Global research trends and hotspots of Helicobacter pylori eradication based on clinical trial registration platforms: A cross-sectional analysis.

BACKGROUND: This study aimed to obtain an overview of clinical trials on Helicobacter pylori (H. pylori) eradication and analyze the global trends and hotspots in this field. METHODS: We collected the data from clinical trials focused on H. pylori eradication in the primary clinical trial registries from 2000 to 2022 in the world. Then we analyzed the research trends and hotspots in H. pylori eradication regimens in different regions at different periods. RESULTS: A total of 780 clinical trials were included, which were mainly conducted in Asia (682), followed by Europe (59), Africa (20), North America (16), South America (7), Oceania (2). The most active countries were China (343), Iran (140), South Korea (63), and Japan (73). "Bismuth-containing quadruple therapy (BQT)" was the most studied regimen (159, 20.38 %). Additionally, clinical trials focused on potassium-competitive acid blockers (P-CABs)-based therapy, probiotics, and high-dose dual therapy (HDDT) were constantly increasing. BQT received the most attention in China (26.53 %) and Iran (22.14 %), while it was tailored therapy in South Korea (23.29 %). P-CABs-based therapy was the main reseach hotspot in Japan (61.90 %). CONCLUSION: How to eradicate H. pylori infection has been a heated research topic. BQT, P-CABs-based therapy, probiotics, and HDDT attracted the most attention in recent years.

Gut microbiota-associated taurine metabolism dysregulation in a mouse model of Parkinson's disease.

IMPORTANCE: PD is recognized as a multisystem disease concerning GI dysfunction and microbiota dysbiosis but still lacks ideal therapies. Recently, aberrant microbiota-derived metabolites are emerging as important participants in PD etiology. However, the alterations of gut microbiota community and serum untargeted metabolite profile have not been fully investigated in a PD mice model. Here, we discover sharply reduced levels of Lactobacillus and taurine in MPTP-treated mice. Moreover, Lactobacillus, Adlercreutzia, and taurine-related metabolites showed the most significant correlation with pathological and GI performance of PD mice. The abundances of microbial transporter and enzymes participating in the degeneration of taurine were disturbed in PD mice. Most importantly, taurine supplement ameliorates MPTP-induced motor deficits, DA neuron loss, and microglial activation. Our data highlight the impaired taurine-based microbiome-metabolism axis during the progression of PD and reveal a novel and previously unrecognized role of genera in modulating taurine metabolism.

Integrating network pharmacology with molecular docking for elucidation of molecular biological mechanisms of Jiedu Qingjin formula for non-small cell lung cancer.

Traditional Chinese medicine is an important part of complementary alternative medicine. Jiedu Qingjin formula (JDQJF) is an effective national invention patent for the treatment of non-small cell lung cancer (NSCLC). We investigated the molecular biological mechanisms based on network pharmacology, molecular docking, and molecular dynamics simulations. Compounds of JDQJF were screened through the TCMSP, ETCM, and literature. Targets were searched by DrugBank and predicted by SwissTargetPrediction. GEO database was applied for screening differentially expressed genes between cancerous tissues and healthy tissues of NSCLC. Subsequently, the protein-protein interaction between JDQJF and NSCLC were obtained by Cytoscape. Visual analyses were carried out to extract candidate genes, then subjected to Metascape for enrichment analyses. Finally, molecular docking was performed by AutoDock, and the best complexes were subjected to molecular dynamics simulation and binding energy calculations by MMPBSA. A total of 273 compounds, 390 targets, 3146 GO terms, and 174 KEGG pathways were obtained. Five potential compounds (quercetin, adenosine, apigenin, heptadecanoic acid, and luteolin) were notably modulated by key targets AKT1, MAPK3, and RAF1. Enrichment results included cell cycle process, growth transduction factor, immune response-activating transduction, and involved PI3K/AKT, MAPK, NF-κB and VEGF pathway. RAF1-quercetin showed the highest binding affinity (-9.1 kcal/mol), revealed stable interactions during the simulation, and the highest estimated relative binding energy of the RAF1-Heptadecanoic was -184.277 kcal/mol. This study suggested that EMT-related, inflammation-related, immune-related, and angiogenesis-related pathways may be associated with JDQJF, and involved in the advancement of NSCLC, which points out the research direction for subsequent utility mechanism validation.Communicated by Ramaswamy H. Sarma.

Xanthoceras sorbifolia Husk Extract Incorporation for the Improvement in Physical and Antioxidant Properties of Soy Protein Isolate Films.

With the increasing awareness of ecological and environmental protection, the research on eco-friendly materials has experienced a considerable increase. The objective of our study was to explore a novel soy protein isolate (SPI) film functionalized with antioxidants extracted from Xanthoceras sorbifolia husk (XSHE) as bio-based active packaging films. The films were evaluated in light of their structure, physical machinery, and antioxidant performance using advanced characterization techniques. The FTIR and microscopy results revealed the hydrogen-bond interaction between the SPI and XSHE and their good compatibility, which contributed to the improvement in various properties of the composite films, such as tensile strength (TS), UV blocking, and the water barrier property. As the XSHE content increased to 5%, the TS of the films dramatically increased up to 7.37 MPa with 47.7% and the water vapor permeability decreased to 1.13 × 10-10 g m m-2 s-1 Pa-1 with 22.1%. Meanwhile, the introduction of XSHE caused further improvement in the antioxidant capacity of films, and the release of active agents from films was faster and higher in 10% ethanol than it was in a 50% ethanol food simulant. Overall, SPI-based films functionalized with XSHE demonstrated promising potential applications in food packaging.

Ferrodifferentiation regulates neurodevelopment via ROS generation.

Iron is important for life, and iron deficiency impairs development, but whether the iron level regulates neural differentiation remains elusive. In this study, with iron-regulatory proteins (IRPs) knockout embryonic stem cells (ESCs) that showed severe iron deficiency, we found that the Pax6- and Sox2-positive neuronal precursor cells and Tuj1 fibers in IRP1-/-IRP2-/- ESCs were significantly decreased after inducing neural differentiation. Consistently, in vivo study showed that the knockdown of IRP1 in IRP2-/- fetal mice remarkably affected the differentiation of neuronal precursors and the migration of neurons. These findings suggest that low intracellular iron status significantly inhibits neurodifferentiation. When supplementing IRP1-/-IRP2-/- ESCs with iron, these ESCs could differentiate normally. Further investigations revealed that the underlying mechanism was associated with an increase in reactive oxygen species (ROS) production caused by the substantially low level of iron and the down-regulation of iron-sulfur cluster protein ISCU, which, in turn, affected the proliferation and differentiation of stem cells. Thus, the appropriate amount of iron is crucial for maintaining normal neural differentiation that is termed ferrodifferentiation.

Impact of body size on efficacy of high-dose dual therapy for Helicobacter pylori eradication.

BACKGROUND: High-dose dual therapy (HDDT) is an emerging and promising therapeutic regime for Helicobacter pylori (H. pylori) eradication. However, the pharmacokinetics of the components of HDDT, amoxicillin and proton pump inhibitor, are likely to be affected by body size. In this study, we aimed to find out the impact of body size on the efficacy of HDDT. METHODS: We collected the medical data of 385 treatment-naive patients infected with H. pylori who received HDDT (esomeprazole 20 mg and amoxicillin 750 mg four times daily) for 14 days from July 2020 to December 2021. The associations among the eradication efficacy, adverse events, and variables (sex, age, height, body weight, body mass index (BMI), body surface area (BSA), smoking, drinking, etc.) were analyzed respectively in our study. Among these factors, continuous variables were classified into categorical variables using the cut-off values which were calculated by receiver operating characteristic analysis. RESULTS: The eradication rate of HDDT was 89.9%. There were 55 (14.3%) patients who occurred adverse events during the treatment. Patients with height <170.5 cm, body weight <60.5 kg, BMI <20.55 kg/m2 , BSA <1.69 m2 had a higher eradication rate (92.1% vs. 84.0%, 93.1% vs. 86.8%, 96.0% vs. 87.8%, 93.4% vs. 84.8%, all p < .05). The multivariate analysis showed that BSA ≥1.69 m2 (OR 2.53, 95% CI: 1.28-4.99, p = .007) was the only independent predictor of eradication failure. CONCLUSION: HDDT could achieve better eradication efficacy in patients with small BSA. Clinicians should be aware of the impact of BSA on the H. pylori eradication rate and pay more attention to patients with large BSA.

Evaluation of the potential of ultrasound-mediated drug delivery for the treatment of ovarian cancer through preclinical studies.

Ovarian cancer (OC) has the greatest mortality rate among gynecological cancers, with a five-year survival rate of <50%. Contemporary adjuvant chemotherapy mostly fails in the case of OCs that are refractory, metastatic, recurrent, and drug-resistant. Emerging ultrasound (US)-mediated technologies show remarkable promise in overcoming these challenges. Absorption of US waves by the tissue results in the generation of heat due to its thermal effect causing increased diffusion of drugs from the carriers and triggering sonoporation by increasing the permeability of the cancer cells. Certain frequencies of US waves could also produce a cavitation effect on drug-filled microbubbles (MBs, phospholipid bilayers) thereby generating shear force and acoustic streaming that could assist drug release from the MBs, and promote the permeability of the cell membrane. A new class of nanoparticles that carry therapeutic agents and are guided by US contrast agents for precision delivery to the site of the ovarian tumor has been developed. Phase-shifting of nanoparticles by US sonication has also been engineered to enhance the drug delivery to the ovarian tumor site. These technologies have been used for targeting the ovarian cancer stem cells and protein moieties that are particularly elevated in OCs including luteinizing hormone-releasing hormone, folic acid receptor, and vascular endothelial growth factor. When compared to healthy ovarian tissue, the homeostatic parameters at the tissue microenvironment including pH, oxygen levels, and glucose metabolism differ significantly in ovarian tumors. US-based technologies have been developed to take advantage of these tumor-specific alterations for precision drug delivery. Preclinical efficacy of US-based targeting of currently used clinical chemotherapies presented in this review has the potential for rapid human translation, especially for formulations that use all substances that are deemed to be generally safe by the U.S. Food and Drug Administration.

Optimized dual therapy for treatment-naive patients of Helicobacter pylori infection: A large-scale prospective, multicenter, open-label, randomized controlled study.

BACKGROUND: The efficacy and safety of high-dose amoxicillin (AMX) and proton pump inhibitors (PPI) dual therapy raises much more attention in recent years. Comparative studies among the dual therapies are required to explore more suitable regimens. This study compared the efficacy, adverse events, and patient compliance of three different high-dose dual regimens in treatment-naive patients of Helicobacter pylori (H. pylori) infection. MATERIALS AND METHODS: The study was a prospective, multicenter, open-label, randomized controlled trial, including H. pylori-infected treatment-naive patients at 12 tertiary hospitals in China. The eligible subjects received high-dose AMX and esomeprazole (ESO) dual therapy of different regimens. They were randomly assigned to group A (ESO 20 mg plus AMX 750 mg, Qid for 14 days), group B (ESO 40 mg Bid plus AMX 1 g Tid for 14 days), or group C (ESO 20 mg plus AMX 1 g, Tid for 14 days). The eradication rates, adverse events, and patient compliance of the three groups were compared. RESULTS: Between April 2021 and January 2022, a total of 1080 subjects were screened and 945 were randomized. The eradication rates in groups A, B, and C were 88.6% (95% CI 84.5%-91.9%), 84.4% (95% CI 80.0%-88.3%), and 86.7% (95% CI 82.4%-90.2%; p = .315), respectively, based on intention-to-treat analysis; 90.3% (95% CI 86.4%-93.3%), 85.5% (95% CI 81.1%-89.2%), and 87.8% (95% CI 83.6%-91.2%; p = .197), respectively, according to modified intention-to-treat analysis; and 90.4% (95% CI 86.5%-93.5%), 85.8% (95% CI 81.4%-89.5%), and 88.3% (95% CI 84.1%-91.7%; p = .202) in per-protocol analysis. History of antibiotics use in 2 years reduced eradication effect in group B (ESO 40 mg Bid, AMX 1 g Tid). The modified intention-to-treat eradication rates were 81.4% vs 90.0% among those with or without a history of antibiotics use in group B (p = .031). The adverse event rates were 13.7%, 12.7%, and 12.1% in groups A, B, and C, respectively (p = .834). Patient compliance of the three groups was similar. CONCLUSIONS: Two optimized AMX and PPI dual regimens (ESO 40 mg Bid or 20 mg Tid plus AMX 1 g Tid for 14 days) had similar efficacy, safety and compliance as compared with classical dual regimen (ESO 20 mg plus AMX 750 mg Qid for 14 days) in H. pylori-infected treatment-naive patients.

Relationship of the methanol production, pectin and pectinase activity during apple wine fermentation and aging.

Understanding pectin structure and pectinase activity was important to control methanol content in apple wine. Therefore, this study compared inoculated fermentation (I), spontaneous fermentation (S) and inoculated fermentation combined with CaCl2 treatment (I & CaCl2) to explore their differences in methanol production, pectin peak molecular weight (Mp), and the activities of pectin methyl esterase (PME), pectin lyase (PL) and polygalacturonase (PG). The results showed that the activities of PME, PL and PG were intensively inhibited during fermentation; however, they still retained 3.41-5.84% (PME), 9.46-17.71% (PL) and 9.17-10.31% (PG) of the initial activities after aging for 30 days. Therefore, the methanol content was increased in all three aged wines even aging at 4 °C. CaCl2 promoted the PME and PL activities, and thus accelerated the methanol production. Because the pectin with Mp 3.07 kDa was retained by CaCl2, the highest pectin content was found in wine I & CaCl2 (160.69 mg/L), which was 95.47 mg/L higher than that in wine I, and 107.03 mg/L higher than that in wine S. In group S, the long lag period allowed pectin to withstand the pectinases inherent in apple juice for a long time, which was conducive to the cleavage of pectin to Mp lower than 3 kDa continuously, its further degradation led to the lowest pectin content (53.65 mg/L) in wine. Hence, inhibiting the pectinases activities, or shortening the aging period would play an important role in decreasing the methanol content in apple wine.

Effect of bentonite and calcium chloride on apple wine.

BACKGROUND: Apple wine is a popular alcoholic beverage for its nutrition and fresh taste. However, the methanol existing in apple wine restricts its quality. Unfortunately, there are no methods to reduce the methanol content in fruit wine. To this end, bentonite (B), calcium chloride (CC) and their combination (B&CC) were added into apple juice in this study. The treated juice (0) and supernatant obtained by standing the juice at 25 °C for 24 h were fermented at 25 °C and 10 °C, respectively. RESULTS: Bentonite was an excellent methanol interrupter, a pectin retainer and a wine quality defender both at 25 and 10 °C. The lowest methanol content of 1.41 mg L-1 and higher pectin content of 84.74 mg L-1 were reached in the finished wine by B0 at 10 °C. Calcium chloride decreased pectin content, elevated methanol content and changed the profile of individual organic acids. In fact, the wine by B&CC0 at 25 °C showed dramatic changes in individual organic acids. The content of l-malic acid and succinic acid was only 2.22% and 6.29% of the control, respectively, while the lactic acid content was 17.72 times that of the control. CONCLUSIONS: It is suggested that B0 and fermented at 10 °C was the most effective way to decrease methanol content, retain pectin content and defend wine quality. © 2021 Society of Chemical Industry.

Ginkgo biloba extract in combination with sorafenib is clinically safe and tolerable in advanced hepatocellular carcinoma patients.

BACKGROUND: Sorafenib is the only therapy shown to improve overall survival in advanced hepatocellular carcinoma (HCC). However, the clinical efficacy of sorafenib is limited. Combination therapy targeting multiple signaling pathways may improve outcomes. Ginkgo biloba extract (GBE) has exhibited antitumor activity in multiple human cancers. HYPOTHESIS/PURPOSE: This study was designed to evaluate the tolerability and effectiveness of GBE combined with sorafenib in patients with advanced HCC. STUDY DESIGN: Patients with advanced HCC were treated with increasing doses of GBE in combination with sorafenib. METHODS: We first determined the maximum tolerated dose (MTD) of GBE, then the patients were treated with GBE at the MTD to evaluate its safety and efficacy. 27 patients were enrolled in the first part of our study and treated with sorafenib 400mg twice daily (BID) and increasing doses (cohort 1: 60mg, cohort 2: 120mg, cohort 3: 240mg, cohort 4: 360mg) of GBE once daily (QD). An additional group of 32 new patients next to the 27 described before were accrued for the second part of our study, and all these 32 patients were eligible for the evaluation of toxicity and efficacy. RESULTS: No patient in cohort 1 and 2 experienced a dose-limiting toxicity (DLT). One of the ten patients in cohort 3 experienced a DLT. DLT occurred in two of the three initial patients in cohort 4. Cohort 3 (GBE 240mg QD plus sorafenib 400mg BID) was considered to be the MTD. Three patients had a partial response, 21 had stable disease, and 8 had progressive disease. The median times to progression and overall survival were 2.5 and 11.6 months, respectively. Compared with previous study, the toxicities of the combination therapy were similar with those observed in sorafenib monotherapy, GBE in combination with sorafenib slightly improved OS. CONCLUSIONS: The combination of GBE (240mg QD) and standard dose sorafenib (400mg BID) is safe and tolerable among patients with advanced HCC. Early signs of antitumor activity may warrant further development of this combination.

Qualitative and quantitative analysis of triterpene saponins from tea seed pomace (Camellia oleifera Abel) and their activities against bacteria and fungi.

A method using LC-ESI-IT-TOF/MS and LC/UV-ELSD was established to qualitatively analyze triterpene saponins obtained from the tea seed pomace (Camellia oleifera Abel). In addition, the quantitative analysis of oleiferasaponin A1 using LC/UV was developed. The purified total saponins did not exhibit any inhibitory effects at concentrations ranging from 0.1 to 10 mg/mL against the tested bacteria, except for Staphyloccocus aureus and Escherichia coli. By contrast, higher inhibitory activity was seen against the tested fungi, especially against Bipolaris maydis. Following treatment with an MIC value of 250 µg/mL for 24 h, the mycelial morphology was markedly shriveled in appearance or showed flattened and empty hyphae, with fractured cell walls, ruptured plasmalemma and cytoplasmic coagulation or leakage. These structural changes hindered the growth of mycelia.

A new saponin from tea seed pomace (Camellia oleifera Abel) and its protective effect on PC12 cells.

A new triterpenoid saponin, oleiferasaponin A1, was isolated from tea seed pomace (Camellia oleifera Abel). The structure of oleiferasaponin A1 was elucidated on the basis of chemical and physicochemical evidence and was found to be 22-O-cis-2-hexenoyl-A1-barrigenol 3-O-[ß-D-galactopyranosyl(1→2)] [ß-D-glucopyranosyl(1→2)-α-L-arabinopyranosyl(1→3)]-ß-D-glucopyranosiduronic acid. PC12 cells injured with H2O2 were used as the model to test the protective effects of oleiferasaponin A1. The results indicated that oleiferasaponin A1 can potentially prevent the H2O2-induced cell death of PC12 cells.

[Combination of acupoints based on the theory of qi tonification, blood regulation and strengthening the primary source].

The acupuncture technique of tonifying qi, regulating blood and strengthening the primary source of human life is established on the base of the new pathology of dementia due to dysfunction of sanjiao by Prof. HAN Jing-xian. It is held that Tanzhong (CV 17), Zhongwan (CV 12), Qihai (CV 6), Xuehai (SP 10), Zusanli(ST 36) and Waiguan (TE 5) were the basic points for treatment of dementia. There are 3 characteristics of the point combination. Firstly, emphasis should be put on regulation of the stomach and the spleen so as to promote transportation, transformation and distribution; secondly, monarch, minister, assistant and guide points should be selected on the base of meridians, and more attention should be paid to the entity and connections among organs; and thirdly, treatment should be given according to physiological functions of the viscera.

Effects of acupuncture on glycometabolic enzymes in multi-infarct dementia rats.

Acupuncture has exhibited therapeutic effects on vascular dementia in our previous research. The mechanism of its anti-dementia effects involves energy metabolism. For brain cells, glucose metabolism is almost the only source of energy, and glucose metabolism disorders are early signs of dementia. In addition, glucose metabolism associates closely with glycometabolic enzymes, thereby maintains normal energy supply in brains and neurological and mental activities. In order to investigate its anti-dementia mechanism, we studied the effects of acupuncture on behavior of multi-infarct dementia (MID) rats and glycometabolic enzymes protein expression and activities in their brains. Results showed acupuncture improved the cognitive disorder, and increased the activities of hexokinase, pyruvate kinase, and glucose 6 phosphate dehydrogenase. Accordingly, it suggests that the anti-dementia effects of acupuncture may be mediated by up regulation of hexokinase, pyruvate kinase, and glucose 6 phosphate dehydrogenase activities, influencing energy metabolic system and thus overcoming the dysfunctional cognition of MID.

[Survival benefit of an herbal formula for invigorating spleen for elderly patients with gastric cancer].

BACKGROUND: Gastric cancer is one of the most common malignant tumors. Traditional Chinese medicine (TCM) has been widely used in treatment of gastric cancer, but still lacking large sample controlled trial to evaluate its efficacy. OBJECTIVE: To analyze the prognostic factors of 220 elderly patients with gastric cancer, and to further study the efficacy of an herbal formula for invigorating spleen and it modifications based on syndrome differentiation of TCM in treatment of gastric cancer in elderly patients and the influence on prognosis. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A total of 220 elderly patients aged 65 years or over with gastric cancer from Longhua Hospital of Shanghai University of Traditional Chinese Medicine, and Renji Hospital and Ruijin Hospital of Shanghai Jiao Tong University Medical College were prospectively enrolled. All patients were assigned to either traditional Chinese herbal medicine (TCHM) group (89 cases) or non-TCHM group (131 cases). Patients in the TCHM group were treated with an herbal formula for invigorating spleen plus chemotherapy, while patients in the non-TCHM group were only treated with chemotherapy. MAIN OUTCOME MEASURES: Univariate and Cox regression analyses were performed to determine all the potential prognostic factors. Kaplan-Meier curves were used to assess the differences in survival time between TCHM group and non-TCHM group after stratification for TNM stage, surgery or chemotherapy. RESULTS: The 220 eligible patients were histologically confirmed adenocarcinoma of the stomach from 2001 to 2007. Eighty-nine cases in the TCHM group received three or more months of TCHM treatment, and 131 cases in the non-TCHM group did not receive TCHM treatment. Cox regression analysis suggested that the TNM stage, radical resection, three or more treatment cycles of chemotherapy, and TCHM treatment were independent prognostic factors (P<0.01). The patients receiving TCHM treatment demonstrated better prognosis than the other prognostic factors in multivariate analysis; the odds ratio [Exp(beta)] of overall group was 0.322, and 95% confidence interval (CI) was from 0.212 to 0.489. Median overall survival of TCHM group was 41.129 months, and one-, three-, and five-year survival rates were 85.2%, 55.6% and 45.7% respectively. Median overall survival of non-TCHM group was 17.195 months, and one-, three-, and five-year survival rates were 63.9%, 26.9% and 21.9% respectively. In stratification analysis of stage for 96 patients who did not accepted radical resection or suffered from recurrence and metastasis (36 cases in the TCHM group, and 60 cases in the non-TCHM group), Cox regression analysis suggested that three or more treatment cycles of chemotherapy and TCHM treatment were independent prognostic factors for improving survival respectively (P<0.01). The hazard ratio [Exp(beta)] of TCHM in stratification for late stage was 0.421, and 95% confidence interval was from 0.255 to 0.693. Median overall survivals were 17.819 months for TCHM group and 8.548 months for non-TCHM group. In stratification analysis of surgery and chemotherapy for 102 patients with Ib-IV (M0) who accepted radical resection (R0 resection) and three or more treatment cycles of chemotherapy (33 cases in the TCHM group, and 69 cases in the non-TCHM group), the disease-free survival and overall survival did not reach the median at the time of analysis. In the TCHM group, one-, three-, and five-year disease-free survival rates were 97.0%, 59.9% and 50.4%, and one-, three-, and five-year survival rates were 100.0%, 74.1% and 61.4%, respectively. In the non-TCHM group, one-, three-, and five-year disease-free survival rates were 82.6%, 51.1% and 51.1%, and one-, three-, and five-year survival rates were 86.9%, 55.6% and 55.6%, respectively. CONCLUSION: The herbal formula for invigorating spleen has an important value for improving the prognosis of elderly patients with gastric cancer. This herbal formula show survival benefit for advanced gastric cancer in elderly patients. The influence of TCHM on disease-free survival and overall survival of postoperative gastric cancer in elderly patients need to be further evaluated.