OBJECTIVE: To explore the genetic etiology of 46 Chinese pedigrees affected with Hereditary multiple exostoses (HME) and provide genetic counseling and reproductive intervention. METHODS: Whole-exome sequencing and Sanger sequencing were carried out on 87 patients from the 46 pedigrees to analyze the variants of EXT1 and EXT2 genes. Pathogenicity of the variants was assessed based on the guidelines from the American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP). Prenatal diagnosis and preimplantation genetic testing (PGT) were provided for couples with identified pathogenic mutations. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: LL-SC-SG-2014-010). RESULTS: In total 17 and 22 pathogenic variants were respectively identified in the EXT1 and EXT2 genes, among which 5 EXT1 and 12 EXT2 variants were unreported previously. Three patients with no family history were found to harbor de novo variants of the EXT1 gene. Twenty nine couples had opted for PGT or underwent prenatal diagnosis following natural conception, and 17 healthy babies were born. CONCLUSION This study has clarified the genetic etiology of 45 HME pedigrees and identified 17 novel variants, which has enriched the mutational spectrum of the EXT1 and EXT2 genes. Reproductive intervention through PGT and prenatal diagnosis have prevented the recurrence of HME in these families.
Humans ; Female ; Male ; Pedigree ; Exostoses, Multiple Hereditary/diagnosis* ; N-Acetylglucosaminyltransferases/genetics* ; Adult ; Exostosin 1 ; Asian People/genetics* ; Genetic Testing ; Exostosin 2 ; Mutation ; China ; Prenatal Diagnosis ; Pregnancy ; Genetic Counseling ; Preimplantation Diagnosis ; Exome Sequencing ; East Asian People

Background/Aims: Reflux symptoms frequently present in patients diagnosed with functional dyspepsia (FD). This investigation sought to elucidate the contribution of gastroesophageal reflux in the overlap relationship. Methods: Consecutive patients presenting with reflux symptoms and/or FD symptoms were prospectively included. Comprehensive assessments, including symptoms evaluation, endoscopy, esophageal functional examinations (high-resolution manometry and reflux monitoring), and proton pump inhibitor (PPI) treatment efficacy evaluation, were conducted in these patients. Results: The study enrolled 315 patients, 43.2% of which had concurrent FD symptoms and overlapping reflux symptoms. Notably, a mere 28.7% of patients in the overlap symptoms group had objective gastroesophageal reflux disease evidences (the grade of esophagitis≥ B or the acid exposure time ≥ 4.2%). Functional heartburn was demonstrated to be the main cause of overlapping reflux symptoms(55.1%). Reflux parameters analysis revealed that the reflux burden in the overlap symptoms group paralleled that of the FD symptoms group, with both registering lower levels than the reflux symptoms group (P < 0.05). Furthermore, PPI response rates were notably diminished in the overlap symptoms group (P < 0.001), even for those with objective gastroesophageal reflux disease evidences. Conclusions The study illuminated that overlapping reflux symptoms in FD was common. Strikingly, these symptoms primarily diverged from reflux etiology and exhibited suboptimal responses to PPI intervention. These findings challenge prevailing paradigms and accentuate the imperative for nuanced therapeutic approaches tailored to the distinctive characteristics of overlapping reflux symptoms in the context of FD.

BACKGROUND: Huaier granule is an important medicinal fungus extract widely used in cancer treatment. Previous retrospective studies have reported its effectiveness in breast cancer patients, but the imbalanced baseline characteristics of participants could have biased the results. Therefore, this retrospective study aimed to examine the efficacy of Huaier granule on the prognosis of breast cancer patients. METHODS: In this single-center cohort study, breast cancer patients diagnosed and treated at the Guangdong Provincial Hospital of Chinese Medicine between 2009 and 2017 were selected. The data were retrospectively analyzed and divided into two groups according to whether the patients received Huaier granules. The propensity score matching (PSM) method was used to eliminate selection bias. The disease-free survival (DFS) and overall survival (OS) for these groups were compared using the Kaplan-Meier method and the Cox regression. RESULTS: This study included 214 early invasive breast cancer patients, 107 in the Huaier group and 107 in the control group. In the Kaplan-Meier analysis, the 2-year and 5-year DFS rates were significantly different in the Huaier group and control group (hazard ratio [HR], 0.495; 95% confidence interval [CI], 0.257-0.953; P = 0.023). The 2-year and 5-year OS rates were also significantly different (HR, 0.308; 95% CI, 0.148-0.644; P = 0.001). On multivariable Cox regression, Huaier granule was associated with improved DFS (HR, 0.440; 95% CI, 0.223-0.868; P = 0.018) and OS (HR, 0.236; 95% CI, 0.103-0.540; P = 0.001). CONCLUSION In this retrospective study, Huaier granules improved the DFS and OS of early invasive breast cancer patients, providing real-world evidence for further prospective studies on treating breast cancer with Huaier granules.
Humans ; Breast Neoplasms/mortality* ; Retrospective Studies ; Female ; Propensity Score ; Middle Aged ; Adult ; Prognosis ; Disease-Free Survival ; Kaplan-Meier Estimate ; Aged ; Proportional Hazards Models ; Complex Mixtures/therapeutic use* ; Drugs, Chinese Herbal/therapeutic use* ; Trametes

Background/Aims: Reflux symptoms frequently present in patients diagnosed with functional dyspepsia (FD). This investigation sought to elucidate the contribution of gastroesophageal reflux in the overlap relationship. Methods: Consecutive patients presenting with reflux symptoms and/or FD symptoms were prospectively included. Comprehensive assessments, including symptoms evaluation, endoscopy, esophageal functional examinations (high-resolution manometry and reflux monitoring), and proton pump inhibitor (PPI) treatment efficacy evaluation, were conducted in these patients. Results: The study enrolled 315 patients, 43.2% of which had concurrent FD symptoms and overlapping reflux symptoms. Notably, a mere 28.7% of patients in the overlap symptoms group had objective gastroesophageal reflux disease evidences (the grade of esophagitis≥ B or the acid exposure time ≥ 4.2%). Functional heartburn was demonstrated to be the main cause of overlapping reflux symptoms(55.1%). Reflux parameters analysis revealed that the reflux burden in the overlap symptoms group paralleled that of the FD symptoms group, with both registering lower levels than the reflux symptoms group (P < 0.05). Furthermore, PPI response rates were notably diminished in the overlap symptoms group (P < 0.001), even for those with objective gastroesophageal reflux disease evidences. Conclusions The study illuminated that overlapping reflux symptoms in FD was common. Strikingly, these symptoms primarily diverged from reflux etiology and exhibited suboptimal responses to PPI intervention. These findings challenge prevailing paradigms and accentuate the imperative for nuanced therapeutic approaches tailored to the distinctive characteristics of overlapping reflux symptoms in the context of FD.

Background/Aims: Reflux symptoms frequently present in patients diagnosed with functional dyspepsia (FD). This investigation sought to elucidate the contribution of gastroesophageal reflux in the overlap relationship. Methods: Consecutive patients presenting with reflux symptoms and/or FD symptoms were prospectively included. Comprehensive assessments, including symptoms evaluation, endoscopy, esophageal functional examinations (high-resolution manometry and reflux monitoring), and proton pump inhibitor (PPI) treatment efficacy evaluation, were conducted in these patients. Results: The study enrolled 315 patients, 43.2% of which had concurrent FD symptoms and overlapping reflux symptoms. Notably, a mere 28.7% of patients in the overlap symptoms group had objective gastroesophageal reflux disease evidences (the grade of esophagitis≥ B or the acid exposure time ≥ 4.2%). Functional heartburn was demonstrated to be the main cause of overlapping reflux symptoms(55.1%). Reflux parameters analysis revealed that the reflux burden in the overlap symptoms group paralleled that of the FD symptoms group, with both registering lower levels than the reflux symptoms group (P < 0.05). Furthermore, PPI response rates were notably diminished in the overlap symptoms group (P < 0.001), even for those with objective gastroesophageal reflux disease evidences. Conclusions The study illuminated that overlapping reflux symptoms in FD was common. Strikingly, these symptoms primarily diverged from reflux etiology and exhibited suboptimal responses to PPI intervention. These findings challenge prevailing paradigms and accentuate the imperative for nuanced therapeutic approaches tailored to the distinctive characteristics of overlapping reflux symptoms in the context of FD.

Objective:To investigate the possible targets of Shugan Jieyu capsules (SGJY) in the treatment of functional dyspepsia (FD).Methods:From January 1, 2022 to September 30, 2023, a total of 36 FD patients who visited the Department of Gastroenterology and Hepatology, the First Affiliated Hospital of Sun Yat-sen University were prospectively enrolled, and 10 healthy controls were included during the same period. The symptoms and quality of life of FD patients and healthy controls were evaluated with FD symptom scale and short form-Nepean dyspepsia index (SF-NDI), respectively, the anxiety and depression status of FD patients and healthy controls were assessed with the hospital anxiety and depression scale (HADS). The mucosal tissues of gastric fundus and descending duodenum were collected to count the numbers of eosinophils, mast cells, 5-hydroxytryptamine-positive (5-HT + ) cells and detect the expression of zonula occluden-1(ZO-1), occludin, and Claudin 2. FD patients received SGJY (0.72 g, twice daily) for 6 weeks. After treatment, a decrease in FD symptom score of >50% compared with baseline was considered as SGJY response, while a decrease of <50% was considered as SGJY non-response. Receiver operating characteristic cuve (ROC) analysis was performed to analyze and evaluate the predictive value of indicators for the response of SGJY, and Spearman rank correlation was used for correlation analysis. One-way analysis of variance, Kruskal-Wallis H test, and chi-square test were used for statistical analysis. Results:A total of 9 FD patients without anxiety or depression, and 27 FD patients with anxiety or depression were included. Among the 36 FD patients, 18 patients responded to SGJY, with a response rate 50.0%. Eleven FD patients with anxiety or depression responded to SGJY, 7 FD patients without anxiety or depression responded to SGJY. HADS scores and SF-NDI scores of FD patients with anxiety or depression were all higher than those of FD patients without anxiety or depression and healthy controls (8.7±0.7 vs. 4.0±0.6 and 3.5±0.8; 10.4±0.6 vs. 4.0±0.7 and 5.0±0.8; 29.0(22.5, 36.0) vs. 21.0 (14.0, 24.5) and 10.0 (10.0, 13.3)); and the differences were statistically significant ( F=14.50, 27.07; H=25.19; all P<0.001). The 5-HT + cell count in the descending duodenum and mast cell count in the gastric fundus and degranulation score of SGJY responders were all higher than those of SGJY non-responders and healthy controls ((65.8±4.1)/mm 2vs. (54.9±3.6) and (48.3±3.7)/mm 2, (14.0±1.2)/high power field vs. (10.5±0.7) and (9.0±1.1)/high power field, 7.5±0.5 vs. 5.7±0.4 and 3.4±0.4); and the differences were statistically significant ( F=4.38, 3.72, 12.56; all P<0.05). There were no statistically significant differences in the 5-HT + cell count in the descending duoclenum and mast cell count in the gastric fundus between non-responders and healthy controls (all P>0.05). The results of Spearman rank correlation showed that mast cell count in the gastric fundus degranulation score positively correlated with total symptom score ( r=0.636, P<0.001). In FD patients with anxiety or depression, the 5-HT + cell count in the descending duodenum and mast cell count in the gastric fundus and degranulation score of SGJY responders were higher than those of SGJY non-responders and healthy controls ((68.9±6.3)/mm 2vs. (48.0±3.4) and (56.0±4.1)/mm 2, (14.8±1.7)/high power field vs. (9.0±1.1) and (11.0±0.8)/high power field, 7.3±0.6 vs. 5.6±0.5 and 3.4±0.4); and the differences were statistically significant ( F=4.10, 5.56, 12.38; all P<0.05). The result of ROC analysis revealed that 5-HT + cell count in the descending duoclenum could predict the response to SGJY. When the cut-off value of 5-HT + cell count in the descending duoclenum was 55.12 /mm 2, the sensitivity was 82.4% and the specificity was 61.1% (area under the curve=0.700, P=0.046). Conclusion:SGJY may alleviate FD symptoms by inhibiting mast cell in the gastric fundus and regulating 5-HT + cell in the descending duoclenum.

Objective:To investigate the effect and adverse reactions of radiotherapy combined with targeted drugs for the treatment of multiple brain metastases (MBM) in patients with non-small cell lung cancer (NSCLC) and the changes in serum tumor marker levels.Methods:A retrospective cohort study was conducted. Eighty-six patients with NSCLC-MBM who were admitted to the Fifth People's Hospital of Datong from June 2019 to June 2022 were selected, and the patients were divided into the study group and the control group according to different treatment methods, with 43 cases in each group. The study group was given radiotherapy to the tumor primary focus combined with erlotinib or gefitinib targeted therapy, and the control group was given radiotherapy to the tumor primary focus based on conventional chemotherapy with pemetrexed combined with platinum-based drugs. The efficacy, overall survival rate and incidence of adverse reactions were compared between the two groups at 1 month after treatment; the levels of serum tumor markers S100-β, carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCCA) were compared between the two groups before and after treatment.Results:The study group was aged (55±5) years old, ranging from 39 to 75 years old, including 15 (34.88%) males and 28 (65.12%) females; the control group was aged (54±5) years old, ranging from 38 to 72 years old, including 17 (39.53%) males and 26 (60.47%) females. The general data such as age and gender of patients were compared between the two groups, and the differences were not statistically significant (all P>0.05). The objective remission rate [53.49% (23/43) vs. 32.56% (14/43)] and disease control rate [93.02% (40/43) vs. 69.77% (30/43)] at 1 month after treatment, and 1-year overall survival rate [58.14% (25/43) vs. 46.51% (20/43)] of the study group were higher than those of the control group, and the differences were statistically significant ( χ2 values were 10.91, 5.76 and 11.02, respectively; P values were 0.001, 0.016 and 0.001, respectively). Before treatment, the differences in serum S100-β, CEA and SCCA levels between the two groups of patients were not statistically significant (all P > 0.05). At 1 month after treatment, the serum S100-β, CEA and SCCA levels of the study group were lower than those of the control group, and the differences were statistically significant (all P < 0.05). The proportion of patients with adverse reactions in the study group was lower than that in the control group [13.95% (6/43) vs. 39.53% (17/43)], and the difference was statistically significant ( χ2 = 8.35, P < 0.05). Conclusions:Radiotherapy combined with targeted drugs therapy may prolong the survival of NSCLC-MBM patients, reduce the occurrence of adverse reactions and decrease the levels of serum tumor markers, which is worthy of clinical promotion.

Background/Aims: Abdominal bloating or distension (AB/D) is a common complaint in the outpatient of gastroenterology department. Since the potential contributors are numerous and complex, a longitudinal study on the disease spectrum and natural history of patients was performed to better understand the key factors of AB/D. Methods: Consecutive patients with the chief complaint of AB/D referred to the outpatient clinic were screened. Functional gastrointestinal disorders (FGIDs) were diagnosed according to Rome IV criteria. A 3-year follow-up was performed to seek for the changes in symptoms as well as disease spectrum. Results: A total of 261 participants were enrolled and 139 completed the follow-up. Most patients suffered from moderate to severe symptoms more than 1 day per week. Common causes of AB/D were FGIDs (51.7%) and organic diseases (17.2%). The latter group was older with lower body mass index (BMI). Functional dyspepsia was the most common type of FGIDs in AB/D. The symptoms of 18.0% of participants failed to improve at the end of the 3-year follow-up, and those diagnosed with FGIDs were most likely to continue to suffer. Abdominal pain was a positive predictive factor for good prognosis in the FGIDs group. Besides, only 22.7% of participants had a consistent diagnosis of FGIDs during follow-up. Conclusions FGIDs are the most common diagnosis in patients with AB/D. Symptoms were especially hard to be improved. Classification diagnoses of FGIDs in AB/D patients fluctuated significantly over time.

Objective:To investigate the possible targets of Shugan Jieyu capsules (SGJY) in the treatment of functional dyspepsia (FD).Methods:From January 1, 2022 to September 30, 2023, a total of 36 FD patients who visited the Department of Gastroenterology and Hepatology, the First Affiliated Hospital of Sun Yat-sen University were prospectively enrolled, and 10 healthy controls were included during the same period. The symptoms and quality of life of FD patients and healthy controls were evaluated with FD symptom scale and short form-Nepean dyspepsia index (SF-NDI), respectively, the anxiety and depression status of FD patients and healthy controls were assessed with the hospital anxiety and depression scale (HADS). The mucosal tissues of gastric fundus and descending duodenum were collected to count the numbers of eosinophils, mast cells, 5-hydroxytryptamine-positive (5-HT + ) cells and detect the expression of zonula occluden-1(ZO-1), occludin, and Claudin 2. FD patients received SGJY (0.72 g, twice daily) for 6 weeks. After treatment, a decrease in FD symptom score of >50% compared with baseline was considered as SGJY response, while a decrease of <50% was considered as SGJY non-response. Receiver operating characteristic cuve (ROC) analysis was performed to analyze and evaluate the predictive value of indicators for the response of SGJY, and Spearman rank correlation was used for correlation analysis. One-way analysis of variance, Kruskal-Wallis H test, and chi-square test were used for statistical analysis. Results:A total of 9 FD patients without anxiety or depression, and 27 FD patients with anxiety or depression were included. Among the 36 FD patients, 18 patients responded to SGJY, with a response rate 50.0%. Eleven FD patients with anxiety or depression responded to SGJY, 7 FD patients without anxiety or depression responded to SGJY. HADS scores and SF-NDI scores of FD patients with anxiety or depression were all higher than those of FD patients without anxiety or depression and healthy controls (8.7±0.7 vs. 4.0±0.6 and 3.5±0.8; 10.4±0.6 vs. 4.0±0.7 and 5.0±0.8; 29.0(22.5, 36.0) vs. 21.0 (14.0, 24.5) and 10.0 (10.0, 13.3)); and the differences were statistically significant ( F=14.50, 27.07; H=25.19; all P<0.001). The 5-HT + cell count in the descending duodenum and mast cell count in the gastric fundus and degranulation score of SGJY responders were all higher than those of SGJY non-responders and healthy controls ((65.8±4.1)/mm 2vs. (54.9±3.6) and (48.3±3.7)/mm 2, (14.0±1.2)/high power field vs. (10.5±0.7) and (9.0±1.1)/high power field, 7.5±0.5 vs. 5.7±0.4 and 3.4±0.4); and the differences were statistically significant ( F=4.38, 3.72, 12.56; all P<0.05). There were no statistically significant differences in the 5-HT + cell count in the descending duoclenum and mast cell count in the gastric fundus between non-responders and healthy controls (all P>0.05). The results of Spearman rank correlation showed that mast cell count in the gastric fundus degranulation score positively correlated with total symptom score ( r=0.636, P<0.001). In FD patients with anxiety or depression, the 5-HT + cell count in the descending duodenum and mast cell count in the gastric fundus and degranulation score of SGJY responders were higher than those of SGJY non-responders and healthy controls ((68.9±6.3)/mm 2vs. (48.0±3.4) and (56.0±4.1)/mm 2, (14.8±1.7)/high power field vs. (9.0±1.1) and (11.0±0.8)/high power field, 7.3±0.6 vs. 5.6±0.5 and 3.4±0.4); and the differences were statistically significant ( F=4.10, 5.56, 12.38; all P<0.05). The result of ROC analysis revealed that 5-HT + cell count in the descending duoclenum could predict the response to SGJY. When the cut-off value of 5-HT + cell count in the descending duoclenum was 55.12 /mm 2, the sensitivity was 82.4% and the specificity was 61.1% (area under the curve=0.700, P=0.046). Conclusion:SGJY may alleviate FD symptoms by inhibiting mast cell in the gastric fundus and regulating 5-HT + cell in the descending duoclenum.

OBJECTIVE: To explore the genetic basis for 7 families with gonadal mosaicism for Duchenne muscular dystrophy (DMD). METHODS: For the 7 families presented at the CITIC Xiangya Reproductive and Genetic Hospital from September 2014 to March 2022, clinical data were collected. Preimplantation genetic testing for monogenic disorders (PGT-M) was carried out for the mother of the proband from family 6. Peripheral venous blood samples of the probands, their mothers and other patients from the families, amniotic fluid samples from families 1 ~ 4 and biopsied cells of embryos cultured in vitro from family 6 were collected for the extraction of genomic DNA. Multiplex ligation-dependent probe amplification (MLPA) was carried out for the DMD gene, and short tandem repeat (STR)/single nucleotide polymorphism (SNP)-based haplotypes were constructed for the probands, other patients, fetuses and embryos. RESULTS: The results of MLPA showed that the probands and the fetuses/probands' brothers in families 1 ~ 4, 5, 7 had carried the same DMD gene variants, whilst the probands' mothers were all normal. The proband in family 6 carried the same DMD gene variant with only 1 embryo (9 in total) cultured in vitro, and the DMD gene of the proband's mother and the fetus obtained through the PGT-M were normal. STR-based haplotype analysis showed that the probands and the fetuses/probands' brothers in families 1 ~ 3 and 5 have inherited the same maternal X chromosome. SNP-based haplotype analysis showed that the proband from family 6 has inherited the same maternal X chromosome with only 1 embryo (9 in total) cultured in vitro. The fetuses in families 1 and 6 (via PGT-M) were both confirmed to be healthy by follow up, whilst the mothers from families 2 and 3 had chosen induced labor. CONCLUSION Haplotype analysis based on STR/SNP is an effective method for judging gonad mosaicism. Gonad mosaicisms should be suspected for women who have given births to children with DMD gene variants but with a normal peripheral blood genotype. Prenatal diagnosis and reproductive intervention may be adapted to reduce the births of further affected children in such families.
Male ; Pregnancy ; Child ; Humans ; Female ; Muscular Dystrophy, Duchenne/diagnosis* ; Dystrophin/genetics* ; Mosaicism ; Exons ; Prenatal Diagnosis/methods* ; Nucleotides