Objective To investigate the protective effect of sodium (s)-2-(dithiocarboxylato((2R,3R,4R,5R,6R)-2,3,4,5,6-pentahydroxyhexyl) amino)-4-(methylthio) butanoate (GMDTC) against cisplatin-induced toxicity during antitumor treatment. Methods Specific pathogen-free female SD rats were inoculated with LLC-WRC-256 tumor cells to establish tumor-bearing models, which were randomly divided into the model control group, cisplatin control group, and low-, medium-, and high-dose GMDTC groups, with 10 rats in each group. Another negative control group with 10 rats was included. Rats in the cisplatin control group and the three GMDTC dose groups were injected intravenously with cisplatin at a dose of 5 mg/kg body mass for one time. After 2.0 hours, rats in the three GMDTC dose groups were injected intravenously with GMDTC at doses of 27, 54, and 108 mg/kg body mass, once per day for five consecutive days. Tumor volume, platinum levels in biological samples (whole blood, urine, kidney, and tumor tissue), serum creatinine (Cr) and urea nitrogen (BUN) levels were measured at different time points. The tumor mass was measured, the pathological changes of renal tissue were observed, and the complete blood count was tested. Results The dilation of renal tubules, cell necrosis and shedding, and the formation of renal tubule patterns in the kidneys of rats in the medium- and high-dose GMDTC groups were significantly reduced compared with those in the cisplatin control group. The tumor volume of rats in the cisplatin control group and the three GMDTC dose groups decreased on the 3rd, 5th and 7th days after cisplatin administration, and the tumor weight decreased on the 7th days compared with the model control group (all P<0.05). However, there was no significant difference in the above indexes among the four groups (all P>0.05). The levels of serum Cr and BUN of rats in the cisplatin control group on the 3rd, 5th, and 6th days after cisplatin administration, as well as the score of renal tubular injury degree on the 7th day, were higher than those in the negative control group and the model control group (all P<0.05). The serum Cr levels of rates on the 3rd and 5th days after cisplatin administration, the serum BUN levels on the 5th day in the medium- and high-dose GMDTC groups, the score of renal tubular injury degree, and renal platinum level on the 7th day decreased compared with the cisplatin control group (all P<0.05), while the serum Cr and BUN levels on the 6th day and the whole-blood platinum levels in the high-dose GMDTC group decreased (all P<0.05). The urinary platinum levels of rats in the three GMDTC dose groups increased on the 1st day after GMDTC administration (all P<0.05), but decreased on the 3rd day compared with the cisplatin control group (all P<0.05). The counts of white blood cells, neutrophils, lymphocytes and platelets of rats in the cisplatin control group were lower than those in the model control group (all P<0.05). There was no significant difference in the above indexes of rats between the three GMDTC dose groups and the cisplatin control group (all P>0.05). Conclusion Intravenous administration of GMDTC at doses of 54 or 108 mg/kg body mass effectively reduce the nephrotoxicity of cisplatin-treated rats with LLC-WRC-256 tumors without affecting the antitumor effect of cisplatin.

Osteoarthritis (OA) causes chronic pain that significantly impairs quality of life, with current treatments often proving insufficient and accompanied by adverse effects. Recent research has identified the dorsal root ganglion (DRG) and its resident macrophages as crucial mediators of chronic OA pain through neuroinflammation driven by macrophage polarization. We present a novel injectable thermo-sensitive hydrogel system, KAF@PLEL, designed to deliver an anti-inflammatory peptide (KAF) specifically to the DRG. This biodegradable hydrogel enables sustained KAF release, promoting the reprogramming of DRG macrophages from pro-inflammatory to anti-inflammatory phenotypes. Through comprehensive in vitro and in vivo studies, we evaluated the hydrogel's biocompatibility, effects on macrophage polarization, and therapeutic efficacy in chronic OA pain management. The system demonstrated significant capabilities in preserving macrophage mitochondrial function, suppressing neuroinflammation, alleviating chronic OA pain, reducing cartilage degradation, and improving motor function in OA rat models. The sustained-release properties of KAF@PLEL enabled prolonged therapeutic effects while minimizing systemic exposure and side effects. These findings suggest that KAF@PLEL represents a promising therapeutic approach for improving outcomes in OA patients through targeted, sustained treatment.

Objective: To prepare hollow mesoporous silicon nanoparticles ( HMSNs) loaded with allicin—diallyl trisulfide (DATS) , and to study their feasibility as a therapeutic agent for ischemic injury of lower limbs . Methods: HMSNs were synthesized by selective etching , and their microstructure was observed by scanning and transmis- sion electron microscopy. Their physical and chemical properties were analyzed by X-ray diffraction and dynamic light scattering (DLS) . Their biological safety was tested by erythrocyte hemolysis and cytotoxicity experiments . DATS was loaded into HMSNs by adsorption to obtain DATS sustained release nanoparticles (DATS-HMSNs) , and the cumulative release curve of DATS was calculated and produced by ultraviolet spectrophotometry. C57BL/6 mice were randomly divided into four groups (sham operation group , normal saline group , DATS group , and DATS-HM- SNs group) . Lower limb ischemia models were made by femoral artery ligation and resection . The exercise ability and the contents of tumor necrosis factor alpha (TNF-α ) , interleukin-6 (IL-6) , monocyte chemoattractant protein- 1 (MCP-1) , reactive oxygen species (ROS) , platelet-endothelial cell adhesion molecule (CD31) , alpha smooth muscle actin ( α-SMA) , basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) in muscles of mice in each group before and after limb ischemia were tested . Results : Scanning and transmission e- lectron microscope observation showed that the prepared HMSNs were hollow , spherical and uniform in particle size . DLS results showed that the particle size was (226. 5 ± 11 . 8) nm. The results of red blood cell hemolysis test and cytotoxicity test showed that HMSNs had good biocompatibility. The maximum drug loading rate of HMSNs on DATS was 27. 89% , the cumulative release rate of DATS in 7 days was about 80. 12% , and could reach 97. 27% in 21 days . Compared with the control group , after DATS-HMSNs were applied to mice with lower limb ischemia , immunohistochemical staining showed that the levels of CD31 , α-SMA , bFGF and VEGF increased ( P < 0. 05) . Elisa test showed that the levels of TNF-α , IL-6 , MCP-1 and ROS decreased (P < 0. 05) , and the exercise ability of mice recovered satisfactorily after ischemia. Conclusion DATS-HMSNs can release DATS slowly and continu- ously , providing protection against ischemic injury of lower limbs .

Immune evasion has made ovarian cancer notorious for its refractory features, making the development of immunotherapy highly appealing to ovarian cancer treatment. The immune-stimulating cytokine IL-12 exhibits excellent antitumor activities. However, IL-12 can induce IFN-γ release and subsequently upregulate PDL-1 expression on tumor cells. Therefore, the tumor-targeting folate-modified delivery system F-DPC is constructed for concurrent delivery of IL-12 encoding gene and small molecular PDL-1 inhibitor (iPDL-1) to reduce immune escape and boost anti-tumor immunity. The physicochemical characteristics, gene transfection efficiency of the F-DPC nanoparticles in ovarian cancer cells are analyzed. The immune-modulation effects of combination therapy on different immune cells are also studied. Results show that compared with non-folate-modified vector, folate-modified F-DPC can improve the targeting of ovarian cancer and enhance the transfection efficiency of pIL-12. The underlying anti-tumor mechanisms include the regulation of T cells proliferation and activation, NK activation, macrophage polarization and DC maturation. The F-DPC/pIL-12/iPDL-1 complexes have shown outstanding antitumor effects and low toxicity in peritoneal model of ovarian cancer in mice. Taken together, our work provides new insights into ovarian cancer immunotherapy. Novel F-DPC/pIL-12/iPDL-1 complexes are revealed to exert prominent anti-tumor effect by modulating tumor immune microenvironment and preventing immune escape and might be a promising treatment option for ovarian cancer treatment.

Objective:To explore the high-risk factors for parenteral nutrition associated cholestasis（PNAC）in extremely/ultra-low birth weight infants，and establish a risk Alignment Diagram prediction model.Methods:We retrospectivly analyzed the clinical data of hospitalized extremely/ultra-low birth weight infants admitted to Neonatology Department at Quanzhou Children's Hospital from January 2019 to December 2020，using multivariate Logistic regression analysis to screen for independent risk factors for the occurrence of PNAC.An Alignment Diagram model prediction model for PNAC was constructed by using R software，and the performance of the model was evaluated through receiver operating characteristic curves.Results:A total of 203 extremely/ultra-low birth weight infants were included，with a median gestational age of 29.14（28.00，30.86）weeks and a median birth weight of 1　170（1　000,1　300）g.Among them，26（12.81%）cases developed PNAC.Multivariate Logistic regression analysis showed that the duration of parenteral nutrition（ OR=1.015 ，95% CI 1.003-1.034），the cumulative amount of glucose（ OR=1.014 ，95% CI 1.001-1.028），small for gestational age（ OR=3.455 ，95% CI 1.127-10.589），and neonatal sepsis（ OR=3.142 ，95% CI 1.039-9.503）were independent risk factors for PNAC（ P＜0.05）；The four independent risk factors mentioned above were introduced into R software to construct an Alignment Diagram model，the area under the receiver operating characteristic curve was 0.835（95% CI 0.842-0.731），and the results of the Hosmer Limeshow goodness of fit test show that：χ 2=5.34，degree of freedom=8， P=0.72.A calibration curve indicated good consistency between the predicted probability of the model and the actual occurrence rate，with good accuracy. Conclusion:The Alignment Diagram model constructed based on four independent risk factors of the duration of parenteral nutrition，glucose accumulation，small for gestational age infants，and neonatal sepsis exhibits high predictive ability，and is expected to provide an intuitive and convenient visualization tool for preventing or reducing the occurrence of PNAC in extremely/ultra-low birth weight infants

Ziziphi spinosae semen mainly contains contents of saponins,flavonoids,alkaloids and aliphatic acids.Meanwhile,it has a variety of activities such as sedative-hypnotic,anti-anxiety,anti-depression,nerve protection,cardiovascular and cerebrovascular protection,liver protection,and antioxidant,which is widely used in medicine,food,health food and other fields.The chemical constituents,pharmacological action and clinical application of Ziziphi spinosae semen were systematically summarized in this paper by reviewing the literature,in order to provide theoretical guidance for the sustainable development of the resources and the rational use of Ziziphi spinosae semen.

Objective: To understand the prevalence of Lying Flat behaviors and its association with depressive symptoms among Chinese college students, so as to provide a scientific basis for promoting the physical and mental health development of adolescents. Methods: From July to October 2023, three universities were selected through convenient sampling from Jiangxi Province, Liaoning Province and Beijing City, respectively. Selfdesigned questionnaire links were distributed on campus to collect basic information and Lying Flat behaviors among college students, and the Patient Health Questionnaire-9 (PHQ-9) was utilized to screen for students with depressive symptoms. Finally, a total of 4 225 valid questionnaires were obtained. Chisquare was used to compare of report rates of Lying Flat behaviors across different demographic characteristics. Ordered Logistic regression analysis was used to explore the association between Lying Flat behaviors and depressive symptoms, with Z test used to assess variations in the strength of associations. Results: The reporting rates of academic, life, and social Lying Flat were 32.7%, 17.8% and 17.5%, respectively. And 6.7% of the participants were found of all three Lying Flat behaviors simultaneously.Among college students with three Lying Flat behaviors, the constituent ratios of no, mild, moderate and above depressive symptoms were 9.9%, 30.5% and 59.6%, respectively. Additionally, college students who had three Lying Flat behaviors were more likely to show mild, moderate and above depressive symptoms [OR(95%CI)=2.49(1.60-3.87), 7.69(5.01-11.79), P<0.01]. Conclusions Academic Lying Flat behavior is most prevalent among college students. Academic, life and social Lying Flat behaviors are all significantly positively correlated with depressive symptoms. Attention should be paid to the Lying Flat behaviors and college students psychological health conditions to promote their physical and mental health development.

ObjectiveTo investigate the protective effect of N-(2R,3R,4R,5R,6R-pentahydroxyhexyl)-(N-disubstituted sodium formate)-L-methylthio-glutamate sodium (GMDTC) against cisplatin-induced acute kidney injury (AKI) in rats. Methods Specific pathogen free male adult SD rats were randomly divided into the control group, model group, low-dose group and high-dose group, with eight rats in each group. The rats in the latter three groups were injected with cisplatin at a dose of 4 mg/kg body mass through the tail vein to establish an AKI model, while the control group was not treated. Rats in the low-dose and high-dose groups were injected with injectable GMDTC at doses of 108 and 433 mg/kg body mass through the tail vein, respectively, in two hours after intoxication, while the rats in the model group were injected with an equal volume of 0.9% sodium chloride solution, once per day for five consecutive days. The 24-hours urine platinum level at day 1, 3, 5 and the level of whole blood platinum, serum platinum, urinary platinum and renal platinum at day 6 were determined using the inductively coupled plasma-mass spectrometry after GMDTC administration. Serum renal functional indicators and electrolyte level were detected, and renal histopathology was observed at day 6 after GMDTC administration. Results The levels of serum urea, serum creatinine, serum calcium ion, whole blood platinum, serum platinum and renal platinum, and the score of renal tubular injury in the model group were higher than those in the control group (all P<0.05). The 24-hours urinary platinum level at day 1, 3 and 5 after GMDTC administration in the model group was also higher than those in the control group (all P<0.05), and AKI changes were observed in histopathology. The levels of serum urea, serum creatinine, serum calcium ion, whole blood platinum, serum platinum, renal platinum, and renal tubular injury scores of rats in the low- and high-dose groups decreased compared with that in the model group (all P<0.05). The 24-hour urinary platinum levels on the first day after GMDTC administration of rats in the low- and high-dose groups increased compared with that in the model group (all P<0.05), as well as the renal histopathological changes of AKI were improved. However, there was no significant difference in the above-mentioned indicators between the low- and high-dose groups (all P>0.05). Conclusion GMDTC can promote the elimination of platinum in urine, effectively reduce the platinum level in blood and renal tissues, alleviate the pathological damage of renal tubules in rats, and improve the cisplatin-induced AKI.

Objective To analyze the ability of micro-implant nails placed in different locations in the posterior re-gion to improve the hard and soft tissues of the labiodental region in patients with gummy smiles to provide a reference for clinicians.Methods This study was reviewed and approved by the Ethics Committee,and informed consent was ob-tained from the patients.Thirty young female patients with anterior tooth protrusions and gummy smiles were included in the retrospective study;18 patients had micro-implant nails implanted between the premolars(group A),and 12 pa-tients had implant nails placed between the roots of the premolar and the molar and an intraoperatively placed rocking-chair archwire(group B).The preoperative and postoperative distances from the incisal end of the upper mesial incisors to the lower point of the upper lip(U1-Stms),the vertical distance from the incisal end of the upper mesial incisors to the palatal plane(U1-PP),the vertical distance from the point of the alveolar ridge to the palatal plane(Spr-PP),the dis-tance from the incisal end of the upper mesial incisors to the point of the alveolar margin(U1-Spr),and the vertical dis-tance from the point of the proximal middle buccal cusp of the maxillary first molar to the palatal plane of the maxillary first molar(U6-PP)were measured in the cephalometric lateral radiographs of the two groups;additionally,the amount of hard and soft tissues of the upper anterior region exposedduring smiling and the maximum amount of gingiva exposed during smiling were assessed from the smile photograph.Results After correction,the lip-dentition relationship im-proved significantly in both groups,with an average reduction of 2.6 mm in U1-Stms,2.4 mm in U1-PP,1.4 mm in Spr-PP,and 0.9 mm in U1-Spr in Group A.In group B,the U1-Stms was reduced by an average of 2.3 mm,the U1-PPs by an average of 1.6 mm,the Spr-PPs by 1.4 mm,and the U1-Spr by 0.2 mm.The difference between pre-and postoperative U6-PP in both groups was not significant(P＞0.05).Group A had greater ?U1-PP and ?U1-Spr changes than group B(P＜0.05).There was no difference between the two groups in terms of ?U1-Stms or ?Spr-PP(P＞0.05).The amount of soft and hard tissue exposed and maximum amount of gingiva exposed in the upper anterior region of the smile were reduced in 30 patients postoperatively,with group A having anaverage reduction of 70.19%of the preoperative amount of soft and hard tissue exposed in the upper anterior region and an average reduction of 24.12%of the preoperative max-imum amount of gingiva exposed,and group B having an average reduction of 76.12%of the preoperative amount of hard and soft tissue exposed in the upper anterior region and an average reduction of 31.88%of the preoperative maxi-mum gingiva exposed after the operation.The difference in the ratio between the two groups was not statistically sig-nificant(P＞0.05).Conclusion For patients with proptosis and gummy smiles,placing micro-implant nails between the roots of maxillary premolars can effectively lead to retraction and intrusion of anterior teeth to improve the lip-denti-tion relationship and improve gummy smile,and placing micro-implant nails between the roots of the maxillary second premolar and the first molar together with the use of rocking chair arches can also achieve a good therapeutic effect.

Objective To evaluate the efficacy and safety of tigecycline combined with cefoperazone-sulbactam sodium in the treatment of multi-/extensively-drug resistant Acinetobacter baumannii(MDRAB/XDRAB)associated central nervous system(CNS)infection,and to provide clinical evidence for antibiotic treatment of MDRAB/XDRAB-related intracranial disease.Methods The Wanfang Data Knowledge Service Platform,Chinese Biomedical Literature Database,VIP Chinese Science and Technology Journal Full-text Database,China National Knowledge Infrastructure(CNKI),Pubmed,Embase database,and Cochrane Library were searched to extract the literature of randomized controlled studies on tigecycline and cefoperazone sulbactam in the treatment of MDRAB/XDRAB CNS infection until September 1st,2022.The included studies were assessed for quality using the Cochrane Collaboration Risk of Bias assessment tool,and valid data were extracted and meta-analyzed using RevMan5.4 software.Results A total of 184 articles were screened and 4 Chinese RCTs were finally included,with a sample size of 267 cases.Meta-analysis showed that the overall efficacy of combination therapy for MDRAB/XDRAB CNS infection was better than monotherapy[OR = 4.30,95%CI =(1.93,9.58),P＜0.01].Combination therapy had a better bacterial clearance[OR=4.20,95%CI=(2.08,8.48),P＜0.01].And combination therapy resulted in a lower incidence of adverse effects[OR= 0.19,95%CI =(0.05,0.67),P＜0.05].There was no apparent difference in cure rate between combination therapy and monotherapy(P＞0.05).Conclusion Current evidence suggests that tigecycline combined with cefoperazone-sulbactam sodium may have better clinical efficacy and safety than monotherapy for MDRAB/XDRAB CNS infections.Limited by the number and quality of included studies,needs to be verified by more and higher-quality studies.