Lysosomes represent a promising target for cancer therapy and reducing drug resistance. However, the short treatment time and low efficiency of lysosomal targeting have limited the application in lysosome-targeting anticancer drugs. In this study, we proposed an adhesive-bandage approach and synthesized a new lysosomal targeting drug, namely long-term lysosome-targeting anticancer drug (LLAD). It contains a SLC38A9-targeting covalently bound moiety and an alkaline component both to prolong the inhibition of SLC38A9 in lysosomes and alkalinize lysosomes. Upon short term and low-dose treatment of HeLa cells, at passage 0, with LLAD, it rapidly alkalinized lysosomes and also can be detected in lysosomes even at passage 15. LLAD induced apoptosis in HeLa cells through long-term lysosomal damage, and showed better long-term anticancer effect than cisplatin in vivo. Overall, our study paves the way for developing long-term lysosomal targeting drugs to treat cancer and overcome the drug resistance of cancer cells, and also provides a candidate drug, LLAD, for treating cancer.

Objective: To compare quality control (relative purity and specific activity) and process control [plasminogen (Pg) antigen recovery and potency recovery] indexes of samples before and after adding the Q chromatography step to the full chromatography process of human Pg, thereby determining whether the addition of this step could improve Pg recovery by affinity chromatography. Methods: A Q chromatography step was added before the Pg affinity chromatography in the original Pg chromatography process. The loading solution, flow through solution and eluate of Q chromatography and Pg affinity chromatography were collected. The potency of coagulation factor Ⅱ (FⅡ), Ⅶ (FⅦ), Ⅷ (FⅧ), Ⅸ (FⅨ), and Ⅹ(FⅩ) were detected by the coagulation method, the total protein content was detected by the BCA method, and the Pg potency was detected by the chromogenic substrate method. The content of specific plasma proteins was detected by immunoturbidimetry, the potency recovery of coagulation factors was calculated, and the flow direction of coagulation factors was analyzed. The recovery of different plasma protein antigens were calculated, and the distribution of impurity proteins was analyzed. The relative purity and specific activity of Pg, antigen content, and potency recovery in the target fractions were calculated and compared with the original process indicators, so as to determine the effect of adding Q chromatography on the original process. Furthermore, the reproducibility after process modification was assessed. Results: 100% of FⅡ, FⅩ, and FⅨ, 87.81% of FⅧ, and 40.44% of FⅦ in filtered plasma were removed by Q chromatography. The residual FⅦ (53.26%) and FⅧ (13.30%) in Q flow-through fraction were completely removed by Pg affinity chromatography. In both the original process (without Q-chromatography) and the modified process (with Q-chromatography), non-target plasma proteins mainly existed in the flow-through fraction of Pg affinity chromatography. The antigen recovery of IgM, ceruloplasmin (CER), and fibronectin (FNC) in Q-chromatography flow-through fraction were reduced. In contrast, antigen recovery of other plasma proteins [IgG, IgA, Pg, albumin (AlB), alpha-1-antitrypsin (AAT), and fibrinogen (Fg)] were all >90%, which were consistent with the protein composition and proportion in the original affinity chromatography loading solution. Compared with the recovery rate of Pg antigen in the original process (74.4%), the total recovery of Pg antigen in the modified process was significantly increased (89.97%). Compared with the recovery of IgG (97.48%) and Fg (95.32%) in the Pg affinity flows-through fraction of the original process, the modified process resulted in a slight reduction in the recovery of IgG (94.60%), while the recovery of Fg was not affected (95.05%). The potency recovery rate, specific activity, and relative purity of Pg after Q chromatography were 99.3%, 0.016 U/mg, and 0.15%. These values were the same as those of Pg affinity chromatography loading solution by the original process, indicating that introduction of Q chromatography did not affect subsequent Pg affinity chromatography. Compared with the recovery of Pg antigen in three batches of the original process (66.49±1.02)%, the recovery of Pg antigen in the affinity chromatography eluent of the modified process [five batches; (77.43±4.43)%] was significantly improved. Furthermore, the potency recovery was (86.80±4.28)%, the relative purity was (81.99±1.25)%, the specific activity was (8.679±1.073)U/mg, and the process was reproducible. Conclusion: The addition of Q chromatography could improve the recovery of Pg affinity chromatography in the full chromatography process.

In recent years, with the rapid development of organ donation after citizen’s death and transplantation, central and local governments in China have successively released incentive policies. To protect the legitimate rights and interests of organ donors after citizen’s death and their families, current status of incentive policies for organ donation after citizen’s death was illustrated and analyzed from the perspective of ethics. Combining with the principles of justice, respect for autonomy, nonmaleficence and beneficence, the problems existing in the implementation of incentive policies for organ donation after citizen’s death were identified in China, such as lack of continuous psychological intervention in spiritual incentives, the misinterpretation of humanitarian assistance in practice and the impact of indirect economic incentives on individual donation autonomy, etc. Relevant countermeasures and suggestions were proposed at the government, society and individual levels, aiming to provide reference for improving the incentive policies for organ donation after citizen’s death and accelerate the development of organ donation in China.

Objective:To investigate the value of systemic inflammatory response syndrome (SIRS), pediatric sequential organ failure assessment (pSOFA) and pediatric critical illness score (PCIS) in predicting mortality of pediatric sepsis in pediatric intensive care units (PICU) from Southwest China.Methods:This was a prospective multicenter observational study. A total of 447 children with sepsis admitted to 12 PICU in Southwest China from April 2022 to March 2023 were enrolled. Based on the prognosis, the patients were divided into survival group and non-survival group. The physiological parameters of SIRS, pSOFA and PCIS were recorded and scored within 24 h after PICU admission. The general clinical data and some laboratory results were recorded. The area under the curve (AUC) of the receiver operating characteristic curve was used to compare the predictive value of SIRS, pSOFA and PCIS in mortality of pediatric sepsis.Results:Amongst 447 children with sepsis, 260 patients were male and 187 patients were female, aged 2.5 (0.8, 7.0) years, 405 patients were in the survival group and 42 patients were in the non-survival group. 418 patients (93.5%) met the criteria of SIRS, and 440 patients (98.4%) met the criteria of pSOFA≥2. There was no significant difference in the number of items meeting the SIRS criteria between the survival group and the non-survival group (3(2, 4) vs. 3(3, 4) points, Z=1.30, P=0.192). The pSOFA score of the non-survival group was significantly higher than that of the survival group (9(6, 12) vs. 4(3, 7) points, Z=6.56, P<0.001), and the PCIS score was significantly lower than that of the survival group (72(68, 81) vs. 82(76, 88) points, Z=5.90, P<0.001). The predictive value of pSOFA (AUC=0.82) and PCIS (AUC=0.78) for sepsis mortality was significantly higher than that of SIRS (AUC=0.56) ( Z=6.59, 4.23, both P<0.001). There was no significant difference between pSOFA and PCIS ( Z=1.35, P=0.176). Platelet count, procalcitonin, lactic acid, albumin, creatinine, total bilirubin, activated partial thromboplastin time, prothrombin time and international normalized ratio were all able to predict mortality of sepsis to a certain degree (AUC=0.64, 0.68, 0.80, 0.64, 0.68, 0.60, 0.77, 0.75, 0.76, all P<0.05). Conclusion:Compared with SIRS, both pSOFA and PCIS had better predictive value in the mortality of pediatric sepsis in PICU.

Objective:To explore the clinical and genetic etiology of a Chinese pedigree affected with type 2 Long QT syndrome (LQTS).Methods:A pedigree with type 2 LQTS presented at Fuwai Central China Cardiovascular Hospital on August 23, 2019 was selected as the study subject. Peripheral blood samples were collected from the proband and her parents. Following extraction of genomic DNA, whole exome sequencing (WES) was carried out for the proband, and candidate variant was screened through functional annotation and protein-protein interaction (PPI) analysis. Sanger sequencing was conducted to verify the pathogenicity of candidate variant. This study was approved by Medical Ethics Committee of the Fuwai Central China Cardiovascular Hospital (Ethics No. 2019-15).Results:WES revealed that the proband has harbored a missense variant of the KCNH2 gene, namely c. 1478A>G (p.Tyr493Cys), which was confirmed by Sanger sequencing to have inherited from her father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PM2_supporting+ PM5+ PP3+ PP4). Conclusion:The KCNH2 gene c. 1478A>G (p.Tyr493Cys) variant probably underlay the type 2 LQTS in this pedigree.

Objective To investigate the clinical efficacy of therapy of replenishing qi,removing stasis and unblocking collaterals(shortened as Yiqi Huayu Tongluo method)for sactosalpinx patients after minimally invasive tubal dredging operation(laparoscopic salpingo-oophorectomy)and to exlore its possible therapeutic mechanism.Methods The analysis was carried out in the infertility patients with mild,moderate,and severe bilateral sactosalpinx,80 cases for each degree,a total of 240 cases,which were confirmed by hysteroscopy and laparoscopic exploration in Haikou Hospital of Traditional Chinese Medicine from February 2014 to February 2020.The infertility patients with mild,moderate,and severe bilateral sactosalpinx were allocated to groups A,B,and C separately,and then each group was divided into 2 subgroups according to the treatment method,namely groups A1,A2,B1,B2,C1,C2,with 40 cases in each group.Among them,groups A1,B1,and C1 were named as the observation groups,and groups A2,B2,and C2 served as the control groups.The patients in the control groups were treated with laparoscopic salpingo-oophorectomy alone,while the patients in the observation groups were treated with oral use of Chinese medicine with the action of Yiqi Huayu Tongluo method together with laparoscopic salpingo-oophorectomy.The oral medication of Chinese medicine lasted for half a month in each menstrual cycle and the medication was performed for a total of 3 menstrual cycles,and one year of postoperative follow-up was carried out.The total pregnancy rate,live birth rate,ectopic pregnancy rate,miscarriage rate and recurrence rate of the patients in the observation groups and the control groups were compared within one year after the treatment.Meanwhile,the changes in serum transforming growth factor β1(TGF-β1)and connective tissue growth factor(CTGF)levels of the patients in the observation groups and the control groups were observed 7 days and 3 months after the operation.Results(1)The one-year postoperative follow-up showed that the total pregnancy rate and live birth rate of patients with mild(group A1),moderate(group B1),and severe(group C1)sactosalpinx in the observation groups were higher than those of patients with the corresponding degree of sactosalpinx in the control groups(groups A2,B2,and C2 respectively),and the recurrence rate was lower than that of patients with the corresponding degree of sactosalpinx in the control groups(groups A2,B2,and C2 respectively),and the differences were statistically significant(P＜0.05 or P＜0.01).However,no statistically significant differences of ectopic pregnancy rate and miscarriage rate(P＞0.05)were shown in the patients with the same degree of sactosalpinx(A1 vs A2,B1 vs B2,C1 vs C2).(2)Seven days after the operation,the serum TGF-β1 and CTGF levels of the observation groups did not differ from those in the control groups(A1 vs A2,B1 vs B2,C1 vs C2),the differences being not statistically significant(P＞0.05).Three months after the operation,the serum TGF-β1 and CTGF levels of patients in the observation groups and the control groups were significantly lower than those at postoperative day 7(P＜0.05),and the reduction of serum TGF-β1 and CTGF levels in the patients with mild(A1 group),moderate(B1 group),and severe(C1 group)sactosalpinx in the observation groups was significantly superior to that of patients with the corresponding degree of sactosalpinx in the control groups(groups A2,B2,and C2 respectively),the differences being statistically significant(P＜0.01).Conclusion Yiqi Huayu Tongluo method can improve the efficacy of minimally invasive tubal dredging operation for sactosalpinx,significantly increase the pregnancy rate and live birth rate and reduce the recurrence rate of patients.Its therapeutic mechanism may be related to the inhibition of the expression levels of serum TGF-β1 and CTGF.

Objective To evaluate the performance of the disposable medical protective clothing in blocking the penetration of infectious agents,in order to provide data support for the setting of such performance indexes when the GB 19082 is revised.Methods Totally 10 batches of different brands and models of protective clothing were selected,and tests were carried out for penetration resistance to synthetic blood,phage,wet microorganisms,dry microorganisms and contaminated liquid aerosol and particle filtration efficiency according to YY/T 0700-2008,YY/T 0689-2008,YY/T 0506.6-2009,GB 19082-2009,YY/T 0506.5-2009 and YY/T 1799-2020.Results There were 2 batches of protective clothing with anti-synthetic blood penetration performance level 2,3,4,5 and 6,respectively;all the protective clothing had the highest level 6 for anti-wet microorganisms penetration,part of whom had the levels for the resistance to phage penetration lower than those for preventing anti-synthetic blood penetration;all of the protective clothing had the particle filtration efficiencies higher than 95％,and had the highest level 3 for anti-dry microorganisms penetration;there're 5 batches of protective clothing with the highest level 3 for contaminated liquid aerosol penetration,1 batch with level 2 and the remained 4 batches with undetermined levels,which all had an average logarithmic reduction higher than 4.5 after penetration.Conclusion Particle filtration efficiency and resistance to phage penetration may be involved in the requirements for resistance to infective agent penetration in revised GB 19082 for evaluating the ability of protective clothing materials to block microorganisms in airborne particles and liquid contaminants.[Chinese Medical Equipment Journal,2024,45(5):16-21]

Objective To explore the clinical efficacy and influencing factors of omadacycline(OMC)in the treat-ment of patients with infectious diseases.Methods Data about hospitalized patients who received OMC monothera-py or combination therapy at Xiangya Hospital of Central South University from January 2022 to December 2023 were analyzed retrospectively.The influencing factors for failure of OMC treatment was analyzed by univariate and multivariate logistic regression analysis.Results A total of 160 patients were included in analysis,with an overall effective treatment rate of 69.4％(n=111).After treatment with OMC,patients in effective group was observed that body temperature improved([36.83±0.52]℃ vs[37.85±0.92]℃,P＜0.001),white blood cell count([7.78±4.07]× 109/L vs[10.06±6.49]× 109/L,P＜0.001),procalcitonin([0.63±1.19]ng/mL vs[4.43±10.14]ng/mL,P=0.001),C-reactive protein([35.16±37.82]mg/L vs[105.08±99.47]mg/L,P＜0.001),and aspartate aminotransferase([50.50±40.04]U/L vs[77.17±91.43]U/L,P=0.004)all decreased signifi-cantly.Only one patient had adverse reactions such as diarrhea,but treatment was not interrupted.Univariate ana-lysis showed that patients in failure treatment group had a higher acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)score(17.0[9.5-22.0]vs 12.0[9.0-19.0],P=0.046)and sequential organ failure assessment(SOFA)score(7.0[4.5-10.0]vs 4.0[2.0-9.0],P=0.019).Multivariate analysis showed that end-stage liver disease(OR=77.691,95％CI:5.448-1 107.880,P=0.001),mechanical ventilation(OR=6.686,95％CI:1.628-27.452,P=0.008)and the combination treatment of vancomycin(OR=6.432,95％CI:1.891-21.874,P=0.003)were risk factors for the failure of OMC treatment,while the course of OMC treatment(OR=0.905,95％CI:0.825-0.994,P=0.037)was a protective factor for the effective treatment.Conclusion OMC can be used as an alternative therapy for refractory severe infection,with fewer adverse reaction.End-stage liver disease,mechanical ventilation and combination treatment of vancomycin are risk factors for failure of OMC treatment in in-fected patients.Adequate OMC treatment course can improve patients'clinical outcome,large-scale case studies are needed to confirm the initial conclusion.

Objective:To study the significance and mechanism of miR-21, interleukin-6, interleukin-17 in the diagnosis of endometrial cancer.Methods:A retrospective analysis was condueted on the clinical data of 40 endometrial cancer patients and 40 healthy volunteers admitted to Lianyungang Second People's Hospital from March 2020 to March 2023. Real time fluorescence quantitative PCR was used to detect serum miR-21 levels and enzyme-linked immunosorbent assay was used to detect serum interleukin-6 and interleukin-17 levels in both groups.Results:The serum levels of interleukin-17 [(37.22 ± 13.08) ng/L], interleukin-6 [(12.09 ± 3.99) ng/L], and miR-21 [(2.83 ± 0.93)] in the endometrial cancer group were significantly higher than those in the normal control group [(15.72 ± 8.96) ng/L, (3.93 ± 2.19) ng/L, (1.20 ± 0.39), respectively] ( t = 8.58, 11.34, 10.20, all P < 0.001). Pearson correlation analysis showed that there was a significant positive correlation between serum interleukin-17 and interleukin-6 levels in patients with endometrial cancer ( r = 0.97, P < 0.001), between interleukin-17 level and miR-21 expression in patients with endometrial cancer ( r = 0.96, P < 0.001), and between interleukin-16 level and miR-21 expression in patients with endometrial cancer ( r = 0.99, P < 0.001). Receiver operating characteristic curve analysis showed that when the cut-off value of interleukin-17 was 21.65 ng/L, the sensitivity of the diagnosis of endometrial cancer was 80%, the specificity was 87.5%, and the area under the curve was 0.894 [95% confidence interval ( CI) = 0.827-0.961, P < 0.001]; when the cut-off value of interleukin-6 was 7.44 ng/L, the diagnostic sensitivity was 85.0%, the specificity was 92.5%, and the area under the curve was 0.959 (95% CI = 0.923-0.995, P < 0.001); when the cut-off value of miR-21 was 1.85, the diagnostic sensitivity was 77.5%, the specificity was 92.5%, and the area under the curve was 0.947 (95% CI = 0.905-0.989, P < 0.001). Conclusion:This study confirmed that serum interleukin-17, interleukin-6, and miR-21 could potentially serve as early predictors of endometrial cancer to a certain extent. The combined evaluation of these three parameters may be more valuable for diagnosis.