OBJECTIVE To compare the metabolomic characteristics of stage T1 papillary thyroid carcinoma(PTC)and nodular goiter(NG),and the relationship between metabolites and lymph node metastasis of PTC.METHODS Serum samples were collected from 60 patients with stage T1 PTC and 30 patients with NG who underwent thyroidectomy at the Department of Otolaryngology Head and Neck Surgery,Civil Aviation General Hospital between September 2021 and April 2022.The PTC group was divided into the N+ group with lymph node metastasis and the N-group without lymph node metastasis according to the presence or absence of lymph node metastasis.The serum metabolites of the N+ and N-groups and the PTC and NG groups were compared and analyzed using an ultra-performance liquid chromatography-mass spectrometry(UPLC-Q-Exactive-MS)coupled platform,and principal component analysis(PCA),partial least squares discriminant analysis(PLS-DA),and orthogonal partial least squares discriminant analysis(OPLS-DA)was performed using SIMCA-P 14.1 software.OPLS-DA modeling,combined with FDR-corrected Mann-Whitney-Wilcoxon test results and metabolite difference multiples in the two groups undergoing comparison,etc.to screen for potential small molecule metabolic markers,and to establish a joint diagnostic model by binary logistic regression analysis.RESULTS There were no significant differential metabolites between the N+ group with lymph node metastasis and the N-group without lymph node metastasis.Seven differential metabolites were found between PCA patients and NG patients,and the five relevant metabolic pathways were the pentose phosphate pathway,pentose and glucuronide interconversion,glycolysis/gluconeogenesis,fructose,and mannose metabolism,and fatty acid biosynthesis.The differential metabolite with an area under the ROC curve>0.9 was D-glyceraldehyde 3-phosphate,and another N-undecanoylglycine,uronic acid,and the area under the ROC curve for three metabolites,N-undecanoylglycine,uric acid,and triiodothyronine glucuronide,was>0.8.CONCLUSION PTC patients differed from NG patients mainly in glucose metabolism and lipid metabolism,and D-glyceraldehyde 3-phosphate could be distinguished from NG patients with the aid of N-undecanoylglycine,uric acid,and triiodothyronine glucuronide,combined with imaging findings.Also,no significant differences in serum metabolites were found in the N+ group compared with the N-group,and the presence or absence of lymph node metastases did not affect serum metabolites in patients with stage T1 PTC.

Objective:To compare the real-world efficacy and safety profile of tenofovir amibufenamid (TMF) and tenofovir alafenamide (TAF) tablets in the treatment of patients with chronic hepatitis B (CHB).Methods:This retrospective study included patients with chronic hepatitis B who received TMF and TAF antiviral treatment at the Infectious Disease Outpatient Department of the First Affiliated Hospital of Zhengzhou University from January 2021 to December 2023. The primary and secondary outcome was to study the patient HBV DNA conversion rate (<20 IU/ml), alanine aminotransferase (ALT) normalization rate, renal function, and lipid levels of patients at 48 weeks of treatment. The comparison of data between measurement data groups was differentiated using a t-test and Mann-Whitney U test. The inter-group comparison rate in count data was performed using the χ2 test or Fisher's exact probability. Results:A total of 440 cases were enrolled, including 220 in the TMF group (63 treatment-na?ve and 157 treatment-experienced) and 220 cases in the TAF group (61 treatment-na?ve and 159 treatment-experienced). In terms of efficacy, the HBV DNA seroconversion rates in the TMF group and TAF group were 90.5% and 85.2% ( P=0.372), respectively, while the ALT normalization rates were 92.1% and 88.5% ( P=0.505), respectively, at 48 weeks of treatment. The HBV DNA-negative conversion rate for the newly treated patients was 99.4% and 98.7%, respectively ( P=1.000), while the rates of ALT normalization were 94.9% and 92.3%, respectively ( P=0.863). In terms of safety profile, the serum creatinine level was lower in the TMF group than that in the TAF group at 48 weeks of treatment [TMF group 66.5 (56.3, 78.3) μmol/L, TAF group 70.6 (60.7, 77.8) μmol/L, Z=-2.282, P=0.022]. However, there was no statistically significant difference in other renal function and tubular function related indicators between the two groups of patients ( P>0.05). The serum high-density lipoprotein levels were higher in the TMF group than those in the TAF group [TMF 1.4 (1.1, 1.6) mmol/L vs. TAF group 1.3 (1.1, 1.6) mmol/L, Z=-2.204, P=0.027] at 48 weeks of treatment. However, there was no statistically significant difference in other blood lipid indicators between the two groups of patients ( P>0.05). Conclusion:There is no statistically significant difference in efficacy and safety profiles between TMF and TAF at 48 weeks in the treatment of patients with chronic hepatitis B, and the overall safety profile is favorable.

Astrocytes are important nerve cells in the central nervous system （CNS）， which mainly play a key role in nutrition and support. Astrocytes and neurons undergo close energy coupling and substance coupling， which are closely related and interact with each other. In recent years， many studies have shown that the astrocyte-neuron coupling imbalance plays a central role in the occurrence and progression of Alzheimer's disease （AD） and serves as an important therapeutic target receiving increasing attention. According to traditional Chinese medicine （TCM） theory， the main pathogenesis of AD is kidney deficiency and marrow inadequacy， and in clinical medication， kidney-tonifying and marrow-filling TCM prescriptions are often employed with satisfactory results achieved. As reported， many kidney-tonifying and marrow-filling prescriptions exhibit regulatory and protective effects on the imbalance of astrocyte-neuron coupling， suggesting that the effect of kidney-tonifying and marrow-filling prescriptions in treating AD may have some internal relationship with its regulation of the imbalance of astrocyte-neuron coupling. This article reviewed the underlying internal relationship between the imbalance of astrocyte-neuron coupling and the pathogenesis of kidney deficiency and marrow inadequacy in AD and the research progress in the intervention mechanism of TCM for tonifying the kidney and filling the marrow.

ObjectiveTo explore the mechanism of Dihuang Yinzi in improving astrocyte injury and glycolysis in Alzheimer's disease （AD） mice via regulating the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， thereby improving the cognitive function of AD mice. MethodForty male APP/PS1 transgenic mice aged four months were randomly divided into a model group and a model + Dihuang Yinzi （0.25 g·kg^-1） group， with 20 mice in each group. Forty C57BL/6J mice with the same background and same age were randomly divided into a control group and a control + Dihuang Yinzi （0.25 g·kg^-1） group， with 20 mice in each group. The mice in the control + Dihuang Yinzi group and the model + Dihuang Yinzi group were administered with Dihuang Yinzi by gavage， and those in the control group and the model group received an equal volume of sterilized normal saline， once a day for 150 days. Morris water maze test was performed to test the ability of navigation and space exploration of mice. The protein expression of p-PI3K， PI3K， p-Akt， Akt， phosphofructokinase-1 （PFK-1）， and aldehyde dehydrogenase 3 family member B2 （ALDH3B2） in mouse brain tissues was measured by Western blot. An immunofluorescence assay was performed to detect astrocyte morphology and the expression level of ALDH3B2. ResultAs compared with the control group， the model group showed prolonged escape latency during the 2^nd to 5^th days of the location-based navigation （P<0.05， P<0.01）， reduced number of times crossing the target area of the platform， shortened residence time in the target quadrant （P<0.05， P<0.01）， prolonged residence time in the opposite quadrant （P<0.05）， increased surface area of the cell body and total length of cell protrusions of astrocytes （P<0.05， P<0.01）， and down-regulated protein expression of p-PI3K， p-Akt， ALDH3B2， and PFK-1 （P<0.01）， while the above experimental indexes were not significantly different in the control + Dihuang Yinzi group. Compared with the model group， the model + Dihuang Yinzi group showed shortened escape latency of APP/PS1 mice during the 2^nd to 5^th days of the location-based navigation （P<0.05， P<0.01）， increased number of times crossing the platform， prolonged target quadrant residence time （P<0.05， P<0.01）， shortened residence time in the opposite quadrant （P<0.05）， reduced surface area of the cell body and total length of cell protrusions of astrocytes （P<0.05）， and up-regulated protein expression of p-PI3K， p-Akt， ALDH3B2， and PFK-1 （P<0.01）. ConclusionDihuang Yinzi can improve the learning and memory ability of AD mice by activating the PI3K/Akt signaling pathway and up-regulating the protein expression of PFK-1 and ALDH3B2 to protect against astrocyte injury in brain tissues and improve glycolysis.

【Objective】 To introduce the key techniques of "one-cut" circumcision, and to compare its clinical efficacy with traditional circumcision. 【Methods】 A retrospective analysis was conducted on 120 cases of circumcision in our center during Jul.2020 and Jul.2022, including 60 cases in the "one-cut" group and 60 cases in the traditional circumcision group. The operation time, postoperative edema time, satisfaction with cosmetics and improvement of sexual life were compared between the two groups. 【Results】 Compared with the tradition group, the "one-cut" group had shorter operation time [(19.2±7.4) min vs. (23.1±1.7) min, P<0.001] , shorter postoperative edema time [(5.5±3.2) d vs. (9.6±5.5) d, P<0.001] , and higher satisfaction with cosmetics [(3.6±0.5) vs. (3.1±0.8), P<0.001)] , but there was no difference in improvement of sexual life between the two groups (P=0.08). 【Conclusion】 "One-cut" circumcision is easy to operate, with short operation time, fast postoperative recovery, neat incision and satisfactory appearance, which is worth popularizing.

Immune escape is one of the ten hallmarks of tumors， which plays an important role in the occurrence and development of tumors. Immune escape refers to a process where tumor cells remodel and edit the immune system through the model of immune clearance， immune balance， and immune escape to "transform" the immune cells into immunosuppressive cells in the tumor microenvironment， so as to support immune escape. The five-stage evolution is the summary of tumor pathogenesis by professor LI Jie. He believes that the gradual development of tumors follows the core pathogenesis of "deficiency-cold-toxin-obstruction-collapse"， in which "depression" runs through the whole process， and cancer toxin is the key. Based on immune editing， this paper combined phenotypic characteristics of tumor cells with the core pathogenesis of the five-stage evolution of professor LI to reveal the biological basis of malignant tumor five-stage evolution. The results indicate that the prominent change from deficiency to cold is the reduction of immune surveillance and the prominent change from toxin to obstruction is immune escape. The final stage of collapse is the outcome of immune failure. Depression is the booster of tumor immune editing. Therefore， the method of reinforcing the healthy Qi and removing toxins was proposed to regulate the immune editing and cut off the five-stage evolution of tumors. Supplementing Qi and warming Yang can reinforce the healthy Qi and restore immune surveillance. Removing toxins and dredging can reverse toxins and immune escape. The harmonizing method can maintain the dynamic balance of immune cells/immunosuppressive cells. Resolving depression can truncate tumor immune editing. Those methods can provide a certain reference for the treatment based on microscopic syndrome differentiation in traditional Chinese medicine （TCM）. In future studies， it is necessary to further explore the specific mechanism of the regulation of immune editing with the methods of supplementing Qi and warming Yang， removing toxins and dredging， their combination， and resolving depression， so as to find out specific Chinese medicines and targets and provide more sufficient evidence for the regulation of tumor immune editing by TCM.

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a child with multiple pterygium syndrome (MPS). METHODS: A child with MPS who was treated at the Orthopedics Department of Guangzhou Women and Children's Medical Center Affiliated to Guangzhou Medical University on August 19, 2020 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and her parents were also collected. Whole exome sequencing (WES) was carried out for the child. Candidate variant was validated by Sanger sequencing of her parents and bioinformatic analysis. RESULTS: The child, an 11-year-old female, had a complain of "scoliosis found 8 years before and aggravated with unequal shoulder height for 1 year". WES results revealed that she has carried a homozygous c.55+1G>C splice variant of the CHRNG gene, for which both of her parents were heterozygous carriers. By bioinformatic analysis, the c.55+1G>C variant has not been recorded by the CNKI, Wanfang data knowledge service platform and HGMG databases. Analysis with Multain online software suggested that the amino acid encoded by this site is highly conserved among various species. As predicted with the CRYP-SKIP online software, the probability of activation and skipping of the potential splice site in exon 1 caused by this variant is 0.30 and 0.70, respectively. The child was diagnosed with MPS. CONCLUSION The CHRNG gene c.55+1G>C variant probably underlay the MPS in this patient.
Humans ; Child ; Female ; Abnormalities, Multiple/genetics* ; Malignant Hyperthermia/genetics* ; Skin Abnormalities/genetics* ; Heterozygote ; Mutation ; Receptors, Nicotinic/genetics*

ObjectiveTo explore the effect of Naoxin'an capsule against mitochondrial dysfunction and oxidative damage in brains of rats with vascular cognitive impairment （VCI） induced by chronic cerebral ischemia. MethodA total of 150 rats were randomized into modeling group （130 rats） and sham-operated group （20 rats） with the random number table method. The two-vessel occlusion （2-VO） was employed to induce VCI in rats， and finally 87 rats developed VCI. The VCI rats were classified into model group， positive drug group （Aricept， 0.5 mg·kg^-1）， and low-， medium- and high-dose Naoxin'an capsule groups （0.18， 0.36， 0.72 g·kg^-1， separately）， with 17-18 rats in each group. The administration lasted 8 weeks. The learning and working memory of VCI rats were assayed by novel object recognition test and Y-maze test. The 8-oxoguanine （8-OxoG） level was measured based on immunofluorescence staining. Spectrophotometry was performed to determine the activity of mitochondrial respiratory chain complexes Ⅰ， Ⅱ， Ⅲ， and Ⅳ， mitochondrial swelling， mitochondrial membrane potential （MMP）， and activity of pyruvate dehydrogenase （PDH） and α-ketoglutarate dehydrogenase （KGDH）. The submicroscopic structure of mitochondria was observed with electron microscope. The phosphorylation of cAMP response element-binding protein （CREB） and the expression of peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α）， nuclear respiratory factor 1 （NRF-1）， and mitochondrial transcription factor A （mt-TFA） were determined by Western blot. The mitochondrial status Ⅳ H₂O₂ generation， activity of cerebral superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px）， and malondialdehyde （MDA） content were measured with the photochemical method. ResultCompared with the sham-operated group， model group showed decrease in new object discrimination index （P<0.01） and spontaneous alternation rate in the Y-maze test （P<0.01）， increase in ROS production in the brain （P<0.01）， reduction in MMP and mitochondrial swelling A value （P<0.01）， obvious mitochondrial swelling， vacuoles and cristae fractures in mitochondria， decrease in the level of phosphorylated CREB， expression of PGC-1α， NRF-1 and mt-TFA （P<0.01）， and activity of the respiratory chain complexes Ⅰ， Ⅱ， Ⅲ， and Ⅳ （P<0.01）， PDH and KGDH in the brain （P<0.01）， rise of the production of H₂O₂ at state IV （P<0.01） and the content of MDA （P<0.01）， and reduction in the activity of SOD and GSH-Px （P<0.01）. Compared with the model group， each dose of Naoxin'an capsules can improve the new object discrimination index （P<0.05， P<0.01） and the rate of spontaneous alternation （P<0.05， P<0.01）， decrease ROS production in the brain （P<0.01）， improve the MMP and swelling A value （P<0.05， P<0.01）， alleviate mitochondrial swelling and mitochondrial submicroscopic damage， elevate the phosphorylated CREB level， the expression of PGC-1α， NRF-1 and mt-TFA （P<0.05， P<0.01）， and the activity of mitochondrial respiratory chain complexes Ⅲ， and Ⅳ， PDH and KGDH （P<0.01）， decrease state Ⅳ H₂O₂ generation （P<0.01） and MDA content （P<0.05， P<0.01）， and raise the activity of SOD and GSH-Px （P<0.01）. ConclusionBy activating the CREB/PGC-1α pathway， Naoxin'an capsule can protect the structure and function of mitochondria， enhance the antioxidant capacity， and inhibit the mitochondrial dysfunction and oxidative damage induced by chronic cerebral ischemia， thus improving the VCI.

Objective To explore the efficacy and safety of traditional Chinese medicine(TCM) combined with chemotherapy in the prevention and treatment of postoperative recurrence and metastasis of locally advanced gastric cancer (LAGC) by meta-analysis. Moreover, we evaluated the efficacy of TCM on the quality of life, immune indexes, and toxic and side effects during adjuvant chemotherapy. Methods The CNKI, Wanfang, PubMed, and other databases were searched by computer. Randomized controlled trials (RCTs) were searched. After literature screening and data extraction, Review Manager 5.3 software provided by Cochrane was used for meta-analysis. Results A total of 18 RCTs were included. Compared with chemotherapy alone, TCM combined with chemotherapy could improve the KPS score and CD3⁺ and CD4⁺/CD8⁺ index levels. The incidence rates of postoperative leucopenia, hemoglobin reduction, thrombocytopenia, nausea and vomiting, diarrhea, and neurotoxicity were reduced. In terms of postoperative QLQ-C30 score, abnormal liver function, and abnormal renal function, the incidence of TCM combined chemotherapy was similar to that of chemotherapy alone, with no statistical difference. Compared with chemotherapy alone, TCM combined chemotherapy could reduce the 1-, 2-, 3-, and 5-year cumulative recurrence and metastasis rates and prolong the disease-free survival time. Conclusion Compared with chemotherapy alone in adjuvant chemotherapy, TCM combined chemotherapy could improve the immune level and KPS score of LACC patients after surgery, reduce the incidence of adverse reactions, as well as reduce the recurrence and metastasis rate of LAGC after surgery and DFS could be improved.

Objective:To compare the clinical effect of Ilizarov frame and unilateral frame in the treatment of tibial segmental bone defect combined with soft tissue defect by open bone transport.Methods:A retrospective case-control study was conducted to analyze the clinical data of 32 patients with tibial segmental bone defect and soft tissue defect-up who underwent open bone transport technique in Tianjin Hospital from August 2008 to August 2016 and obtained complete followed-up. There were 22 males and 10 females, aged 22-64 years (mean, 36.8 years). Nineteen patients in the Ilizarov group showed the mean bone defect length of 7.9 cm and mean soft tissue defect area of 41.4 cm 2. Thirteen patients in the unilateral group showed the mean bone defect length of 7.8 cm and the mean soft tissue defect area of 39.2 cm 2. The results of fracture healing, wound healing time, radiological consolidation index, external fixation index, Association for the Study and Application of the Method of Ilizarov (ASAMI) bone and lower-limb function score and incidence of complications were compared between the groups. Results:All patients were followed up for 24 to 60 months [(32.6±1.3)months]. Bone healing was achieved in all patients. The wound healing time was (2.7±2.3)days in Ilizarov group and (2.4±1.8)days in unilateral group ( P>0.05). The consolidation index was (43.4±8.7)d/cm in Ilizarov group and (45.8±10.3)d/cm in unilateral group ( P>0.05). The external fixation index was (52.6±8.9)d/cm in Ilizarov group and (58.7±12.9)d/cm in unilateral group ( P<0.05). The results of ASAMI bone score was excellent in 10 patients, good in 6, fair in 2 and poor in 1 in Ilizarov group, with the excellent rate of 84%; and excellent in 6 patients, good in 4, fair in 2, and poor in 1 in unilateral group, with the excellent rate of 77%, with insignificant difference between two groups ( P>0.05). The results of ASAMI lower-limb function score was excellent in 8 patients, good in 7, fair in 3, poor in 1 in Ilizarov group, with the excellent rate of 79%; and excellent in 6, good in 3, fair in 3, poor in 1 in unilateral group, with the excellent rate of 69%, with insignificant difference between the two groups ( P>0.05). Incidence of axial deviation was zero in Ilizarov group versus 23% in unilateral group ( P<0.05). After operation, Ilizarov group had refracture in 1 patient and pin site infection in 5, and unilateral group had refracture in 1 patient and pin site infection in 1, showing no significant difference between the two groups ( P>0.05). Conclusions:Tibial segmental bone defect with soft tissue defect can be effectively treated by open bone transport with Ilizarov and unilateral frame. Ilizarov frame has better biomechanical properties and is more convenient for correction of poor postoperative axial alignment.