Recent progress in targeted metabolic therapy of cancer has been limited by the considerable toxicity associated with such drugs. To address this challenge, we developed a smart theranostic prodrug system that combines a fluorophore and an anticancer drug, specifically 6-diazo-5-oxo-l-norleucine (DON), using a thioketal linkage (TK). This system enables imaging, chemotherapy, photodynamic therapy, and on-demand drug release upon radiation exposure. The optimized prodrug, DON-TK-BM3, incorporating cyanine dyes as the fluorophore, displayed potent reactive oxygen species release and efficient tumor cell killing. Unlike the parent drug DON, DON-TK-BM3 exhibited no toxicity toward normal cells. Moreover, DON-TK-BM3 demonstrated high tumor accumulation and reduced side effects, including gastrointestinal toxicity, in mice. This study provides a practical strategy for designing prodrugs of metabolic inhibitors with significant toxicity stemming from their lack of tissue selectivity.

OBJECTIVE To investigate the effect of polymorphisms of solute carrier organic anion transporter family, member 1B3(SLCO1B3) gene on the pharmacodynamics of mycophenolate mofetil(MMF) in patients with lupus nephritis. METHODS Patients with lupus nephritis who were treated in Jieyang People’s Hospital from September 2019 to April 2021 were selected. All subjects were treated with MMF for at least 12 months, or discontinued due to poor efficacy. The efficacy of MMF was evaluated. The SLCO1B3 334T>G/699G>A(rs4149117/rs7311358) genotype was detected using Agena MassARRAY®, and the correlation between gene polymorphisms and MMF pharmacodynamics was analyzed using SPSS 25.0 software. RESULTS The genotype frequencies of SLCO1B3 334T>G/699G>A were in Hardy-Weinberg equilibrium. The probability of poor MMF treatment effect of 334GG/699AA carriers was significantly higher than that of 334TT/699AA and 334TG/699GA carriers(P<0.001); Logistic regression showed that both 334GG/699AA and urine protein>2.5 g·(24 h)−1 were the risk factors for poor MMF treatment[OR=4.038(1.731, 9.420), P<0.001; OR=4.157(1.705, 10.137), P=0.002]. Combined analysis showed that patients with both 334GG/699AA genotype and urine protein>2.5 g·(24 h)−1 were at higher risk for poor efficacy[OR=8.563(3.301, 22.216), P<0.001]. CONCLUSION SLCO1B3 334T>G/699G>A is related to the efficacy of MMF treating lupus nephritis, and 334GG/699AA carriers are more likely to result in poor efficacy.

Objective To isolate the Japanese encephalitis virus carried by Culex tritaeniorhynchus in Dongchuan District of Yunnan Province and analyze its molecular characteristics, so as to provide insights into the prevention and control of Japanese encephalitis in Yunnan Province. Methods Mosquito specimens were collected using mosquito-trapping lamps from pig farms in Batang Village and Xiaoxin Village, Dongchuan District, Kunming City, Yunnan Province in July 2016, and the mosquito species was identified according to the mosquito morphology. Then, 60 to 100 mosquitoes of each species served as a group and were ground. Baby hamster kidney-21 (BHK-21) cells and Aedes albopictus clone C6/36 cells were used for virus isolation, and positive isolates were identified using flavivirus primers. The positive isolates were amplified using reverse transcription polymerase chain reaction (RT-PCR) assay with 15 pairs of specific primers covering the full length of the genotype I Japanese encephalitis virus, and DNA sequence assembly was performed using the software SeqMan in the DNASTAR package. The obtained sequences were aligned with the complete sequences of 38 Japanese encephalitis virus downloaded from the GenBank with the software MegAlign, and the nucleotide and amino acid homology analyses of the obtained sequences were performed. The difference in amino acid sites was analyzed with the software GeneDoc, and phylogenetic trees were created based on the sequences of the coding region and E protein of the isolated Japanese encephalitis virus with the software Mega X. In addition, the secondary and tertiary structures of the E protein of the Japanese encephalitis virus were predicted using the online tool SOPMA and the software Swiss-Model. Results A total of 5 820 mosquitoes were collected and 3 843 Cx. tritaeniorhynchus (66.03%) were identified according to the mosquito morphology. A positive virus isolate, termed YNDC55-33, was isolated from Cx. tritaeniorhynchoides following batches of virus isolation from mosquito specimens, and cytopathic effect was observed following inoculation into BHK-21 and C6/36 cells. The YNDC55-33 virus isolate was successfully amplified with the flavivirus primes, and a long sequence containing 300 nucleotides was obtained. Following sequence alignment using the BLAST tool, the sequence of the YNDC55-33 virus isolate had high homology with that of the genotype I Japanese encephalitis virus. A long sequence with 10 845 nucleotides in length, which encoded 3 432 amino acids, was obtained by splicing the full sequence of the YNDC55-33 virus isolate. Phylogenetic analysis based on the whole-genome sequence and E gene sequence of the YNDC55-33 virus isolate showed that the new YNDC55-33 virus isolate was most closely related to the genotype I Guizhou isolate (GenBank accession number: HM366552), with nucleotide homology of 98.5% and amino acid homology of 99.4%, and the YNDC55-33 virus isolate shared 97.96% ± 0.33% nucleotide homology and 99.35% ± 0.08% amino acid homology with other genotype I Japanese encephalitis virus isolates, and < 90% nucleotide homology and < 98% amino acid homology with other genotypes of Japanese encephalitis virus. The YNDC55-33 virus isolate and the live attenuated virus vaccine candidate SA14-14-2 isolate differed at 16 amino acid sites on E gene, and 7 out of 8 key amino acid sites related to neurovirulence. The secondary and tertiary structures of the E protein of the YNDC55-33 virus isolate were predicted to be characterized by random coils. Conclusions A genotype I Japanese encephalitis virus was isolated from Cx. tritaeniorhynchus in Dongchuan District, Kunming City. This virus isolate and the live attenuated virus vaccine candidate SA14-14-2 isolate does not differ at antigenic epitopes-related key amino acid sites, and the major protein structure of the virus isolate is random coils. This study adds new data for the epidemiological distribution of Japanese encephalitis virus in Yunnan Province, which may provide insights into the prevention and control of Japanese encephalitis in the province.

Objectives:To report the sexual functional outcomes of vaginal dilation therapy in Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome patients.Methods:From March 2020 to February 2023, 97 MRKH syndrome patients performed vaginal dilation therapy with guidance from Peking Union Medical College Hospital, and 45 of them engaged in penetrative intercourse and were included in this prospective cohort study. The Chinese version of female sexual function index (FSFI) was used to assess sexual function. Functional success was defined as FSFI>23.45. Forty age-matched healthy women were selected as controls. Kaplan-Meier survival analysis was used to calculate the median time to success. Pearson correlation analysis was used to explore the relationship between neovagina length and sexual function. Complications were collected using follow-up questionnaires.Results:The functional success rate of vaginal dilation therapy was 89% (40/45) with a median time to success of 4.3 months (95% CI: 3.0-6.1 months). Compared to controls, MRKH syndrome patients had significantly lower scores in the orgasm domain (4.72±1.01 vs 4.09±1.20; P=0.013) and pain domain (5.03±0.96 vs 4.26±0.83; P<0.001). However, there were no significant differences in the FSFI total score (26.77±2.70 vs 26.70±2.33; P=0.912), arousal domain (4.43±0.77 vs 4.56±0.63; P=0.422) and satisfaction domain (4.88±0.98 vs 4.65±0.86; P=0.269) between MRKH syndrome patients and controls. MRKH syndrome patients had significantly higher scores in the desire domain (3.33±0.85 vs 3.95±0.73; P<0.001) and lubrication domain (4.37±0.56 vs 5.20±0.67; P<0.001). The prevalence of sexual dysfunction in MRKH patients was non-inferior to controls: low desire [3% (1/40) vs 23% (9/40); P=0.007], arousal disorder [3% (1/40) vs 3% (1/40); P>0.999], lubrication disorder [5% (2/40) vs 25% (10/40); P=0.012], orgasm disorder [40% (16/40) vs 20% (8/40); P=0.051], sexual pain [30% (12/40) vs 15% (6/40); P=0.108]. Conclusions:MRKH syndrome patients undergoing non-invasive vaginal dilation therapy could achieve satisfactory sexual life. Given its high functional success rate and slight complication, vaginal dilation therapy should be recommended as the first-line option, reducing the need for unnecessary surgeries.

In the backdrop of the new era,enhancing Party building in public hospitals,particularly the united front work,holds great significance for elevating medical service standards,fostering harmonious doctor-patient relationships,consoli-dating mechanisms of unity,and promoting the high-quality development of hospitals.In this case study with the First Affiliated Hospital of Soochow University,the authors explored how public hospitals can effectively conduct united front work in the context of strengthening Party construction and leveraging this work to promote comprehensive development in all aspects of the hospital.

Objective:To retrieve the relevant guidelines and expert consensus on self-management of patients with high-risk foot diabetes, and analyze the content of high-quality guidelines and expert consensus recommendations, so as to provide a reference for the construction of a guidance program for self-management of patients with high-risk foot diabetes.Methods:Computer-retrieved clinical practice guidelines and expert consensus for self-management of patients with high-risk foot for diabetes from databases, guideline networks, and related professional websites. The search period was from January 1, 2012 to June 5, 2022. The quality of the included literature was evaluated and the evidence was extracted and integrated by 2 researchers. Experts were invited to evaluate the summarized evidence.Results:According to the quality of literature, a total of 12 guidelines (10 at level A and 2 at level B) and 3 expert consensus (expert discussion and decision) were included, and 8 themes were defined as regular follow-up, self-assessment, foot and decompression management, exercise management, nutrition management, indicator management, psychological management, and health education, a total of 28 recommendations. Among them, there were 23 A-level recommendations and 5 B-level recommendations.Conclusions:The quality of the guidelines and expert consensus included in this study is high,the recommended level of the summarized evidence is high. This study provides the reference and basis for the clinical staff to construct and guide the clinical practice of self-management of high-risk diabetic foot patients.

The clinical data of a case diagnosed with MIRAGE syndrome in the Respiratory Department of Shenzhen Children′s Hospital in June 2020 were analyzed retrospectively.The 11-month-old boy was admitted to the hospital because of " intermittent fever for 1.5 months and blood oxygen decline for half a day" . Whole exome detection was carried out by using second-generation sequencing technology.The results showed spontaneous, heterozygous, missense variation in SAMD9 gene (NM_017654) and the mutation site was c. 2471G>A.Review of the literature found that all of the children (47 cases) were born prematurely and their parents were not intermarriage.Besides, they had overall growth retardation, and some suffered from myelodysplasia, recurrent infection, adrenal insufficiency, genital phenotypes and enteropathy.Among SAMD9 gene variation, mutations c. 1376G>A and c. 2471G>A are most frequent.Attention should be paid to the MIRAGE syndrome in children with premature birth and full development lag after birth.

Objective:To summarize the characteristics of eosinophilia in peripheral blood in children with parasitic diseases.Methods:All clinical data of children with parasitic diseases who were diagnosed in Shenzhen Children′s Hospital from June 2002 to June 2020 were collected to analyze the characteristics of eosinophil changes in peripheral blood after parasitic infection.Results:(1)A total of 37 cases of parasitic diseases were diagnosed in children, with 25 males and 12 females, aged from 10 months to 12 years and 7 months, and the median age was 5 years and 3 months.(2)Among 37 cases, the absolute number of eosinophils in peripheral blood was increased in 32 cases (86.49%), with a range of (0.55-43.80)×10 9/L: 6 cases (18.75%) were slightly increased, 8 cases (25.00%) were moderately increased, and 18 cases (56.25%) were severely increased.(3)As for eosinophilia in peripheral blood of different insect species, there were 16 cases (50.00%) of fasciola infection, 4 cases (12.50%) of fasciola infection, 3 cases (9.38%) of mixed infection, 2 cases (6.25%) of schistosomiasis, plerocercoid, hydatid and cysticercosis infection, and 1 case (3.13%) of ascaris infection.The degrees of the increase of eosinophils in peripheral blood infected by different species of parasites were different ( Fisher′ s value 17.97, P=0.01), with statistically significant differences.(4)Eosinophilia in peripheral blood was involved in different systems, with respiratory system in 18 cases (48.65%), digestive system in 13 cases (35.14%), skin in 7 cases (18.92%), central nervous system in 5 cases(13.51%), circulatory system in 3 cases (8.11%), and others in 2 cases (5.41%). (5)There were 5 cases of parasitic infection without eosinophilia, including 2 cases of Blastocystis hominis, and 1 case of mixed infection with plerocercoid and cysticercosis, 1 case of cysticercosis and 1 case of trichinella spiralis.The increase of eosinophils in peri-pheral blood after different systems was different, without statistically significant differences ( Fisher′ s value 7.37, P=0.06). Conclusions:Eosinophil in peripheral blood is a common phenomenon of parasitic infection in children.The increased severity is related to parasite species, instead of the site of systemic involvement.

Objective:To evaluate and summarize the relevant evidence on skin flap management in patients with breast cancer after mastectomy at home and abroad.Methods:Domestic and foreign clinical decision-making systems, guideline websites, professional societies websites, evidence-based databases, and original research databases were systematically searched for clinical practice guidelines, expert consensus, evidence summary and systematic evaluation on skin flap management in patients with breast cancer after mastectomy. The retrieval period was from January 2010 to April 2020. Two researchers with evidence-based nursing knowledge independently screened the search results and evaluated the quality.Results:A total of 24 articles were included, including 17 systematic reviews, 2 evidence summaries, 3 expert consensus and 2 clinical decisions. The 17 best pieces of evidence were summarized from three aspects, including preoperative, intraoperative and postoperative management.Conclusions:Existing evidence covers the three aspects of preoperative, intraoperative and postoperative management. In clinical applications, system changes should be taken as the main entry point to realize the transformation of evidence to the clinic, so as to reduce the occurrence of postoperative flap complications, increase patient satisfaction, improve the quality of nursing and reduce medical costs.

OBJECTIVE： To establish the quality standard for Bushen quyu granules. METHODS： TLC was used for qualitative identification of Rosa laevigata， Cuscuta chinensis， processed Fallopia multiflora and Lithospermum erythrorhizon in Bushen quyu granules. And then， the content of total polysaccharides in Bushen quyu granules was determined by UV spectrophotometry. HPLC method was used for the content determination of rutin， quercetin and hyperin in Bushen quyu granules. The determination was performed on BDS C18 column with mobile phase consisted of acetonitrile-0.08％ phosphoric acid solution （gradient elution） at the flow rate of 1 mL/min. The column temperature was 30 ℃， and detection wavelength was set at 370 nm. The sample size was 10 μL. RESULTS： TLC test sample chromatogram of 4 medicinal materials showed the same spot or fluorescence at the corresponding position with the reference substance and control medicinal materials. The linear range of glucose， rutin， quercetin and hyperin were 0.003-0.018 mg/mL， 0.225-7.20 μg/mL， 0.07-2.24 μg/mL and 1.25-39.88 μg/mL（r＝0.999 5 or 0.999 9， n＝6）. RSDs of precision， stability and reproducibility tests were all less than 3％ （n＝6）. Average recoveries were 102.2％， 101.2％， 100.9％， 101.0％ （RSD＝1.28％， 2.93％， 2.41％， 1.59％， n＝6）. Average contents were 0.46 g/g， 5.48        μg/g， 8.18 μg/g and 102.88 μg/g（n＝3）. CONCLUSIONS： Established quality standard of Bushen quyu granules is accurate and reliable， and can provide scientific reference for quality control of Bushen quyu granules.