Background/Aims: Distal mean nocturnal baseline impedance (MNBI) measuring via pH-impedance may be valuable in diagnosing patients with suspected laryngopharyngeal reflux (LPR). However, its wide adoption is hindered by cost and invasiveness. This study investigates whether baseline impedance measured during high-resolution impedance manometry (HRIM-BI) can predict pathological MNBI. Methods: A cross-sectional study in Taiwan included 74 subjects suspected of LPR, who underwent HRIM (MMS) and pH-impedance testing (Diversatek), after stopping proton pump inhibitors for more than 7 days. Subjects with grade C or D esophagitis or Barrett’s esophagus were excluded. The cohort was divided into 2 groups: those with concomitant typical reflux symptoms (CTRS, n = 28) and those with isolated LPR symptoms (ILPRS, n = 46). HRIM-BI measurements focused on both distal and proximal esophagi. Pathological MNBI was identified as values below 2065 Ω, measured 3 cm above the lower esophageal sphincter. Results: In all subjects, distal HRIM-BI values correlated weakly with distal MNBI(r = 0.34-0.39, P < 0.005). However, in patients with ILPRS, distal HRIM-BI corelated moderately with distal MNBI(r = 0.43-0.48, P < 0.005). The areas under the receiver operating characteristic curve was 0.78 (P = 0.001) with a sensitivity of 0.83 and a specificity of 0.68. No correlation exists between distal HRIM-BI and distal MNBI in patients with CTRS, and between proximal HRIM-BI and proximal MNBI in both groups. Conclusions Distal HRIM-BI from HRIM may potentially predict pathological MNBI in patients with ILPRS, but not in those with CTRS. Future outcome studies linked to the metric are warranted.

Background/Aims: Distal mean nocturnal baseline impedance (MNBI) measuring via pH-impedance may be valuable in diagnosing patients with suspected laryngopharyngeal reflux (LPR). However, its wide adoption is hindered by cost and invasiveness. This study investigates whether baseline impedance measured during high-resolution impedance manometry (HRIM-BI) can predict pathological MNBI. Methods: A cross-sectional study in Taiwan included 74 subjects suspected of LPR, who underwent HRIM (MMS) and pH-impedance testing (Diversatek), after stopping proton pump inhibitors for more than 7 days. Subjects with grade C or D esophagitis or Barrett’s esophagus were excluded. The cohort was divided into 2 groups: those with concomitant typical reflux symptoms (CTRS, n = 28) and those with isolated LPR symptoms (ILPRS, n = 46). HRIM-BI measurements focused on both distal and proximal esophagi. Pathological MNBI was identified as values below 2065 Ω, measured 3 cm above the lower esophageal sphincter. Results: In all subjects, distal HRIM-BI values correlated weakly with distal MNBI(r = 0.34-0.39, P < 0.005). However, in patients with ILPRS, distal HRIM-BI corelated moderately with distal MNBI(r = 0.43-0.48, P < 0.005). The areas under the receiver operating characteristic curve was 0.78 (P = 0.001) with a sensitivity of 0.83 and a specificity of 0.68. No correlation exists between distal HRIM-BI and distal MNBI in patients with CTRS, and between proximal HRIM-BI and proximal MNBI in both groups. Conclusions Distal HRIM-BI from HRIM may potentially predict pathological MNBI in patients with ILPRS, but not in those with CTRS. Future outcome studies linked to the metric are warranted.

Background/Aims: Distal mean nocturnal baseline impedance (MNBI) measuring via pH-impedance may be valuable in diagnosing patients with suspected laryngopharyngeal reflux (LPR). However, its wide adoption is hindered by cost and invasiveness. This study investigates whether baseline impedance measured during high-resolution impedance manometry (HRIM-BI) can predict pathological MNBI. Methods: A cross-sectional study in Taiwan included 74 subjects suspected of LPR, who underwent HRIM (MMS) and pH-impedance testing (Diversatek), after stopping proton pump inhibitors for more than 7 days. Subjects with grade C or D esophagitis or Barrett’s esophagus were excluded. The cohort was divided into 2 groups: those with concomitant typical reflux symptoms (CTRS, n = 28) and those with isolated LPR symptoms (ILPRS, n = 46). HRIM-BI measurements focused on both distal and proximal esophagi. Pathological MNBI was identified as values below 2065 Ω, measured 3 cm above the lower esophageal sphincter. Results: In all subjects, distal HRIM-BI values correlated weakly with distal MNBI(r = 0.34-0.39, P < 0.005). However, in patients with ILPRS, distal HRIM-BI corelated moderately with distal MNBI(r = 0.43-0.48, P < 0.005). The areas under the receiver operating characteristic curve was 0.78 (P = 0.001) with a sensitivity of 0.83 and a specificity of 0.68. No correlation exists between distal HRIM-BI and distal MNBI in patients with CTRS, and between proximal HRIM-BI and proximal MNBI in both groups. Conclusions Distal HRIM-BI from HRIM may potentially predict pathological MNBI in patients with ILPRS, but not in those with CTRS. Future outcome studies linked to the metric are warranted.

The v-Raf murine sarcoma viral oncogene homolog B (BRAF) gene is one of the most critical proto-oncogenes and functions as a key regulator in the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway. The incidence of BRAF mutations in non-small cell lung cancer (NSCLC) patients ranges from 1.5% to 5.5%, with BRAF V600 mutations accounting for approximately 30%-50% of all BRAF mutations, among which BRAF V600E represents the most prevalent mutation type. Currently, the combination of Dabrafenib and Trametinib has been recommended as first-line therapy for BRAF V600-mutant NSCLC by multiple domestic and international guidelines including National Comprehensive Cancer Network (NCCN), European Society of Medical Oncology (ESMO), and Chinese Society of Clinical Oncology (CSCO). However, there are no clear targeted treatment recommendations for BRAF non-V600 mutations. Although case reports suggest that Dabrafenib combined with Trametinib may be effective for patients with BRAF non-V600 mutations, the efficacy and safety require further validation due to limited sample size and lack of large-scale clinical trial data. This article reports a case of NSCLC with a rare BRAF insertion and deletion mutation that responded well to the treatment of Dabrafenib in combination with Trametinib, aiming to enhance clinicians' understanding of such NSCLC cases with extremely rare mutation and provide a reference for future treatment strategies.
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Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Imidazoles/administration & dosage* ; Lung Neoplasms/pathology* ; Mutation ; Neoplasm Metastasis ; Oximes/administration & dosage* ; Proto-Oncogene Mas ; Proto-Oncogene Proteins B-raf/genetics* ; Pyridones/administration & dosage* ; Pyrimidinones/administration & dosage*

The purpose of this survey was to understand the occurrence of hypocalcemia in dairy cows in large-scale pasture and its relationship with production performance,disease and culling.Eighty-one large-scale pastures were selected in China to carry out a questionnaire survey on the lactation performance,reproductive performance,disease status and culling situations of dairy cows,and analyzed the production data of dairy farms by SPSS software.The survey results show that the incidence of hypocalcemia in dairy cows in pasture was different,the subclinical type was nearly twice as high as the clinical type,and the incidence rate of hypocalcemia was higher in about 30％of pasture.Hypocalcemia has no obvious effect on the lactation performance of dairy cows on dairy farms.However,a high incidence rate can reduce the conception rate,increase the incidence of subclinical mastitis,ketosis,and other common internal diseases,and raise the annual culling rate and culling rate of adult cows.Clinical,subclinical and total incidence of hypocalcemia have differ-ent effects on reproduction and diseases such as mastitis and ketosis,but clinical hypocalcemia is more harmful.Hypocalcemia is still an important metabolic disease that harms the health and pro-duction of dairy cows in large-scale pastures in China.For farms with a high incidence rate,it is recommended to conduct regular monitoring of blood calcium levels in dairy cows before and after calving,and to conduct in-depth investigations into the related pathogenic factors.This will provide a scientific basis for improving the prevention measures for hypocalcemia,reducing the incidence of the disease,increasing reproductive efficiency,and reducing culling rates.

To clarify the current situation of ketosis in dairy cattle on large-scale pastures in China and provide new insights,a questionnaire survey was conducted to analyze the incidence,preven-tion,treatment methods,and associated costs of ketosis in 79 large-scale pastures.The results showed that the average incidence of ketosis in dairy cows was 3.97％,with a cure rate of 92.40％.The order of importance of methods for preventing and controlling ketosis was as follows:feed for-mulation optimization＞blood ketone monitoring＞negative energy balance monitoring＞feed in-take monitoring＞milk yield monitoring.The most important treatment methods are intravenous glucose＞propylene glycol butyl phosphate＞vitamins＞choline.The most important diagnostic methods are blood ketone testing＞milk ketone testing＞negative energy balance testing＞clinical symptoms＞blood glucose testing.Economic analysis revealed that treatment costs were lower on larger farms and higher milk yields farms.Continuous optimization of feeding management,preven-tion,and control measures should be implemented on large-scale farms in China to reduce the oc-currence of ketosis in dairy cows.Additionally,more effective diagnostic and treatment methods should be employed to improve the cure rate and overall farm income.

To clarify the current situation of ketosis in dairy cattle on large-scale pastures in China and provide new insights,a questionnaire survey was conducted to analyze the incidence,preven-tion,treatment methods,and associated costs of ketosis in 79 large-scale pastures.The results showed that the average incidence of ketosis in dairy cows was 3.97％,with a cure rate of 92.40％.The order of importance of methods for preventing and controlling ketosis was as follows:feed for-mulation optimization＞blood ketone monitoring＞negative energy balance monitoring＞feed in-take monitoring＞milk yield monitoring.The most important treatment methods are intravenous glucose＞propylene glycol butyl phosphate＞vitamins＞choline.The most important diagnostic methods are blood ketone testing＞milk ketone testing＞negative energy balance testing＞clinical symptoms＞blood glucose testing.Economic analysis revealed that treatment costs were lower on larger farms and higher milk yields farms.Continuous optimization of feeding management,preven-tion,and control measures should be implemented on large-scale farms in China to reduce the oc-currence of ketosis in dairy cows.Additionally,more effective diagnostic and treatment methods should be employed to improve the cure rate and overall farm income.

The purpose of this survey was to understand the occurrence of hypocalcemia in dairy cows in large-scale pasture and its relationship with production performance,disease and culling.Eighty-one large-scale pastures were selected in China to carry out a questionnaire survey on the lactation performance,reproductive performance,disease status and culling situations of dairy cows,and analyzed the production data of dairy farms by SPSS software.The survey results show that the incidence of hypocalcemia in dairy cows in pasture was different,the subclinical type was nearly twice as high as the clinical type,and the incidence rate of hypocalcemia was higher in about 30％of pasture.Hypocalcemia has no obvious effect on the lactation performance of dairy cows on dairy farms.However,a high incidence rate can reduce the conception rate,increase the incidence of subclinical mastitis,ketosis,and other common internal diseases,and raise the annual culling rate and culling rate of adult cows.Clinical,subclinical and total incidence of hypocalcemia have differ-ent effects on reproduction and diseases such as mastitis and ketosis,but clinical hypocalcemia is more harmful.Hypocalcemia is still an important metabolic disease that harms the health and pro-duction of dairy cows in large-scale pastures in China.For farms with a high incidence rate,it is recommended to conduct regular monitoring of blood calcium levels in dairy cows before and after calving,and to conduct in-depth investigations into the related pathogenic factors.This will provide a scientific basis for improving the prevention measures for hypocalcemia,reducing the incidence of the disease,increasing reproductive efficiency,and reducing culling rates.

Objective To investigate the efficacy of bevacizumab combined with raltitrexed in the treatment of unresectable hepatocellular carcinoma(HCC)and its effect on adverse reactions and survival rate.Methods A retrospective analysis was performed on 71 patients with unresectable hepatocellular carcinoma admitted to the oncology department of our hospital from February 2020 to June 2022.Among them,35 cases were treated with raltitrexed as control group,and 36 cases were treated with bevacizumab combined with raltitrexed as observation group.All patients received transcatheter arterial chemoembolization(TACE).After 1 month of treatment,the short-term treatment effect of the two groups was evaluated.The adverse reactions of the two groups were observed.Follow-up review was performed to record progression free survival(PFS)and overall survival(OS)in both groups.Results After 1 month of treatment,the disease control rate(DCR)and objective response rate(ORR)of control group were 74.29%and 45.71%respectively.The DCR and ORR of observation group were 83.33%and 55.56%respectively.There was no significant difference in short-term efficacy between the two groups(P>0.05).Following treatment,the vascular endothelial growth factor(VEGF)level in the observation group was considerably lower than in the control group(P<0.05).After treatment,18 months of follow-up,OS curve showed:observation group OS was 50.00%,control group OS was 31.40%;PFS curve showed:observation group PFS was 43.33%,control group PFS was 26.92%.Using the Log-rank test,between the two groups,there was a statistically significant difference in OS(χ2=4.381,P=0.036),although there was no statistically significant difference in PFS between the two groups(χ2=3.264,P=0.071).There was no significant difference in adverse reactions between the two groups(P>0.05).Conclusion Bevacizumab combined with raltitrexed can reduce tumor neovascularization,inhibit tumor growth and spread,prolong the survival time of patients,and do not increase adverse drug reactions.

Objective: Danshensu, a phenylpropanoid compound, is derived from the dry root and rhizome of Danshen (Salvia miltiorrhiza), a traditional Chinese medicinal herb. Evidence suggests that danshensu protects isolated rat hearts against ischemia/reperfusion injury by activating the protein kinase B (Akt)/extracellular signal-regulated kinase (ERK) pathway or by inhibiting autophagy and apoptosis through the activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, danshensu promotes the postischemic regeneration of brain cells by upregulating the expression of brain-derived neurotrophic factor (BDNF) in the peri-infarct region. However, basic and clinical studies are needed to investigate the antidepressant effects danshensu and determine whether brain mTOR signaling and BDNF activation mediate these effects. The aforementioned need prompted us to conduct the present study. Methods: Using a C57BL/6 mouse model, we investigated the antidepressant-like effects of danshensu and the mechanisms that mediate these effects. To elucidate the mechanisms, we analyzed the roles of Akt/ERK–mTOR signaling and BDNF activation in mediating the antidepressant-like effects of danshensu. Results: Danshensu exerted its antidepressant-like effects by activating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) of Akt/ERK–mTOR signaling and promoting BDNF release. Treatment with danshensu increased the level of glutamate receptor 1 phosphorylation at the protein kinase A site. Conclusion Our study may be the first to demonstrate that the antidepressant effects of danshensu are dependent on the activation of the AMPAR–mTOR signaling pathway, are correlated with the elevation of BDNF level, and facilitate the insertion of AMPAR into the postsynaptic membrane. This study also pioneers in unveiling the potential of danshensu against depressive disorders.