OBJECTIVE To evaluate the effect of manipulation of Imipenem and cisplatin sodium （ICS） for injection on the consistency of its main drug imipenem （IPN） content， and the stability of different concentrations of ICS solution， to provide a reference for the safe and effective use of ICS in children. METHODS Three operators prepared ICS solutions according to the two commonly used dosage methods for children （10 mL or 20 mL 0.9% Sodium chloride injection to prepare the initial ICS solution and draw the required dose from the initial suspension）. The content of IPN was determined by ultra-high performance liquid chromatography-tandem mass spectrometry after parallel processing. The content consistency of solutions in each group was determined according to the coefficient of variation （CV）＜15% of the IPN content. ICS test solution X1 was prepared according to the instructions， and then test solutions X2 and X3 were prepared by diluting X1 with 0.9% Sodium chloride injection in the volume ratios of 1∶1 and 1∶2， which were stored at room temperature （[ 23.0±0.5） ℃]， in a thermostatic water bath at 30 ℃， and in a refrigerator at 2-8 ℃. The stability of the drug solution was determined by the ratio of the IPN mass concentration measured at the specified temperature and time to the initial （0 h） mass concentration （if the ratio was≥90%， it was considered that the drug solution was stable）. RESULTS CV of IPN content was ＜15% in each group of solutions prepared with two manipulation methods by each operator， indicating a small deviation in IPN content. The solutions at the three concentration levels were stable at room temperature for 6 h or refrigerated for 18 h. The test solutions X1 and X2 were also stable when placed at 30 ℃ for 6 h， but the IPN concentration in test solution X3 decreased by about 20% compared with that of 0 h. CONCLUSIONS The consistency of the content of IPN is good in the two commonly used methods for ICS manipulation in children. The stability of ICS solution is affected by concentration， temperature and time. Lower concentrations at higher temperatures resulted in decreased stability of IPN. Clinical attention should be paid to controlling the amount of solvent as well as temperature and time during preparation and use.

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Objective To clone the full-length sequence,subcellular localization,and analyze the expression patterns of the β-caryophyllene synthase gene(AaCPS)of Artemisia argyi,in order to lay a foundation for the gene function analysis of sesquiterpene biosynthesis pathway in A.argyi.Methods The genes annotated as CPS were selected from the transcriptome data of A.argyi.The full-length cDNA sequence of the target gene was obtained by PCR,and the coding region was analyzed using bioinformatics.A prokaryotic expression vector was constructed and transformed into Escherichia coli competent cells to express recombinant protein.A green fluorescent protein(GFP)fused expression vector was constructed,and the subcellular localization of AaCPS was observed using Agrobacterium tumefaciens transient expression method in tobacco.Real-time quantitative PCR(qRT-PCR)was used to analyze the expression patterns of the AaCPS at different harvest times(April,May,June,July).Determination of β-caryophyllene by HS-SPME-GC-MS and correlation analysis.Results The AaCPS gene was cloned from A.argyi.The full-length open reading frame(ORF)was 1647 bp,encoding 548 amino acids.The molecular weight was 63 667 Da with a theoretical pI of 5.94.AaCPS contained conserved Terpen_synth and Terpen_synth_C domains.Phylogenetic analysis indicated that AaCPS was closely related to the CPS protein of Artemisia annua.SDS-PAGE showed the presence of target protein bands between 75 000-120 000 Da(containing 28 132 Da of the labeled protein),indicating successful expression of the AaCPS protein.The protein was found to be localized in the cytoplasm.As shown by qRT-PCR,the expression of AaCPS gene showed an upward trend,reaching the highest in July.The results of HS-SPME-GC-MS showed that the content of β-caryophyllene increased gradually from April to the highest in June.It is consistent with the trend of AaCPS gene expression from April to June.Conclusion Through the cloning and analysis of AaCPS gene,a foundation has been laid for further study of the functional identification of the AaCPS gene in the sesquiterpenes biosynthesis pathway in A.argyi.

Objective:To observe the therapeutic effect of autologous neurosensory retinal transplantation in repairing unhealed giant macular hole after pars plana vitrectomy (PPV).Methods:A prospective clinical study. From July 2022 to December 2023, 12 patients (12 eyes) with refractory large macular hole who received autologous neurosensory retinal transplantation treatment in Department of Ophthalmology of the First Affiliated Hospital of Zhengzhou University were selected for the study. The macular hole in affected eyes still did not close after PPV combined with inner limiting membrane removal or tamponade, and the diameter of macular hole were greater than 600 μm. All affected eyes received best corrected visual acuity (BCVA) and optical coherence tomography (OCT) examinations. The BCVA examination employed the international standard visual acuity chart, with results converted to logarithm of the minimum angle of resolution (logMAR) visual acuity for statistical analysis. During the surgery, a piece of healthy retinal neuroepithelial tissue, approximately 0.3 optic disc diameters larger than the macular hole, was removed from the upper retinal periphery and used as a graft. The graft was inserted into the macular hole with the aid of intraoperative OCT. Post-surgery, the vitreous cavity was filled with silicone oil or sterile air. The follow-up period after surgery was 6 months. The thickness of the retinal grafts was measured using the same equipment as before surgery at 3 days, 1, 3, and 6 months post-surgery. The primary focus was on observing the macular hole closure rate and changes in BCVA at 6 months post-operation. A paired t-test was used to compare BCVA before and after surgery. Results:In the sample of 12 cases (12 eyes), there were 5 males with 5 eyes and 7 females with 7 eyes. The mean age was (50.4±12.6) years. The mean macular hole diameter was (1 085.6±344.0) μm; The mean eye axis length was (27.64±4.19) mm. At 6 months after surgery, all affected eyes showed macular hole were completely closed (100.0%, 12/12). The thickness of the retinal graft was measured as (206.8±21.0), (170.8±23.3), (165.6±31.6), and (157.9±31.1) μm at 3 days, 1, 3, and 6 months post-surgery, respectively. At before and 6 months after surgery, the logMAR BCVA of the affected eyes was 1.28±0.39 and 0.95±0.22, respectively. The difference in logMAR BCVA before and after surgery was statistically significant ( t=3.40, P<0.05). Conclusion:Autologous neurosensory retinal transplantation could effectively improve the closure rate of refractory large macular hole and improve or stabilize vision in the short run.

Objective:To explore the effect of tumor plastic surgery in breast conserving surgery for early breast cancer.Methods:From March 2015 to March 2021, 80 female patients with breast cancer, aged 31 to 55 (43±12) years, who were admitted to the Department of Breast and Thyroid Surgery, the First People′s Hospital of Chenzhou City, Hunan Province, were divided into plastic breast conserving group and conventional breast conserving group, with 40 cases in each group. The plastic surgery breast conserving group used plastic surgery techniques to repair local breast defects after surgery, while the conventional breast conserving group used fascial fat flaps around the cutting edge to repair local defects; the differences in surgical related indicators and postoperative complications were compared between two groups of patients, and the postoperative cosmetic effect was evaluated.Results:Both groups successfully completed the conservative surgery. The operation time, blood loss, and drainage tube retention time in the oncoplastic conservative surgery group were longer than those in the conventional conservative surgery group, and the differences were statistically significant (all P<0.001). The 2nd cut margin expansion rate was 2.5% (1/40) in the oncoplastic conservative surgery group, which was lower than that in the conventional conservative surgery group (20%, 8/40), and the difference was statistically significant ( P=0.034). There were 3 cases of partial necrosis and 2 cases of subcutaneous fat embolism in the oncoplastic conservative surgery group after surgery, and 1 case of partial necrosis and 1 case of subcutaneous fat embolism in the conventional conservative surgery group. All of them healed after drainage and dressing changes. The postoperative aesthetic effect evaluation showed that the excellent rate in the oncoplastic conservative surgery group was 95% (38/40), and the excellent rate in the conventional conservative surgery group was 70% (28/40). The difference was statistically significant ( P=0.003). After a follow-up of 36 to 96 months, no local recurrence or distant metastasis was found in either group. Conclusions:Breast-conserving surgery can enable early breast cancer patients to achieve wider tumor margins and better aesthetic effects, with good safety and is worth clinical application.

Objective To comprehensively characterize the diterpene alkaloids in Radix Aconiti Kusnezoffii.Methods The diterpene alkaloids were isolated and purified by strong acid cation exchange resin solid phase extraction column(SCX-SPE),and identified by ultra high performance liquid chromatography-Q-Exactive Orbitrap mass spectrometry(UHPLC-Q-Exactive Orbitrap MS).Results A total of 99 diterpene alkaloids were identified from Radix Aconiti Kusnezoffii,including 27 diester diterpene alkaloids(DDA),29 monoester diterpene alkaloids(MDA),40 amide diterpene alkaloids(ADA),2 polyester diterpene alkaloids(PDA)and 1 long-chain ester diterpene alkaloid(LDA).Conclusion The SCX-SPE combined with UHPLC-Q-Exactive Orbitrap MS method,established in this paper,can rapidly identify a large number of diterpene alkaloids in Radix Aconiti Kusnezoffii,which provides scientific proof for the study of pharmacodynamic substance basis and quality control of Radix Aconiti Kusnezoffii.

Objective:To observe the efficacy and safety of Tofacitinib in treating elderly rheumatoid arthritis(RA), in order to provide clinical evidence.Methods:In the randomized control trial, a total of 90 elderly RA patients admitted to the Department of Rheumatology of the First Affiliated Hospital of Soochow University from January 2019 to January 2021 were selected and divided into Methotrexate group(MTX group, MTX 10mg, qw, n=45)and Tofacitinib group(TOF group, oral 5mg, bid, n=45). The efficacy and safety of the two groups were evaluated at week 12.The primary endpoint was the proportion of patients meeting the American College of Rheumatology 50%(ACR50)improvement response criteria at week 12.Secondary endpoints included ACR20/70 improvement response, proportion of patients who met treat-to-target(T2T)criteria, including Disease Activity Score in 28 joints using erythrocyte sedimentation rate(DAS28-ESR), Disease Activity Score in 28 joints using C-reactive protein level(DAS28-CRP), clinical disease activity index(CDAI), and simplified disease activity index(SDAI), and patient-reported outcomes(PROs)which included changes compared to baseline in pain visual analog scale(VAS)and Health Assessment Questionnaire Disability Index(HAQ-DI)score, at week 12.Safety outcomes including drug-related adverse events, serious adverse events, dropping out due to adverse events, and deaths were assessed throughout.Results:Five patients in each group withdrew from the trial due to adverse events, and the number of patients who finally completed the observation was 40 in each group.At week 12, the ACR50 response rate was higher in TOF group than in MTX group[35%(14/40) vs.12.5%(5/40), χ2=5.591, P=0.018)], achieving the primary endpoint.When comparing TOF vs.MTX group, the ACR20 response rate[55%(22/40) vs.25%(10/40), χ2=7.500, P=0.006]and ACR70 response rate[25%(10/40) vs.7.5%(3/40), χ2=4.501, P=0.034], and proportions of indexes of disease remission including DAS28-ESR<2.6[25%(11/40) vs.7.5%(3/40), χ2=4.501, P=0.034], or DAS28-CRP<2.6[27.5%(11/40) vs.7.5%(3/40), χ2=5.541, P=0.019], or CDAI≤2.8[30%(12/40) vs.10%(4/40), χ2=5.000, P=0.025], or SDAI≤3.3[27.5%(11/40) vs.7.5%(3/40), χ2=5.541, P=0.019], and the proportions of patients with low disease activity including DAS28-ESR≤3.2[32.5%(14/40) vs.12.5%(5/40), χ2=5.591, P=0.018], or DAS28-CRP≤3.2[32.5%(14/40) vs.12.5%(5/40), χ2=5.591, P=0.018], or CDAI≤10[37.5%(15/40) vs.17.5%(7/40), χ2=4.013, P=0.045], or SDAI≤11[37.5%(15/40) vs.15%(6/40), χ2=5.230, P=0.022], as well as changes compared to baseline data in pain VAS[(26.51±8.32)scores vs.(14.16±4.39)scores, t=8.371, P<0.001]and in HAQ-DI score(0.65±0.24 vs.0.32±0.06, t=9.387, P<0.001)were all better in the TOF group than in the MTX group at week 12.During the 12-week observation period, the number of patients with infection and hyperlipidemia was higher in TOF group than in MTX group, while the number of patients with abnormal blood cell count and liver function was lower than that in MTX group, but the differences were not statistically significant(all P<0.05). Conclusions:Tofacitinib has good efficacy and safety in the elderly RA.In patients over 70 years of age who are at high risk of infection, tofacitinib should be used with caution.

Objective:To observe the histopathological changes in peripheral retinal lesions under intraoperative optical coherence tomography (iOCT).Methods:A retrospective case series study. Eighty-eight patients (194 eyes) who underwent vitreoretinal surgery in the Department of Ophthalmology at the East Ward of the First Affiliated Hospital of Zhengzhou University from October 2021 to May 2022 in 94 eyes were included in the study. Among them, 49 cases were male and 39 cases were female, with the mean age of (50.93±17.55) years. Ninety-four eyes included 32 eyes with retinal detachment, 6 eyes with proliferative diabetic retinopathy, 28 eyes with vitreous hemorrhage, 8 eyes with ocular trauma, 14 eyes with the macular lesion, 1 eye with uveitis, 1 eye with family exudative vitreoretinopathy (FEVR), 1 eye with acute retinal necrosis (ARN), and 3 eyes with lens dislocation. All affected eyes were examined with iOCT during vitreoretinal surgery. The iOCT scanning of the peripheral retina was performed with the help of episcleral pressure. The pre-equatorial and serrated edge anterior and posterior of retinas were scanned according to the characteristics of different fundus diseases. Various abnormal fundus manifestations were recorded.Results:In 94 eyes, 53 eyes (56.38%, 53/94) have different types of retinopathy in the peripheral retina. Of these, 7 eyes (7.45%) have retinal cystoid degeneration; 19 eyes (20.21%) have lattice degeneration; and 8 eyes (8.51%) have pigment degeneration; 9 eyes (9.57%) have pavement-like degeneration; 7 eyes (7.45%) have small occult holes; 1 eye (1.06%) has familial exudative vitreoretinopathy (FEVR) serrated edge "dyke-like" proliferative degeneration; 4 eyes (4.26%) have vitreous and retinopathy adhesions; and one eye (1.06%) has ARN.Conclusion:With clear refractive media, iOCT can provide clear scans of different peripheral retinal lesions.

Objective:To study the effect of Long non-coding RNA(LncRNA)small nucleolar RNA host gene 12(SNHG12)regulating miR-138-5p/hypoxia inducible factor-1(HIF-1α)axis on improving the damage of hypoxia/reoxygenation(H/R)human vas-cular endothelial cells.Methods:Human umbilical vein endothelial cells(HUVECs)were cultured in vitro and randomly divided into control group,H/R model group,H/R+LncRNA SNHG12 overexpression group,H/R+miR-138-5p mimics group,H/R+co-transfec-tion group and H/R+co-transfection negative control group,each transfection group was transfected separately,and except for control group,the remaining groups were given hypoxia for 5 hours and then reoxygenated for 1 hour to induce the cell models,and then the cell viability of each group was detected by CCK-8 experiment;the cell apoptosis in each group was detected by flow cytometry experi-ment,and the apoptosis rate of each group was compared;the levels of reactive oxygen species(ROS),lactate dehydrogenase(LDH)and inflammatory factors IL-6,IL-17 and IL-18 in each group were measured by the kit;the expressions of miR-138-5p and HIF-1α mRNA in cells of each group were measured by real-time quantitative PCR(qRT-PCR)experiment;the expressions of apoptotic pro-teins caspase-9,Bcl-2-associated X protein(Bax)and HIF-1α in each group were evaluated by Western blot.Results:Compared with control group,the apoptosis rate,cellular ROS,LDH,IL-6,IL-17 and IL-18 levels,cellular HIF-1α mRNA and protein levels,cellular caspase-9,Bax and HIF-1α protein levels were increased in H/R model group(P<0.05),the cell viability and miR-138-5p level were decreased(P<0.05).Compared with H/R model group and H/R+co-transfection group,the cell viability,cell HIF-1αmRNA and protein levels were increased in H/R+LncRNA SNHG12 overexpression group(P<0.05),the apoptosis rate,cellular ROS,LDH,IL-6,IL-17 and IL-18 levels,cellular caspase-9 and Bax protein levels,and miR-138-5p level were decreased(P<0.05);the cell viability,cellular HIF-1α mRNA and protein levels were decreased in H/R+miR-138-5p mimics group(P<0.05),the apoptosis rate,cellular ROS,LDH,IL-6,IL-17 and IL-18 levels,cellular caspase-9 and Bax protein levels were increased(P<0.05).Com-pared with H/R model group,there was no significant difference in cell index levels between the H/R+co-transfection negative control group and the H/R+co-transfection group(P>0.05).Conclusion:LncRNA SNHG12 can upregulate HIF-1α expression by downregulat-ing miR-138-5p expression,inhibit H/R-induced inflammation and oxidative stress in HUVECs,and reduce cell damage and apoptosis.

【Objective】 To investigate the risk factors of frailty syndrome in elderly patients with acute coronary syndrome （ACS） and their impact on prognosis. 【Methods】 The elderly patients with ACS aged 65 and over， who were hospitalized in the Department of Cardiology and Geriatric Cardiology of The First Affiliated Hospital of Xi’an Jiaotong University from September 2020 to February 2021， were selected in the cross-sectional survey. The patients were divided into frailty syndrome and non-frailty syndrome groups via the Chinese revised version of Tilburg Frailty Scale. We collected the patients’ activities of daily living， nutrition， depression， sleep quality， total cholesterol， triglycerides， low-density lipoprotein， and adverse events during hospitalization and within 30 days of discharge. We then performed LOG-BINOMIAL regression to analyze the risk factors of frailty syndrome. 【Results】 A total of 250 elderly ACS patients were enrolled， and 118 patients were diagnosed with frailty syndrome with 47.2% prevalence of frailty syndrome. There was a significant difference in the average score between the frailty syndrome group and the non-frailty syndrome group （11.06±2.53 vs. 5.77±1.54， P<0.01）. Multivariate regression analysis revealed that age （PR=2.01 CI： 1.81-2.22， P<0.001）， hypertension （PR=1.20 CI： 1.09-1.30， P<0.001）， chronic kidney disease （PR=1.16 CI：1.04-1.29， P=0.012）， and NT-proBNP （PR=1.20 CI： 1.07-1.35， P=0.004） were risk factors for frailty syndrome in elderly ACS patients. The incidence of arrhythmia and pulmonary infection during hospitalization and the rate of readmission within 30 days after discharge were significantly higher in the frailty syndrome group than those in the non-frailty syndrome group （P<0.05）. 【Conclusion】 There is a higher incidence of frailty syndrome in elderly patients with ACS. Older age， hypertension， chronic kidney disease and high NT-proBNP can increase the risk of frailty syndrome. In clinical practice， attention should be paid to the above factors， and reasonable intervention should be provided in time.