Objective: To explore the efficacy and surgical techniques of ultrasound-assisted transurethral flexible ureteroscopic holmium laser incision and internal drainage in the treatment of special renal cystic diseases，so as to provide reference for the diagnosis and treatment of such diseases. Methods: The clinical data of 48 patients with special renal cystic diseases treated during Jan.2019 and May 2023 were retrospectively analyzed.The diagnosis was made by computed tomography urography (CTU) and three dimensional urinary tract reconstruction before operation.All patients received the abovementioned surgery in semisupine lithotomy position.The general information，clinical data，and incidence of complications were analyzed. Results: There were 27 males and 21 females，with an average age of (48.0±7.5) years，including 22 cases of parapelvic cysts，6 cases of endogenic simple renal cysts with an average diameter of (5.0±1.0) cm，and 20 cases of renal calyceal diverticulum with stones，with an average diameter of (2.5±1.3) cm for the diverticulum and an average diameter of (1.5±1.0) cm for the stones，which were located in the upper or middle calyces.In 7 cases，ureteroscopic localization was difficult，and the surgery was completed with percutaneous renal puncture needle assisted localization.Ureteral stenosis was detected in 2 cases during surgery，and surgery was performed 4 weeks after double J tubes were placed.The remaining operations were successfully completed.The average operation time was (42.0±14.5) minutes，and average hospital stay was (2.0±0.5) days.During the follow-up of (12.0±8.5) months，lumbar pain improved in 27 cases (100%)，renal cysts disappeared in 23 cases (82.1%,23/28)，cysts significantly reduced by ≥50% in 4 cases (14.3%,4/28)，slightly reduced by <50% in 1 case (3.6%,1/28)，and the renal calyx diverticulum disappeared in 20 cases (100%).Gross hematuria and lower back pain occurred in 2 cases，and no other complications developed. Conclusion: Ultrasound-guided transurethral flexible ureteroscopic holmium laser incision and internal drainage is a safe and effective treatment for special benign renal cystic diseases.When ultrasound-guided flexible ureteroscope localization is difficult to perform，percutaneous renal puncture needle may be applied.

In order to isolate Mycoplasma hyopneumoniae(Mhp)and select virulent strains with high growth titer from the isolates to acclimate at high temperature to obtain attenuated strains.Forty lung and trachea tissues were aseptically collected from pigs suspected of Mhp in several farms in Nanyang City.A total of 6 strains of Mhp were isolated through pathogen isolation,colony observation,PCR identification and sequencing.For each isolate,round colonies with neat edges,dewdrop like particles and ridges in the center were observed on solid medium.PCR could amplify the target gene bands of each isolated P36.After sequencing,the amplified products were compared with the gene sequences of ATCC 25934 reference strain(J strain)P36 registered in NCBI,and the homology was more than 99％.The growth titer of TH-1 strain measured by CCU experiment could reach 1011 CCU/mL,which showed a high growth titer.TH-1 strain was selected for continu-ous passage at high temperature(40 ℃)in vitro to obtain different passages(P50,P1 00,P1 50).TH-1 P150 still had a higher growth titer(1010 CCU/mL)at 40 ℃ growth temperature.TH-1 P1,P50,P100 and P150 were injected into the trachea to infect 25-day-old weaned piglets,and the re-sults of virulence evaluation showed that 4 pigs(4/5)in the P1 infection group had typical"meat or shrimp meat"lesions,and serious monocyte and lymphocyte infiltration were found in the lung HE pathological sections,and the cilia were clutter-tangled,shortened and exfoliated.P150 infec-tion group did not show typical Mhp characteristic lesions,lung HE and tracheal scan sections did not show microscopic pathological changes,indicating that TH-1 was a virulent strain,but its viru-lence was continuously decreased after continuous in vitro passage,and TH-1 P150 was a low-viru-lence strain.TH-1 P150 strain,as a attenuated vaccine strain,has good immunogenicity,and the av-erage reduction rate of pneumonia disease after immune challenge was 83.3％.In conclusion,a low-virulence strain with high growth titer(TH-1 P150)was obtained by continuous passage at high temperature in vitro for the first time,and its immunogenicity was good,which laid the foundation for further research and development of Mhp attenuated vaccine.

Objective:To investigate the association between congenital hypothyroidism (CH) and the adverse outcomes during hospitalization in very low birth weight infants (VLBWI).Methods:This prospective, multicenter observational cohort study was conducted based on the data from the Sino-northern Neonatal Network (SNN). Data of 5 818 VLBWI with birth weight <1 500 g and gestational age between 24-<37 weeks that were admitted to the 37 neonatal intensive care units from January 1 st, 2019 to December 31 st, 2022 were collected and analyzed. Thyroid function was first screened at 7 to 10 days after birth, followed by weekly tests within the first 4 weeks, and retested at 36 weeks of corrected gestational age or before discharge. The VLBWI were assigned to the CH group or non-CH group. Chi-square test, Fisher exact probability method, Wilcoxon rank sum test, univariate and multivariate Logistic regression were used to analyze the relationship between CH and poor prognosis during hospitalization in VLBWI. Results:A total of 5 818 eligible VLBWI were enrolled, with 2 982 (51.3%) males and the gestational age of 30 (29, 31) weeks. The incidence of CH was 5.5% (319 VLBWI). Among the CH group, only 121 VLBWI (37.9%) were diagnosed at the first screening. Univariate Logistic regression analysis showed that CH was associated with increased incidence of extrauterine growth retardation (EUGR) ( OR=1.31(1.04-1.64), P<0.05) and retinopathy of prematurity (ROP) of stage Ⅲ and above ( OR=1.74(1.11-2.75), P<0.05). However, multivariate Logistic regression analysis showed no significant correlation between CH and EUGR, moderate to severe bronchopulmonary dysplasia, grade Ⅲ to Ⅳ intraventricular hemorrhage, neonatal necrotizing enterocolitis in stage Ⅱ or above, and ROP in stage Ⅲ or above ( OR=1.04 (0.81-1.33), 0.79 (0.54-1.15), 1.15 (0.58-2.26), 1.43 (0.81-2.53), 1.12 (0.70-1.80), all P>0.05). Conclusion:There is no significant correlation between CH and in-hospital adverse outcomes, possibly due to timely diagnosis and active replacement therapy.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been reapproved for heart failure (HF) therapy in patients with and without diabetes. However, the initial glucose-lowering indication of SGLT2i has impeded their uses in cardiovascular clinical practice. A challenge of SGLT2i then becomes how to separate their anti-HF activity from glucose-lowering side-effect. To address this issue, we conducted structural repurposing of EMPA, a representative SGLT2 inhibitor, to strengthen anti-HF activity and reduce the SGLT2-inhibitory activity according to structural basis of inhibition of SGLT2. Compared to EMPA, the optimal derivative JX01, which was produced by methylation of C2-OH of the glucose ring, exhibited weaker SGLT2-inhibitory activity (IC₅₀ > 100 nmol/L), and lower glycosuria and glucose-lowering side-effect, better NHE1-inhibitory activity and cardioprotective effect in HF mice. Furthermore, JX01 showed good safety profiles in respect of single-dose/repeat-dose toxicity and hERG activity, and good pharmacokinetic properties in both mouse and rat species. Collectively, the present study provided a paradigm of drug repurposing to discover novel anti-HF drugs, and indirectly demonstrated that SGLT2-independent molecular mechanisms play an important role in cardioprotective effects of SGLT2 inhibitors.

Objective:The study aimed to investigate the effects of exercise on the expression of ferroptosis-related proteins and the associated mechanisms in a post-traumatic stress disorder(PTSD)model induced by transient foot shock.Methods:Thirty-five male C57BL/6J mice(8 weeks old)were randomly divided into three groups:Control group,PTSD group,and Exe+PTSD group.PTSD model mice were established by foot-shock and PTSD behaviors were assessed using a fear conditioning box.Iron distribution areas were detected by Fe3+staining.Western Blot analysis were performed to determine the expression level of ferroptosis-related proteins in the mice.Results:Compared to the control group,the freezing time and Fe3+distribution areas in the cortex and hippocampus were significantly increased in the mice with PTSD(P＜0.05).The levels of ferroportin1(FPN1),glutathione peroxidase 4(GPX4),and brain-derived neurotrophic factor(BDNF)proteins were significantly decreased(P＜0.05),while the expression of high mobility group box 1(HMGB1)protein was significantly elevated(P＜0.05).Exercise significantly reduced freezing time and Fe3+accumulation in the cortex and hippocampus(P＜0.05),and it also up-regulated the expression of FPN1,GPX4,and BDNF proteins(P＜0.05),while down-regulating HMGB1 expression compared to the PTSD group(P＜0.05).Conclusion:This study demonstrates that PTSD induces the ferroptosis-related pathway in mice,and exercise can inhibit iron accumulation and reverse the expression of ferroptosis-related proteins induced by PTSD,there-by alleviating PTSD-like behavior in mice.

[摘 要] 目的：分析甲状旁腺激素样激素（PTHLH）基因与肺鳞状细胞癌（LSCC）患者预后及其与肿瘤微环境（TME）免疫细胞浸润的相关性。方法：通过UALCAN、TIMER、cBioPortal数据库在泛癌水平分析PTHLH在泛癌中的表达情况，运用Kaplan-Meier Plotter数据库分析PTHLH在LSCC中的表达及其与患者的预后关联。选用2017年1月至2020年12月在甘肃省肿瘤医院手术切除的24例LSCC患者的癌及癌旁组织标本，用qPCR和WB法分别检测LSCC组织中PTHLH mRNA和蛋白的表达，用qPCR法检测各种趋化因子和MHC分子的表达水平。采用TIMER数据库联合CIBERSORT反卷积法分析PTHLH基因表达和LSCC的TME中免疫细胞浸润的关系。结果：LSCC组织中PTHLH mRNA和蛋白的表达水平均显著高于癌旁组织（均P<0.05），且PTHLH高表达LSCC患者的OS明显缩短（P<0.01）。PTHLH的表达与LSCC患者TME密切相关（P<0.01）。PTHLH的表达与B细胞、CD8+ T细胞、CD4+ T细胞、中性粒细胞和DC等免疫浸润呈显著负相关（r=-0.142、-0.123、-0.224、-0.166、-0.213，均P<0.01）。PTHLH高表达抑制趋化因子、MHC分子的表达，从而抑制炎症反应、免疫浸润、抗肿瘤免疫反应等。PTHLH的表达与免疫检查点分子CTLA-4、PDCD1、TIGIT呈负相关（r=-0.340、-0.441、-0.38，均P<0.01）。结论：PTHLH与肿瘤免疫抑制相关，有望成为预测LSCC患者预后和免疫治疗效果的潜在生物标志物。

Objective To explore the role of multi-department cooperation in the prevention and control of nosocomial infection of multi-drug-resistant bacteria(MDRO). Methods Theretrospective analysis was conducted on 1 478 inpatients before the implementation of multi-department cooperative management (January 2019 to December 2019). The implementation of multi-department cooperative management began in January 2020, including :(1) the establishment of multi-department cooperative management organization system; (2) Establish a three-level MANAGEMENT network of MDRO; (3) Multidisciplinary joint training; (4) Clinical departments shall be equipped with clinical pharmacists; (5) The hospital infection monitoring system was used to conduct real-time monitoring on the submission of microbial samples, the detection rate of MDRO, the changes of drug-resistant bacteria and the use of antibiotics; (6) Led by the department of hospital pathology and medical Service, regular joint ward rounds should be conducted in the departments and key departments with high DETECTION rate of MDRO; (7) PDCA cycle mode was adopted for quality control of all links of nosocomial infection prevention and control measures; After the implementation of multi-department cooperative management (January 2020 to December 2020), all the hospitalized patients in 1849 cases were detected and counted, and the incidence of nosocomial infection, the detection rate of MDRO, the compliance rate of hand hygiene, the implementation rate of contact isolation, and the specimen inspection rate of therapeutic use of antibiotics and the reasonable utilization rate of antibiotics were compared before and after the implementation. Results The incidence of nosocomial infection and the detection rate of MDRO were significantly lower after the implementation of multi-department cooperative management than before (χ²=46.611, χ²=16.814, P < 0.05). The hand hygiene compliance rate and contact isolation implementation rate were significantly higher after the implementation of multi-department cooperative management than before (χ² = 25.357, χ²=29.227, P<0.05). After the implementation of multi-department cooperative management, the sample test rate of therapeutic use of antibiotics was significantly higher than that before the implementation of multi-department cooperative management (χ²=25.576, χ²=33.624, P<0.05). Conclusion The practice of multi-department cooperative management brings into full play the advantages of interdisciplinary complementarity, improves the ability of medical staff to implement the prevention and control measures for MDRO, and can effectively reduce the incidence of nosocomial infection in MDRO.

Objective:To explore the effect of systematic pain management on pain of children with traumatic limb fractures.Methods:A total of 185 children with traumatic limb fracture who were treated in Children's Hospital of Hebei Province from January 2019 to December 2020 were selected as the research objects by the convenient sampling method. According to the random number table method, they were randomly divided into the intervention group (93 cases) and the control group (92 cases) . Children in both groups were treated with fracture surgery under general anesthesia. The intervention group used systematic pain management for intervention, and the control group used conventional pain management for intervention. The operation time, wake up time, extubation time, Ramsay sedation score after wake-up and Modified Objective Pain Score (MOPS) at admission, 24, 48 h after admission, and 24, 48 h after surgery were compared between the two groups.Results:There was no statistically significant difference in operation time, wake-up time, extubation time and Ramsay sedation scores after wake-up between the two groups ( P>0.05) . On admission, there was no statistically significant difference in the MOPS scores of children between the two groups ( P>0.05) . At 24 and 48 hours after admission and 24 and 48 hours after operation, MOPS scores of the intervention group were lower than those of the control group, and the differences were statistically significant ( P<0.01) . Conclusions:Compared with conventional pain management, systemic pain management can alleviate the pain of traumatic limb fractures in children.

Objective:To explore the advantages of the novel individualized 3D printing artificial vertebral body in spine reconstruction and to evaluate its clinical effect.Methods:From January 2017 to December 2018, the 15 patients who underwent total vertebrectomy and spine reconstruction with individualized 3D printing artificial vertebral body were analyzed retrospectively. There were 8 males and 7 females, with the mean age 39.5 years (range: 20-57), including 12 primary tumors and 3 metastatic tumors. According to tumor location and surrounding soft tissue invasion range, simple posterior or combined anterior and posterior approach were used for total vertebral resection, and the defection was reconstructed by 3D printing artificial vertebral body. The operation time, intraoperative bleeding volume, postoperative stability of artificial vertebral body and bone ingrowth of adjacent vertebral body, preoperative and postoperative neurological changes, preoperative and postoperative VAS score, local control and survival of patients were analyzed.Results:The mean operation time was 412.0 min (range: 135-740 min), and the mean blood loss was 4 140.0ml (range: 100-14 000 ml). The mean follow-up time was 23.2 months (range: 12-35 months), and no one loss to follow-up. One case had pleural rupture, one case had cerebrospinal fluid leakage and one case had L5 nerve root palsy. All patients recovered after active symptomatic treatment. Compare with the preoperative VAS score (4.7±1.1), the differences of VAS score at 7 d postoperative and last follow-up (1.6±0.6 and 1.0±0.5) were significantly reduced ( P<0.001). Three patients with Frankel grade C gradually recovered to grade D, and no change were found in grade D and Grade E patients, there was no significant improved at last follow-up. Preliminary bone growth was found between the artificial vertebral body and the adjacent vertebral body 3 months after operation. The bone growth was more obvious at 12 months post-operation, and the artificial vertebral body fused with the adjacent vertebral bodies to form bone integration. At 24 months post-operation, the integration of the artificial vertebral body was more accurate. During the follow-up period, there was no loosening or displacement of the artificial vertebral body and no failure of internal fixation. A case of hemangioendothelioma and a case of epithelioid angiosarcoma died at 33 months and 35 months postoperatively. One patient with chondrosarcoma had local recurrence at16 months post-operation. After treated with arotinib, the tumor did not progress. The other 12 patients had no tumor recurrence or distant metastasis. Conclusion:After spinal tumor resection, individualized 3D printing artificial vertebral body can be used to accurate restoration of spinal continuity, and provide nice interface matching and bone growth between artificial vertebral body and the adjacent vertebral endplates. Moreover, the immediate and long-term stability of the artificial vertebral body can meet the needs of spinal reconstruction.

Ischemic stroke is a severe disorder resulting from acute cerebral thrombosis. Here we demonstrated that post-ischemic treatment with ciclopirox olamine (CPX), a potent antifungal clinical drug, alleviated brain infarction, neurological deficits and brain edema in a classic rat model of ischemic stroke. Single dose post-ischemic administration of CPX provided a long-lasting neuroprotective effect, which can be further enhanced by multiple doses administration of CPX. CPX also effectively reversed ischemia-induced neuronal loss, glial activation as well as blood-brain barrier (BBB) damage. Employing quantitative phosphoproteomic analysis, 130 phosphosites in 122 proteins were identified to be significantly regulated by CPX treatment in oxygen glucose deprivation (OGD)-exposed SH-SY5Y cells, which revealed that phosphokinases and cell cycle-related phosphoproteins were largely influenced. Subsequently, we demonstrated that CPX markedly enhanced the AKT (protein kinase B, PKB/AKT) and GSK3 (glycogen synthase kinase 3) phosphorylation in OGD-exposed SH-SY5Y cells, and regulated the cell cycle progression and nitric oxide (NO) release in lipopolysaccharide (LPS)-induced BV-2 cells, which may contribute to its ameliorative effects against ischemia-associated neuronal death and microglial inflammation. Our study suggests that CPX could be a promising compound to reduce multiple ischemic injuries; however, further studies will be needed to clarify the molecular mechanisms involved.