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.

Background Mitochondrial biogenesis is pivotal in coal workers' pneumoconiosis fibrosis, yet the role of the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)-nuclear respiratory factor 1 (NRF1)-mitochondrial transcription factor A (TFAM) pathway inmitochondrial biogenesis remains elusive, warranting further investigation. Objective To elucidate the role of the PGC-1α-NRF1-TFAM pathway in mitochondrial biogenesis in a rat coal workers' pneumoconiosis model through in vivo and in vitro experiments. Methods (1)n vivo: twelve SPF male SD rats (200-220 g) were randomized into a control group and a coal dust group (n=6 per group). After acclimatization, the coal dust group received 1 mL 50 mg·mL⁻¹ coal dust suspension via intratracheal instillation; the controls received saline. Lung tissues were harvested after two months for histopathology [HE, Masson, and transmission electron microscopy (TEM) ], protein and mRNA analysis, and mitochondrial DNA (mtDNA) quantification by quantitative real-time polymerase chain reaction (qPCR). (2) In vitro: rat lung type II epithelial cells (RLE-6TN) cells were exposed to coal dust (50, 100, 200, and 400 mg·L⁻¹, 24 h). CCK-8 assay determined optimal doses. Ultrastructural changes were analyzed by TEM. Cells were transfected with OE-PGC-1α (PGC-1α overexpression) or shRNA-PGC-1α plasmids (PGC-1α knockdown), and the transfection efficiency was determined by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). The expression levels of alpah-smooth muscle actin (α-SMA), citrate synthase (CS), PGC-1α, NRF1, TFAM, and fibronectin (Fn) proteins and their corresponding mRNA were detected using Western blot and RT-qPCR, respectively. The relative content of mtDNA was determined by qPCR. Results In vivo: the control group lung samples exhibited soft, pink parenchyma, while the coal dust-exposed lungs showed blackened surfaces with soft texture. The histopathological evaluation revealed intact alveolar walls in the controls versus structural destruction, micro-nodules, and fibrotic areas in the coal dust group. After Masson staining, coal dust deposits were found surrounded by blue collagen fibers in the exposed lungs, but absent in the controls. The coal dust group displayed significant upregulation of fibrotic marker α-SMA and downregulation of mitochondrial biogenesis markers (CS, PGC-1α, NRF1, TFAM) and mtDNA compared to the controls (P<0.05). In vitro: coal dust exposure reduced cell density and induced morphological alterations. TEM revealed evenly distributed normal mitochondria in controls versus mitochondrial swelling, disrupted cristae, and reduced numbers in exposed cells. The mitochondrial biogenesis markers were elevated in the coal dust + OE-PGC-1α group compared to the coal dust + OE-NC group (P<0.05); in contrast, they were decreased in the coal dust + shRNA-PGC-1α group compared to the coal dust + shRNA-NC group (P<0.05). Compared to the control group, the expression levels of the fibrosis marker α-SMA mRNA and protein were increased in the coal dust group (P<0.05). Overexpression of PGC-1α reduced α-SMA expression, while downregulation of PGC-1α increased its expression (P<0.05). Conclusion Coal dust exposure induces mitochondrial dysfunction and pulmonary fibrosis in vivo and in vitro via the PGC-1α-NRF1-TFAM pathway dysregulation. Targeting this pathway may mitigate coal dust-induced fibrosis by restoring mitochondrial biogenesis.

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 The application effect of bedside ultrasound combined with joint movement protractor on the accurate monitoring and management of joint range of motion in extremely low birth weight infants was evaluated to reduce the incidence of secondary ectopic PICC in extremely low birth weight infants.Methods Convenience sampling was used to select 128 extremely low birth weight infants admitted to the neonatal intensive care unit of a tertiary hospital in Zhengzhou,Henan Province from February to September 2024.Among them,infants enrolled between June and September 2024 were assigned to an experimental group,while those enrolled between February and May 2024 were assigned to a control group,with 64 cases in each group.Whereas the experimental group,based on the control group,combined bedside ultrasound with a joint goniometer for precise monitoring and management of limb movement range in children with upper limb catheterization;the control group received routine prevention and management of PICC secondary displacement.After intervention,the incidence of PICC secondary displacement,the rate of PICC secondary displacement removal,the incidence of complications related to PICC secondary displacement,and the average length of stay of the infants were compared between the 2 groups.Results Ultimately,60 cases were included in each of the 2 groups.The incidence of secondary ectopic PICC in the post-intervention experimental group was 8.33％,lower of 23.33％in the control group;the extubation rate of secondary ectopic PICC was 3.33％,lower of 16.67％in the control group;the incidence of complications related to secondary ectopic PICC was 13.33％,lower of 51.67％in the control group;the average hospitalization day was 50(48,55)d,shorter of 61(55,65)d in the control group.The difference between the 2 groups was statistically significant(P＜0.05).Conclusion The combination of bedside ultrasound and joint movement protractor was used to accurately monitor and manage the range of motion of limbs in children with upper limb catheterization,which effectively guaranteed the safe position of the catheter tip and reduced the incidence of secondary ectopic complications related to PICC.It can be further promoted and applied in clinical practice.

Objective:To investigate the clinical, pathological, and molecular biological characteristics of gastric hepatoid adenocarcinoma (HAS) in order to provide reference for clinical treatment.Methods:Thirty-two patients diagnosed with hepatoid adenocarcinoma after radical gastrectomy for gastric cancer at Shanxi Cancer Hospital were included from January 2019 to December 2021. Immunohistochemistry, in situ hybridization, and next-generation sequencing (NGS) methods were used to analyze immune markers and molecular characteristics in the pathological tissues from 32 patients with HAS. Cox regression analysis and Kaplan-Meier method were used to analyze the prognostic factors of overall survival and disease-free survival.Results:Among the 32 patients with HAS, 26 were male, 6 were female; aged 28-77 years, with an median age 62.0 (53.8, 67.2) years. Fifteen cases of HAS were located in the cardia, 10 cases in the antrum, and 7 cases in the body of the stomach. The maximum diameter of the mass was 3-10 cm, and mainly ulcerative in gross. The immunohistochemistry and in situ hybridization results showed that the positive rates of AFP, SALLA4, and Glypican-3 were 68.8% (22/32), 68.8% (22/32), 78.1% (25/32), respectively; Seven patients had microsatellite status of dMMR. Two cases of HER2 gene amplification and 2 cases of EB virus positivity. The NGS results showed that HAS was often accompanied by multiple gene mutations, with 23 cases having ≥ 2 gene mutations and 6 cases having ≥10 gene mutations. The TP53 gene had the highest mutation frequency; 4 cases had genetic structural variations; 28 cases had copy number variation. In addition, there were 7 cases of MSI-H and 9 cases of TMB-H. Follow-up results showed that 12 cases died, 9 cases developed metastasis, and the shortest survival time was 5 months.Conclusions:Gastric HAS is a type of tumor with high invasiveness and poor prognosis. The combined detection of AFP, SALLA4 and Glypican-3 can improve the diagnostic rate of tumors. dMMR/MSI-H and TMB-H patients in HAS are significantly higher than those in ordinary gastric cancer, and the high frequency mutation genes in HAS are often accompanied by multiple potential therapeutic targets. Immunotherapy combined with chemotherapy and targeted therapy are expected to become the treatment direction of HAS.

The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Humans ; Malocclusion, Angle Class III/classification* ; Orthodontics, Corrective/methods* ; Consensus ; Child

Objective:This study aimed to evaluate the effects of hypertensive disorders of pregnancy (HDP), including their clinical subtypes, on neonatal heel blood methionine levels and explore potential dose-effect relationships.Methods:A retrospective cohort study was conducted among 11 007 singleton pregnancies and their neonates delivered at Beijing Obstetrics and Gynecology Hospital, Capital Medical University, from July 2021 to October 2022. Participants were stratified into an HDP group [ n=992; 480 with gestational hypertension, 512 with preeclampsia (including 229 severe cases)] and a non-HDP control group ( n=10 015). Methionine concentrations were measured using tandem mass spectrometry from heel blood dried filter paper samples collected within 72 hours post-delivery. Statistical analyses included non-parametric tests to compare intergroup differences, multiple linear regression to evaluate the effects of HDP on methionine levels, and multivariate logistic regression to identify risk factors for hypermethioninemia (>50 μmol/L). Results:(1) Baseline data: Maternal age was higher in the HDP group compared to controls [33 (30-36) vs. 33 (30-35) years, Z=－2.29, P=0.022], with elevated pre-pregnancy body mass index (BMI) [23 (21-26) vs. 21 (20-23) kg/m2, Z=－17.15, P<0.001] and increased gestational hyperglycemia prevalence [26.5% (263/992) vs. 19.8% (1 986/10 015), χ2=27.95, P<0.001]. (2) Methionine level: Neonates in the HDP group exhibited higher methionine levels [25.96 (21.58-30.89) vs. 24.77 (20.45-29.53) μmol/L, Z=－5.26, P<0.001], with a severity-dependent gradient: gestational hypertension [25.83 (21.77-30.61)], preeclampsia [26.05 (21.23-31.11)], and severe preeclampsia [26.15 (21.25-32.13)] ( Z=2.97, 3.92, 2.26; all P<0.05). Trend analysis confirmed a dose-effect relationship between HDP and neonatal methionine ( χ2=7.82, P=0.005). (3) Multivariate analysis: After adjusting for confounding factors such as maternal age and BMI, HDP remained independently associated with elevated methionine levels ( β=0.93, 95% CI: 0.47-1.40, t=3.92, P<0.001) and increased hypermethioninemia risk ( OR=2.75, 95% CI: 1.13-6.68). Subgroup analysis revealed ORs of 3.20 (95% CI: 1.07-9.57) for gestational hypertension, 3.25 (95% CI: 1.09-9.72) for preeclampsia, and 5.23 (95% CI: 1.54-17.82) for severe preeclampsia (all P<0.05). (4) Neonatal outcomes: Neonates in the HDP group had lower birth weights [3 230 (2 910-3 560) vs. 3 335 (3 070-3 600) g, Z=－7.43, P<0.001] and higher fetal growth restriction rates [10.3% (102/992) vs. 3.1% (306/10 015), χ2=136.47, P<0.001]. Conclusions:HDP demonstrates an elevation of neonatal methionine levels, correlating with disease severity, particularly in severe preeclampsia. These findings underscore the necessity for enhanced metabolic monitoring and long-term follow-up in offspring of mothers with HDP, especially those with severe preeclampsia.

Objective The application effect of bedside ultrasound combined with joint movement protractor on the accurate monitoring and management of joint range of motion in extremely low birth weight infants was evaluated to reduce the incidence of secondary ectopic PICC in extremely low birth weight infants.Methods Convenience sampling was used to select 128 extremely low birth weight infants admitted to the neonatal intensive care unit of a tertiary hospital in Zhengzhou,Henan Province from February to September 2024.Among them,infants enrolled between June and September 2024 were assigned to an experimental group,while those enrolled between February and May 2024 were assigned to a control group,with 64 cases in each group.Whereas the experimental group,based on the control group,combined bedside ultrasound with a joint goniometer for precise monitoring and management of limb movement range in children with upper limb catheterization;the control group received routine prevention and management of PICC secondary displacement.After intervention,the incidence of PICC secondary displacement,the rate of PICC secondary displacement removal,the incidence of complications related to PICC secondary displacement,and the average length of stay of the infants were compared between the 2 groups.Results Ultimately,60 cases were included in each of the 2 groups.The incidence of secondary ectopic PICC in the post-intervention experimental group was 8.33％,lower of 23.33％in the control group;the extubation rate of secondary ectopic PICC was 3.33％,lower of 16.67％in the control group;the incidence of complications related to secondary ectopic PICC was 13.33％,lower of 51.67％in the control group;the average hospitalization day was 50(48,55)d,shorter of 61(55,65)d in the control group.The difference between the 2 groups was statistically significant(P＜0.05).Conclusion The combination of bedside ultrasound and joint movement protractor was used to accurately monitor and manage the range of motion of limbs in children with upper limb catheterization,which effectively guaranteed the safe position of the catheter tip and reduced the incidence of secondary ectopic complications related to PICC.It can be further promoted and applied in clinical practice.

Objective:To investigate the clinical, pathological, and molecular biological characteristics of gastric hepatoid adenocarcinoma (HAS) in order to provide reference for clinical treatment.Methods:Thirty-two patients diagnosed with hepatoid adenocarcinoma after radical gastrectomy for gastric cancer at Shanxi Cancer Hospital were included from January 2019 to December 2021. Immunohistochemistry, in situ hybridization, and next-generation sequencing (NGS) methods were used to analyze immune markers and molecular characteristics in the pathological tissues from 32 patients with HAS. Cox regression analysis and Kaplan-Meier method were used to analyze the prognostic factors of overall survival and disease-free survival.Results:Among the 32 patients with HAS, 26 were male, 6 were female; aged 28-77 years, with an median age 62.0 (53.8, 67.2) years. Fifteen cases of HAS were located in the cardia, 10 cases in the antrum, and 7 cases in the body of the stomach. The maximum diameter of the mass was 3-10 cm, and mainly ulcerative in gross. The immunohistochemistry and in situ hybridization results showed that the positive rates of AFP, SALLA4, and Glypican-3 were 68.8% (22/32), 68.8% (22/32), 78.1% (25/32), respectively; Seven patients had microsatellite status of dMMR. Two cases of HER2 gene amplification and 2 cases of EB virus positivity. The NGS results showed that HAS was often accompanied by multiple gene mutations, with 23 cases having ≥ 2 gene mutations and 6 cases having ≥10 gene mutations. The TP53 gene had the highest mutation frequency; 4 cases had genetic structural variations; 28 cases had copy number variation. In addition, there were 7 cases of MSI-H and 9 cases of TMB-H. Follow-up results showed that 12 cases died, 9 cases developed metastasis, and the shortest survival time was 5 months.Conclusions:Gastric HAS is a type of tumor with high invasiveness and poor prognosis. The combined detection of AFP, SALLA4 and Glypican-3 can improve the diagnostic rate of tumors. dMMR/MSI-H and TMB-H patients in HAS are significantly higher than those in ordinary gastric cancer, and the high frequency mutation genes in HAS are often accompanied by multiple potential therapeutic targets. Immunotherapy combined with chemotherapy and targeted therapy are expected to become the treatment direction of HAS.