By selecting stable and detectable drug prototypes or metabolites in sewage samples, near real-time detection of disease conditions can be achieved. This study selected oseltamivir carboxylate, the primary metabolite of first-line antiviral oseltamivir, as a biomarker. Based on the concentration of oseltamivir carboxylate in wastewater, the consumption and usage rate of oseltamivir were calculated by reverse engineering. Quarterly sampling was conducted at 46 urban sewage treatment plants in representative 5 cities in the middle and lower reaches of the Yangtze River, from November 2022 to December 2023. The concentration range of oseltamivir acid in sewage samples is 1.270−1 279 ng/L, the daily mass load of oseltamivir per 1 000 inhabitants in the surveyed cities ranged from 9.560 to 544.7 mg/d, and the average utilization rate is 0.06‰−3.63‰. The research results indicate that in March 2023, Wuxi City experienced a spring influenza peak, while Bengbu, Tongling, Suzhou, and Changzhou City experienced a small summer influenza peak in May. In November and December 2023, Wuxi, Changzhou, and Bengbu City experienced a winter influenza peak, the results are consistent with the official statistics of the National Center for Disease Control and Prevention and the National Influenza Center, which reflect the influenza epidemic situation in southern cities. The integration of this methodology with clinical diagnostic rates could provide near real-time data support for future influenza prevention and control strategies.

OBJECTIVE To improve the diagnosis and treatment level of critically ill infectious diseases， standardize the clinical application of nanopore sequencing and promote the sound development of the technology. METHODS Division of Therapeutic Drug Monitoring of Chinese Pharmacological Society and Expert Committee of Precision Medicine for Clinical Treatment of Guangdong Pharmaceutical Association initiated and organized multidisciplinary experts to discuss and determine the consensus writing outline by using the nominal group method， forming a preliminary consensus draft； expert consultation was performed by using Delphi method， and then experts’ opinions were analyzed and revised to form consensus. RESULTS & CONCLUSIONS Consensuses of Experts on the Application of Nanopore Sequencing Technology in the Detection of Pathogenic Microorganisms covers targeted sequencing， metagenomic sequencing and whole genome sequencing， and is standardized in terms of sample collection and storage， detection process， bioinformatics analysis and report interpretation； the recommendations are provided for the key issues.

Objective:To investigate the relationship between intramuscular adipose tissue index (IATI) calculated from computed tomography images at transverse process of the first lumbar and all-cause mortality in maintenance dialysis patients, and to provide a reference for improving the prognosis in these patients.Methods:It was a multicenter retrospective cohort study. The clinical data of patients who received maintenance hemodialysis or peritoneal dialysis treatment from January 1, 2017 to December 31, 2019 in 4 grade Ⅲ hospitals including Zhongda Hospital Affiliated to Southeast University, Taizhou People's Hospital Affiliated to Nanjing Medical University, Affiliated Hospital of Yangzhou University, and the Third Affiliated Hospital of Soochow University were retrospectively collected. IATI was calculated by low attenuation muscle (LAM) density/skeletal muscle density. The receiver-operating characteristic curve was used to determine the optimal cut-off value of IATI, and the patients were divided into high IATI group and low IATI group according to the optimal cut-off value. The differences of baseline clinical data and measurement parameters of the first lumbar level between the two groups were compared. The follow-up ended on December 23, 2022. The endpoint event was defined as all-cause mortality within 3 years. Kaplan-Meier survival curve and log-rank test were used to analyze the survival rates and the differences between the two groups. Multivariate Cox regression analysis models were used to analyze the association between IATI and the risk of all-cause mortality in maintenance dialysis patients. Multivariate logistic regression analysis model was used to analyze the influencing factors of high IATI.Results:A total of 478 patients were eligibly recruited in this study, with age of (53.55±13.19) years old and 319 (66.7%) males, including 365 (76.4%) hemodialysis patients and 113 (23.6%) peritoneal dialysis patients. There were 376 (78.7%) patients in low IATI (<0.42) group and 102 (21.3%) patients in high IATI (≥0.42) group. The proportion of age ≥ 60 years old ( χ2=24.746, P<0.001), proportion of diabetes mellitus ( χ2=5.570, P=0.018), fasting blood glucose ( t=-2.145, P=0.032), LAM density ( t=-3.735, P<0.001), LAM index ( t=-7.072, P<0.001), and LAM area/skeletal muscle area ratio ( Z=-9.630, P<0.001) in high IATI group were all higher than those in low IATI group, while proportion of males ( χ2=11.116, P<0.001), serum albumin ( Z=2.708, P=0.007) and skeletal muscle density ( t=12.380, P<0.001) were lower than those in low IATI group. Kaplan-Meier survival analysis showed that the 3-years overall survival rate of low IATI group was significantly higher than that in high IATI group (Log-rank χ2=19.188, P<0.001). Multivariate Cox regression analysis showed that IATI<0.42 [<0.42/≥0.42, HR(95% CI): 0.50 (0.31-0.83), P=0.007] was an independent protective factor of all-cause mortality, and age ≥60 years old [ HR (95% CI): 2.61 (1.60-4.23), P<0.001], diabetes mellitus [ HR (95% CI): 1.71 (1.06-2.78), P=0.029] and high blood neutrophil/lymphocyte ratio [ HR (95% CI): 1.04 (1.00-1.07), P=0.049] were the independent risk factors of all-cause mortality in maintenance dialysis patients. Stepwise Cox regression analysis showed that IATI<0.42 was still an independent protective factor of all-cause mortality in maintenance dialysis patients [<0.42/≥0.42, HR (95% CI): 0.45 (0.27-0.76), P=0.003]. Multivariate logistic regression analysis showed that low skeletal muscle density [ OR (95% CI): 0.84 (0.81-0.88), P<0.001] and high serum triglyceride [ OR (95% CI): 1.39 (1.07-1.82), P=0.015] were the independent influencing factors of IATI≥0.42. Conclusion:IATI<0.42 of the first lumbar level is an independent protective factor of all-cause mortality in maintenance dialysis patients. Localized myosteatosis within high-quality skeletal muscle may reduce the risk of all-cause mortality in these patients.

Objectives:To explore the antitumor effects of redox-responsive nanoparticles containing platinum(Ⅳ)—NP@Pt(Ⅳ) in ovarian cancer.Methods:Redox-responsive polymer carriers were synthesized. Polymer carriers and platinum(Ⅳ)—Pt(Ⅳ) can self-assemble into NP@Pt(Ⅳ). Inductively coupled plasma mass spectrometry was performed to detect the platinum release from NP@Pt(Ⅳ) in reducing environment and the platinum content in ovarian cancer cells ES2 treated with cisplatin, Pt(Ⅳ) and NP@Pt(Ⅳ). The proliferation ability of the ovarian cancer cells were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cellular apoptosis was assessed by flow cytometry. Collection of primary ovarian cancer tissues from patients with primary high-grade serous ovarian cancer who were surgically treated at the Cancer Hospital of the Chinese Academy of Medical Sciences from October to December 2022. The high-grade serous ovarian cancer patient-derived xenograft (PDX) mice were intravenously injected with Cy7.5 labeled NP@Pt(Ⅳ) followed by in vivo imaging system. Mice were treated with PBS, cisplatin and NP@Pt(Ⅳ). Tumor volume and weight were measured in each group. Necrosis, apoptosis and cell proliferation of tumor tissues were detected by hematoxylin-eosin (HE) staining, TUNEL fluorescence staining and Ki-67 immunohistochemistry staining. Body weight and HE staining of heart, liver, spleen, lung and kidney of mice in each group were measured.Results:The platinum release of NP@Pt(Ⅳ) after 48 hours in reducing environment was 76.29%, which was significantly higher than that of 26.82% in non-reducing environment ( P<0.001). The platinum content in ES2 cells after 4 hours and 7 hours of treatment with NP@Pt(Ⅳ) (308.59, 553.15 ng/million cells) were significantly higher than those of Pt(Ⅳ) (100.21, 180.31 ng/million cells) and cisplatin (43.36, 50.36 ng/million cells, P＜0.05). The half inhibitory concentrations of NP@Pt(Ⅳ) in ovarian cancer cells ES2, A2780, A2780DDP were 1.39, 1.42 and 4.62 μmol/L, respectively, which were lower than those of Pt(IV) (2.89, 7.27, and 16.74 μmol/L) and cisplatin (5.21, 11.85, and 71.98 μmol/L). The apoptosis rate of ES2 cells treated with NP@Pt(Ⅳ) was (33.91±3.80)%, which was significantly higher than that of Pt(Ⅳ) [(16.28±2.41)%] and cisplatin [(15.01±1.17)%, P＜0.05]. In high-grade serous ovarian cancer PDX model, targeted accumulation of Cy7.5 labeled NP@Pt(Ⅳ) at tumor tissue could be observed. After the treatment, the tumor volume of mice in NP@Pt(IV) group was (130±98) mm 3, which was significantly lower than those in control group [(1 349±161) mm 3, P<0.001] and cisplatin group [(715±293) mm 3, P=0.026]. The tumor weight of mice in NP@Pt(IV) group was (0.17±0.09)g, which was significantly lower than those in control group [(1.55±0.11)g, P<0.001] and cisplatin group [(0.82±0.38)g, P=0.029]. The areas of tumor necrosis and apoptosis in mice treated with NP@Pt(Ⅳ) were higher than those in mice treated with cisplatin. Immunohistochemical staining revealed that there were low expressions of Ki-67 at tumor tissues of mice treated with NP@Pt(Ⅳ) compared with cisplatin. The change in body weight of mice in NP@Pt(Ⅳ) group was not significantly different from that of the control group [(18.56±2.04)g vs.(20.87±0.79)g, P=0.063]. Moreover, the major organs of the heart, liver, spleen, lung, and kidney were also normal by HE staining. Conclusion:Redox-responsive NP@Pt(Ⅳ), produced in this study can enhance the accumulation of cisplatin in ovarian cancer cells and improve the efficacy of ovarian cancer chemotherapy.

Lipopolysaccharides (LPS) are major outer membrane components of Gram-negative bacteria. Unlike most Gram-negative bacteria, Acinetobacter baumannii can still survive and acquire polymyxin resistance after complete loss of LPS. Previous studies of LPS-deficient Acinetobacter baumannii mostly focused on LPS-deficient strains induced by polymyxin, whose background was complex and unstable. To investigate LPS loss-mediated polymyxin resistant-Acinetobacter baumannii, this study constructed a stable and clear background LPS-deficient strain by knocking out lpxC gene in Acinetobacter baumannii ATCC 19606 with CIRSPR/Cas9, and then studied the phenotypic changes of the lpxC-deficient strain including morphology, growth rate, antibiotic susceptibility, virulence, membrane permeability, and membrane potential. Animal experiments were approved by the Animal Care and Welfare Committee Institute of Medicinal Biotechnology, CAMS and PUMC (approval number: IMB-20240119D₉). The results indicated that the lpxC gene of Acinetobacter baumannii ATCC 19606 was successfully knocked out. After losing the lpxC, the strain underwent the morphological change from rod-shaped to spherical. Furthermore, it leads to reduced growth rate, enhanced membrane permeability, decreased membrane potential, lower virulence, and increased antibiotic susceptibility to β-lactams, quinolones, aminoglycosides, macrolides, glycopeptides. The lpxC deletion results in significant changes in membrane homeostasis and adaptability of Acinetobacter baumannii. Understanding the phenotypic changes of colistin-resistant Acinetobacter baumannii mediated by LPS loss is useful for exploring the resistance mechanism of Acinetobacter baumannii and developing new therapeutic strategies.

Endodontic diseases are a kind of chronic infectious oral disease.Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha.However,it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy(RCT).Recent research,encompassing bacterial etiology and advanced imaging techniques,contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT.Success in RCT hinges on factors like patients,infection severity,root canal anatomy,and treatment techniques.Therefore,improving disease management is a key issue to combat endodontic diseases and cure periapical lesions.The clinical difficulty assessment system of RCT is established based on patient conditions,tooth conditions,root canal configuration,and root canal needing retreatment,and emphasizes pre-treatment risk assessment for optimal outcomes.The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT.These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

Objective To observe the clinical efficacy of Chang'an Juntai Granules(mainly composed of Pseudostellariae Radix,Atractylodis Macrocephalae Rhizoma,Poria,Glycyrrhizae Radix et Rhizoma Praeparata cum Melle,Paeoniae Radix Alba,Saposhnikoviae Radix,Citri Reticulatae Pericarpium,Coptidis Rhizoma,and Aucklandiae Radix)in the treatment of diarrhea-predominant irritable bowel syndrome(IBS-D)with liver depression and spleen deficiency syndrome,and to evaluate its safety.Methods A single-center,randomized,double-blind,placebo-controlled clinical trial was designed.A total of 130 patients with IBS-D of liver depression and spleen deficiency were included.The patients were randomly divided into a treatment group and a control group by random number table method,with 65 cases in each group.The treatment group was treated with Chang'an Juntai Granules,and the control group was treated with Chang'an Juntai Placebo Granules.The course of treatment covered 12 weeks.The changes in the scores of IBS Symptom Severity Scale(IBS-SSS),Bristol Stool Form Scale(BSFS),IBS Quality of Life Questionnaire(IBS-QOL)and Hospital Anxiety and Depression Scale(HADS)in the two groups were observed before and after treatment.After treatment,the clinical efficacy and medication safety in the two groups were evaluated.Results(1)During the trial,six cases in the treatment group and eight cases in the control group fell off.Eventually,a total of 116 patients completed the clinical trial,including 59 cases in the treatment group and 57 cases in the control group.(2)After 12 weeks of treatment,the total effective rate of the treatment group was 88.14％(52/59),and that of the control group was 45.61％(26/57).The intergroup comparison(tested by chi-square test)showed that the clinical efficacy of the treatment group was significantly superior to that of the control group,and the difference was statistically significant(P＜0.01).(3)After treatment,the IBS-SSS scores of the two groups and the BSFS and IBS-QOL scores of the treatment group were significantly lower than those before treatment(P＜0.01),while the scores of Hospital Anxiety and Depression Scale-Anxiety subscale(HADA)and Hospital Anxiety and Depression Scale-Depression subscale(HADD)in the two groups and the BSFS and IBS-QOL scores in the control group showed no obvious changes(P＞0.05).Compared with the control group,the decrease of IBS-SSS,BSFS and IBS-QOL scores in the treatment group was significantly superior to that in the control group(P＜0.05 or P＜0.01).(4)During the trial,no serious adverse reactions or adverse events occurred in the two groups,no drug-related abnormalities of liver and kidney function,blood,and heart function were found,either.Conclusion Chang'an Juntai Granules are effective on improving the clinical symptoms and fecal characteristics of IBS-D patients with liver depression and spleen deficiency syndrome,and on enhancing the quality of life of patients.The granules excert definite curative effect and high safety,and has certain value of clinical application.

Objective:To investigate COVID-19 vaccination status and relevant adverse reactions in patients with psoriasis treated with biological agents, and to explore the effect of COVID-19 vaccination on psoriatic lesions.Methods:Clinical data were collected from 572 psoriasis patients aged 18 - 60 years, who were registered in the management system of psoriasis patients treated with biological agents in the University of Hong Kong-Shenzhen Hospital from May 2019 to June 2021. The COVID-19 vaccination status was investigated by telephone interviews, and the vaccination-related information was obtained by fixed healthcare workers during a fixed time period according to a predesigned questionnaire. Measurement data were compared between two groups by using t test, and enumeration data were compared by using chi-square test or Fisher′s exact test. Results:The COVID-19 vaccination coverage rate was 43.13% (226 cases) among the 524 patients who completed the telephone interview, and was significantly lower in the biological agent treatment group (30.79%, 105/341) than in the traditional drug treatment group (66.12%, 121/183; χ2 = 60.60, P < 0.001) . The main reason for not being vaccinated was patients′ fear of vaccine safety (49.66%, 148/298) , followed by doctors′ not recommending (26.51%, 79/298) . In the biological agent treatment group after vaccination, the exacerbation of psoriatic lesions was more common in patients receiving prolonged-interval treatment (42.86%, 6/14) compared with those receiving regular treatment (4.40%, 4/91; Fisher′s exact test, P < 0.001) . Skin lesions were severely aggravated in two patients after COVID-19 vaccination, who ever experienced allergic reactions and whose skin lesions did not completely subside after the treatment with biological agents. Conclusions:The COVID-19 vaccination coverage rate was relatively low in the psoriasis patients treated with biological agents, and no serious adverse reaction was observed after vaccination. Prolonged-interval treatment due to COVID-19 vaccination ran the risk of exacerbation of skin lesions.

ObjectiveTo review the classification of orthopedic insoles, common techniques of 3D printing orthopedic insoles, common materials and their application for flatfoot. MethodsLiteratures were retrieved from PubMed, Web of Science, CNKI and Wanfang Data from 2012 to 2022, and the relevant contents were summarized. ResultsA total of ten studies were finally included, from 5 countries, involving 290 participants, which published from 2019 to 2022. Orthotic insoles were classified as prefabricated, semi-custom, and custom, while custom ones were classified as traditional custom and 3D printed custom. 3D printed orthotic insoles were often made with selective laser sintering, fused deposition modeling (FDM) and PolyJet printing technologies, and commonly used materials included ethylene-vinyl acetate (EVA), polylactic acid, thermoplastic polyurethane, polyamide, and polypropylene. For flatfoot, 3D printed orthotic insoles could improve plantar pressure, relieve foot pain and the combined use of insole posting could control rearfoot valgus. Conclusion3D printed custom insoles can be made more efficiently and accurately than traditional custom insoles. The printing technologies and materials often chosen for 3D printed orthotic insoles are mainly FDM and EVA. 3D printed orthotic insoles is effective on plantar pressure, comfort and foot movement function of flatfoot.

The traditional Chinese medicine(TCM) enterprises have accumulated a large amount of product quality review(PQR) data. Mining these data can reveal the hidden knowledge in production and helps improve pharmaceutical manufacturing technology. However, there are few studies involving the mining of PQR data and thus enterprises lack the guidance to analyze the data. This study proposed a method to mine the PQR data, which consisted of 4 functional modules: data collection and preprocessing, risk classification of variables, risk evaluation by batches, and the regression analysis of quality. Further, we carried out a case study of the formulation process of a TCM product to illustrate the method. In the case study, the data of 398 batches of products during 2019-2021 were collected, which contained 65 process variables. The risks of variables were classified according to the process performance index. The risk of each batch was analyzed through short-term and long-term evaluation, and the critical variables with the strongest impact on the product quality were identified by partial least square regression. The results showed that 1 variable and 13 batches were of high risk, and the critical process variable was the quality of the intermediates. The proposed method enables enterprises to comprehensively mine the PQR data and helps to enhance the process understanding and improve the quality control.
Medicine, Chinese Traditional ; Drugs, Chinese Herbal ; Data Mining/methods* ; Quality Control ; Technology, Pharmaceutical