Registration: PROSPERO CRD4202341054.

Efficacy and safety of Shenqi Fuzheng injection combined with chemotherapy for cancer: An overview of systematic reviews.

BACKGROUND: In China, Shenqi Fuzheng injection (SFI) has been used as an adjuvant therapy to treat all kinds of cancer for many years. A large number of systematic reviews or meta-analyses (SRs/MAs) were published to assess its efficacy and safety in the past few years. However, the quality of SRs/MAs was unclear and did not generate high-quality clinical evidence. OBJECTIVE: We conducted an overview to integrate relevant SRs/MAs published in the past with the aim of providing new clinical evidence for SFI in combination with chemotherapy in the treatment of cancer. OBJECTIVE: We conducted an overview to integrate relevant SRs/MAs published in the past with the aim of providing new clinical evidence for SFI in combination with chemotherapy in the treatment of cancer. METHODS: A comprehensive search of PubMed, Web of Science, Embase, the Cochrane Library, CNKI, VIP, WanFang, and CBM was performed from the database inception to September 30, 2023. SRs/MAs of randomized controlled trials (RCTs) on SFI combined with chemotherapy for cancer were included. Four reviewers screened the literature and extracted relevant information. Five reviewers assessed the quality of reporting, methodological quality, risk of bias, and quality of evidence for SRs/MAs. We used corrected covered area (CCA) to assess the degree of overlap among the RCTs included in SRs/MAs. We performed a descriptive analysis for the results of the included SRs/MAs. RESULTS: A total of 32 SRs/MAs of SFI combined with chemotherapy for cancer were included. We assessed the reporting quality of SRs/MAs using the PRISMA 2020 statement. 1 SR/MA had relatively complete reports, 20 SRs/MAs had some deficiencies in reporting, and 11 SRs/MAs had serious deficiencies in reporting. We assessed the methodological quality of SRs/MAs using the AMSTAR 2 tool. The methodological quality of all SRs/MAs was very low. We assessed the risk of bias for SRs/MAs using the ROBIS tool. The risk of bias was low for 19 SRs/MAs and unclear for 13 SRs/MAs. We assessed the quality of evidence for SRs/MAs using the GRADE evidence quality evaluation system. 50 items were moderate quality, 46 items were low quality, 27 items were very low quality, and 85 items were unclear. SFI combined with chemotherapy played a role in increasing efficacy and decreasing toxicities in all kinds of cancer, including clinical efficacy (except liver cancer), quality of life, immune function (except CD8+), leukopenia, thrombocytopenia, hemoglobinopenia, nausea and vomiting, liver damage, kidney damage, neurotoxicity, alopecia, and diarrhea. CONCLUSION: The overview showed that SFI combined with chemotherapy may improve clinical efficacy (except for liver cancer), quality of life, and immune (except for CD8+) function in all types of cancer, as well as adverse events (AEs) such as leukopenia, thrombocytopenia, etc. Since most of the clinical evidence was low, higher quality clinical trials will be expected to improve the reliability of the above conclusions in the future.

Network analysis to explore the pharmacological mechanism of Shenmai injection in treating granulocytopenia and evidence-based medicine approach validation.

BACKGROUND: Shenmai injection is frequently utilized in China to clinically treat granulocytopenia in oncology patients following chemotherapy. Despite this, the drug's therapeutic benefits remain a topic of contention, and its active components and potential treatment targets have yet to be established. The present study utilizes a network pharmacology approach to investigate the drug's active ingredients and possible therapeutic targets, and to evaluate the effectiveness of Shenmai injection in treating granulocytopenia through meta-analysis. METHODS: In our subject paper, we utilized the TCMID database to investigate the active ingredients present in red ginseng and ophiopogon japonicus. To further identify molecular targets, we employed SuperPred, as well as OMIM, Genecards, and DisGeNET databases. Our focus was on targets associated with granulocytopenia. The DAVID 6.8 database was utilized to perform gene ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Additionally, a protein-protein interaction network was established. The resulting "drug-key component-potential target-core pathway" network was used to predict the mechanism of action of Shenmai injection in the treatment of granulocytopenia. In order to evaluate the quality of the studies included in our analysis, we utilized the Cochrane Reviewers' Handbook. We then conducted a meta-analysis of the clinical curative effect of Shenmai injection for granulocytopenia, utilizing the Cochrane Collaboration's RevMan 5.3 software. RESULTS: After conducting a thorough screening, the study identified 5 primary ingredients of Shenmai injection - ophiopogonoside a, ß-patchoulene, ginsenoside rf, ginsenoside re, and ginsenoside rg1-that can potentially target 5 essential proteins: STAT3, TLR4, PIK3CA, PIK3R1, and GRB2. Additionally, Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that Shenmai injection can be beneficial in treating granulocytopenia by interacting with pathways such as HIF-1 signaling, T-cell receptor signaling, PI3K-Akt signaling, chemokine signaling, and FoxO signaling. The results of meta-analysis indicate that the treatment group exhibited superior performance in terms of both efficiency and post-treatment leukocyte count when compared to the control group. CONCLUSION: In summary, studies in network pharmacology demonstrate that Shenmai injection exerts an impact on granulocytopenia via various components, targets, and mechanisms. Additionally, evidence-based studies provide strong support for the effectiveness of Shenmai injection in preventing and treating granulocytopenia.

Severe leukocytopenia due to copper deficiency induced by zinc supplementation in a patient on peritoneal dialysis: a case report.

Zinc deficiency is one cause of anemia. However, it has been reported that some patients who were treated with zinc supplementation to resolve this anemia subsequently experienced copper deficiency, which lead to continued anemia, as well as leukocytopenia and other symptoms. However, only two patients with copper deficiency induced by zinc supplementation undergoing peritoneal dialysis have been reported. Here, we report the case of a 59 year-old man with copper deficiency after zinc supplementation undergoing peritoneal dialysis (PD). He took meals only once a day and drank about 750 mL/day of wine every day. He had been receiving zinc supplementation for 4 months. He was diagnosed with severe leukocytopenia and worsening anemia at a planned outpatient visit; in addition, his copper levels had markedly decreased. Thus, zinc supplementation was discontinued, and the patient was instructed to take cocoa for copper supplementation. Because of severe leukocytopenia, he was admitted to our hospital, and granulocyte colony-stimulating factor was administered. Red blood cell transfusions were performed for anemia. After discontinuing zinc supplementation, his white blood cell count and hemoglobin levels improved.To avoid Cu deficiency, patients' dietary history should be checked in detail and Cu should be monitored carefully when Zn is supplemented in patients undergoing PD.

Chinese patent medicine Kanglaite injection for non-small-cell lung cancer: An overview of systematic reviews.

ETHNOPHARMACOLOGICAL RELEVANCE: Kanglaite injection (KLTi), a Chinese herbal medicine, is used as an adjuvant treatment for non-small-cell lung cancer (NSCLC). AIMS OF THE STUDY: To provide an evidence-based endorsement for the clinical application and selection of KLTi by evaluating the reporting quality, methodological quality, risk of bias, and evidence quality of systemic reviews (SRs). MATERIALS AND METHODS: SRs of KLTi adjuvant therapy of NSCLC were searched by using 12 databases, consulting experts, and retrieving relevant conference papers until 2022.03.24. The treatment group received KLTi in combination with other therapies, regardless of dosage, duration, or the therapy combined. Network meta-analyses and SRs using repeated data were excluded. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines 2009, A MeaSurement Tool to Assess systematic Reviews, Risk of Bias in Systematic Review, and the Grading of Recommendations Assessment, Development and Evaluation were used to assess the quality of reports, methodological quality, risk of bias, and level of evidence; R was used for visual analysis of the relevant contents. RESULTS: Twenty SRs (13 Chinese and 7 English articles), all authored by Chinese authors as the first author, were included. The reporting information of most included studies was relatively complete (21-27 points), accounting for three-fourths of the total literature. The quality of the methods used in all studies was critically low. The risk of bias was mostly high. Results of the evidence summary showed that among the "moderate" evidence, KLTi combined with chemotherapy had benefits of 9.7-16.4% for objective response rate (ORR) (11 SRs), 8.1-14% for disease control rate (four SRs), and 20.1-28.6% for quality of life (12 SRs) compared with those of chemotherapy alone. The incidence of gastrointestinal symptoms (five SRs) was reduced by 11.5%-23.2%, while that of leukopenia (four SRs) improved by 19.5-29.2%. Combined radiotherapy and targeted therapy had benefits of 25.9% and 16.8%, respectively, in ORR and 31.3% and 22.8%, respectively, in quality of life (the quality of evidence was "low"). The results depicted that treatment with two courses of KLTi produce the best results. CONCLUSION: Our results suggest that KLTi, whether combined with chemotherapy, radiotherapy, or targeted therapy, has an effect on ORR and quality of life and induces adverse reactions, such as leukopenia, nausea, and vomiting. It may improve patient survival; however, the impact of its low-grade quality on the immune function remains undetermined. Owing to the low reporting quality and methodological quality and high risk of bias of the SRs and the included studies, clinical application of KLTi remains unelucidated; higher-quality SRs and randomized controlled trials are necessary in the future.

Efficacy and safety of acupuncture for chemotherapy-induced leukopenia: A systematic review and meta-analysis.

BACKGROUND: Leukopenia is one of most common types of myelosuppression secondary to chemotherapy. The main methods used to treat leukopenia after chemotherapy have various limitations. Several studies have reported the role of acupuncture in the prevention and treatment of leukopenia, but the quality of the study is uneven. Here, we used a systematic review and meta-analysis to evaluate the efficacy and safety of acupuncture in the treatment of leukopenia after chemotherapy. METHODS: We searched the databases of the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Library, Medline (via PubMed), EMBASE (via embase.com), the China National Knowledge Infrastructure Database (CNKI), the Chinese Biomedical Literature Database (CBM), the Chinese Scientific Journal Database (VIP database) and the Wanfang database to collect randomized clinical trials (RCTs) on acupuncture in the treatment of leukopenia after chemotherapy. Cochrane systematic reviewer manual 5.2 was used for bias risk assessment. RevMan5.3 statistical software was applied for statistical analysis. RESULTS: Fifteen RCTs were included in this study, with a total of 1130 patients. Meta-analysis results showed that acupuncture can increase white blood cell (WBC) count after chemotherapy [MD = 1.18, 95% CI (0.80, 1.57), P < .00001], reduce the incidence of myelosuppression [RR = 0.38, 95% CI (0.23, 0.63), P = .0002], and improve the clinical treatment effectiveness [RR = 1.20, 95% CI (1.00, 1.43), P = .05]. The differences were statistically significant. CONCLUSION: It is recommended to use acupuncture in the treatment of leukocytopenia after chemotherapy, but this result needs further research for verification.

Clinical Efficacy of Potato Extract for Alleviating Chemoradiotherapy-Related Leukopenia: a Randomized, Single-Blind, Placebo-Controlled Trial.

BACKGROUND: Leukopenia is the most common adverse event in chemotherapy, which natural products can prevent and treat. The aim of this study was to investigate the clinical efficacy of potato extract for alleviating chemoradiotherapy-induced leukopenia in cancer patients. METHODS: This was a single-blinded randomized placebo-controlled trial that enrolled 184 cancer patients. The participants were scheduled to undergo chemoradiotherapy in two hospitals, where they were randomized to receive potato extract or a placebo in a 1:1 ratio for a period of 49 days. Change in leukocyte value was considered the primary outcome of this clinical trial. Secondary outcomes included tumor response rate, blood test, and quality of life score. RESULTS: The leukopenia was relieved in the potato extract group compared with the placebo group. Of note, a significant difference in leukopenia between the two groups was found after 14 days (p = 0.04). In addition, there was no statistically significant difference in leucocyte levels in the potato extract group (before and after potato extract treatment; p = 0.13), but in the placebo group, the leukocyte value significantly decreased compared to before treatment (p = 0.06). CONCLUSIONS: Potato extract can alleviate chemoradiotherapy-induced leukopenia in cancer patients. These results show the potential function of potato extract as a protective agent in management of cancer chemoradiotherapy.

Efeito protetivo do extrato de Echinodorus grandiflorus sobre o urotelio vesical de ratos com cistite induzida por ciclofosfamida / Extract of echinodorus grandiflorus presents renoprotetic effect on rats with acute nephrotoxicity induced by cyclophosphamid / Extracto de Echinodorus grandiflorus presenta efecto renoprotético en ratas con nefrotoxicidad aguda inducida por ciclofosfamida

cistite hemorrágica e a cistite intersticial expressam uma etiologia variável, desde idiopática à provocada por fármacos, dentre eles a ciclofosfamida. A cistite apresenta tratamento multifatorial, e o potencial efeito satisfatório do uso da medicina complementar, vem ganhando espaço na prática médica. Assim o objetivo do presente estudo foi avaliar o efeito protetivo do extrato bruto de Echinodorus grandiflorus sobre a bexiga de ratos induzidos a cistite por ciclofosfamida. Utilizou-se neste estudo, 35 ratos, machos, Wistar, com peso médio de 321g, que foram submetidos a indução de cistite com uso de ciclofosfamida por via intraperitoneal e tratados com diferentes doses de extrato de Echinodorus grandiflorus (30, 100, 300mg) e o grupo controle com o fármaco Mesna. Todos os animais foram mortos no décimo sétimo dia e suas bexigas urinarias foram ressecadas para avaliação macro e microscópica, além da análise de hemograma e leucograma. A análise do sangue mostrou leucopenia com diferença significativa em todos os animais que receberam a ciclofosfamida. Observou-se que a dose de 300mg/kg do extrato bruto da planta, apresentou efeito protetivo no urotélio vesical, porém, inferior ao uso de Mesna. Diante dos resultados apresentados neste estudo sugere-se que o extrato de Echinodorus grandiflorus apresenta efeito protetivo no urotélio vesical na dose de 300mg/kg, porém estudos futuros quanto a dose e também a uma possível associação terapêutica ao Mesna devam ser realizados. Por se tratar de uma patologia com prevalência importante e ser muitas vezes desagradável e limitante à vida, faz-se necessário o empenho em métodos terapêuticos alternativos aos atuais, afim de, diminuírem os custos e efeitos colaterais dos métodos já documentados.

Hemorrhagic cystitis and interstitial cystitis have a variable etiology, from idiopathic to drug-induced, including cyclophosphamide. Cystitis has a multifactorial treatment, and the potential satisfactory effect of the use of complementary medicine has been gaining ground in medical practice. Thus, the aim of the present study was to evaluate the protective effect of the crude extract of Echinodorus grandiflorus on the bladder of rats induced to cystitis by cyclophosphamide. In this study, 35 male Wistar rats, with an average weight of 321g, were submitted to cystitis induction with intraperitoneal use of cyclophosphamide and treated with different doses of Echinodorus grandiflorus extract (30, 100, 300mg) and the control group with the drug Mesna. All animals were killed on the seventeenth day and their urinary bladders were resected for macro and microscopic evaluation, in addition to the analysis of blood count and leukogram. Blood analysis showed leukopenia with a significant difference in all animals that received cyclophosphamide. It was observed that the dose of 300mg/kg of the crude extract of the plant had a protective effect on the vesical urothelium, however, it was inferior to the use of Mesna. In view of the results presented in this study, it is suggested that the Echinodorus grandiflorus extract has a protective effect on the vesical urothelium at a dose of 300mg/kg, but future studies regarding the dose and also a possible therapeutic association with Mesna should be carried out. Because it is a pathology with significant prevalence and is often unpleasant and life-limiting, it is necessary to commit to alternative therapeutic methods to the current ones, in order to reduce the costs and side effects of the methods already documented.

cistitis hemorrágica y la cistitis intersticial tienen una etiología variable, desde idiopática hasta inducida por fármacos, incluida la ciclofosfamida. La cistitis tiene un tratamiento multifactorial, y el potencial efecto satisfactorio del uso de la medicina complementaria ha ido ganando terreno en la práctica médica. Así, el objetivo del presente estudio fue evaluar el efecto protector del extracto crudo de Echinodorus grandiflorus sobre la vejiga de ratas inducidas a cistitis por ciclofosfamida. En este estudio, 35 ratas Wistar macho, con un peso promedio de 321g, fueron sometidas a inducción de cistitis con uso intraperitoneal de ciclofosfamida y tratadas con diferentes dosis de extracto de Echinodorus grandiflorus (30, 100, 300mg) y el grupo control con el fármaco Mesna. Todos los animales fueron sacrificados al decimoséptimo día y sus vejigas urinarias fueron resecadas para evaluación macro y microscópica, además del análisis de hemograma y leucograma. El análisis de sangre mostró leucopenia con una diferencia significativa en todos los animales que recibieron ciclofosfamida. Se observó que la dosis de 300 mg/kg del extracto crudo de la planta tuvo un efecto protector sobre el urotelio vesical, sin embargo, fue inferior al uso de Mesna. En vista de los resultados presentados en este estudio, se sugiere que el extracto de Echinodorus grandiflorus tiene un efecto protector sobre el urotelio vesical a una dosis de 300 mg/kg, pero se deben realizar estudios futuros sobre la dosis y también una posible asociación terapéutica con Mesna. llevado a cabo. Por tratarse de una patología con una prevalencia importante y muchas veces desagradable y

The first Aotearoa New Zealand case of NUDT15-variant-related thiopurine-induced myelotoxicity.

A 37-year-old Han Chinese man, with a history of severe ulcerative colitis with incomplete response to oral glucocorticoids, was commenced on azathioprine [AZA] 200mg once a day. His pre-treatment thiopurine S-methyltransferase [TPMT] levels were in the normal range. Eleven days later he developed symptoms of stomatitis and gingivitis. Chinese herbal medications were taken in an attempt to treat these symptoms. He presented to the emergency department with this, with normal vital signs. A full blood count five days post-onset of symptoms showed pancytopenia with an absolute neutrophil count [ANC] of 0.0x10(9)/l, C-reactive protein was 120 mg/L. Initial chest radiograph, urinalysis and peripheral blood cultures were unremarkable and he was commenced on broad spectrum antibiotics and granulocyte colony stimulating factor [G-CSF]. He remained an inpatient under the gastroenterology team for 16 days and developed infectious complications of herpes simplex stomatitis, oral candidiasis, dental abscess, and scalp abscess. On day 16 his ANC recovered to 1.0x10(9)/L and was discharged from the hospital. He underwent nudix hydrolase 15 [NUDT15] genotyping and was found to have homozygosity for the variant NUDT15:c.415C>T. This case demonstrates the importance of pre-treatment testing for NUDT15 genetic variants, to predict the risk of severe leucopaenia, particularly in a patient of East Asian ethnicity.

The efficacy and safety of Xihuang Pill/capsule in adjuvant treatment of breast cancer: A systematic review and meta-analysis of 26 randomized controlled trials.

ETHNOPHARMACOLOGICAL RELEVANCE: Xihuang Pill is a traditional Chinese medicine prescription for the treatment of breast cancer. There are many randomized controlled trials (RCTs) of Xihuang Pill in the treatment of breast cancer that have been published. Hence, a comprehensive systematic review and meta-analysis is needed. AIM: To evaluate the safety of Xihuang pill/capsule and its effect on the improvement of tumor progression, quality of life, immunity and prognosis in adjuvant treatment of breast cancer. METHODS: Chinese and English databases such as Sinomed, PubMed, Embase were searched to collect the RCTs of Xihuang pill/capsule in adjuvant treatment of breast cancer. Then the researchers extracted data from the RCTs that met the inclusion criteria, and used Cochrane standard risk bias to assess the quality of the data, and used Rev Man 5.3 statistical software for statistical analysis. RESULTS: A total of 26 RCTs with 2272 participants were included. The primary outcomes showed that Xihuang pill combined with chemotherapy and with endocrine therapy may suppress of tumor progression {Chemotherapy: risk ratio (RR) = 0.59, 95%Confidence interval (CI) [0.48,0.73], P < 0.00001; Endocrine therapy: RR = 0.56, 95%CI [0.33,0.96], P = 0.04}. Xihuang pill combined with chemotherapy, with endocrine therapy and with radiotherapy may improve the quality of life (chemotherapy: RR = 1.73, 95%CI[1.11, 2.70], P = 0.02; Endocrine therapy: RR = 1.18, 95%CI [1.01,1.38], P = 0.03; radiotherapy:RR = 1.51, 95%CI [1.01,2.27], P = 0.05). Xihuang pill combined with TCM + chemotherapy may decrease the inefficiency rate for clinical symptom improvement (RR = 0.50, 95%CI [0.28, 0.88], P = 0.02). Xihuang pill combined with chemotherapy may increase the Karnofsky Performance Scale (KPS) {Weighted Mean Difference (WMD) = 15.40, 95%CI [8.18, 22.62], P < 0.0001}. For adverse events, Xihuang pill combined with chemotherapy may alleviate adverse digestive events and leukopenia; Xihuang pill combined with endocrine therapy will not increase adverse events; Xihuang pill combined with non-antitumor therapy may reduce the incidence of leukopenia and red blood cell or hemoglobin reduction. CONCLUSION: The addition of Xihuang pill/capsule to breast cancer in conventional anti-tumor therapy may inhibit tumor progression, improve patient quality of life, reduce toxic reactions, regulate immunity, and reduce tumor markers. However, due to the overall low quality of RCTs, the research results need more high-quality RCTs to further test the conclusions.

High dilution in Leukopenia treatment in five dogs

Leukopenia is associated with the consumption of peripheral leukocytes, decreasedproduction due to endotoxemia and septicemia, medullary hypoplasia, nutritional diseases orautoimmune reactions. In a case report by Narita et al, Echinacea angustifolia demonstrated theeffectiveness of treatment of leukopenia in penguins. Aims:Report the evolution of homeopathictreatment in 5 dogs' patients between 3 and 5 years old, presenting leukopenia. Methodology:The homeopathic treatment was chosen, using Echinaceaangustifolia due to its immunostimulant andimmunomodulatory actions, which evolution was analyzed by blood tests. The exposedinformation is consented by the tutors. Results:The same protocol was made for all of the patients, including 4 globules of Echinacea angustifolia 6 cH orally, every 12 hours for 30 days. The first dog attended on 07/21/2021, presented 4.000 leukocytes, which increased to 6.800 on 08/17/2021. Thesecond patient attend on 12/07/2021 presented 4.700 leukocytes, increasing to 6.800 on 01/25/2022. The third patient attended on 08/24/2021 presented 5.400 leukocytes, which increased to 6.800 on 10/15/2021. The fourth patient presented 4.300 leukocytes on 01/13/2022, increasing to 5.500 on 02/11/2022. The fifth patient presented on12/12/2021 4.600 leukocytes, increasing to 8.400 on 02/03/2022. Therefore, the average of the first collection was 3.681 leukocytes and in the second there was an increase to 6.860 leukocytes (T-test, p= 0,0167). Conclusion:The use of the homeopathic medicine Echinacea angustifolia shows great results, being a viableoption for the treatment of leukopenia, without the side effects.

Choline deficiency-related multi-omics characteristics are susceptible factors for chemotherapy-induced thrombocytopenia.

The XELOX chemotherapy protocol that includes capecitabine and oxaliplatin is the routine treatment for colorectal cancer (CRC), but it can cause chemotherapy-related adverse events such as thrombocytopenia (TCP). To identify predictive biomarkers and clarify the mechanism of TCP susceptibility, we conducted integrative analysis using normal colorectal tissue (CRT), plasma, and urine samples collected before CRC patients received adjuvant XELOX chemotherapy. RNA-sequencing and DNA methylation arrays were performed on CRT samples, while liquid chromatography-mass spectrometry was performed on CRT, plasma, and urine samples. Differentially expressed features (DEFs) from each uni-omics analysis were then subjected to integrative analysis using Multi-Omics Factor Analysis (MOFA). Choline-deficiency in plasma and CRT was found as the most critical TCP-related feature. Based on bioinformatic analysis and literature research, we further concluded that choline-deficiency was the possible reason for most of the other TCP-related multi-omics DEFs, including metabolites representing reduced sphingolipid de novo synthesis and elevated solute carrier-mediated transmembrane transportation in CRT and plasma, DNA hypermethylation and elevated expression of genes involved in neuronal system genes. In terms of thrombocytopoiesis, these TCP-related DEFs may cause atypical maintenance and differentiation of megakaryocyte, resulting a suppressed ability of thrombocytopoiesis, making patients more susceptible to chemotherapy-induced TCP. At last, prediction models were developed and validated with reasonably good discrimination. The area under curves (AUCs) of training sets were all > 0.9, while validation sets had AUCs between 0.778 and 0.926. In conclusion, our results produced reliable marker systems for predicting TCP and promising target for developing precision treatment to prevent TCP.

NOVEL-1st: an observational study to assess the safety and efficacy of nilotinib in newly diagnosed patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase in Taiwan.

Nilotinib has been approved for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP). However, the real-world evidence of nilotinib in newly diagnosed untreated Ph+ CML-CP is limited in Taiwan. The NOVEL-1st study was a non-interventional, multi-center study collecting long-term safety and effectiveness data in patients with newly diagnosed and untreated Ph+ CML-CP receiving nilotinib. We enrolled 129 patients from 11 hospitals. Overall, 1,466 adverse events (AEs) were reported; among these, 151 were serious and 524 were nilotinib-related. Common hematological AEs were thrombocytopenia (31.0%), anemia (20.9%), and leukopenia (14.0%); common nilotinib-related AEs were thrombocytopenia (29.5%), anemia (14.7%), and leukopenia (12.4%). Early molecular response, defined as BCR-ABL ≤ 10% at Month 3, was seen in 87.6% of patients. By 36 months, the cumulative rates of complete hematologic response, complete cytogenetic response, major molecular response, molecular response 4.0-log reduction, and molecular response 4.5-log reduction were 98.5, 92.5, 85.8, 65.0, and 45.0%, respectively. Nilotinib is effective and well-tolerated in patients with newly diagnosed Ph+ CML-CP in the real-world setting. Long-term holistic care and a highly tolerable AE profile may contribute to good treatment outcomes in Ph+ CML-CP under first-line treatment with nilotinib.

Effectiveness of Acupuncture in Relieving Chemotherapy-induced Leukopenia in Patients With Breast Cancer: A Systematic Review With A Meta-Analysis and Trial Sequential Analysis.

BACKGROUND: Breast cancer is one of the most common cancers and a major cause of death in women worldwide. Chemotherapy is mainly used to treat and control the progression of breast cancer. Leukopenia is the most common side effect of chemotherapy which may decrease immune function and further lead to serious fatal infections. The purpose of this study was to evaluate the effect of acupuncture on regulating hematopoietic function in chemotherapy-induced leukopenia among patients with breast cancer. METHODS: PubMed, Embase, Cochrane Library, CINAHL Plus, Web of Science, and Chinese articles in the Airiti Library and China National Knowledge Infrastructure (CNKI) databases were searched to August 2021 for papers to include in a systematic review and meta-analysis. A random-effects model was applied. The effect size was calculated by Hedges' g. Heterogeneity was determined using Cochran's Q test. Moderator analyses were performed to examine potential sources of heterogeneity. A trial sequential analysis (TSA) was conducted to determine whether the current sample size was sufficient. RESULTS: Ten randomized controlled trials involving 650 participants were eligible for inclusion. Analysis by the random-effects model showed a significant effect by acupuncture of ameliorating leukopenia during chemotherapy. Levels of white blood cells (WBCs) were increased (Hedges' g = 0.70, P < .001, I2 = 34%), neutrophil counts (Hedges' g = 0.80, P < .001, I2 = 0%) were significantly enhanced. Moreover, regardless of the manner through which acupuncture was applied, overall values of WBCs increased. CONCLUSIONS: The current meta-analysis supports acupuncture possibly ameliorating chemotherapy-induced leukopenia, as WBC and neutrophil values significantly increased after acupuncture in patients undergoing chemotherapy. Additionally, regardless of the type of acupuncture, values of WBCs increased. These findings are actionable and support both the clinical use of acupuncture to relieve chemotherapy-induced leukopenia and further research regarding the use of acupuncture in patients experiencing immunosuppression when undergoing chemotherapy.Trial Registration: PROSPERO-CRD42020215759.

Efficacy of Aidi Injection and Brucea javanica Oil Emulsion Injection in Rectal Cancer during CapeOX Adjuvant Chemotherapy.

BACKGROUND: Adjuvant chemotherapy with CapeOX regimen is widely used in resected rectal cancer, which brings benefits to patients. But drug-related toxicities are severe during this process; thus, survival outcomes may potentially be affected. This study explored the efficacy of two Chinese herbal injections, Aidi injection (ADI) and Brucea javanica oil emulsion injection (BJOEI), as adjuvant drugs in CapeOX adjuvant chemotherapy on rectal cancer patients. METHODS: A total of 240 cases were enrolled in this retrospective study. 80 cases received CapeOX with ADI (the ADI group), 80 cases received CapeOX with BJOEI (the BJOEI group), and the rest 80 cases received CapeOX alone (the control group). After four cycles' chemotherapy, adverse reactions (ADRs) and quality of life (QOL) were analyzed. Then, patients received follow-up for at least one year, and the endpoint was disease-free survival (DFS). RESULTS: All patients completed at least four cycles' adjuvant chemotherapy. The incidence of leukopenia and thrombocytopenia was significantly lower in the ADI group; the incidence of nausea was significantly lower in the BJOEI group; the incidence of hand-foot syndrome was significantly lower in both the ADI group and BJOEI group. Significant difference was found in the control group regarding the Karnofsky Performance Status (KPS) scores prior and posttreatment. No difference was found among three groups regarding one-year DFS. CONCLUSION: As adjuvant drugs for rectal cancer during CapeOX chemotherapy, ADI shows advantages in decreasing leukopenia and thrombocytopenia, while BJOEI results better in remitting nausea. Both two CHIs had positive impacts on decreasing hand-foot syndrome and the maintenance of patients' QOL. It is worthy of further study and promotion for CHIs.

PAC1 Receptor Mediates Electroacupuncture-Induced Neuro and Immune Protection During Cisplatin Chemotherapy.

Platinum-based chemotherapy is an effective treatment used in multiple tumor treatments, but produces severe side effects including neurotoxicity, anemia, and immunosuppression, which limits its anti-tumor efficacy and increases the risk of infections. Electroacupuncture (EA) is often used to ameliorate these side effects, but its mechanism is unknown. Here, we report that EA on ST36 and SP6 prevents cisplatin-induced neurotoxicity and immunosuppression. EA induces neuroprotection, prevents pain-related neurotoxicity, preserves bone marrow (BM) hematopoiesis, and peripheral levels of leukocytes. EA activates sympathetic BM terminals to release pituitary adenylate cyclase activating polypeptide (PACAP). PACAP-receptor PAC1-antagonists abrogate the effects of EA, whereas PAC1-agonists mimic EA, prevent neurotoxicity, immunosuppression, and preserve BM hematopoiesis during cisplatin chemotherapy. Our results indicate that PAC1-agonists may provide therapeutic advantages during chemotherapy to treat patients with advanced neurotoxicity or neuropathies limiting EA efficacy.

[Therapeutic Effect of Spleen Low Molecular Weight Extracts on Leukopenia Caused by Epirubicin in Mice and Its Mechanism].

OBJECTIVE: To investigate the therapeutic effect of spleen low molecular weight extracts on epileptics hydrochloride-induced leukopenia in mice and explore its mechanism. METHODS: The model of leukopenia in mice was established by the injection of epirubicin hydrochloride (10 mg/kg). After the injection of chemotherapeutic drugs, leukocytopenia mice were treated with different doses of spleen low molecular weight extract, Ganoderma oral solution and recombinant granulocyte colony stimulating factor (rhG-CSF). The general survival status indicators such as body weight, coat color and athletic ability of mice in each group were recorded; the tail vein blood of mice in each group was collected and the white blood cell count in them was calculated; bone marrow of mice was taken and bone marrow smears were observed. RESULTS: In the model group, the weight of the mice gradually decreased in the later period, their coat became dark and rough, and the ability to exercise decreased, while the mice in the treatment groups showed different degrees of improvement in their survival status except for the mice treated by rhG-CSF. There was no significant fluctuation in the white blood cell count of the blank control mice. After injection of epirubicin, the white blood cell count of peripheral blood in the model mice and treated mice were decreased. The white blood cell count was lower in the mice treated with high-dose low molecular weight extract and rhG-CSF than that in other experimental groups. Bone marrow smear showed that the proportion of bone marrow nucleated cells in the mice treated with the low molecular weight extract of the spleen was significantly higher than that of model mice (P<0.05). CONCLUSION: The low molecular weight spleen extracts can significantly improve the hematopoietic state of mouse bone marrow, promote the proliferation of inhibited bone marrow cells, and thus has the effect of treating leukopenia in mice.