[Objective] To study on the genotyping of a sample with inconsistent forward and reverse serological tests, and to conduct a pedigree investigation and molecular biological mechanism study. [Methods] The ABO blood group of the proband and his family members were identified using blood group serological method. The ABO gene exon 1-7 of samples of the proband and his family were sequenced by Sanger and single molecule real-time sequencing (SMRT). DeepTMHMM was used to predict and analyze the transmembrane region of proteins before and after mutation. [Results] The proband and his mother have the Bw phenotype, while his maternal grandfather has ABw phenotype. The blood group results of forward and reverse typing of other family members were consistent. ABO gene sequencing results showed that there was B new mutation of c.3 G>C in exon 1 of ABO gene in the proband, his mother and grandfather, leading to a shift in translation start site. DeepTMHMM analysis indicated that the shift in the translation start site altered the protein topology. [Conclusion] The c.3G>C mutation in the first exon of the ABO gene leads to a shift in the translation start site, altering the protein topology from an α-transmembrane region to a spherical signaling peptide, reducing enzyme activity and resulting in the Bw serological phenotype.

OBJECTIVE: To investigate the effectiveness and safety of simultaneous bilateral total knee athroplasty (SB-TKA) for the treatment of patients aged 65 years and younger with bilateral knee osteoarthritis (KOA) by comparing with patients undergoing unilateral total knee arthroplasty (U-TKA). METHODS: A clinical data of patients, who underwent primary TKA for KOA and met the selection criteria between June 2019 and July 2023, was retrospectively analyzed, including 181 patients in the U-TKA group and 52 patients in the SB-TKA group. The baseline data of age, gender, disease duration, body mass index, and preoperative hemoglobin (Hb), knee range of motion (ROM), Oxford knee score (OKS), and visual analogue scale (VAS) score for pain were compared between the two groups, with no significant difference ( P>0.05). The operation time, postoperative hospital stay, and all complications related to knee arthroplasty were recorded. Hb was measured at 2 days after operation and the difference between pre- and post-operation was calculated. The knee function and pain were evaluated by using ROM, OKS score, and VAS score and compared between the two groups. RESULTS: The operation time and postoperative hospital stay duration were significantly shorter in the U-TKA group than in the SB-TKA group ( P<0.05). The difference of Hb was significantly lower in the U-TKA group ( P<0.05). All patients were followed up 12-61 months (mean, 37.2 months). There was no significant difference in follow-up time between the two groups ( P>0.05). At last follow-up, the ROM, OKS score, and VAS score of both groups were better than the preoperative ones, and the differences were significant ( P<0.05); there were significant differences between the two groups in the ROM and OKS score ( P<0.05), while no significant difference was found in the VAS score ( P>0.05). Mild complications were observed in 31 cases (17.13%) and severe complications in 3 cases (1.66%) in the U-TKA group, while mild complications were observed in 14 cases (26.92%) in the SB-TKA group, and no severe complication occurred. There was no significant difference in the incidences of mild and severe complications between the two groups ( P>0.05). CONCLUSION In patients aged 65 years and younger with bilateral KOA, knee function and mobility can significantly improved when treated by SB-TKA. While patients had lower postoperative knee mobility and function scores compared with U-TKA, there was no significant difference in pain scores or overall incidence of complication. Strict patient selection and scientific perioperative management are important to achieve good effectiveness after operation in patients with SB-TKA.
Humans ; Arthroplasty, Replacement, Knee/adverse effects* ; Male ; Female ; Retrospective Studies ; Osteoarthritis, Knee/physiopathology* ; Range of Motion, Articular ; Treatment Outcome ; Middle Aged ; Operative Time ; Length of Stay ; Knee Joint/physiopathology* ; Pain Measurement ; Postoperative Complications/epidemiology* ; Aged

OBJECTIVE: To examine the effectiveness of Chinese medicine (CM) Lianhua Qingwen Granule (LHQW) and Jingyin Gubiao Prescription (JYGB) in asymptomatic or mild patients with Omicron infection in the shelter hospital. METHODS: This single-center retrospective cohort study was conducted in the largest shelter hospital in Shanghai, China, from April 10, 2022 to May 30, 2022. A total of 56,244 asymptomatic and mild Omicron cases were included and divided into 4 groups, i.e., non-administration group (23,702 cases), LHQW group (11,576 cases), JYGB group (12,112 cases), and dual combination of LHQW and JYGB group (8,854 cases). The length of stay (LOS) in the hospital was used to assess the effectiveness of LHQW and JYGB treatment on Omicron infection. RESULTS: Patients aged 41-60 years, with nadir threshold cycle (C_T) value of N gene <25, or those fully vaccinated preferred to receive CM therapy. Before or after propensity score matching (PSM), the multiple linear regression showed that LHQW and JYGB treatment were independent influence factors of LOS (both P<0.001). After PSM, there were significant differences in LOS between the LHQW/JYGB combination and the other groups (P<0.01). The results of factorial design ANOVA proved that the LHQW/JYGB combination therapy synergistically shortened LOS (P=0.032). CONCLUSIONS Patients with a nadir C_T value <25 were more likely to accept CM. The LHQW/JYGB combination therapy could shorten the LOS of Omicron-infected individuals in an isolated environment.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Female ; Middle Aged ; Adult ; China/epidemiology* ; Hospitalization ; COVID-19 Drug Treatment ; COVID-19/epidemiology* ; SARS-CoV-2 ; Retrospective Studies ; Treatment Outcome ; Length of Stay ; Young Adult ; Aged

Objective To develop a machine learning-based risk prediction model for postoperative acute kidney injury(AKI)and a model for mortality in obese patients admitted to intensive care unit(ICU)in order to improve early warning and prognostic evaluation to support clinical decision-making.Methods Data of obese postoperative ICU patients were retrospectively retrieved from the MIMIC-Ⅳ and eICU databases for statistical analysis.Ultimately,2 520 patients(670 from MIMIC-Ⅳ and 1 850 from eICU databases)were included to build the risk prediction models for AKI and mortality.The data included demographic information,vital signs,laboratory findings,surgical types,comorbidities,and medication use.After data cleaning and preprocessing,Boruta feature selection was applied,followed by the construction of prediction models using 7 machine learning algorithms,that is,Gradient Boosting Machine(GBM),Generalized Linear Model(GLM),k-Nearest Neighbors(KNN),Na?ve Bayes(NB),Neural Network(NNET),Support Vector Machine(SVM),and XGBoost.Model performance was evaluated through cross-validation and external validation.Results In the risk prediction models of AKI,the SVM model achieved the highest AUC value of 0.80 in the testing set and 0.71 in the external validation test.For the risk prediction models of mortality,the GBM model outperformed others in the prediction,attaining an AUC value of 0.91 in the testing set.Conclusion Risk predictive models for postoperative AKI and mortality in obese ICU patients are successfully constructed,and are valuable tools for clinicians to optimize early intervention and improve clinical outcomes for the patients.

Objective To systematic analyze the risk factors for new-onset urethral stricture after transurethral holmium laser enucleation of the prostate(HoLEP)in the treatment of benign prostatic hyperplasia(BPH).Methods A case-control study was conducted on 746 BPH patients undergoing HoLEP treatment in Department of Urology of the Third Medical Center of Chinese PLA General Hospital from November 2021 to August 2024.After 23 cases were excluded because of complication of prostate cancer,finally 723 patients were included.General clinical data such as age,height,weight,history of smoking and drinking,perioperative parameters,and follow-up data at 1,3 and 6 months after operation were collected.Univariate and multivariate logistic regression analyses were used to identify the clinical risk factors for new-onset urethral stricture after HoLEP.Results The subjected patients had a median age of 66.5(64.0,75.0)years,and a preoperative median prostate volume of 66(45,92)mL,and a median indwelling catheter time of 4(4,5)d.The incidence of new urethral stricture after operation was 5.8%(42/723),with membranous part of the urethra(61.9%)the most common site,followed by the external urethral orifice(21.4%)and the bladder neck(7.1%).Risk factor analysis indicated that low BMI(<18.5 kg/m2)(OR=4.682,P=0.037),young age(OR=0.946,P=0.005),and postoperative urinary tract infection(OR=4.513,P=0.001)were independent risk factors for new-onset urethral stricture after surgery.Prostate volume and indwelling time of urinary catheter had no significant association with the occurrence of new urethral stricture after surgery.Conclusion The occurrence of new-onset urethral stricture after HoLEP is significantly correlated with BMI,age and urinary tract infection.The above 3 factors can be used as better predictors of new-onset urethral stricture after HoLEP.

Residual formaldehyde(FA)in environmental water samples,certain aquatic products,vegetables,and other food items poses a severe threat to environmental safety and human health.Therefore,the rapid,sensitive and selective detection of FA is very essential for food safety and environmental protection.In this work,a new 1,8-naphthalimide-based fluorescent probe NIPh for FA detection was synthesized by using hydrazide group as a reactive site for FA and naphthalimide as a fluorophore.Based on the photoinduced electron transfer(PET)process,the prepared probe NIPh showed a remarkable fluorescence lighting-up response towards FA in aqueous medium with high selectivity,fast response(within 4 min)and a low limit of detection(0.16 μmol/L).Further,the probe NIPh was also successfully applied as optical probe to detection of FA in cabbage,enoki mushroom,pond and tap water samples,with recoveries over 96%,and relative standard deviations less than 4%,demonstrating tremendous potential in FA monitoring in the field of food industry and environment.

In recent years, nucleic acid therapy, as a revolutionary therapeutic tool, has shown great potential in the treatment of genetic diseases, infectious diseases and cancer. Lipid nanoparticles (LNPs) are currently the most advanced mRNA delivery carriers, and their emergence is an important reason for the rapid approval and use of COVID-19 mRNA vaccines and the development of mRNA therapy. Currently, mRNA therapeutics using LNP as a carrier have been widely used in protein replacement therapy, vaccines and gene editing. Conventional LNP is composed of four components: ionizable lipids, phospholipids, cholesterol, and polyethylene glycol (PEG) lipids, which can effectively load mRNA to improve the stability of mRNA and promote the delivery of mRNA to the cytoplasm. However, in the face of the complexity and diversity of clinical diseases, the structure, properties and functions of existing LNPs are too homogeneous, and the lack of targeted delivery capability may result in the risk of off-targeting. LNPs are flexibly designed and structurally stable vectors, and the adjustment of the types or proportions of their components can give them additional functions without affecting the ability of LNPs to deliver mRNAs. For example, by replacing and optimizing the basic components of LNP, introducing a fifth component, and modifying its surface, LNP can be made to have more precise targeting ability to reduce the side effects caused by treatment, or be given additional functions to synergistically enhance the efficacy of mRNA therapy to respond to the clinical demand for nucleic acid therapy. It is also possible to further improve the efficiency of LNP delivery of mRNA through machine learning-assisted LNP iteration. This review can provide a reference method for the rational design of engineered lipid nanoparticles delivering mRNA to treat diseases.

BACKGROUND:Semaphone 3A(Sema3A)is an important neurovascular growth inhibitor.It is not clear how Sema3A is involved in the pathogenesis of discogenic low back pain.Exploring the potential mechanism of Sema3A in intervertebral disc degeneration can provide a new target and theoretical basis for the prevention and treatment of discogenic low back pain. OBJECTIVE:To explore the mechanism of interleukin-1β inhibiting the expression of Sema3A by activating the nuclear factor-κB signaling pathway to induce intervertebral disc degeneration in rats. METHODS:RT-qPCR was used to detect the expression of Sema3A mRNA in normal and degenerative human nucleus pulposus tissues.Nucleus pulposus cells of Sprague-Dawley rats were isolated,cultured,and passaged to the 3rd generation.Then,passage 3 cells were divided into three groups:the blank control group was routinely cultured for 48 hours,the degeneration group was intervened with 10 ng/mL interleukin 1β for 48 hours,and the degeneration+inhibitor group was treated by 5 μmol/L nuclear factor-κB signaling pathway-specific inhibitor BAY11-7082 for 1 hour,followed by interleukin-1β for 48 hours.At the end of the intervention,cell viability was detected by cell counting kit-8,cell apoptosis was detected by Annexin V/FITC staining,mRNA expression of cellular matrix,vascular and neural markers and Sema3A was detected by RT-qPCR,and protein expression of marker proteins,p65 and p-p65 was detected by western blot. RESULTS AND CONCLUSION:RT-qPCR assay showed that the expression of Sema3A mRNA was lower in degenerative human nucleus pulposus tissue than in normal human nucleus pulposus tissue(P＜0.05).Compared with the blank control group,the nucleus pulposus cell viability decreased and the apoptotic rate increased in the degeneration group(P＜0.05);compared with the degeneration group,the nucleus pulposus cell viability increased and the apoptotic rate decreased in the degeneration + inhibitor group(P＜0.05).Compared with the blank control group,mRNA expression of type Ⅱ collagen,polyproteoglycan,and Sema3A was decreased in the degeneration group(P＜0.05),while mRNA expression of CD31 and neurofilament 200 was increased(P＜0.05).Compared with the degeneration group,mRNA expression of type Ⅱ collagen,polyproteoglycan,and Sema3A was elevated in the degeneration+inhibitor group(P＜0.05)and mRNA expression of CD31 and neurofilament 200 decreased(P＜0.05).Compared with the blank control group,the protein expression of type Ⅱ collagen,polyproteoglycan,and Sema3A was decreased in the degeneration group(P＜0.05),and the protein expression of CD31,neurofilament protein 200,p65,and p-p65 was elevated(P＜0.05);compared with the degeneration group,the protein expression of type Ⅱ collagen,polyproteoglycan,and Sema3A was elevated in the degeneration+inhibitor group(P＜0.05),and protein expression of CD31,neurofilament 200,p65,and p-p65 was decreased(P＜0.05).To conclude,interleukin-1β does inhibit the expression of Sema3A by activating the nuclear factor-κB signaling pathway,which can also increase the degradation of extracellular matrix,promote the innervation and angiogenesis in degenerative intervertebral disc,and may be one of potential factors that contribute to intervertebral disc degeneration and discogenic low back pain.

Objective To analyze the pathogenic bacteria and drug resistance of peritoneal dialysis-associated peritonitis(PDAP),and provide a clinical reference for the rational use of antibiotics.Methods The demographic data of PDAP patients admitted to the peritoneal dialysis(PD)Center of the First Affiliated Hospital of Soochow University from July 1,2015 to December 30,2021 were collected,and the pathogens,drug resistance and prognosis were retrospectively analyzed.Results A total of 150 episodes of PDAP occurred in 92 patients.The positive rate of PD fluid culture was 61.33％,including 65 cases(70.65％)of Gram-positive(G+)bacteria,mainly Staphylococcus and Streptococcus.Gram-negative(G-)bacteria were in 16 cases(17.39％),mainly Escherichia coli and Enterobacter cloacae.There were 11 cases(11.96％)of multiple infections,including 5 cases of combined fungal infection.From 2016 to 2021,the incidence of G+bacteria-related PDAP decreased from 14 to 8 cases.G+strains were resistant to methicillin(35.00％),and were sensitive to linezolid(100.00％),teicoplanin(100.00％)and rifampicin(100.00％).The sensitivity rate to vancomycin was 98.59％.G-strains were sensitive to ceftazidime(86.36％),ceftizoxime(88.89％)and amikacin(100.00％).The MIC of vancomycin against Staphylococcus showed an upward trend in 2019-2021.The overall cure rate of PDAP was 81.33％in patients who responded to antibiotic treatment,and the cure rate of G+bacteria was higher than that of multiple infections(89.23％vs.36.36％,P＜0.01).The outcome of patients with multiple infections,especially those with concurrent fungal infection was poor.Conclusion The incidence of PDAP in the PD center has shown a decreasing trend in recent years.G+bacteria are still the main pathogenic bacteria causing PDAP,and they are highly resistant to methicillin,so vancomycin should be used as empirical therapy.For G-bacteria,cefotaxime and amikacin can be chosen as empirical therapy.There is a drift in the MIC values of vancomycin against Staphylococcus in the study period,so it is necessary to monitor the MIC of vancomycin against Staphylococcus and its changing trend.

Objective To explore the characteristics of traditional Chinese medicine(TCM)syndromes in patients with cervical high-risk human papillomavirus(HR-HPV)infection,and to provide reference for clinical syndrome differentiation and treatment of cervical HR-HPV patients.Methods From September 2020 to October 2022,the TCM syndrome manifestations of cervical HR-HPV infection diagnosed by HPV detection in the Gynecology Department of The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine were investigated,and then the distribution of disease-location syndrome elements,disease-nature syndrome elements and syndrome types was analyzed.Results The patients with cervical HR-HPV infection were usually manifested with abnormal vaginal secretions,which accounted for 63.40%.The disease-location syndrome elements of cervical HR-HPV infection were uterus,spleen,liver,kidney,meridians,stomach,heart spirit and heart.Among them,uterus,spleen and liver were most commonly-seen,accounting for 67.00%,58.80%and 55.80%respectively.The disease-nature syndrome elements were dampness,heat,qi stagnation,blood stasis,qi deficiency,yang deficiency,yin deficiency,phlegm and cold.Among them,dampness,heat,qi stagnation and blood stasis were most commonly-seen,accounting for 66.40%,56.60%,36.00%and 31.80%,respectively.In various age groups of the infected patients,the uterus was the predominated disease-location syndrome element,and dampness and heat were the predominated disease-nature syndrome elements.The uterus-spleen was the predominated double disease-location syndrome element,and the uterus-spleen-liver was the predominated triple disease-location syndrome element.Damp-heat was the predominated double disease-nature syndrome element,and damp-heat-blood stasis was the predominated triple disease-nature syndrome element.According to the results of cluster analysis and with reference to the clinical practice,it was found that the main syndrome types of the patients with cervical HR-HPV infection were damp-heat stasis stagnation,liver depression and qi stagnation,heart-kidney incoordination,spleen-stomach yang deficiency.Conclusion In the view of the TCM syndrome,cervical HR-HPV infection is mainly affected with the uterus,and also involves the spleen,liver and kidney.The disease-nature syndrome elements are characterized by dampness and heat,showing the characteristics of deficiency interweaved with excess.The main TCM syndrome types are damp-heat stasis stagnation,liver depression and qi stagnation,heart-kidney incoordination,and spleen-stomach yang deficiency.