A 71-year-old male presented with esophageal cancer and severe aortic valve regurgitation. Treatment strategies for such patients are controversial. Considering the risks of cardiopulmonary bypass and potential esophageal cancer metastasis, we successfully performed transcatheter aortic valve implantation and minimally invasive three-incision thoracolaparoscopy combined with radical resection of esophageal cancer (McKeown) simultaneously in the elderly patient who did not require neoadjuvant treatment. This dual minimally invasive procedure took 6 hours and the patient recovered smoothly without any surgical complications.

ObjectiveTo investigate the liver histopathological features of HBeAg-negative patients in the indeterminate phase of low-viral-load chronic hepatitis B virus （HBV） infection. MethodsA total of 271 patients with low-viral-load HBeAg-negative chronic HBV infection who underwent liver biopsy in Department of Infectious Diseases， Affiliated Hospital of Yan’an University， from September 2013 to June 2021 were enrolled as subjects， and the degree of liver injury was compared between patients based on age， sex， presence or absence of the family history of hepatitis B， HBsAg， and alanine aminotransferase （ALT） level. The chi-square test was used for comparison of categorical data between two groups. ResultsAmong the 271 patients with HBeAg-negative chronic HBV infection， 86 patients （31.73%） grade≥A2 liver inflammatory activity， 72 （26.57%） had a liver fibrosis stage of ive， and 112 （41.33%） had moderate or severe liver histological injury. The proportion of patients with grade≥A2 liver inflammatory activity in the patients with ALT>20 U/L was significantly higher than that in the patients with ALT≤20 U/L （χ²=3.938， P=0.047）. There were no significant differences in the proportion of patients with grade≥A2 liver inflammatory activity between the patients with different ages， sexes， family history of hepatitis B， HBsAg levels （all P>0.05），there were no significant differences in the proportion of patients with a liver fibrosis stage of ≥F2 between the patients with different ages， sexes， family history of hepatitis B， HBsAg， and ALT levels （all P>0.05）， and the stratified analysis of patients aged≤30 years and patients without the family history of hepatitis B showed no statistical significance between groups （all P>0.05）. There was no significant difference in the degree of liver histological injury between the patients with different ages， sexes， family history of hepatitis B， HBsAg， and ALT levels （all P>0.05）. ConclusionSignificant liver injury is observed in more than 40% of the patients with low-viral-load HBeAg-negative chronic HBV infection， and there is no significant difference in the degree of liver histological injury between the patients with different ages， sexes， family history of hepatitis B， HBsAg， and ALT levels. Even for the patients aged≤30 years who deny the family history of hepatitis B， there is still a considerable proportion of patients with liver injury， which should be taken seriously by clinicians.

ObjectiveTo investigate the mechanism by which Mingshi prescription regulates the retinal melanopsin-dopamine （Opn4-DA） axis in myopic mice to inhibit endoplasmic reticulum （ER） stress in the retina and sclera， thereby delaying axial elongation associated with myopia. MethodsSixty 4-week-old male SPF-grade C57BL/6J mice were randomly divided into a normal group， a form-deprived myopia group （FDM group）， an intrinsically photosensitive retinal ganglion cells ablation group （ipRGCs group）， a Mingshi Prescription group （MSF group， 5.2 g·kg^-1）， and an ipRGCs + MSF group （5.2 g·kg^-1）. Except for the normal group， all other groups underwent FDM modeling. Additionally， the ipRGCs and ipRGCs + MSF groups received retinal ipRGC ablation. Three weeks after modeling， the MSF and ipRGCs + MSF groups were administered Mingshi prescription via continuous gavage for six weeks. After refraction and axial length were measured in all mice， eyeballs were collected along with retinal and scleral tissues. Pathological and morphological changes in the retina， choroid， and sclera were observed using periodic acid-Schiff （PAS） staining. Western blot was employed to detect the relative protein expression levels of dopamine D1 receptor （DRD1）， C/EBP homologous protein （CHOP）， and glucose-regulated protein 78 （GRP78） in the retina， and CHOP and GRP78 in the sclera. Real-time PCR was used to detect the relative mRNA expression of Opn4， CHOP， and GRP78 in the retina， and CHOP and GRP78 in the sclera. Immunofluorescence staining （IF） was performed to detect the expression of Opn4 and DRD1 in retinal tissues. ResultsCompared with the normal group， the FDM group showed a significant myopic shift in refraction （P<0.05） and a significant increase in axial length （P<0.05）. The retinal layers were thinner， the number of ganglion cells was reduced， and collagen fibers in the sclera were loosely arranged with evident gaps. Opn4 and DRD1 protein and mRNA expression in the retina were significantly decreased （P<0.05）， while CHOP and GRP78 protein and mRNA expression in both retinal and scleral tissues were significantly increased （P<0.05）. Compared with the FDM group， the ipRGCs group exhibited further increases in myopic refraction and axial length （P<0.05）， more pronounced thinning and looseness in the retinal， choroidal， and scleral layers， lower expression of Opn4 and DRD1 protein and mRNA in the retina （P<0.05）， and higher expression of CHOP and GRP78 protein and mRNA in the retina and sclera （P<0.05）. Compared with the FDM group， the MSF group showed significantly reduced refractive error and axial length （P<0.05）， with improved cellular number， arrangement， and thickness in ocular tissues， increased Opn4 and DRD1 protein and mRNA expression in the retina （P<0.05）， and reduced CHOP and GRP78 protein and mRNA expression in both retina and sclera （P<0.05）. Similarly， the ipRGCs + MSF group showed significant improvements in terms of the above items compared with the ipRGCs group （P<0.05）. ConclusionMingshi Prescription delays myopic axial elongation and refractive progression by regulating the Opn4-DA axis in the retina of myopic mice， thereby inhibiting ER stress in the retina and sclera. This intervention promotes Qi and blood nourishment of the eyes， softens the fascia， and restores ocular rhythm.

OBJECTIVE To analyze the influential factors on trough concentration （cmin） and area under the drug concentration time curve （AUC） of voriconazole （VRZ） in pediatric patients with thalassemia undergoing hematopoietic stem cell transplantation （HSCT）. METHODS A total of 60 pediatric patients with thalassemia undergoing HSCT who used VRZ for prevention or treatment of invasive fungal infection were collected in our hospital from January 2021 to January 2024. The plasma concentration of VRZ was measured by high-performance liquid chromatography and the AUC was calculated. The factors affecting cmin and AUC of VRZ were analyzed using multiple linear regression. RESULTS A total of 120 cases of VRZ cmin in 60 pediatric patients was obtained and 27 cases of VRZ AUC in 26 pediatric patients were obtained. The median concentration of VRZ cmin was 0.31 mg/L； 46 cases had a cmin in 0.5-5 mg/L（ 38.33%）， 2 cases had a cmin＞5 mg/L（ 1.67%）， and 72 cases had a cmin＜0.5 mg/L. The median AUC of VRZ was 11.68 mg·h/L. The patient’s body weight， HSCT postoperative days， lymphocyte count， and combined use of phenytoin sodium， tacrolimus or cyclosporine had significant effects on VRZ cmin （P＜0.05）. Lymphocyte count and combined use of phenytoin sodium had significant effects on VRZ AUC （P＜0.05）. CONCLUSIONS The body weight， HSCT postoperative days， lymphocyte count， and combined use of phenytoin sodium， tacrolimus or cyclosporine are independent factors affecting VRZ cmin. Lymphocyte count and combined use of phenytoin sodium are independent factors affecting VRZ AUC.

Objective:To analyze the clinical characteristics of HBeAg-negative chronic hepatitis B virus (HBV) infection in indeterminate phase with a low viral load.Methods:One hundred and thirty-nine cases with persistent normal alanine aminotransferase (ALT) and HBeAg-negative chronic HBV infection with low viral load who visited the Department of Infectious Diseases of the Affiliated Hospital of Yan'an University from September 2013 to July 2021 were retrospectively collected. Patients were divided into low hepatitis B surface antigen (HBsAg) group ( n=59) and high HBsAg group ( n=80) according to the baseline hepatitis B surface antigen (HBsAg) level. The changes of various indicators at baseline and follow-up endpoints were analyzed between the two groups. The rate of HBsAg decrease ≥0.5 log 10IU/ml, HBV DNA negative conversion rate, ALT persistently normal rate, and liver stiffness measurement (LSM) persistently normal rate at the end of the follow-up were compared. The t-test, or non-parametric Mann-Whitney U test, and Wilcoxon signed rank test were used for comparison of continuous data between the two groups. The χ2 test, or Fisher's exact probability method, was used for comparing count data between the two groups. Results:There were statistically significant differences in age, gender, and HBsAg at baseline, but there was no statistically significant difference in terms of family history of hepatitis B, follow-up time, anti-HBe, anti-HBc, HBV DNA, ALT, aspartate aminotransferase (AST), albumin (Alb), and LSM between the two groups. There were statistically significant differences in HBsAg, anti-HBc, and ALT levels before and after follow-up in the low HBsAg group, but no statistically significant differences in anti-HBe, HBV DNA, AST, Alb, and LSM levels. There were statistically significant differences in HBsAg and anti-HBc before and after follow-up in the high HBsAg group, but no statistically significant differences in anti-HBe, HBV DNA, ALT, AST, Alb, and LSM. A liver biopsy was performed in 66 patients during follow-up, and 27.27% of the patients had moderate liver damage. In the low HBsAg group, 45.76% of patients had a HBsAg decrease rate of ≥0.5 log 10IU/ml, 10.17% of patients had HBV DNA negative conversion, 88.14% of patients had a persistently normal ALT, and 96.61% of patients had a persistently normal LSM at the end of follow-up. In the high HBsAg group, 3.75% of patients had a HBsAg decrease of ≥0.5 log 10IU/ml, no patient had a HBV DNA negative conversion, 90% of patients had a persistently normal ALT, and 98.75% of patients had a persistently normal LSM. There were statistically significant differences in the HBsAg decrease rate (45.76% vs. 3.75%, χ2=32.975, P＜0.001) and HBV DNA negative conversion rate (10.17% vs. 0, χ2=6.219, P=0.013) between the two groups at the end of follow-up, but there were no statistically significant differences in the persistently normal ALT and LSM rates. Conclusion:The vast majority of patients with HBeAg-negative chronic HBV infection in the indeterminate phase with low viral load had persistent hypoviremia over the long term. Some patients have liver tissue damage and may progress to cirrhosis and liver cancer as a result of HBV DNA positivity, so antiviral treatment should be initiated in all.

Objective:To investigate the immunophenotypic and molecular biological characteristics of patients with elevated serum alpha-fetoprotein (AFP) and enteroblastic differentiated gastric adenocarcinoma (GAED).Methods:The clinicopathological data of 13 patients with elevated serum AFP and GAED admitted to Shanxi Cancer Hospital from 2018 to 2020 were collected. Immunohistochemistry (IHC) and next-generation sequencing (NGS) were used to analyze the immune markers and molecular biological characteristics of the pathological tissues of the patients. Kaplan-Meier method and log rank test were used for survival analysis.Results:Among the 13 patients with GAED, 12 were male and 1 was female, aged 41-70 years, with a median age of 64 years. The lesions were mainly located in the gastric antrum (5 cases) and gastric body (4 cases). IHC results showed that the tumor embryonic protein (AFP, SALL4, GPC3), intestinal epithelial differentiation protein (CDX-2, CD10), and some original intestinal epithelial phenotype markers (OCT3/4, Claudin6) were expressed in the tumor tissues. Combined application of multiple markers can reduce the rate of missed diagnosis. Among the 13 patients, 12 had at least one mutation (1 mutation: 1 case, 2-5 mutations: 3 cases, 6-15 mutations: 8 cases), and 1 case was not detected. The gene with the highest mutation frequency was TP53 (10 cases), and other mutant genes included EPHB1 (3 cases), ATRX (2 cases), EPHA5 (2 cases), GATA3 (2 cases), LRP1B (2 cases) and MAP2K4 (2 cases) were also detected. Three of the 13 patients had structural variations, which were C14orf177- GNAS, AIM1- FGFR3, and EPHA6- ROS1 gene rearrangements. All 13 patients had copy number variation, and 11 patients had copy number variation of more than 2 genes. The common amplification genes were IRS2 (5 cases), PTEN (5 cases), GNAS (4 cases), CCNE1 (3 cases), CEBPA (3 cases), PCK1 (3 cases) and ERBB2 (2 cases). The common deletion genes were SOX2 (5 cases) and MYC (5 cases). Among the 13 patients, 4 died, and 2 of the dead patients had liver metastasis. There were 4 patients with disease-free survival and 5 patients with disease progression, including 3 cases of abdominal metastasis and 2 cases of liver metastasis. The 3-year survival rate of patients was 65.9 %, and the 3-year progression-free survival rate was 30.7 %. Gene LRP1B point mutation was associated with poor prognosis ( P＜0.001). There was no significant improvement in the prognosis of patients treated with immunotherapy compared with those treated with chemotherapy alone ( P=0.595), but the prognosis of patients treated with postoperative chemotherapy or postoperative chemotherapy plus immunotherapy was better than that of patients treated with surgery alone ( P＜0.05). Conclusions:Elevated serum AFP with GAED is a highly invasive tumor with unique molecular characteristics, often accompanied by multiple molecular events. TP53 mutation is the most common type of gene mutation. In addition, some cases are accompanied by HER2 amplification and gene rearrangement.

Objective:To investigate the immunophenotypic and molecular biological characteristics of patients with elevated serum alpha-fetoprotein (AFP) and enteroblastic differentiated gastric adenocarcinoma (GAED).Methods:The clinicopathological data of 13 patients with elevated serum AFP and GAED admitted to Shanxi Cancer Hospital from 2018 to 2020 were collected. Immunohistochemistry (IHC) and next-generation sequencing (NGS) were used to analyze the immune markers and molecular biological characteristics of the pathological tissues of the patients. Kaplan-Meier method and log rank test were used for survival analysis.Results:Among the 13 patients with GAED, 12 were male and 1 was female, aged 41-70 years, with a median age of 64 years. The lesions were mainly located in the gastric antrum (5 cases) and gastric body (4 cases). IHC results showed that the tumor embryonic protein (AFP, SALL4, GPC3), intestinal epithelial differentiation protein (CDX-2, CD10), and some original intestinal epithelial phenotype markers (OCT3/4, Claudin6) were expressed in the tumor tissues. Combined application of multiple markers can reduce the rate of missed diagnosis. Among the 13 patients, 12 had at least one mutation (1 mutation: 1 case, 2-5 mutations: 3 cases, 6-15 mutations: 8 cases), and 1 case was not detected. The gene with the highest mutation frequency was TP53 (10 cases), and other mutant genes included EPHB1 (3 cases), ATRX (2 cases), EPHA5 (2 cases), GATA3 (2 cases), LRP1B (2 cases) and MAP2K4 (2 cases) were also detected. Three of the 13 patients had structural variations, which were C14orf177- GNAS, AIM1- FGFR3, and EPHA6- ROS1 gene rearrangements. All 13 patients had copy number variation, and 11 patients had copy number variation of more than 2 genes. The common amplification genes were IRS2 (5 cases), PTEN (5 cases), GNAS (4 cases), CCNE1 (3 cases), CEBPA (3 cases), PCK1 (3 cases) and ERBB2 (2 cases). The common deletion genes were SOX2 (5 cases) and MYC (5 cases). Among the 13 patients, 4 died, and 2 of the dead patients had liver metastasis. There were 4 patients with disease-free survival and 5 patients with disease progression, including 3 cases of abdominal metastasis and 2 cases of liver metastasis. The 3-year survival rate of patients was 65.9 %, and the 3-year progression-free survival rate was 30.7 %. Gene LRP1B point mutation was associated with poor prognosis ( P＜0.001). There was no significant improvement in the prognosis of patients treated with immunotherapy compared with those treated with chemotherapy alone ( P=0.595), but the prognosis of patients treated with postoperative chemotherapy or postoperative chemotherapy plus immunotherapy was better than that of patients treated with surgery alone ( P＜0.05). Conclusions:Elevated serum AFP with GAED is a highly invasive tumor with unique molecular characteristics, often accompanied by multiple molecular events. TP53 mutation is the most common type of gene mutation. In addition, some cases are accompanied by HER2 amplification and gene rearrangement.

Objectives:To investigate the mutation of PIK3CA in colorectal cancer and to analyze their clinicopathological features, and evaluate their role in clinical treatment and prognostication.Methods:A total of 128 paraffin-embbeded tissue samples of colorectal cancer from Shanxi Cancer Hospital from 2018 to 2021 were collected. DNA was extracted from the samples, and next-generation sequencing (NGS) was used to detect PIK3CA mutation. The relationship between PIK3CA mutation, their clinicopathological features, and prognosis were analyzed.Results:Among the 128 colorectal cancer samples, there were 75 males and 53 females; with aged range 32-86 years, median 61.5 years, 27 (21.09%) had PIK3CA mutations. Colorectal cancer with PIK3CA mutation was more likely to occur in male patients ( P=0.007), which was related to tumor site ( P=0.032), tumor size ( P=0.029) and TP53 wild-type ( P=0.001). The common site mutations of PIK3CA mostly occurred in tumors with tumor mutation burden≥10 Muts/Mb ( P=0.031).PIK3CA mutation had no significant effect on the survival prognosis of patients, but the efficacy of anti-angiogenic therapy was poor in these patients. Conclusions:PIK3CA mutation is a common mutation in colorectal cancer and plays an important role in the occurrence and development of colorectal cancer. PIK3CA mutation may lead to resistance to anti-angiogenic drugs in colorectal cancer, but its impact on survival and prognosis to patients needs further study.

Objective:To explore the effect of health education based on symptom management strategy on the psychological status, self-management ability and quality of life of maintenance hemodialysis patients.Methods:A randomized controlled trial method was used. One hundred and fifty hemodialysis maintenance patients in the Blood Purification Center, Jinan People's Hospital from August 2019 to August 2020, were selected as the research subjects by convenience sampling. Patients were divided into a control group and observation group by random number table method, with 75 cases in each group. The control group was given routine health education, and the observation group was given health education based on symptom management strategies. Self-rating Anxiety Scale (SAS), self-rating Depression Scale (SDS), self-management ability scale of dialysis patients, and SF-36 quality of life scale were used to compare the improvement of negative emotion, self-management ability, and quality of life in the two groups.Results:There was no statistically significant difference between the control group and the observation group before the intervention (all P>0.05). After 3 months of intervention, the SAS and SDS scores of the patients in the observation group were (36.42 ± 4.09) and (35.74 ± 3.64) respectively, which were lower than those of the control group (46.37 ± 4.64) and (49.38 ± 2.49). The difference was statistically significant ( t=8.46, 9.42, P<0.05); the self-management score of patients in the observation group (80.11 ± 7.83) was higher than that in the control group (47.21 ± 6.62), with a statistically significant difference ( t=32.29, P<0.05); the total score of SF-36 quality of life in the observation group (594.32 ± 35.03) was higher than that in the control group (501.42 ± 32.78),with a statistically significant difference ( t=24.66, P<0.05). Conclusions:Health education based on symptom management strategy can improve the psychological status of maintenance hemodialysis patients, and has important value in improving their self-management ability and quality of life.

Objective:To explore the effects of graded nutritional nursing based on Prognostic Nutritional Index (PNI) in patients with cervical cancer undergoing concurrent chemoradiotherapy.Methods:Totally 414 patients with cervical cancer who were treated in Henan Cancer Hospital from December 2020 to December 2021 were selected by convenience sampling, and they were randomly divided into the study group and the control group according to the random number table, with 207 patients in each group. All patients received the same concurrent chemoradiotherapy. Patients in the control group were given nutritional nursing under the guidance of NRS2002, while patients in the study group were given graded nutritional nursing based on PNI. The PNI, levels of albumin (ALB) , prealbumin (PA) , transferrin (TRF) , immunoglobulin A (IgA) , immunoglobulin G (IgG) and adverse reactions were compared between the two groups.Results:Finally, 197 patients were included in the study group, and 195 patients were included in the control group. At the eighth week of treatment, the PNI of the study group was better than that of the control group, and the difference was statistically significant ( P<0.05) . In the first and third weeks of treatment, the levels of ALB, PA, TRF, IgA and IgG in the two groups gradually decreased, but the levels of ALB, PA, TRF, IgA and IgG in the study group were higher than those in the control group, and the difference was statistically significant ( P<0.01) . During concurrent chemoradiotherapy, the incidences of nausea and vomiting, enteral nutrition intolerance, bone marrow suppression, and cancer-related fatigue in the study group were lower than those in the control group, with statistically significant differences ( P<0.05) . Conclusions:PNI-based graded nutritional nursing to cervical cancer patients undergoing concurrent chemoradiotherapy can improve the nutritional status and immune level of patients and reduce the incidence of related complications.