OBJECTIVE: To analyze the phenotype and genotype of a neonate with Osteo-oto-hepato-enteric syndrome (O2HE) and review the literature. METHODS: A female neonate diagnosed with O2HE syndrome on December 13, 2024 at the First Affiliated Hospital of Zhengzhou University was selected as the study subject, and her clinical characteristics were analyzed, and pathogenic variants were explored by whole exome sequencing (WES). This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: 2025-KY-1038). RESULTS: The proband, a female infant, was delivered by Cesarean section at 36⁺¹ weeks of gestation. Five days after birth, she had developed severe diarrhea, mild cholestasis, sensorineural hearing loss, and growth retardation. WES revealed that she has harbored novel compound heterozygous variants c.512delA (p.Lys171Serfs*64) and c.698C>A (p.Thr233Asn) of the UNC45A gene, which were inherited from her mother and father, respectively. A total of 8 English papers were retrieved, which involved 16 patients from 14 families. Combined with our case, the 17 patients included 13 (76.5%) females and 4 (23.5%) males. Four patients (23.5%) had consanguineous parents. One case was excluded from further genetic analysis due to co-morbidity with other genetic variants. The primary clinical features included diarrhea (87.5%), cholestasis (81.3%), sensorineural hearing loss (31.3%), bone fragility (37.5%), and developmental delay (50.0%). Bi-allelic compound heterozygous mutations were identified in 12 patients (75.0%), and homozygous variants in 4 (25.0%). These included missense, nonsense, frameshift and deletional variants. The c.710T>C (p.Leu237Pro) variant was identified for 5 times, 3 of which were in homozygote forms. CONCLUSION O2HE syndrome should be suspected in cases with diarrhea, cholestasis, and hearing abnormalities during early postnatal period. Genetic testing facilitate early identification, genetic diagnosis and treatment.
Humans ; Female ; Infant, Newborn ; Male ; Mutation ; Hearing Loss, Sensorineural/genetics* ; Diarrhea, Infantile/genetics* ; Exome Sequencing ; Phenotype ; Fetal Growth Retardation ; Hair Diseases ; Facies

Objective:To analyze the phenotype and genotype of a neonate with Hypoparathyroidism-sensorineural deafness-renal dysplasia syndrome (HDR).Methods:A female neonate with HDR syndrome and thyroid deficiency detected at the First Affiliated Hospital of Zhengzhou University in on December 6, 2023 was selected as the study subject, Low-coverage whole-genome sequencing (Lc WGS) and whole exome sequencing (WES) were carried out. Using " hypoparathyroidism" " sensorineural deafness" " renal dysplasia" " HDR" " Barakat" and" GATA3" as keywords, the CNKI, Wanfang Data Knowledge Service Platform and PubMed database were searched, and the retrieval time was set from the establishment to March 2025. Results:A proband, a full-term female infant, had presented with feeding difficulty, micrognathia, and low-set ears. Serological test revealed hypocalcemia, hyperphosphatemia, hypoparathyroidism, low T3, low T4 and high TSH. Hearing test revealed bilateral sensorineural deafness. Ultrasonic test revealed absence of right kidney and thyroid. WES revealed that the she has harbored a deletion of approximately 6.67 Mb at 10p15.1p13, and Lc WGS confirmed the presence of a 6.70 Mb deletion in the same region, which was verified as a de novo variant. Literature review suggested that HDR was rarely diagnosed among neonates. Among the nine cases diagnosed in neonatal period, 66.6% (6/9) exhibited the typical triad, 77.7% (7/9) had hypoparathyroidism with hypocalcemic convulsion as the initial symptom, 22.2% (2/9) had sensorineural hearing loss or renal malformation, and 66.6% (6/9) had multiple malformations including facial dysmorphism and congenital heart disease. 55.5% (5/9) had a large deletion in the 10p15 region, whilst 33.3% (3/9) had a single gene variant. The range of the deletion had correlated with the diversity of clinical phenotypes in HDR syndrome, but the classic triad of symptoms may presented in any combination, independent of deletion size. Association of HDR with thyroid deficiency has been unreported previously.Conclusion:For neonates presenting with one of the symptoms of HDR triad or in combination with other malformations, genetic testing should be carried out.

OBJECTIVE: To analyze the phenotype and genotype of a neonate with Hypoparathyroidism-sensorineural deafness-renal dysplasia syndrome (HDR). METHODS: A female neonate with HDR syndrome and thyroid deficiency detected at the First Affiliated Hospital of Zhengzhou University on December 6,2023 was selected as the study subject, Low-coverage whole-genome sequencing (Lc WGS) and whole exome sequencing (WES) were carried out. Using "hypoparathyroidism""sensorineural deafness""renal dysplasia""HDR""Barakat" and"GATA3" as keywords, the CNKI, Wanfang Data Knowledge Service Platform and PubMed database were searched, and the retrieval time was set from the establishment to March 2025. RESULTS: A proband, a full-term female infant, had presented with feeding difficulty, micrognathia, and low-set ears. Serological test revealed hypocalcemia, hyperphosphatemia, hypoparathyroidism, low T3, low T4 and high TSH. Hearing test revealed bilateral sensorineural deafness. Ultrasonic test revealed absence of right kidney and thyroid. WES revealed that the she has harbored a deletion of approximately 6.67 Mb at 10p15.1p13, and Lc WGS confirmed the presence of a 6.70 Mb deletion in the same region, which was verified as a de novo variant. Literature review suggested that HDR was rarely diagnosed among neonates. Among the nine cases diagnosed in neonatal period, 66.6% (6/9) exhibited the typical triad, 77.7% (7/9) had hypoparathyroidism with hypocalcemic convulsion as the initial symptom, 22.2% (2/9) had sensorineural hearing loss or renal malformation, and 66.6% (6/9) had multiple malformations including facial dysmorphism and congenital heart disease. 55.5% (5/9) had a large deletion in the 10p15 region, whilst 33.3% (3/9) had a single gene variant. The range of the deletion had correlated with the diversity of clinical phenotypes in HDR syndrome, but the classic triad of symptoms may presented in any combination, independent of deletion size. Association of HDR with thyroid deficiency has been unreported previously. CONCLUSION For neonates presenting with one of the symptoms of HDR triad or in combination with other malformations, genetic testing should be carried out.
Humans ; Hypoparathyroidism/diagnosis* ; Female ; Infant, Newborn ; Hearing Loss, Sensorineural/diagnosis* ; GATA3 Transcription Factor/genetics* ; Nephrosis/genetics* ; Phenotype ; Exome Sequencing

Objective To compare the impact of NaClO and EDTA pretreatment on the enamel surfaces pore exposure rate,resin in-filtration effectiveness and shear bond strength between the enamel white spot lesions(WSLs)and resin composite.Methods A total of 104 sound premolars were selected for the study.4 mm×4 mm×2 mm enamel blocks from 64 sound premolars were cut in the center of the buccal surfaces of the teeth.All blocks were randomly divided into five groups:group SE(sound enamels as negative control);group DE(enamel blocks demineralised as positive control);group RI(resin infiltration);group N/RI(5.25％NaClO pretreatment and resin infiltration)and group E/RI(17％EDTA pretreatment and resin infiltration).The pore exposure rate of enamel surfaces and resin penetration depths were observed by scanning electron microscopy(SEM)and confocallaser scanning microscopy(CLSM)in each group.The remaining 40 premolars were cut from the cervical roots and the residual crowns were embedded in self-condensing resin ma-terial(buccal surfaces of the enamel exposed only).According to the grouping information,the samples were given the corresponding pretreatments and resin infiltration respectively and were bonded with a cylindrical resin cylinder on the buccal enamel surface for shear bond test.The shear bond strength and fracture modes were recorded and analyzed in each group.Results Compared to group RI,the pore exposure rate of the enamel surface,resin penetration depths,and percentage of resin penetration area in the N/RI and E/RI groups were significantly increased(P＜0.05).The shear bond strength of the samples in group SE was the highest,and the lowest in group DE.Compared to group DE,the shear bond strength in groups RI,N/RI,and E/RI was significantly increased(P＜0.05).Con-clusion Enamel surface pretreatment with 5.25％NaClO or 17％EDTA has been demonstrated to effectively enhance the enamel pore exposure rate,resin penetration depth and the shear bond strength between WSLs and resin composite.

Objective To explore the effect of Baofei Yiqi pill on immune function of patients with lung cancer.Methods A total of 100 patients with lung cancer diagnosed and treated in Leping Hospital of Traditional Chinese Medicine from September 2020 to September 2023 were selected and divided into experimental group and control group according to random number table method,with 50 cases in each group.The control group was treated with docetaxel combined with cisplatin,and the experimental group was treated with Baofei Yiqi pill on the basis of control group.Both groups were treated with 3 cycles of chemotherapy.The clinical efficacy,quality of life,changes in weight,immune function and adverse reactions were compared between two groups.Results The total response rate of experimental group was significantly higher than that of control group(x2=14.620,P＜0.001).After treatment,the Karnofsky performance status score and weight of experimental group were significantly higher than those of control group(P＜0.05),and the levels of CD3+,CD4+and CD4+/CD8+in experimental group were significantly higher than those in control group,and the levels of CD8+was significantly lower than than in control group(P＜0.05).The incidence of gastrointestinal reactions in experimental group was significantly lower than that in control group(P＜0.05).There was no significant difference in the incidence of abnormal renal function and liver function between two groups(P＞0.05).Conclusion Baofei Yiqi pill can effectively improve the immune function of patients with lung cancer,improve the quality of life of patients,reduce the adverse reactions of chemotherapy,and alleviate the disease of patients to a certain extent,which is worthy of promotion and application.

Objective To compare the impact of NaClO and EDTA pretreatment on the enamel surfaces pore exposure rate,resin in-filtration effectiveness and shear bond strength between the enamel white spot lesions(WSLs)and resin composite.Methods A total of 104 sound premolars were selected for the study.4 mm×4 mm×2 mm enamel blocks from 64 sound premolars were cut in the center of the buccal surfaces of the teeth.All blocks were randomly divided into five groups:group SE(sound enamels as negative control);group DE(enamel blocks demineralised as positive control);group RI(resin infiltration);group N/RI(5.25％NaClO pretreatment and resin infiltration)and group E/RI(17％EDTA pretreatment and resin infiltration).The pore exposure rate of enamel surfaces and resin penetration depths were observed by scanning electron microscopy(SEM)and confocallaser scanning microscopy(CLSM)in each group.The remaining 40 premolars were cut from the cervical roots and the residual crowns were embedded in self-condensing resin ma-terial(buccal surfaces of the enamel exposed only).According to the grouping information,the samples were given the corresponding pretreatments and resin infiltration respectively and were bonded with a cylindrical resin cylinder on the buccal enamel surface for shear bond test.The shear bond strength and fracture modes were recorded and analyzed in each group.Results Compared to group RI,the pore exposure rate of the enamel surface,resin penetration depths,and percentage of resin penetration area in the N/RI and E/RI groups were significantly increased(P＜0.05).The shear bond strength of the samples in group SE was the highest,and the lowest in group DE.Compared to group DE,the shear bond strength in groups RI,N/RI,and E/RI was significantly increased(P＜0.05).Con-clusion Enamel surface pretreatment with 5.25％NaClO or 17％EDTA has been demonstrated to effectively enhance the enamel pore exposure rate,resin penetration depth and the shear bond strength between WSLs and resin composite.

Objective To explore the effect of Baofei Yiqi pill on immune function of patients with lung cancer.Methods A total of 100 patients with lung cancer diagnosed and treated in Leping Hospital of Traditional Chinese Medicine from September 2020 to September 2023 were selected and divided into experimental group and control group according to random number table method,with 50 cases in each group.The control group was treated with docetaxel combined with cisplatin,and the experimental group was treated with Baofei Yiqi pill on the basis of control group.Both groups were treated with 3 cycles of chemotherapy.The clinical efficacy,quality of life,changes in weight,immune function and adverse reactions were compared between two groups.Results The total response rate of experimental group was significantly higher than that of control group(x2=14.620,P＜0.001).After treatment,the Karnofsky performance status score and weight of experimental group were significantly higher than those of control group(P＜0.05),and the levels of CD3+,CD4+and CD4+/CD8+in experimental group were significantly higher than those in control group,and the levels of CD8+was significantly lower than than in control group(P＜0.05).The incidence of gastrointestinal reactions in experimental group was significantly lower than that in control group(P＜0.05).There was no significant difference in the incidence of abnormal renal function and liver function between two groups(P＞0.05).Conclusion Baofei Yiqi pill can effectively improve the immune function of patients with lung cancer,improve the quality of life of patients,reduce the adverse reactions of chemotherapy,and alleviate the disease of patients to a certain extent,which is worthy of promotion and application.

Objective:To analyze the phenotype and genotype of a neonate with Hypoparathyroidism-sensorineural deafness-renal dysplasia syndrome (HDR).Methods:A female neonate with HDR syndrome and thyroid deficiency detected at the First Affiliated Hospital of Zhengzhou University in on December 6, 2023 was selected as the study subject, Low-coverage whole-genome sequencing (Lc WGS) and whole exome sequencing (WES) were carried out. Using " hypoparathyroidism" " sensorineural deafness" " renal dysplasia" " HDR" " Barakat" and" GATA3" as keywords, the CNKI, Wanfang Data Knowledge Service Platform and PubMed database were searched, and the retrieval time was set from the establishment to March 2025. Results:A proband, a full-term female infant, had presented with feeding difficulty, micrognathia, and low-set ears. Serological test revealed hypocalcemia, hyperphosphatemia, hypoparathyroidism, low T3, low T4 and high TSH. Hearing test revealed bilateral sensorineural deafness. Ultrasonic test revealed absence of right kidney and thyroid. WES revealed that the she has harbored a deletion of approximately 6.67 Mb at 10p15.1p13, and Lc WGS confirmed the presence of a 6.70 Mb deletion in the same region, which was verified as a de novo variant. Literature review suggested that HDR was rarely diagnosed among neonates. Among the nine cases diagnosed in neonatal period, 66.6% (6/9) exhibited the typical triad, 77.7% (7/9) had hypoparathyroidism with hypocalcemic convulsion as the initial symptom, 22.2% (2/9) had sensorineural hearing loss or renal malformation, and 66.6% (6/9) had multiple malformations including facial dysmorphism and congenital heart disease. 55.5% (5/9) had a large deletion in the 10p15 region, whilst 33.3% (3/9) had a single gene variant. The range of the deletion had correlated with the diversity of clinical phenotypes in HDR syndrome, but the classic triad of symptoms may presented in any combination, independent of deletion size. Association of HDR with thyroid deficiency has been unreported previously.Conclusion:For neonates presenting with one of the symptoms of HDR triad or in combination with other malformations, genetic testing should be carried out.

Malignant tumors are a major disease threatening human health with disability and mortality rates increasing yearly.Protein tyrosine phosphatase 2(SHP2)of Src homology 2,an important member of the protein tyrosine phosphatase family,has a wide range of functions,and its expression is elevated in a wide range of solid tumors.SHP2 plays an important regulatory role in invasion,metastasis,proliferation,apoptosis,and drug resistance.A large number of studies have shown that SHP2 plays a very important role in the genesis and development of many solid tumors,but no systematic studies have reported on the role of SHP2 in digestive system tumors.Here,we reviewed the biological functions and clinical significance of SHP2 in seven tumor types of the digestive system,explored its roles and mechanisms in cancer development stages,and summarized the development of SHP2 inhibitors to further search for potential targets for effective early diagnosis and gene therapy,which is of great significance to improvement the cancer patient survival rate.

OBJECTIVE To explore the effects and mechanism of atorvastatin on the proliferation， autophagy and glucose metabolism of AGS cells in human gastric cancer. METHODS The effects of low， medium and high concentrations of atorvastatin （12.5， 25， 50 μmol/L） on the viability of AGS cells were investigated through preliminary experiments， and the concentration of action was screened. The formal experiment was divided into control group （no intervention）， atorvastatin group （25 μmol/L）， positive control group （50 mg/L 5-fluorouracil）， inhibitor group [25 μmol/L atorvastatin +10 μmol/L phosphatidylinositol-3-kinase （PI3K）/protein kinase B （Akt） signaling pathway inhibitor LY294002] and activator group （25 μmol/L atorvastatin +10 μmol/L PI3K/Akt signaling pathway activator SC79）， all of which were treated for 24 h. Glucose metabolism （glucose and lactic acid contents） and cell proliferation rate were detected， as well as the expression of autophagy-associated protein light chain 3 （LC3） Ⅰ， LC3Ⅱ and PI3K/Akt signaling pathway-associated proteins in cells. RESULTS Both medium and high concentrations of atorvastatin could significantly inhibit the viability of AGS cells （P＜0.05）， and 25 μmol/L atorvastatin was selected for the official experiment for follow-up experiments. Compared with the control group， the contents of glucose and lactic acid， cell proliferation rate， p-PI3K/PI3K and p-Akt/Akt ratios in the positive control group and atorvastatin group were significantly decreased （P＜ 0.05）， and the protein expression levels of LC3 Ⅰ and LC3 Ⅱ were significantly increased （P＜0.05）. Compared with the atorvastatin group， the inhibitor further promoted the changes in the above indexes （P＜0.05）， and the activator significantly reversed the changes in the above indexes （P＜0.05）. CONCLUSIONS Atorvastatin could inhibit glucose metabolism and proliferation of AGS cells in human gastric cancer and promote autophagy. The mechanism may be related to the inhibition of the PI3K/Akt signaling pathway.