ObjectiveTo observe the effects of Yangjing Zhongyutang （YJZYT） on mitochondrial biogenesis and oxidative stress damage mediated by the silent information regulator 1 （SIRT1）/peroxisome proliferator-activated receptor gamma coactivator-1alpha （PGC-1α） signaling pathway in cyclophosphamide （CTX）-induced rats with diminished ovarian reserve （DOR）， and to explore its mechanism in improving ovarian reserve function and follicular development. MethodsForty-two 8-week-old female SD rats with normal estrous cycles were randomly divided into a blank control group （n=7） and a model group （n=35）. Rats in the model group received a single intraperitoneal injection of CTX （90 mg·kg^-1） to establish the DOR model. After modeling， estrous cycles were monitored for 7 consecutive days， and model success was confirmed based on criteria for estrous cycle disruption. After successful modeling， rats were divided into groups for intervention： estradiol valerate group （0.09 mg·kg^-1）， and YJZYT high-， medium-， and low-dose groups （19.98， 9.99， 5.00 g·kg^-1）. The blank control group and model group were given an equal volume of distilled water by gavage. All groups received daily gavage once for 4 consecutive weeks. The general state， body weight， and ovarian wet weight of rats were observed and recorded， and the ovarian organ index was calculated. Enzyme-linked immunosorbent assay （ELISA） was used to measure serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， anti-Müllerian hormone （AMH）， superoxide dismutase （SOD）， and glutathione peroxidase （GSH-Px）. Hematoxylin-eosin （HE） staining was performed to observe ovarian histomorphological changes and follicular development status. Immunofluorescence was used to detect reactive oxygen species （ROS） expression levels. Colorimetric assays were employed to measure adenosine triphosphate （ATP） and malondialdehyde （MDA） content in ovarian tissues. Quantitative Real-time polymerase chain reaction （Real-time PCR） was used to detect mitochondrial DNA （mtDNA） copy number and the mRNA expression levels of key genes including SIRT1， PGC-1α， nuclear respiratory factor 1 （NRF1）， and mitochondrial transcription factor A （TFAM）. Western blot was performed to detect the protein expression levels of SIRT1， PGC-1α， NRF1， and TFAM. ResultsCompared with the blank group， rats in the model group exhibited disrupted estrous cycles， obviously reduced body weight， and decreased ovarian index （P<0.05）. Ovarian histopathology revealed cortical thinning， loose structure， and a significant reduction in both primordial and growing follicles （P<0.01）. Serum FSH and LH levels were significantly elevated （P<0.01）， while E₂ and AMH levels were obviously reduced （P<0.05， P<0.01）. ATP content and mtDNA copy number decreased in ovarian tissue （P<0.01）， ROS expression increased， MDA levels rose， while SOD and GSH-Px activities obviously decreased （P<0.05， P<0.01）， mRNA and protein expression levels of SIRT1， PGC-1α， NRF1， and TFAM were obviously downregulated （P<0.05， P<0.01）. After treatment， compared with the model group， body weight and ovarian index obviously recovered in rats administered various doses of YJZYT （P<0.05）， serum E₂ and AMH levels increased， while FSH and LH levels obviously decreased （P<0.05， P<0.01）， ovarian tissue ATP content and mtDNA copy number were up-regulated， ROS and MDA levels decreased， and antioxidant enzymes SOD and GSH-Px activity obviously increased （P<0.05， P<0.01）， Gene and protein expression levels related to the SIRT1/PGC-1α /NRF1/TFAM signaling pathway were obviously up-regulated compared to the model group （P<0.05， P<0.01）， HE staining revealed that ovarian structure gradually recovered to integrity in all treatment groups， with a obviously increase in the number of primordial and growing follicles （P<0.05， P<0.01）. Granulosa cells were neatly arranged， indicating marked improvement in ovarian function. ConclusionYJZYT may improve ovarian function and follicular development in rats with diminished ovarian reserve by activating the SIRT1/PGC-1α signaling pathway， promoting mitochondrial biogenesis， enhancing mitochondrial function， and alleviating oxidative stress damage.

Objective To study the chemical constituents of Fallopia aubertii L.Henry Holub. Methods The chemical constituents of Fallopia aubertii L.Henry Holub. were separated and purified by online two-dimensional preparative liquid chromatography and identified by physical and chemical constants and spectral analysis. The inhibitory activities on xanthine oxidase were determined by ultraviolet spectrophotometry. Results Ten compounds were isolated from the extract of Fallopia aubertii L.Henry Holub, including isotachioside（1）, 3,4,5-trimethoxyphenyl-（6'-O-galloyl）-O-β-D-Glucopyranoside（2）, 1-hydroxy-,4,5-1-O-[6'-O-（4''-carboxy-1'',3'',5'trihydrotrimethoxyphenylxy）-phenyl]-β-D-glucopyranoside（3）, myricetrin（4）, myricetin（5）, rutin（6）, quercetin-3-O-β-D-galactoside（7）, quercetin-3-O-β-D-glucopyranoside（8）, lyciumideA（9）, and N-trans-Feruloyltyramine（10）. The inhibitory activity test results showed that the IC₅₀ of compound 5 was 15.92 μmol/L, and the IC₅₀ of compound 6 was 87.36 μmol/L. Conclusion Compounds 1,2,3,4 and 8 were isolated from Medicago polymorpha for the first time. Compounds 5 and 6 had xanthine oxidase inhibitory activity.

【Objective】 To investigate the sperm retrieval rate (SRR) of microdissection testicular sperm extraction (M-TESE) in patients with non-obstructive azoospermia (NOA) caused by different causes. 【Methods】 A retrospective analysis was performed on 225 NOA patients during Jan.2020 and Dec.2022. The relation between SRR and patients’ age,body mass index (BMI),testicular volume,endocrine hormones and different etiological classifications were analyzed. 【Results】 According to whether sperm was obtained by surgery,the patients were divided into two groups,including 107 cases in the sperm group and 118 cases in the non-sperm group. There were no significant differences in patients’ age,testicular volume and levels of endocrine hormones between the two groups (P>0.05). According to the different causes,NOA patients with mumps history,cryptorchidism history,AZFc deletion or Klinefelter syndrome (KS) had higher SRR,while idiopathic NOA patients had the lowest SRR (P<0.05). 【Conclusion】 M-TESE is an effective treatment of NOA. There is no correlation between SRR and patients’ age,MBI,testicular volume and levels of endocrine hormones. NOA caused by different etiological classifications may have different SRR.

Objective:To understand the prevalence of human parechovirus (HPeV) in neonates of Hunan Provincial People’s Hospital, and analyze genetic evolutionary characteristics.Methods:From June to September 2021, fecal samples of inpatient neonates were collected in Hunan Provincial People′s Hospital. TaqMan real-time qPCR and RT-PCR were used for HPeV screening and genotyping. High-throughput sequencing and PCR were used to obtain whole genomes. Phylogenetic analysis was performed after sequencing.Results:A total of 123 fecal samples of neonates were collected, of which 22 were HPeV positive, with 17.89% positive rate. All the strains belonged to the HPeV-1 genotype. One full-length genomic sequence of 7 269 bp were obtained, and provisionally named Hunan/HPeV/2021, which has the highest nucleotide identity with known HPeV-1 genotype, with 86.6%-91.9% nucleotide identity. The nucleotide and amino acid identity of open reading frame (ORF) with known similar sequences were 90.3%-92.6% and 97.3%-98.3%, respectively. The phylogenetic analysis showed that Hunan/HPeV/2021 belongs to the HPeV-1 genotype, which is clustered into the same clade as the popular HPeV-1 strains in China.Conclusions:HPeV has a high prevalence in inpatient neonates of Hunan Provincial People’s Hospital and belong to the HPeV-1 genotype.

Objective:To explore the clinical effect of Bobath manipulation combined with traditional Chinese medicine fumigation and intradermal acupuncture on shoulder hand syndrome(SHS) after stroke.Methods:From April 2017 to August 2019, 80 patients with SHS after stroke admitted to the People's Hospital of Deqing County were selected, and they were divided into control group and observation group according to the random digital table method, with 40 cases in each group.The control group was treated by Bobath therapy, and the observation group was treated by Bobath therapy combined with acupuncture(intradermal acupuncture) and traditional Chinese medicine fumigation.After 8 weeks of treatment, the ROM scale, FMA scale, BI scale and VAS scores were used to evaluate the improvement in the mobility of the shoulder and wrist joints, motor function of the upper limbs, quality of life and pain, and the clinical efficacy of the two groups was compared.Results:Compared with before treatment, the ROM scale score of all dimensions of shoulder and wrist mobility, FMA scale score and BI scale score of all patients after treatment increased significantly, and the VAS score decreased significantly, the differences were statistically significant(all P<0.05). Compared with the control group after treatment, the improvement of the indicators mentioned above of the observation group were better[shoulder joint flexion ROM score: (154.83±25.63)points vs.(133.82±22.03)points; shoulder joint abduction ROM score: (152.36±25.68)points vs.(133.35±19.96 )points; shoulder joint external rotation ROM score: (75.87±14.69)points vs.(60.82±16.57 )points; wrist joint palm flexion ROM score: (73.94±14.37)points vs.(57.37±9.47)points; wrist joint back extension ROM score: (60.83±7.61)points vs.(42.27±6.37 )points; FMA scale score: (45.74±6.82)points vs.(34.19±4.07)points; BI scale score: (70.36±12.09)points vs.(58.70±12.53)points; VAS score: (1.05±0.49)points vs.(3.37±1.14)points, t=3.703, 3.715, 3.257, 5.576, 7.964, 3.037, 8.746, 3.153, all P<0.05]. The total effective rate of the observation group was significantly higher than that of the control group[97.5%(39/40) vs.62.5%(25/40), χ 2=15.313, P<0.05)]. Conclusion:The combination of Bobath therapy with traditional Chinese medicine fumigation and intradermal acupuncture can improve the pain degree, joint mobility disorder, upper limb motor function and quality of life of SHS patients, the efficacy is better than single Bobath therapy.The clinical effect is accurate, and it is worthy of further promotion and application.

Objective: To investigate the mechanism of lncRNA HCG18/miR-17-5p/HMGA2 axis regulating the proliferation and metastasis of non-small cell lung cancer (NSCLC) cells. Methods: Sixty-two pairs of NSCLC tissues and corresponding para-cancerous tissues collected at Central Hospital of Chengde City from June 2017 to June 2018 were used for this study; in addition, NSCLC cell lines (A549, NCI-H1299, H1650, NCI-H460) and human lung epithelial BEAS-B cells were also collected. mRNA expression levels of HCG18, miR-17-5p and high-mobility group AT-hook 2 (HMGA2) in NSCLC tissues and cell lines were measured by quantitative Real-time polymerase chain reaction (qPCR). Si-HCG18, miR-17-5p, miR-17-5p+HCG18 or pcDNA3.1-HMGA2 were transfected into A549 cells and NCI-H460 cells; CCK-8 assay was used to detect the proliferation of transfected cells, Transwell assay was used to detect the migration and invasion ability of cells, and Wb was used to analyze the expressions of HMGA2 and EMT associated proteins (E-cadherin, N-cadherin and vimentin). The target relationships between HCG18 and miR-17-5p, or between miR-17-5p and HMGA2 were confirmed by dual luciferase reporter gene assay. Mice A549 cell xenograft model with HCG18 knockdown was constructed, and the growth of transplanted tumor was observed. Results: lncRNA HCG18 was highly expressed in NSCLC tissues and cells (all P<0.01); HCG18 level was significantly increased in patients at late stage or with lymphnode metastasis; and high HCG18 level was correlated with poor prognosis and low survival rates of NSCLC patients (all P<0.01). Knockdown of HCG18 significantly inhibited NSCLC cell proliferation, migration and invasion (all P<0.01), up-regulated E-cadherin expression but suppressed N-cadherin and vimentin expression (all P<0.01), and the volume of xenograft was obviously decreased (P<0.05). Dual luciferase reporter gene assay confirmed the relationship between HCG18 and miR-17-5p as well as miR-17-5p and HMGA2. miR-17-5p transfection significantly inhibited NSCLC cell proliferation, migration and invasion (all P<0.01), and up-regulated E-cadherin expression, reversely suppressed N-cadherin and vimentin expression (all P<0.01); however, miR-17-5p + HCG18 transfection reversed the effect of miR-17-5p on NSCLCcells.Conclusion:HCG18promotes the proliferationandmigrationofNSCLCcellsthrough regulating miR-17-5p/HMGA2 axis.

EGFR tyrosine kinase inhibitor (EGFR-TKI) has been used successfully in clinic for the treatment of solid tumors. In the present study, we reported the discovery of from our in-house diverse compound library, which was validated to be a potent and selective EGFR-TKI. showed excellent inhibitory activities against EGFR (IC = 0.81 nmol/L), EGFR (IC = 1.2 nmol/L) and EGFR (IC = 1.1 nmol/L), but was less effective or even inactive against other nine kinases. also displayed excellent antiproliferative activities against a panel of human cancer cell lines, and exhibited the ability to reduce colony formation and wound healing the same as gefitinib. We found that upon oral administration showed better anti-tumor activity in A431 bearing xenograft mouse models compared to gefitinib. In addition, showed better intestinal absorption than gefitinib and had favorable pharmacokinetic properties and microsomal metabolic stability in different species. These studies indicate that has strong antitumor activity and , and could be used for the development of anti-lung cancer agent targeting EGFR.

Objective To explore the clinical,imaging,genetic features in a case of fatal familial insomnia (FFI),and review related literatures.Methods A case of middle-aged woman diagnosed as frontotemporal dementia based on the preliminary manifestation of abnormal mental behavior was reported.The clinical features,imaging characteristics,electroencephalogram and polysomnogram of the patient were analyzed,and the blood samples from the patient and some of her familial members were collected for the sequencing of prion protein gene (PRNP).Results This patient was a middle-aged woman,whose clinical manifestations were abnormal mental behavior,rapid progressive dementia and intractable insomnia,abnormal night sleep behavior and laryngeal stridor.Brain MRI indicated frontotemporal lobe atrophy.Non-sleep disturbance was observed in polysomnography.The cerebrospinal fluid was negative for 14-3-3 protein.The results of PRNP sequencing revealed that the mutation of gene D178N/129M was detected.Conclusions Detection of PRNP plays an important role in the diagnosis of FFI.Patients suspected of FFI in clinic should be detected for genetic testing.Whether the frontotemporal lobe atrophy was caused by FFI or concurrent with FFI remains to be further verified.

Objective To investigate curative efficacy of chemotherapy with oxaliplatin and tegafur gimeracil oteracil potassium capsule versus oxaliplatin-assisted xihuang capsules in the treatment of advanced gastric cancer and its effects on T cell subsets,survival rate and adverse reaction.Methods A total of 84 patients with gastric cancer in our hospital were randomly divided into control group and test group according to random number table method,control group was given chemotherapy with oxaliplatin and tegafur gimeracil oteracil potassium capsule,and test group was additionally given adjuvant treatment of xihuang capsules on the basis of the control group.T cell subsets and KPS score,clinical efficacy,adverse reactions and survival rate were compared.Results The total effec tive rate in the test group was 59.5％,which was significantly higher than 38.1％ in the controlgroup (P ＜0.05).Disease control rate was 78.6％ in the test group,which was significantly higher than5 7.1 ％ in the control group (P ＜ 0.0 5).The KPS scores showed no significant difference before and after treatment in two groups (P ＞ 0.05).The levels of CD3 +,CD4 +,and CD4 + / CD8 + inthe experimental group at 4 weeks after treatment were significantly higher than that 1 week before treatment (P ＜ 0.05).Patients with adverse reactions for grade Ⅲ or Ⅳ in the test group were significantly less than that in the control group (1 case vs.5 cases,P ＜ 0.05).One and a half year survival rate and 2-year survival rate in the test group were 57.1％ and 40.5％,which were significantly higher than 35.7％,19％ in the control group (P ＜ 0.05).Conclusion Adjuvant therapy of xihuang capsules can effectively improve the immunity and survival rate,and reduce adverse reactions,so it is worthy of popularization in clinic.

Objective To investigate curative efficacy of chemotherapy with oxaliplatin and tegafur gimeracil oteracil potassium capsule versus oxaliplatin-assisted xihuang capsules in the treatment of advanced gastric cancer and its effects on T cell subsets,survival rate and adverse reaction.Methods A total of 84 patients with gastric cancer in our hospital were randomly divided into control group and test group according to random number table method,control group was given chemotherapy with oxaliplatin and tegafur gimeracil oteracil potassium capsule,and test group was additionally given adjuvant treatment of xihuang capsules on the basis of the control group.T cell subsets and KPS score,clinical efficacy,adverse reactions and survival rate were compared.Results The total effec tive rate in the test group was 59.5％,which was significantly higher than 38.1％ in the controlgroup (P ＜0.05).Disease control rate was 78.6％ in the test group,which was significantly higher than5 7.1 ％ in the control group (P ＜ 0.0 5).The KPS scores showed no significant difference before and after treatment in two groups (P ＞ 0.05).The levels of CD3 +,CD4 +,and CD4 + / CD8 + inthe experimental group at 4 weeks after treatment were significantly higher than that 1 week before treatment (P ＜ 0.05).Patients with adverse reactions for grade Ⅲ or Ⅳ in the test group were significantly less than that in the control group (1 case vs.5 cases,P ＜ 0.05).One and a half year survival rate and 2-year survival rate in the test group were 57.1％ and 40.5％,which were significantly higher than 35.7％,19％ in the control group (P ＜ 0.05).Conclusion Adjuvant therapy of xihuang capsules can effectively improve the immunity and survival rate,and reduce adverse reactions,so it is worthy of popularization in clinic.