Based on the traditional Chinese medicine theory that "all pain， itching， and sores are related to the heart"， this paper proposes treating recurrent aphthous ulcers from the perspective of the heart. It suggests that excessive heart fire and tissue erosion due to flaming fire in the heart meridian constitute the core pathogenesis of this condition. Hyperactive heart fire is identified as the key pathogenic factor， while heart yin deficiency， obstruction of the heart collaterals， and malnourishment of the heart spirit are considered significant contributing factors. Clinically， the treatment follows the principle of clearing heart fire as the main strategy， supplemented by nourishing yin， activating collaterals， and calming the spirit. The self-formulated Qingxin Yuchuang Formulation （清心愈疮方） serves as the base prescription， with flexible modifications incorporating the Yuyin Formulation （育阴方）， Huoxue Formulation （活血方）， and Yu'an Formulation （郁安方） to address specific syndromes involving heart yin deficiency， collateral blockage， and emotional disturbance.

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

This article summarized Professor Liu Qiquan's clinical experience in the treatment of acne from the perspective of"internal retention and stagnation of heat pathogen".Professor Liu believes that the core pathogenesis of acne lies in the internal retention and stagnation of heat pathogen,which manifests as external skin inflammation,with the primary focus being on the heat pathogen.With the pathogen inside the body,the progress of disease and syndrome is related to"toxin,depression,blood stasis and deficiency".At the same time,the disease is also closely related to the dysfunction of the five-zang organs.Professor Liu points out that"to resist the outside,one must first settle the inside",and treats acne from the five internal organs.Based on the idea of"internal retention and stagnation of heat pathogen",according to the symptoms of the patients,the comprehensive use of methods to guide the treatment,such as penetrating turbidity,removing pathogenic factors and detoxifying heat,promoting qi and dispersing stagnant heat,cooling collaterals to control blood and breaking stasis heat,and restraining qi,softening yin and supporting deficiency heat,has been proved to have a good clinical effect.One medical case was attached as evidence.

Objective:To explore the effectiveness, safety, and cost among urinary follicle-stimulating hormone (u-FSH), recombinant FSH (r-FSH)α, and r-FSHβ in the early follicular phase prolonged protocol for patients under 35 years old with normal ovarian function.Methods:It was a retrospective cohort study. Patients under 35 years old with normal ovarian function who underwent early follicular phase prolonged protocol for ovulation stimulation and using in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) for fertilization in Reproductive Health Hospital of the Third Affiliated Hospital of Zhengzhou University from January 2018 to December 2023 were recruited, including the fresh and frozen-thawed embryo transfer (FET) cycles. Patients were divided into u-FSH group, r-FSHα group, and r-FSHβ group. A total of 1 048 ovarian stimulation cycles were included, with 150 cycles, 490 cycles and 408 cycles in the three groups respectively. A total of 710 FET cycles with fresh cycle cancellation were included, with 95 cycles, 320 cycles and 295 cycles in the three groups respectively. The baseline data, pregnancy outcomes, safety, and cost were compared among the three groups. The main observation indicators were cumulative pregnancy rate and cumulative live birth rate (CLBR). A binary logistic regression model was used to control confounding factors, and to analyze the relationship between three ovulation inducing medicine and CLBR. Results:The difference in the number of oocytes retrieved among the u-FSH group, r-FSHα group, and r-FSHβ group was statistically significant [13.0 (10.0, 16.0), 14.0 (11.0, 18.0), 15.0 (11.0, 19.0), respectively, P=0.012], and the difference in the number of 2PN embryos was statistically significant [9.0 (6.0, 12.0), 10.0 (7.0, 13.0), 10.0 (7.0, 13.0), respectively, P=0.046]. There were no statistically significant differences in the number of available embryos, available embryo rate, the number of high-quality embryos, high-quality embryo rate, available blastocyst formation rate, fresh cycle clinical pregnancy rate, live birth rate in fresh cycle, cumulative pregnancy rate of frozen embryos with fresh cycle cancellation, CLBR of frozen embryos with fresh cycle cancellation, cumulative clinical pregnancy rate, CLBR, moderate to severe ovarian hyperstimulation syndrome incidence, ectopic pregnancy rate, multiple pregnancy rate and neonatal malformation rate among the three groups (all P>0.05). In terms of economy, the u-FSH group had the lowest total gonadotropin cost for each patient, while the r-FSHα group had the highest. The differences among the three groups were statistically significant [u-FSH group 4 429.08 (3 198.78, 5 044.23) yuan, r-FSHα group 6 023.72 (5 433.75, 7 529.65) yuan, r-FSHβ group 5 480.00 (4 550.90, 6 437.86) yuan, P<0.001]. Binary logistic regression analysis was conducted, using u-FSH as a control. The CLBR of the r-FSHα group and r-FSHβ group showed no statistically significant difference compared with the u-FSH group (a OR=0.95, 95% CI: 0.57-1.58, P=0.838; a OR=0.89, 95% CI: 0.54-1.48, P=0.654). Conclusion:For patients under 35 years old with normal ovarian function undergoing long protocol ovarian stimulation, the effectiveness and safety of the three ovarian-stimulating medicine are similar, but u-FSH has economic advantages.

Objective:To explore the effectiveness, safety, and cost among urinary follicle-stimulating hormone (u-FSH), recombinant FSH (r-FSH)α, and r-FSHβ in the early follicular phase prolonged protocol for patients under 35 years old with normal ovarian function.Methods:It was a retrospective cohort study. Patients under 35 years old with normal ovarian function who underwent early follicular phase prolonged protocol for ovulation stimulation and using in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) for fertilization in Reproductive Health Hospital of the Third Affiliated Hospital of Zhengzhou University from January 2018 to December 2023 were recruited, including the fresh and frozen-thawed embryo transfer (FET) cycles. Patients were divided into u-FSH group, r-FSHα group, and r-FSHβ group. A total of 1 048 ovarian stimulation cycles were included, with 150 cycles, 490 cycles and 408 cycles in the three groups respectively. A total of 710 FET cycles with fresh cycle cancellation were included, with 95 cycles, 320 cycles and 295 cycles in the three groups respectively. The baseline data, pregnancy outcomes, safety, and cost were compared among the three groups. The main observation indicators were cumulative pregnancy rate and cumulative live birth rate (CLBR). A binary logistic regression model was used to control confounding factors, and to analyze the relationship between three ovulation inducing medicine and CLBR. Results:The difference in the number of oocytes retrieved among the u-FSH group, r-FSHα group, and r-FSHβ group was statistically significant [13.0 (10.0, 16.0), 14.0 (11.0, 18.0), 15.0 (11.0, 19.0), respectively, P=0.012], and the difference in the number of 2PN embryos was statistically significant [9.0 (6.0, 12.0), 10.0 (7.0, 13.0), 10.0 (7.0, 13.0), respectively, P=0.046]. There were no statistically significant differences in the number of available embryos, available embryo rate, the number of high-quality embryos, high-quality embryo rate, available blastocyst formation rate, fresh cycle clinical pregnancy rate, live birth rate in fresh cycle, cumulative pregnancy rate of frozen embryos with fresh cycle cancellation, CLBR of frozen embryos with fresh cycle cancellation, cumulative clinical pregnancy rate, CLBR, moderate to severe ovarian hyperstimulation syndrome incidence, ectopic pregnancy rate, multiple pregnancy rate and neonatal malformation rate among the three groups (all P>0.05). In terms of economy, the u-FSH group had the lowest total gonadotropin cost for each patient, while the r-FSHα group had the highest. The differences among the three groups were statistically significant [u-FSH group 4 429.08 (3 198.78, 5 044.23) yuan, r-FSHα group 6 023.72 (5 433.75, 7 529.65) yuan, r-FSHβ group 5 480.00 (4 550.90, 6 437.86) yuan, P<0.001]. Binary logistic regression analysis was conducted, using u-FSH as a control. The CLBR of the r-FSHα group and r-FSHβ group showed no statistically significant difference compared with the u-FSH group (a OR=0.95, 95% CI: 0.57-1.58, P=0.838; a OR=0.89, 95% CI: 0.54-1.48, P=0.654). Conclusion:For patients under 35 years old with normal ovarian function undergoing long protocol ovarian stimulation, the effectiveness and safety of the three ovarian-stimulating medicine are similar, but u-FSH has economic advantages.

Objective This study aims to explore the application value of spectral CT and perfusion CT parameters in the pathological classification and prognostic assessment of lung cancer.Methods A total of 94 lung cancer patients confirmed by pathology at Shanghai Chest Hospital from January 2023 to November 2024 were included in the study,including 49 cases of lung adenocarcinoma(LUAD),30 cases of lung squamous cell carci-noma(LUSC),and 15 cases of small cell lung cancer(SCLC).All patients underwent spectral CT combined with perfusion scanning using a 256-slice Revolution Apex from GE.Two radiologists independently measured the spectral and perfusion parameters of the three groups of images,including spectral curve slope(K),iodine concentration in the lesion area(ICL),effective atomic number(Zeff),surface permeability(PS),and perfusion index(PI),and established a lung cancer pathological subtype discrimination prediction model based on spectral CT radiomics features.All subjects were randomly divided into a training group and a validation group at a ratio of 3∶1.The discrimination efficacy of the spectral discrimination model between different pathological subtypes and the discrimination efficacy of arterial and venous phase images were compared in multiple dimensions.The performance of the model was evaluated using the receiver operating characteristic(ROC)curve.Results Statistical analysis showed that the spectral curve slope,ICL,NIC,and Zeff of LUAD patients were significantly higher than those of LUSC and SCLC patients(P<0.05),while there were no significant differences in these parameters between LUSC and SCLC patients(P>0.05).Among the perfusion CT parameters,surface permeability(PS)showed significant differences among the three groups(P<0.05),while blood volume(BV),blood flow(BF),perfusion index(PI),time to peak(TTP),and mean transit time(MTT)did not show statistical differences.The multi-factor logistic regression model based on spectral parameters showed strong discriminatory performance:the area under the curve(AUC)of the LUAD and LUSC discrimination model was 0.806/0.77(training group/test group)in the arterial phase and 0.867/0.9(training group/test group)in the venous phase;the AUC of the LUAD and SCLC discrimination model was 0.885/0.883(training group/test group)in the arterial phase and 0.851/0.776(training group/test group)in the venous phase.Conclusion This study indicates that the multi-dimensional functional metabolic analysis indicators of spectral and perfusion CT imaging have significant value in the differential diagnosis of lung cancer pathological subtypes.The diagnostic model constructed by combining multiple spectral parameters can significantly improve the discrimination efficacy of lung adenocarcinoma,squamous cell carcinoma,and small cell lung cancer,providing precise imaging evidence for the formulation of individualized treatment plans.

Objective This study aims to explore the application value of spectral CT and perfusion CT parameters in the pathological classification and prognostic assessment of lung cancer.Methods A total of 94 lung cancer patients confirmed by pathology at Shanghai Chest Hospital from January 2023 to November 2024 were included in the study,including 49 cases of lung adenocarcinoma(LUAD),30 cases of lung squamous cell carci-noma(LUSC),and 15 cases of small cell lung cancer(SCLC).All patients underwent spectral CT combined with perfusion scanning using a 256-slice Revolution Apex from GE.Two radiologists independently measured the spectral and perfusion parameters of the three groups of images,including spectral curve slope(K),iodine concentration in the lesion area(ICL),effective atomic number(Zeff),surface permeability(PS),and perfusion index(PI),and established a lung cancer pathological subtype discrimination prediction model based on spectral CT radiomics features.All subjects were randomly divided into a training group and a validation group at a ratio of 3∶1.The discrimination efficacy of the spectral discrimination model between different pathological subtypes and the discrimination efficacy of arterial and venous phase images were compared in multiple dimensions.The performance of the model was evaluated using the receiver operating characteristic(ROC)curve.Results Statistical analysis showed that the spectral curve slope,ICL,NIC,and Zeff of LUAD patients were significantly higher than those of LUSC and SCLC patients(P<0.05),while there were no significant differences in these parameters between LUSC and SCLC patients(P>0.05).Among the perfusion CT parameters,surface permeability(PS)showed significant differences among the three groups(P<0.05),while blood volume(BV),blood flow(BF),perfusion index(PI),time to peak(TTP),and mean transit time(MTT)did not show statistical differences.The multi-factor logistic regression model based on spectral parameters showed strong discriminatory performance:the area under the curve(AUC)of the LUAD and LUSC discrimination model was 0.806/0.77(training group/test group)in the arterial phase and 0.867/0.9(training group/test group)in the venous phase;the AUC of the LUAD and SCLC discrimination model was 0.885/0.883(training group/test group)in the arterial phase and 0.851/0.776(training group/test group)in the venous phase.Conclusion This study indicates that the multi-dimensional functional metabolic analysis indicators of spectral and perfusion CT imaging have significant value in the differential diagnosis of lung cancer pathological subtypes.The diagnostic model constructed by combining multiple spectral parameters can significantly improve the discrimination efficacy of lung adenocarcinoma,squamous cell carcinoma,and small cell lung cancer,providing precise imaging evidence for the formulation of individualized treatment plans.

This article summarized Professor Liu Qiquan's clinical experience in the treatment of acne from the perspective of"internal retention and stagnation of heat pathogen".Professor Liu believes that the core pathogenesis of acne lies in the internal retention and stagnation of heat pathogen,which manifests as external skin inflammation,with the primary focus being on the heat pathogen.With the pathogen inside the body,the progress of disease and syndrome is related to"toxin,depression,blood stasis and deficiency".At the same time,the disease is also closely related to the dysfunction of the five-zang organs.Professor Liu points out that"to resist the outside,one must first settle the inside",and treats acne from the five internal organs.Based on the idea of"internal retention and stagnation of heat pathogen",according to the symptoms of the patients,the comprehensive use of methods to guide the treatment,such as penetrating turbidity,removing pathogenic factors and detoxifying heat,promoting qi and dispersing stagnant heat,cooling collaterals to control blood and breaking stasis heat,and restraining qi,softening yin and supporting deficiency heat,has been proved to have a good clinical effect.One medical case was attached as evidence.

Background and aims Cancer cachexia is prevalent in various cancers and is associated with chemotherapy toxicity. However, limited data exist on the relationship between cachexia and immune-related adverse events (irAEs). The aim of this study is to explore the correlation between cancer cachexia and irAEs and its possible mechanism. Methods A murine model of orthotopic hepatocellular carcinoma (HCC) with cachexia was developed to evaluate the impact of T-cell infiltration into multiple tumor-free organs on the occurrence of irAEs. Single-cell RNA sequencing of thymic stromal cells was performed. Additionally, patients with advanced cancers receiving anti-programmed cell death protein 1/ligand 1 (PD-1/L1) antibody treatment were followed to investigate the relationship between cachexia and irAEs. Results Inflammatory cell infiltration was observed in multiple tumor-free organs of cachexic HCC mice but not in non-cachexic controls. Immunofluorescence confirmed that the infiltrating cells included CD4+ and CD8+ T cells. Morphological assessment and hematoxylin–eosin staining revealed thymic atrophy in cachexic HCC mice. Single-cell RNA sequencing of thymic stromal cells showed a reduction in medullary thymic epithelial cells (mTECs) II and III in cachexic mice. Autoimmune regulator (Aire) downregulation was accompanied by decreased expression of tissue-restricted antigens in mTECs. T cells from cachexic HCC mice induced organ-specific inflammation and T-cell infiltration in multiple organs of tumor-free mice. Following anti-mouse PD-1 antibody treatment, the incidence of inflammation in multiple organs markedly increased in cachexic HCC mice and in tumor-free mice that had received T cells from the cachexic HCC mice. Flow cytometry and immunofluorescence analyses revealed enrichment of thymic monocytic myeloid-derived suppressor cells (M-MDSCs) in cachexic HCC mice. M-MDSCs infiltrated the thymus in cachexic mice with cancer, and they induced apoptosis of mTECs from tumor-free mice in vitro via nitric oxide production. Transfer of M-MDSCs led to inflammatory cell infiltration in multiple organs and thymic involution in tumor-free mice without affecting body weight. Sixty-four patients with advanced cancer receiving anti-PD-1/L1 therapy were enrolled. Patients who developed irAEs had higher levels of circulating M-MDSCs than those who did not. Moreover, patients with cachexia (body mass index (BMI) < 20 kg/m2 or ≥5% weight loss over the past 6 months) had elevated M-MDSC levels. Patients with both high M-MDSC levels and low BMI or weight loss ≥5% experienced more irAEs (hazard ratio: 2.333; 95% confidence interval: 1.231–4.423). Conclusions M-MDSCs in cachexic mice induced mTEC apoptosis through nitric oxide production, impairing T-cell negative selection and promoting autoimmune T-cell infiltration into tumor-free organs. Cancer cachexia-related M-MDSCs may serve as predictive biomarkers for irAEs in patients with advanced cancer. Graphical abstract

Objective:To explore the genetic etiology of a child with delayed growth and development and carry out a literature review.Methods:A child suspected for Al Kaissi syndrome at the First Affiliated Hospital of Zhengzhou University on March 6, 2021 was selected as the study subject. Following extraction of genomic DNA, the child was subjected to copy number variation sequencing (CNV-seq) and whole exome sequencing (WES), and candidate variants were verified by PCR-agarose gel electrophoresis and quantitative real-time PCR (qPCR). Prenatal diagnosis was conducted on chorionic villi sample upon subsequent pregnancy.Results:The child, a 6-year-and-4-month-old boy, has dysmorphic features including low-set protruding ears and triangular face, delayed language and intellectual development, and ventricular septal defect. CNV-seq result has found no obvious abnormality, whilst WES revealed homozygous deletion of exons 1 and 2 of the CDK10 gene, which was confirmed by PCR -agarose gel electrophoresis and qPCR. Both of his parents were heterozygous carriers. Prenatal diagnosis using chorionic villi samples suggested that the fetus also carried the heterozygous deletion.Conclusion:The clinical features of Al Kaissi syndrome in this child can probably be attributed to the homozygous deletion of exons 1 and 2 of the CDK10 gene.