To summarize the distribution characteristics of human papillomavirus(HPV) infection types in patients with cervical squamous intraepithelial lesion(SIL) and cervical cancer(CC), and to explore the impact of HPV vaccination, HPV infection types, and general clinical data on different grades of cervical lesions.

Transdermal drug delivery offers advantages such as safety, convenience, and high patient compliance. However, the complex structure of the skin and significant individual variability, particularly the barrier function of the stratum corneum, result in generally low bioavailability for topical formulations. The formulation of topical drug products is complex, with numerous factors influencing quality, which requires strict control of product quality. Raman spectroscopy, as a non-destructive vibrational technique, combined with chemometric methods, imaging technology, and other spectroscopic techniques, can be applied to study the key quality attributes of topical drug formulations. The applications of Raman spectroscopy in studies of the crystal form, particle size distribution, excipient research, and in vitro transdermal experiments of topical drug formulations were summarized. In particular, it focused on the use of Raman spectroscopy in the selection of skin samples for in vitro permeation tests, the study of drug spatial distribution in the skin, and the interactions between drugs and the skin.

Objective:To determine the prevalence, risk factors, and longitudinal associations of loneliness during mid- to late pregnancy with anxiety and depressive symptoms in late pregnancy.Methods:In this prospective cohort study, 1 107 pregnant women at 24-28 weeks' gestation were enrolled between June 2021 and December 2022. Psychological status was assessed during mid-pregnancy (24-28 weeks) and late pregnancy (≥32 weeks) using standardized electronic questionnaires, including the Revised University of California Los Angeles Loneliness Scale (UCLA) Loneliness Scale-Short Form (Cronbach's α=0.82), Patient Health Questionnaire-9 ( α=0.86), and Generalized Anxiety Disorder-7 ( α=0.88). Multivariate logistic regression identified independent risk factors for loneliness. Cross-lagged path models analyzed the longitudinal predictions between loneliness and anxiety/depressive symptoms. Results:The prevalence of loneliness decreased significantly from 10.8% (120/1 107) in mid-pregnancy to 4.8% (37/777) in late pregnancy ( χ2=21.81, P<0.001). Multivariate analysis identified independent risk factors for loneliness: age <30 years ( OR=1.70, 95% CI: 1.15-2.50), annual household income <50 000 CNY ( OR=2.53, 95% CI: 1.28-5.02), unemployment during pregnancy ( OR=1.57, 95% CI: 1.03-2.39), history of alcohol consumption ( OR=1.63, 95% CI: 1.03-2.56), and the presence of mid-pregnancy depressive ( OR=2.76, 95% CI: 1.51-5.04) and anxiety symptoms ( OR=1.65, 95% CI: 1.01-2.71) (all P<0.05). Cross-lagged path models indicated bidirectional associations between loneliness and both anxiety ( β=0.32, P<0.01) and depressive symptoms ( β=0.28, P<0.01). However, the predictive effect of loneliness on subsequent depressive and anxiety symptoms ( β=0.28-0.32) was substantially stronger than the reverse prediction (mid-pregnancy anxiety on late-pregnancy loneliness: β=0.12; mid-pregnancy depression on late-pregnancy loneliness: β=0.11). Loneliness demonstrated high temporal stability (autoregressive effects β=0.29-0.32). Conclusion:Loneliness in mid-pregnancy exhibits a symmetric bidirectional association with anxiety and depressive symptoms in late pregnancy, suggesting it may be a core driver in the development of these emotional symptoms. Younger maternal age (<30 years), low household income (<50 000 CNY/year), unemployment during pregnancy, and a history of alcohol consumption were associated with a higher risk of loneliness and should be prioritized for psychological screening and intervention.

Objective:To determine the prevalence, risk factors, and longitudinal associations of loneliness during mid- to late pregnancy with anxiety and depressive symptoms in late pregnancy.Methods:In this prospective cohort study, 1 107 pregnant women at 24-28 weeks' gestation were enrolled between June 2021 and December 2022. Psychological status was assessed during mid-pregnancy (24-28 weeks) and late pregnancy (≥32 weeks) using standardized electronic questionnaires, including the Revised University of California Los Angeles Loneliness Scale (UCLA) Loneliness Scale-Short Form (Cronbach's α=0.82), Patient Health Questionnaire-9 ( α=0.86), and Generalized Anxiety Disorder-7 ( α=0.88). Multivariate logistic regression identified independent risk factors for loneliness. Cross-lagged path models analyzed the longitudinal predictions between loneliness and anxiety/depressive symptoms. Results:The prevalence of loneliness decreased significantly from 10.8% (120/1 107) in mid-pregnancy to 4.8% (37/777) in late pregnancy ( χ2=21.81, P<0.001). Multivariate analysis identified independent risk factors for loneliness: age <30 years ( OR=1.70, 95% CI: 1.15-2.50), annual household income <50 000 CNY ( OR=2.53, 95% CI: 1.28-5.02), unemployment during pregnancy ( OR=1.57, 95% CI: 1.03-2.39), history of alcohol consumption ( OR=1.63, 95% CI: 1.03-2.56), and the presence of mid-pregnancy depressive ( OR=2.76, 95% CI: 1.51-5.04) and anxiety symptoms ( OR=1.65, 95% CI: 1.01-2.71) (all P<0.05). Cross-lagged path models indicated bidirectional associations between loneliness and both anxiety ( β=0.32, P<0.01) and depressive symptoms ( β=0.28, P<0.01). However, the predictive effect of loneliness on subsequent depressive and anxiety symptoms ( β=0.28-0.32) was substantially stronger than the reverse prediction (mid-pregnancy anxiety on late-pregnancy loneliness: β=0.12; mid-pregnancy depression on late-pregnancy loneliness: β=0.11). Loneliness demonstrated high temporal stability (autoregressive effects β=0.29-0.32). Conclusion:Loneliness in mid-pregnancy exhibits a symmetric bidirectional association with anxiety and depressive symptoms in late pregnancy, suggesting it may be a core driver in the development of these emotional symptoms. Younger maternal age (<30 years), low household income (<50 000 CNY/year), unemployment during pregnancy, and a history of alcohol consumption were associated with a higher risk of loneliness and should be prioritized for psychological screening and intervention.

Objective To analyze the resistance mechanism,characteristics of drug sensitivity,and homology of polymyxin resistant Escherichia coli,and provide molecular epidemiological basis for the effective prevention and control of its outbreak and epidemic.Methods The strains of polymyxin resistant Escherichia coli isolated from our hospital during May 2016 and June 2022 were collected.The PCR technology was used to screen for the mobile colistin resistance(MCR)gene and the micro broth dilution method was used to determine the minimum inhibitory concentration.The clinical data of the patients were collected.The homology of the collected strains was analyzed by the pulsed field gel electrophoresis(PFGE).One of the strains was performed whole genome sequencing.Results Four strains of polymyxin resistant Escherichia coli carrying the MCR-1 gene were isolated and identified.Except for being sensitive to tigecycline,all four strains showed varying degrees of resistance to the vast majority of clinically common antibiotics.Clinical data showed that no polymyxin was used in the patients with polymyxin resistant Escherichia coli.The four strains of bacteria could be divided into two types,including three strains of type A and one strain of type B.The whole genome sequencing analysis of one of the bacteria revealed that the MCR-1 gene was located on a plasmid with a size of 70 kb.Conclusion The Escherichia coli carrying the MCR-1 gene has a potential threat to clone transmission and exhibits high resistance to common antibiotics in clinical practice,posing a serious challenge to clinical treatment.Therefore,it is necessary to strengthen protective measures to prevent its outbreak and epidemic.

Liver fibrosis is a wound healing response that occurs in the setting of chronic liver injury and is caused by imbalance in the synthesis and degradation of extracellular matrix （ECM）. If left untreated， it can progress to liver cirrhosis and hepatocellular carcinoma. The activation of hepatic stellate cell （HSC） is now well established as a central driver of liver fibrosis. The activated HSC will transform into myofibroblasts that produce ECM protein. Transforming growth factor-β₁ （TGF-β₁） can induce the activation of hepatic stellate cell （HSC）， and TGF-β₁/Smads signaling pathway is one of the important pathways to promote liver fibrosis. Non-coding RNA （ncRNA） does not encode proteins during the transcription but plays an important regulatory role in the post-transcriptional process of genes. Accumulating evidence shows that the occurrence of liver fibrosis is closely related to the abnormal expression of ncRNA which participates in the activation of HSC by regulating TGF-β₁ signal transduction and then affects the process of liver fibrosis. MiRNA-mediated TGF-β₁/Smads signaling pathway can not only promote liver fibrosis but also play a role in anti-fibrosis. Long non-coding RNA （lncRNA） not only promotes the development of liver fibrosis by binding to target genes but also enhances TGF-β₁ signal transduction by acting as competitive endogenous RNA. circular RNA （circRNA） acts as a ''sponge'' to regulate TGF-β₁/Smads pathway， thereby inhibiting HSC activation and exerting the anti-liver fibrosis effect. Chinese medicinal plays an essential part in the prevention and treatment of liver fibrosis， and the active components can inhibit TGF-β₁/Smads pathway by regulating the expression of miRNA， thus alleviating liver fibrosis. This article reviews the role and mechanism of miRNA-， lncRNA- and circRNA-mediated TGF-β₁/Smads signaling pathway in liver fibrosis and summarizes the anti-liver fibrosis effect of active components of Chinese medicinals by regulating miRNA-mediated TGF-β₁/Smads signaling pathway， which can serve as a reference for clinical treatment of liver fibrosis and the development of new drugs.

Abstract OBJECTIVE To investigate the effect of isodon ternifolia-containing serum(ITS) on the activation of rat primary hepatic Kupffer cell(KC) induced by lipopolysaccharide(LPS) through TLR4/NF-κB/NLRP3 signal pathway. METHODS The primary KC of rats were isolated and cultured, and the primary KC induced by LPS were divided into blank control group, model control group, blank serum group, positive control group(colchicine containing serum group), ITS group, TLR4 blocker group and TLR4 blocker+ITS group. MTT assay was used to detect the effect of different concentrations of ITS on the proliferation activity of KC. The content of interleukin-1β(IL-1β), interleukin-18(IL-18), tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in KC supernatant were detected by ELISA. Fluorescence quantitative polymerase chain reaction(PCR), Western blotting and immunofluorescence were used to detect the expression of TLR4, nuclear factor κB inhibitor protein α(IκBα), cysteine protease-1(Caspase-1), NLRP3 mRNA and TLR4, IκBα, phosphorylated IκBα(p-IκBα), Caspase-1, NLRP3 and NF-κBp65 in KC. RESULTS Compared with the model control group, the contents of IL-1β, IL-18, TNF-α and IL-6 in the supernatant of KC and the expression of TLR4, IκB α, Caspase-1, NLRP3 mRNA and TLR4, IκBα, p-IκBα, Caspase-1, NLRP3, NF-κBp65 protein in the supernatant of KC in all drug groups were down-regulated or decreased(P<0.05 or P<0.01). Compared with TLR4 blocker group, the improvement of most of the above indexes in TLR4 blocker+ITS group was more obvious. CONCLUSION Isodon ternifolia may inhibit the activation of KC and reduce the expression and release of inflammatory factors by down-regulating TLR4/NF-κB/NLRP3 signal pathway, thus alleviating the inflammatory injury of liver.

Objective:To construct evaluation indicators system for functional capability of the elderly, so as to provide reference for evaluating their functional capability.Methods:The evaluation indicators for functional capability of the elderly were extracted and integrated through literature analysis. From March to April 2023, 15 experts were selected for two rounds of expert consultation to screen, modify, and improve indicators, and ultimately determine evaluation indicators system for functional capability of the elderly.Results:The effective response rates of the two rounds of expert consultation questionnaires were both 100.00% (15/15) , and the expert authority coefficients were all 0.930. The Kendall's W of importance and applicability of the first level indicators in the first round were 0.437 and 0.573 ( P<0.05) , while the Kendall's W of importance and applicability of the second level indicators were 0.285 and 0.287 ( P<0.05) . The Kendall's W of importance and applicability of the second level indicators in the second round were 0.380 and 0.345 ( P<0.05) . The final evaluation indicators system for functional capability of the elderly included 5 first level indicators and 28 second level indicators. Conclusions:The evaluation indicators system for functional capability of the elderly are scientific and reliable, providing reference for evaluating the functional capability of the elderly.

Objective:To explore the spatial autocorrelation and macro influencing factors of stroke mortality in Zhejiang Province in 2015-2020 and provide a scientific basis for stroke prevention and control strategy.Methods:The data on stroke death were obtained from Zhejiang Chronic Disease Surveillance System. The spatial distribution of stroke mortality was explored by mapping and spatial autocorrelation analysis. The spatial panel model analyzed the correlation between stroke mortality and socioeconomic and healthcare factors.Results:From 2015 to 2020, the average stroke mortality was 68.38/100 thousand. The standard mortality of stroke was high in the areas of east and low in the west, high in the south and low in the north. Moreover, positive spatial autocorrelation was observed (Moran's I=0.274-0.390, P<0.001). Standard mortality of stroke was negatively associated with per capita gross domestic product (GDP) ( β=-0.370, P<0.001), per capita health expenditure ( β=-0.116, P=0.021), number of beds per thousand population ( β=-0.161, P=0.030). Standard mortality of ischemic stroke was negatively associated with per capita GDP ( β=-0.310, P=0.002) and standard management rate of hypertension ( β=-0.462, P=0.011). Standard mortality of hemorrhagic stroke was negatively associated with per capita GDP ( β=-0.481, P<0.001), per capita health expenditure ( β=-0.184, P=0.001), number of beds per thousand population ( β=-0.288, P=0.001) and standard management rate of hypertension ( β=-0.336, P=0.029). Conclusions:A positive spatial correlation existed between stroke mortality in Zhejiang Province in 2015-2020. We must focus more on preventing and controlling strokes in relatively backward economic areas. Moreover, to reduce the mortality of stroke, increasing the investment of government medical and health funds, optimizing the allocation of medical resources, and improving the standard management rate of hypertension are important measures.

Objective: To examine the correlation between frailty and lifestyle factors among middle-aged and elderly populations, so as to provide insights into the management of frailty among middle-aged and elderly populations. Methods : Middle-aged and elderly residents at ages of 45 ot 69 years were recruited using the convenient sampling method from seven townships in Changxing County of Zhejiang Province from 2019 to 2020. The demographic characteristics and lifestyle factors were collected using questionnaires, and the frailty was measured using the Chinese version of Tilburg Frailty Indicator ( TFI ). Factors affecting frailty were identified among middle-aged and elderly populations using the multivariable logistic regression model. Results: A total of 7 170 residents were surveyed, including 2 780 males ( 38.77% ) and 4 390 females ( 61.23% ), which had a median age of 56 (interquartile range, 10) years. The median frailty score was 2 (interquartile range, 3 ) among the study subjects, and the median frailty score was 2 ( interquartile range, 2 ) among residents at ages of 45 to 59 years, and 2 (interquartile range, 3) among residents at ages of 60 to 69 years. The overall detection of frailty was 16.07%, and the detection of frailty was 13.52% among subjects at ages of 45 to 59 years and 21.01% among subjects at ages of 60 to 69 years. Multivariable logistic regression analysis identified physical activity ( OR=0.826, 95%CI: 0.719-0.949 ) and sleep quality ( OR: 3.376-11.493, 95%CI: 2.907-15.808 ) as factors affecting frailty among middle-aged and elderly residents. Following age stratification, physical activity ( OR=0.817, 95%CI: 0.681-0.981 ) and sleep quality ( OR: 3.076-11.566, 95%CI: 2.518-18.216 ) as factors affecting frailty among subjects at ages of 45 to 59 years, while sleep quality ( OR: 3.777-11.827, 95%CI: 3.002-18.547 ) significantly correlated with frailty among residents at ages of 60 to 69 years. Conclusion Physical activity and sleep quality are associated with the risk of frailty among middle-aged and elderly populations.