Tonghua Liyan granules in the treatment of Laryngopharyngeal reflux disease with stagnation of phlegm and qi syndrome: a randomized, double-blind, placebo-controlled study.

Background: Laryngopharyngeal reflux disease (LPRD) is an extraesophageal syndromic manifestation of gastroesophageal reflux disease (GERD). Despite the increasing incidence of and concern about LPRD, treatment with proton pump inhibitors (PPIs) is unsatisfactory. Here, LPRD was treated with Tonghua Liyan (THLY) granules in combination with PPIs to evaluate treatment efficacy and possible adverse reactions. Methods: Seventy-six LPRD patients with stagnation of phlegm and qi syndrome (SPQS) were randomly divided into an experimental group and a control group. The experimental group received THLY granules combined with rabeprazole capsules. The control group received THLY granule placebo combined with rabeprazole capsules. A parallel, randomized, double-blind, placebo-controlled clinical trial was conducted with these two groups. The treatment cycle was 8 weeks. The reflux symptom index (RSI), clinical symptom score, salivary pepsin content, reflux finding score (RFS) and gastroesophageal reflux disease questionnaire (GerdQ) were used to evaluate clinical efficacy. The final efficacy rate was evaluated according to the RSI and clinical symptom score. Results: Compared with those at baseline, all the indicators in the experimental group and control group significantly improved (p < 0.01). In terms of the RSI, clinical symptom score, and RFS, the experimental group had a higher degree of improvement (p < 0.05), and the overall efficacy rate was higher (p < 0.05). In terms of the salivary pepsin concentration and GerdQ, there was no significant difference between the test group and the control group (p > 0.05). Both groups of safety indicators showed no abnormalities and did not cause any allergic reactions in the body. Conclusion: Compared with PPIs alone, THLY granules combined with PPIs are more effective in the treatment of LPRD patients with SPQS in terms of symptoms and signs. This combination treatment, because of its higher clinical efficacy and lack of obvious adverse reactions, is worthy of clinical promotion and further in-depth study. Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR2100046614.

Da-Cheng-Qi decoction improves severe acute pancreatitis-associated acute lung injury by interfering with intestinal lymphatic pathway and reducing HMGB1-induced inflammatory response in rats.

CONTEXT: Da-Cheng-Qi Decoction (DCQD) has a significant effect on Severe Acute Pancreatitis-Associated Acute Lung Injury (SAP-ALI). OBJECTIVE: To explore the mechanism of DCQD in the treatment of SAP-ALI based on intestinal barrier function and intestinal lymphatic pathway. MATERIALS AND METHODS: Forty-five Sprague-Dawley rats were divided into three groups: sham operation, model, and DCQD. The SAP model was induced by a retrograde infusion of 5.0% sodium taurocholate solution (1 mg/kg) at a constant rate of 12 mL/h using an infusion pump into the bile-pancreatic duct. Sham operation and model group were given 0.9% normal saline, while DCQD group was given DCQD (5.99 g/kg/d) by gavage 1 h before operation and 1, 11 and 23 h after operation. The levels of HMGB1, RAGE, TNF-α, IL-6, ICAM-1, d-LA, DAO in blood and MPO in lung were detected using ELISA. The expression of HMGB1, RAGE, NF-κB p65 in mesenteric lymph nodes and lung were determined. RESULTS: Compared with SAP group, DCQD significantly reduced the histopathological scoring of pancreatic tissue (SAP, 2.80 ± 0.42; DCQD, 2.58 ± 0.52), intestine (SAP, 3.30 ± 0.68; DCQD, 2.50 ± 0.80) and lung (SAP, 3.30 ± 0.68; DCQD, 2.42 ± 0.52). DCQD reduced serum HMGB1 level (SAP, 134.09 ± 19.79; DCQD, 88.05 ± 9.19), RAGE level (SAP, 5.05 ± 1.44; DCQD, 2.13 ± 0.54). WB and RT-PCR showed HMGB1-RAGE pathway was inhibited by DCQD (p < 0.01). DISCUSSION AND CONCLUSIONS: DCQD improves SAP-ALI in rats by interfering with intestinal lymphatic pathway and reducing HMGB1-induced inflammatory response.

Research trends on clinical fecal microbiota transplantation: A biliometric analysis from 2001 to 2021.

Background: Numerous studies on fecal microbiota transplantation (FMT) have been conducted in the past two decades. We aimed to assess the research trends and hotspots in the field of FMT through a quantitative method. Materials and Methods: The clinical studies of FMT published from 2001 to 2021 were extracted from the Web of Science database. We analyzed the countries, institutions, authors, and keywords of these articles and visually illustrated using VOSviewer and CiteSpace software. The current application of FMT in clinical practice, including indications, efficacy, adverse events, as well as its methodology, such as donor, delivery route, were also evaluated. Results: A total of 227 records were finally identified. The number and rate of annual publications increased gradually. The USA ranked highest in the number of publications. Harvard University was the most influential institution, and Digestive Diseases and Sciences was the most productive journal. Kassam Zain published the most papers, and the high-frequency keywords were mainly related to diseases and techniques. Healthy donors were the most widely used donors, and frozen stool had the highest frequency of use. The predominant delivery route was endoscopy followed by oral capsules and enema. FMT was most frequently performed for the treatment of recurrent Clostridium Difficile Infection. The overall efficacy of FMT was 76.88%, and the incidence of minor and severe adverse events were 11.63% and 1.59%, respectively. Conclusions: This study delineated a comprehensive landscape of the advancement in FMT field. Although in its infancy, FMT is a burgeoning option for the treatment of a variety of diseases associated with gut dysbiosis. To improve the efficacy and reduce adverse events, future studies are warranted to optimize the methodology of FMT.

Analysis of oral microbiota alterations induced by Helicobacter pylori infection and vonoprazan-amoxicillin dual therapy for Helicobacter pylori eradication.

BACKGROUND: The oral cavity is considered a potential reservoir of Helicobacter pylori (H. pylori), and the imbalance of oral microbiota directly reflects the health of the host. We aimed to explore the relationship among oral microbiota, H. pylori infection, and vonoprazan-amoxicillin (VA) dual therapy for H. pylori eradication. METHODS: Helicobacter pylori-positive patients were randomized into low- or high-dose VA dual therapy (i.e., amoxicillin 1 g b.i.d. or t.i.d. and vonoprazan 20 mg b.i.d) for 7 or 10 days. H. pylori-negative patients served as normal controls. Saliva samples were collected from 41 H. pylori-positive patients and 13 H. pylori-negative patients. The oral microbiota was analyzed by 16S rRNA gene sequencing, followed by bioinformatics analysis. RESULTS: Helicobacter pylori-positive patients had higher richness and diversity and better evenness of oral microbiota than normal controls. Beta diversity analysis estimated by Bray-Curtis or weighted UniFrac showed distinct clustering between H. pylori-positive patients and normal controls. The number of bacterial interactions was reduced in H. pylori-positive patients compared with that in negative patients. Forty-one patients evaluated before and after successful H. pylori eradication were divided into low (L-VA) and high dose (H-VA) amoxicillin dose groups. The alpha and beta diversity of the oral microbiota between L-VA and H-VA patients exhibited no differences at the three time points (before eradication, after eradication, and at confirmation of H. pylori infection cure). CONCLUSION: Helicobacter pylori infection could alter the diversity, composition, and bacterial interactions of the oral microbiota. Both L-VA and H-VA dual therapy showed minimal influence on the oral microbiota.

Altered Gut Microbiota and Short-Chain Fatty Acids After Vonoprazan-Amoxicillin Dual Therapy for Helicobacter pylori Eradication.

The combination of vonoprazan (VPZ) and amoxicillin (VA therapy) has been shown to achieve acceptable eradication rates for Helicobacter pylori (H. pylori). Herein, our aim was to explore the short-term effect of VA therapy on the gut microbiota and short-chain fatty acids (SCFAs) using human fecal samples. A total of 119 H. pylori-positive patients were randomized into low- or high-dose VA therapy (i.e., amoxicillin 1 g b.i.d. or t.i.d. and VPZ 20 mg b.i.d.) for 7 or 10 days. Thirteen H. pylori-negative patients served as controls. Fecal samples were collected from H. pylori-positive and H. pylori-negative patients. The gut microbiota and SCFAs were analyzed using 16S rRNA gene sequencing and gas chromatography-mass spectrometry, respectively. The gut microbiota in H. pylori-positive patients exhibited increased richness, diversity, and better evenness than matched patients. Fifty-three patients studied before and after H. pylori eradication were divided into low (L-VA) and high (H-VA) amoxicillin dose groups. The diversity and composition of the gut microbiota among L-VA patients exhibited no differences at the three time points. However, among H-VA patients, diversity was decreased, and the microbial composition was altered immediately after H-VA eradication but was restored by the confirmation time point. The decreased abundance of Anaerostipes, Dialister, and Lachnospira induced by H-VA was associated with altered SCFA levels. VA dual therapy for H. pylori eradication has minimal negative effects on gut microbiota and SCFAs.

Optimization of vonoprazan-amoxicillin dual therapy for eradicating Helicobacter pyloriinfection in China: A prospective, randomized clinical pilot study.

BACKGROUND: Vonoprazan-amoxicillin (VA) dual therapy has been shown to achieve acceptable cure rates for treatment of Helicobacter pylori(H. pylori) in Japan. Its effectiveness in other regions is unknown. We aimed to explore the efficacy of VA dual therapy as first-line treatment for H. pyloriinfection in China. METHODS: This was a single center, prospective, randomized clinical pilot study conducted in China. Treatment naive H. pyloriinfected patients were randomized to receive either low- or high-dose amoxicillin-vonoprazan consisting of amoxicillin 1 g either b.i.d. or t.i.d plus VPZ 20 mg b.i.d for 7 or 10 days. 13 C-urea breath tests were used to access the cure rate at least 4 weeks after treatment. RESULTS: Three hundred and twenty-three patients were assessed, and 119 subjects were randomized. The eradication rates of b.i.d. amoxicillin for 7 and 10 days, t.i.d. amoxicillin for 7 and 10 days were 66.7% (16/24), 89.2% (33/37), 81.0% (17/21), and 81.1% (30/37) (p = .191) by intention-to-treat analysis, respectively, and 72.7% (16/22), 89.2% (33/37), 81.0% (17/21), and 81.1% (30/37) (p = .454) by per-protocol analysis, respectively. CONCLUSION: Neither 7- or 10-day VA dual therapy with b.i.d. or t.i.d. amoxicillin provides satisfied efficacy as the first-line treatment for H. pyloriinfection in China. Further optimization is needed.

Fourteen-day vonoprazan and low- or high-dose amoxicillin dual therapy for eradicating Helicobacter pylori infection: A prospective, open-labeled, randomized non-inferiority clinical study.

Background and aim: We previously reported that vonoprazan-amoxicillin (VA) dual therapy for 7 or 10 days is not satisfactorily efficacious for Helicobacter pylori (H. pylori) eradication. We aimed to explore the efficacy of VA dual therapy for 14 days as a first-line treatment for H. pylori infection. Methods: This was a single center, prospective, open-labeled, randomized non-inferiority clinical study conducted in China. Treatment naïve H. pylori infected patients were randomized into two groups: 20 mg vonoprazan (VPZ) b.i.d. in combination with low-dose (1000 mg b.i.d.) or high-dose (1000 mg t.i.d) amoxicillin for 14 days. 13C-urea breath tests were used to access the cure rate at least 4 weeks after treatment. Results: A total of 154 patients were assessed and 110 subjects were randomized. The eradication rate of VPZ with b.i.d. amoxicillin or t.i.d. amoxicillin for 14 days was 89.1% and 87.3% by intention-to-treat analysis, respectively, and 94.1% and 95.9% by per-protocol analysis, respectively. The eradication rate and incidence of adverse events were not different between the two groups. Conclusion: VPZ with b.i.d. or t.i.d. amoxicillin for 14 days provides satisfactory efficacy as a first-line treatment for H. pylori infection in China.

Hyaluronic acid-modified manganese dioxide-enveloped hollow copper sulfide nanoparticles as a multifunctional system for the co-delivery of chemotherapeutic drugs and photosensitizers for efficient synergistic antitumor treatments.

This paper presents the design of a new type of intelligent and versatile all-in-one therapeutic nanoplatform for the co-delivery of chemotherapeutic drugs and photosensitizers to facilitate multimodal antitumor treatment; the system is based on hyaluronic acid (HA)-modified manganese dioxide (MnO2)-enveloped hollow porous copper sulfide (CuS) nanoparticles (CuS@MnO2/HA NPs). In this system, a CuS inner shell allows for the co-loading of doxorubicin (DOX) and indocyanine green (ICG) and induces photothermal effects, and a biodegradable MnO2 external shell affords on-demand tumor microenvironment (TME)-triggered release and catalase- andFenton-like activities. Moreover, the HA modification endows the system with a CD44 receptor-mediated tumor-targeting property. The formulated DOX and ICG co-loaded CuS@MnO2/HA (DOX/ICG-CuS@MnO2/HA) NPs were found to exhibit excellent photothermal performance both in vitro and in vivo. In addition, DOX/ICG-CuS@MnO2/HA NPs were found to display both TME and near-infrared (NIR)-responsive controlled release properties. The NPs also have a superior reactive oxygen species (ROS) generation capacity due to the combination of enhanced ICG-induced singlet oxygen and CuS@MnO2-mediated hydroxyl radicals. The cellular uptake, fluorescence imaging property, cytotoxicity, and thermal imaging of these NPs were also evaluated. In tumor-bearing mice, the DOX/ICG-CuS@MnO2/HA NPs displayeda superior antitumor efficacy (2.57-fold) as compared with free DOX. Therefore, the developed DOX/ICG-CuS@MnO2/HA NPs have a great potential for use as an all-in-one nanotherapeutic agent for the efficient and precise induction of chemo/photothermal/photodynamic/chemodynamic therapy with superior antitumor efficacy and fewer side effects.

Progress on biosynthesis and function of the natural products of Zi Cao as a traditional Chinese medicinal herb.

Zi Cao is an important traditional medicinal plant resource in China. Shikonin and its derivatives, as the purple-red naphthoquinones among natural products of its roots, are commonly used clinically in the treatment of sores and skin inflammations. Over the past few decades, due to their highly effective multiple biological activities, pharmacological effects, good clinical efficacy and high utilization value, shikonin and its derivatives have attracted increasing attention of domestic and foreign researchers. For this reason, the wild plant germplasm resources have been suffering a grievous exploitation, leading to a serious threat to the habitat. With the development of the biosynthesis, molecular metabolism and biotechnology, as well as the continuous innovation of research methods on the biological activities and pharmacological effects of plant natural products, significant progress has been made in the research on the biosynthetic pathways and related regulatory genes of shikonin. The pharmacological action and its mechanism of shikonin have also been deeply elucidated, which greatly promoted the basic research and clinical application development of shikonin. In this review, we briefly introduce and analyze the classification of Zi Cao, structure and composition of natural shikonin and its biosynthesis pathway, functional genes related to the regulation of shikonin biosynthesis, and biological activities and pharmacological functions of shikonin. Finally, we address possible prospective for the trend on the future research and development of natural shikonin and its derivatives, hoping to provide a useful reference for the deep mining and development of medicinal natural products from important Chinese medicinal materials, and to promote the modern development of traditional Chinese medicine.

Adjuvant Therapy: YiqiDitanTongfu Decoction With External Diaphragm Pacer for Chronic Obstructive Pulmonary Disease Patients With Difficulty Weaning From Mechanical Ventilation.

CONTEXT: Global morbidity from chronic obstructive pulmonary disease (COPD) is high worldwide. Diaphragm pacing (DP) can maintain the natural, negative pressure breathing of COPD patients with diaphragmatic muscle dysfunction. The YiqiDitanTongfu (YDTF) decoction has been used clinically with COPD patients to help them to wean from mechanical ventilation, with their ventilation functions being improved and the success rate of weaning being largely increased. OBJECTIVE: The study intended to investigate the combined therapeutic effects of external DP and the YDTF decoction for COPD patients who have had difficulty weaning from mechanical ventilation. DESIGN: This study was a retrospective cohort study. SETTING: The study occurred at the Hebei General Hospital and Hebei Province Chest Hospital (Hebei Province, Shijiazhuang, China). PARTICIPANTS: Participants were 90 patients with COPD + type 1 respiratory failure, 101 patients with COPD + Type 2 respiratory failure, and 96 patients with COPD at the compensated stage. INTERVENTION: The participants were randomly divided into 3 groups: (1) traditional treatment (control group), (2) traditional treatment plus treatment with a diaphragm pacemaker (DP group), and (3) traditional treatment plus treatment with a DP and a YDTF decoction (DP + YDTF group). All treatments occurred for 12 d. OUTCOME MEASURES: Relevant outcomes were measured and compared at baseline and postintervention, including the rapid shallow breathing index, tidal volume, maximum inspiratory pressure, degree of diaphragmatic muscle activity, maximum expiratory pressure, the successful rates of weaning from mechanical ventilation, the potential of hydrogen, the partial pressure of oxygen, partial pressure of carbon dioxide, and oxygen saturation. RESULTS: The patients treated with the DP plus the YDTF decoction were more successful in weaning from mechanical ventilation than those treated with DP. Of the patients with COPD + type 1 respiratory failure, 86.67% succeeded vs 70.00% of the DP patients. Of patients with COPD + type 2 respiratory failure, 87.88% succeeded vs 79.41% of the DP patients. CONCLUSION: The DP plus the YDTF concoction acted as a successful treatment for heart failure caused by CPOD in comparison with the DP or YDTF alone, providing evidence that the DP + YDTF concoction can serve as a competitive method for helping COPD patients to wean from mechanical ventilation.

Zn2+ reduction induces neuronal death with changes in voltage-gated potassium and sodium channel currents.

In the present study, cultured rat primary neurons were exposed to a medium containing N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), a specific cell membrane-permeant Zn2+ chelator, to establish a model of free Zn2+ deficiency in neurons. The effects of TPEN-mediated free Zn2+ ion reduction on neuronal viability and on the performance of voltage-gated sodium channels (VGSCs) and potassium channels (Kvs) were assessed. Free Zn2+ deficiency 1) markedly reduced the neuronal survival rate, 2) reduced the peak amplitude of INa, 3) shifted the INa activation curve towards depolarization, 4) modulated the sensitivity of sodium channel voltage-dependent inactivation to a depolarization voltage, and 5) increased the time course of recovery from sodium channel inactivation. In addition, free Zn2+ deficiency by TPEN notably enhanced the peak amplitude of transient outward K+ currents (IA) and delayed rectifier K+ currents (IK), as well as caused hyperpolarization and depolarization directional shifts in their steady-state activation curves, respectively. Zn2+ supplementation reversed the effects induced by TPEN. Our results indicate that free Zn2+ deficiency causes neuronal damage and alters the dynamic characteristics of VGSC and Kv currents. Thus, neuronal injury caused by free Zn2+ deficiency may correlate with its modulation of the electrophysiological properties of VGSCs and Kvs.

[Preliminary Studies on the Relationship Between Meiosis of Pollen Mother Cells and Pollen Abortion of Aloe arboresense Mill.].

The main reason for pollen abortion in Aloe arboresens Mill. was studied through the observation of meiosis and the microspore development of its pollen mother cells(PMCs). There are 14 chromosomes in the PMC of Aloe arboresens Mill., containing four pairs of long chromosomes and three pairs of short ones, and this karyotype belongs to dichotocarpism. Abnormalities observed were fallen into four categories:(1) Univalents, they were caused by failure in pairing, asynapsis and precocious cancellation of terminal chiasma. Oriented univalent pair was distributed at two poles normally in anaphase, while non-oriented univalent pair only at one pole. Another factor leading to univalents was that chromosomes were paired but without substantial exchange. (2) Multivalents. They might be produced by translocation heterozygote.(3) Chromosome bridges. There were three kinds of bridges in anaphase I and anaphase II: single and double chromosome bridge as well as "diagonal bridge".(4) A few cells were found with lagged chromosomes, micronuclei and unbalanced segregation of the chromosomes. In the later stages of meiosis, well-spread chromosomal configurations were rare because of the extremely sticky nature of the chromosome. The number and ratio of abnormalities were analysed and the relationship between abnormalities and pollen sterility were discussed. It is concluded that the sticky nature of the chromosome is the main reason for abnormal meiosis of Aloe arboresens Mill.PMC and pollen sterility. More than 90% of matured pollen grains were sterile.