OBJECTIVE: To explore the clinical features and genetic etiology of a child with Hoyeraal-Hreidarsson syndrome (HHS). METHODS: A child with HHS diagnosed at the Affiliated Hospital of Jining Medical University due to "developmental delay and anaemia" on April 27, 2024 was selected as the study subject. Clinical data of the child was collected. Genomic DNA was extracted from peripheral blood samples of the child and his family members. Whole-exome sequencing was carried out, and candidate variant was verified by Sanger sequencing of his family members and bioinformatics analysis using CASAVA v1.8.2. The pathogenicity of the candidate variant was rated according to the Standards and Guidelines for the Interpretation of Sequence Variants released by the American College of Medical Genetics and Genomics (ACMG). Relevant literature on HHS cases reported in China was reviewed to analyze the clinical and genetic characteristics. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: 2024-10-C003). RESULTS: The child, a 7-month-old boy, had mainly manifested with growth retardation, developmental delay, microcephaly, cerebellar hypoplasia, immunodeficiency and bone marrow failure. Routine blood test indicated pancytopenia. The immunological workup showed reduction of B cells, NK cells and immunoglobulins. Cranial MRI demonstrated the volume of bilateral cerebellar hemispheres and brainstem and corpus callosum was small. Whole-exome sequencing revealed that he has harbored a hemizygous c.103_105del (p.Glu35del) variant of the DKC1 gene. Sanger sequencing showed that his mother and two sisters have carried the same variant. Based on the ACMG guidelines, the variant was predicted to be likely pathogenic (PM1+PM4+PS4_Supporting+PM2_Supporting). Four relevant literature were retrieved, which has involved 8 HHS cases. Together with the patient from this study, they have consisted of 8 males and 1 females. The most common symptoms of the 9 patients were blood system abnormalities and developmental delay. All patients had shown cerebellar dysplasia and anemia/erythrocytopenia. Among them, 3 cases have harbored TINF2 gene variants, and 6 cases had harbored DKC1 gene variants. The c.103_105del variant has not been reported in China previously. CONCLUSION The hemizygous c.103_105del (p.Glu35del) variant of the DKC1 gene probably underlay the disease in this child. Above finding has expanded the mutational and phenotypic spectra of the DKC1 gene, and has facilitated early diagnosis of HHS in this child.
Humans ; Infant ; Male ; Cell Cycle Proteins/genetics* ; Dyskeratosis Congenita/genetics* ; Exome Sequencing ; Fetal Growth Retardation/genetics* ; Intellectual Disability/genetics* ; Microcephaly/genetics* ; Mutation ; Nuclear Proteins/genetics* ; X-Linked Intellectual Disability/genetics*

Objective:To investigate microstructural alterations in the optic chiasm and optic radiations of multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) based on diffusion kurtosis imaging (DKI).Methods:This study was a cross-sectional study. Retrospective analyses were conducted on the clinical and imaging data of 63 patients with relapsing-remitting MS (RRMS) and 62 patients with NMOSD diagnosed at First Affiliated Hospital of Chongqing Medical University from January 2019 to December 2023. According to the occurrence of optic neuritis (ON), they were categorized into ON-positive MS (ON+MS) group (40 cases), ON-negative MS (ON-MS) group (23 cases), ON-positive NMOSD (ON+NMOSD) group (40 cases) and ON-negative NMOSD (ON-NMOSD) group (22 cases). In addition, 40 healthy controls were enrolled during the same period. DKI data of all subjects were collected, and DKI post-processing was performed to obtain fractional anisotropy (FA), mean kurtosis (MK), axial kurtosis (AK), and radial kurtosis (RK) values of the optic chiasm and bilateral optic radiations. The scores of the mini-mental state examination (MMSE), montreal cognitive assessment (MoCA), and expanded disability status scale (EDSS) were obtained. The Kruskal-Wallis test was used to analyze the differences in DKI parameters of the optic chiasm and bilateral optic radiation among the 5 groups, and the Holm-Bonferroni method was employed for multiple comparison correction in pairwise comparisons.Results:There were statistically significant overall differences in the DKI parameters of the optic chiasm and bilateral optic radiations among healthy control group, ON+MS group, ON-MS group, ON+NMOSD group, and ON-NMOSD group (all P0.05). The FA value of the optic chiasm in ON+NMOSD group was significantly lower than that of healthy control group and ON-MS group, as well as ON-NMOSD group ( P0.05). The FA value of the left optic radiation in ON+NMOSD group was lower than that in healthy control group and the ON-MS group. The RK value of the optic chiasm in ON+MS group was lower than that in the healthy control group and ON-NMOSD group ( P0.05). The MK and RK values of the left optic radiation in ON-MS group were significantly lower than those in the ON+NMOSD group and ON-NMOSD group ( P0.05). Conclusions:NMOSD and RRMS patients demonstrate varying degrees of microstructural damage in the optic chiasm and optic radiations. Differences of DKI parameters suggest different pathological mechanisms of visual pathway damage between NMOSD and MS, which may be helpful for early detection of occult visual pathway lesions.

Objective To investigate the impact of different lymph node dissection(RLNLN)around the recurrent laryngeal nerve(RLN)on the clinical efficacy of esophagectomy(EC)with thoracoscopic radical surgery.Methods Ninety-eight EC patients were selected from 2022-01 to 2022-10 in our hospital and divided into the control group and the study group,each with 49 cases,using simple randomization method.Both groups underwent EC thoracoscopic radical surgery,with conventional RLNLN clearance in the control group and modified RLNLN clearance in the study group.The operation and postoperative recovery of the two groups were compared,as well as myeloid triggered receptor-1(TREM-1),tumor necrosis factor receptor-associated protein-1(TRAP1),and complications before and after the operation,and the recurrence rate and survival rate of the two groups were counted at 1 year after the operation.Results The RLNLN dissection time in the study group was(11.93±3.57)minutes,which was shorter than that in the control group(17.15±4.28)minutes.The number of RLNLN dissections on both sides was(7.19±1.24),which was higher than that in the control group(5.56±1.10),and the differences were statistically significant(P＜0.05).Three and seven days after surgery,the CD3+,CD4+/CD8+of the study group were higher than those of the control group,while CRP,PCT,TREM-1,and TRAP1 were lower than those of the control group,and the differences were statistically significant(P＜0.05).The postoperative complication and recurrence rates in the study group were 4.08％(2/49)and 10.87％(5/46),respectively,which were lower than the control group[18.37％(9/44),29.55％(13/44)].Conclusion Thoracoscopic radical resection of esophageal cancer with modified RLNLN dissection can can enhance the effect of lymph node clearance,down-regulate the expression of TREM-1 and TRAP1,reduce the inflammatory response of the body,regulate the immune function,reduce the risk of complications and recurrence,and improve the quality of life.

Objective:Analyze the imaging and clinical data of cases undergoing thoracoscopic subsegmental resection for non-small cell lung cancer(NSCLC) with a diameter≤2 cm, and explore the clinical outcomes of subsegmental resection.Methods:A retrospective analysis was conducted on the clinical data of 58 patients who underwent thoracoscopic subsegmentectomy in China-Japan Friendship Hospital from January 2020 to July 2024. Three-dimensional reconstruction technology was used for surgical planning before the operation, and thoracoscopic subsegmentectomy was performed, including single lung subsegmentectomy(Group 1), multiple lung subsegmentectomy(Group 2), and combined segmentectomy and subsegmentectomy(Group 3).Results:All patients successfully completed the surgery, with 23 cases of single lung subsegmentectomy, 6 cases of multiple lung subsegmentectomy, and 29 cases of combined segmentectomy and subsegmentectomy. The median intraoperative blood loss was 30.0(20.0, 30.0)ml, the average operation time was(2.03±0.68) h, the average pathological size of the nodules was(10.53±4.45) mm, and the average postoperative tube retention was(2.55±0.92) days. There were 6 cases of postoperative complications, including pulmonary air leakage in 2 cases, cerebral embolism in 1 case, pulmonary embolism in 1 case, pulmonary infection in 1 case, and atrial fibrillation in 1 case. All patients had negative surgical margins in the postoperative pathology. Group 1 had less average intraoperative blood loss than Group 2, with statistically significant differences( P=0.027). Surgical procedures for the upper lobe of the lung mainly involve the resection of combined segments and subsegments, while those for the lower lobe primarily consist of single segmentectomy. Conclusion:Subsegmentectomy is an effective surgical approach when the nodule is small and a clear margin can be ensured, allowing for better preservation of remaining lung tissue. Bleeding during multiple subsegmentectomies is greater than that in single subsegmentectomy and combined segmentectomy with subsegmentectomy, which may be related to the more complex vascular variations in multiple subsegmentectomies.

Objective:To investigate the optimal processing technology for Sophorae Fructus Carbonisata(char-coal-processed immature fruit of Sophora japonica)by integrating thermal analysis,response surface methodology(RSM),and intelligent sensory technology.Methods:The thermal analysis technology was used to simulate the processing process of traditional Chinese medicine(TCM),the pyrolysis characteristics of Sophorae Fructus powder were studied,and the processing process was discussed by intelligent sensory analysis to determine the temperature range.Using the contents of genistein,kaempferol,and quercetin as comprehensive evaluation indices,the RSM was applied to optimize the processing technology for Sophorae Fructus Carbonisata.Results:The optimal process-ing technology for Sophorae Fructus Carbonisata was identified as:Stir-frying temperature was 290 ℃,Stir-frying time was 14 min.Conclusion:The integrated approach of thermal analysis-RSM and intelligent sensory technology has successfully established an accurate predictive model for active components in Sophorae Fructus.The optimized processing technology not only enhances the reproducibility of charcoal processing but also lays a foundation for the formulation of national quality standards for this TCM.

Objective:To investigate the neural function and Insulin-like growth factor-1 (IGF-1) in post-stroke depression (PSD) model rats. The effect of IGF-1 on mitogen activated protein kinase (MAPK) signaling pathway.Methods:15 male SD rats were selected as sham-operation group. PSD rat model was prepared by Longa method and chronic unpredictability mild stress method with 70 rats. The successfully constructed PSD rats were divided into model group, fluoxetine group (2.31 mg/kg fluoxetine, gavage), electroacupuncture group [stimulation of "Baihui"(GV20), "Fengfu"(GV16), "Shenting"(GV24) and "Taichong"(LR3) acupoints by electroacupuncture]and positive drug group [stimulation of "Baihui"(GV20), "Fengfu"(GV16), "Shenting"(GV24) and "Taichong"(LR3) acupoints by electroacupuncture + 5 μl of Sb202190 solution was injected into the lateral ventricle with a concentration of 10 μmol/L]. According to random number table method, with 15 rats in each group. Each group received relevant administration, and the rats' body mass was measured at the end of treatment. mNSS scale was used to evaluate the neurological impairment of rats; the behavioral function of rats was evaluated by sugar water preference test and forced swimming test; Nissl and TUNEL staining were used to observe the number of NissL bodies and the apoptosis rate of neurons in hippocampus; the level of serum IGF-1 was Nissl by enzyme-linked immunosorbent assay (ELISA); Western blot was used to detect the expressions of Caspase-3, Bax, Bcl-2, brain-derived neurotrophic factor (BDNF), cyclic adenosine monophosphate response element binding protein (CREB), p-CREB, IGF-1, mitogen activated protein kinase (MEK), p-MEK, ERK, p-ERK, JNK, p-JNK, p38 mitogen activated protein kinase (p38), p-p38 protein in brain tissue.Results:Compared with the model group, the weight of rats increased in the fluoxetine, electroacupuncture, and positive drug groups ( P<0.05); mNSS and forced swim test immobility time decreased ( P<0.05). Sucrose consumption percentage and struggling time in the forced swim test were markedly elevated ( P<0.05); Nissl body counts in hippocampal neurons increased ( P<0.05), accompanied by reduced neuronal apoptosis rates ( P<0.05); serum IGF-1 level significantly increased ( P<0.05); the protein expressions of Caspase-3 and Bax in hippocampus decreased ( P<0.05), while the protein expressions of Bcl-2, p-CREB/CREB, BDNF, IGF-1, p-MEK/MEK, p-ERK/ERK, p-JNK/JNK and p-p38/p38 increased ( P<0.05). Conclusions:Electroacupuncture can improve neural function and depressive behavior in rats, reduce pathological damage in hippocampus, increase the number of Nissl bodies, and inhibit apoptosis. The mechanism of electroacupuncture may be related to the increase of IGF-1 and the activation of MAPK signaling pathway.

Objective To observe the effects of electroacupuncture at"Neiguan"and"Gongsun"on autophagy and apoptosis related indexes of interstitial cells of Cajal(ICC)in rats with functional dyspepsia(FD);To explore its possible mechanism on improving gastrointestinal motility of FD.Methods Totally 32 SPF grade SD rats were randomly divided into blank group,model group,electroacupuncture group and Western medicine group,with 8 rats in each group.An FD model was constructed using a composite etiology modeling method.The electroacupuncture group received electroacupuncture at"Neiguan"and"Gongsun",while the Western medicine group received oral administration of mosapride once a day for 7 consecutive days.The general condition,body mass and average daily intake of rats were observed every week,and gastric emptying rate and small intestine propulsion rate were detected,transmission electron microscopy was used to observe the structure of gastric antrum ICC,Western blot was used to observe the expressions of c-kit,Beclin1,LC3Ⅱ/Ⅰ,p62,Caspase-3 protein in gastric antrum tissue,qPCR was used to observe the mRNA expressions of Beclin1,LC3Ⅱ/Ⅰ,p62 and c-kit in gastric antrum tissue,TUNEL staining was used to detect the apoptosis rate of cells in gastric antrum tissue.Results Compared with the blank group,the model group rats were mentally lethargic,clustered and curled up,with reduced activity,rough and dull hair,loose and unformed feces,reduced body mass and daily food intake(P<0.05),and gastric emptying rate and small intestine propulsion rate decreased(P<0.01),ICC mitochondria swelled and dissolved,with varying degrees of vacuolar formation,rough endoplasmic reticulum dilation and destruction,and a large number of autophagosomes,the expressions of Beclin1 and LC3 Ⅱ/Ⅰ protein and mRNA in gastric antrum tissue increased(P<0.01),the expressions of p62,c-kit protein and mRNA decreased(P<0.01),while Caspase-3 protein expression increased(P<0.01),and the apoptosis rate of gastric antral tissue cells increased(P<0.01).Compared with the model group,the condition of rats in electroacupuncture group and the Western medicine group were improved,with increased responsiveness,increased mobility,neat hair,formed feces,increased body mass and daily food intake(P<0.01),and gastric emptying rate and small intestine propulsion rate increase(P<0.01),a normal ICC structure,and a small amount of autophagosomes were still visible,the expressions of Beclin1,LC3Ⅱ/Ⅰ protein and mRNA in gastric antrum tissue decreased(P<0.01),the expressions of p62,c-kit protein and mRNA increased(P<0.01),while Caspase-3 protein expression decreased(P<0.01),and the apoptosis rate of gastric antral tissue cells decreased(P<0.01).There was no statistically significant difference in various indicators between electroacupuncture group and Western medicine group(P>0.05).Conclusion Electroacupuncture at"Neiguan"and"Gongsun"can restore the number and structure of ICC and improve gastrointestinal motility,and its mechanism may be related to the inhibition of autophagy and apoptosis levels.

Objective:To investigate the optimal processing technology for Sophorae Fructus Carbonisata(char-coal-processed immature fruit of Sophora japonica)by integrating thermal analysis,response surface methodology(RSM),and intelligent sensory technology.Methods:The thermal analysis technology was used to simulate the processing process of traditional Chinese medicine(TCM),the pyrolysis characteristics of Sophorae Fructus powder were studied,and the processing process was discussed by intelligent sensory analysis to determine the temperature range.Using the contents of genistein,kaempferol,and quercetin as comprehensive evaluation indices,the RSM was applied to optimize the processing technology for Sophorae Fructus Carbonisata.Results:The optimal process-ing technology for Sophorae Fructus Carbonisata was identified as:Stir-frying temperature was 290 ℃,Stir-frying time was 14 min.Conclusion:The integrated approach of thermal analysis-RSM and intelligent sensory technology has successfully established an accurate predictive model for active components in Sophorae Fructus.The optimized processing technology not only enhances the reproducibility of charcoal processing but also lays a foundation for the formulation of national quality standards for this TCM.

Objective To investigate the impact of different lymph node dissection(RLNLN)around the recurrent laryngeal nerve(RLN)on the clinical efficacy of esophagectomy(EC)with thoracoscopic radical surgery.Methods Ninety-eight EC patients were selected from 2022-01 to 2022-10 in our hospital and divided into the control group and the study group,each with 49 cases,using simple randomization method.Both groups underwent EC thoracoscopic radical surgery,with conventional RLNLN clearance in the control group and modified RLNLN clearance in the study group.The operation and postoperative recovery of the two groups were compared,as well as myeloid triggered receptor-1(TREM-1),tumor necrosis factor receptor-associated protein-1(TRAP1),and complications before and after the operation,and the recurrence rate and survival rate of the two groups were counted at 1 year after the operation.Results The RLNLN dissection time in the study group was(11.93±3.57)minutes,which was shorter than that in the control group(17.15±4.28)minutes.The number of RLNLN dissections on both sides was(7.19±1.24),which was higher than that in the control group(5.56±1.10),and the differences were statistically significant(P＜0.05).Three and seven days after surgery,the CD3+,CD4+/CD8+of the study group were higher than those of the control group,while CRP,PCT,TREM-1,and TRAP1 were lower than those of the control group,and the differences were statistically significant(P＜0.05).The postoperative complication and recurrence rates in the study group were 4.08％(2/49)and 10.87％(5/46),respectively,which were lower than the control group[18.37％(9/44),29.55％(13/44)].Conclusion Thoracoscopic radical resection of esophageal cancer with modified RLNLN dissection can can enhance the effect of lymph node clearance,down-regulate the expression of TREM-1 and TRAP1,reduce the inflammatory response of the body,regulate the immune function,reduce the risk of complications and recurrence,and improve the quality of life.

Objective:To investigate microstructural alterations in the optic chiasm and optic radiations of multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) based on diffusion kurtosis imaging (DKI).Methods:This study was a cross-sectional study. Retrospective analyses were conducted on the clinical and imaging data of 63 patients with relapsing-remitting MS (RRMS) and 62 patients with NMOSD diagnosed at First Affiliated Hospital of Chongqing Medical University from January 2019 to December 2023. According to the occurrence of optic neuritis (ON), they were categorized into ON-positive MS (ON+MS) group (40 cases), ON-negative MS (ON-MS) group (23 cases), ON-positive NMOSD (ON+NMOSD) group (40 cases) and ON-negative NMOSD (ON-NMOSD) group (22 cases). In addition, 40 healthy controls were enrolled during the same period. DKI data of all subjects were collected, and DKI post-processing was performed to obtain fractional anisotropy (FA), mean kurtosis (MK), axial kurtosis (AK), and radial kurtosis (RK) values of the optic chiasm and bilateral optic radiations. The scores of the mini-mental state examination (MMSE), montreal cognitive assessment (MoCA), and expanded disability status scale (EDSS) were obtained. The Kruskal-Wallis test was used to analyze the differences in DKI parameters of the optic chiasm and bilateral optic radiation among the 5 groups, and the Holm-Bonferroni method was employed for multiple comparison correction in pairwise comparisons.Results:There were statistically significant overall differences in the DKI parameters of the optic chiasm and bilateral optic radiations among healthy control group, ON+MS group, ON-MS group, ON+NMOSD group, and ON-NMOSD group (all P0.05). The FA value of the optic chiasm in ON+NMOSD group was significantly lower than that of healthy control group and ON-MS group, as well as ON-NMOSD group ( P0.05). The FA value of the left optic radiation in ON+NMOSD group was lower than that in healthy control group and the ON-MS group. The RK value of the optic chiasm in ON+MS group was lower than that in the healthy control group and ON-NMOSD group ( P0.05). The MK and RK values of the left optic radiation in ON-MS group were significantly lower than those in the ON+NMOSD group and ON-NMOSD group ( P0.05). Conclusions:NMOSD and RRMS patients demonstrate varying degrees of microstructural damage in the optic chiasm and optic radiations. Differences of DKI parameters suggest different pathological mechanisms of visual pathway damage between NMOSD and MS, which may be helpful for early detection of occult visual pathway lesions.