Objective To investigate the therapeutic effect of Huangkui capsules on targeted drug-related proteinuria in patients with hepatocellular carcinoma (HCC). Methods A retrospective analysis was conducted on clinical data of HCC patients with targeted drug-related proteinuria from June 2023 to December 2024 at Zhongshan Hospital, Fudan University. According to the treatment plan, patients were divided into the conventional treatment group and the Huangkui combination treatment group (Huangkui capsules combined with conventional treatment), and the clinical efficacy between the two groups was compared. The logistic regression analysis was used to identify the main factors affecting treatment efficacy. Results The Huangkui combination treatment group (n＝29) showed a significantly higher overall effective rate (79.3% vs 42.3%, P＝0.005), and an earlier proteinuria improvement (median time: 3 months vs 6 months, P＝0.008) than the conventional treatment group (n＝26) . The multivariate logistic regression analysis showed angiotensin-converting enzyme inhibitor (ACEI) or angiotensin Ⅱ receptor blocker (ARB) using (OR＝0.190, 95%CI 0.045-0.808, P＝0.025), targeted drug adjustment (OR＝0.132, 95%CI 0.030-0.581, P＝0.007), and Huangkui capsules using (OR＝0.168, 95%CI 0.039-0.730, P＝0.017) were protective factors for treatment efficacy of targeted drug-related proteinuria. Conclusions On the basis of conventional treatment, additive treatment with Huangkui capsules can alleviate targeted drug-related proteinuria faster and more effectively in HCC patients.

BACKGROUND:SOX5 is an important transcription factor of the SRY-related HMG-box(SOX)family,which plays a key role in regulating the expression of genes related to bone development and remodeling,especially during osteoblast differentiation and chondrocyte maturation,through its unique HMG box DNA structural domains in concert with SOX6 and SOX9.In addition,the expression and activity of SOX5 and its family are regulated by a variety of diseases and different forms of exercise,among other factors,suggesting that SOX5 and its family have the potential to be effective as drugs and therapeutics to ameliorate related diseases in the future.OBJECTIVE:To provide new perspectives for future research on SOX5 and to provide scientific basis for the application of exercise intervention and drug therapy in the prevention and treatment of bone diseases.METHODS:CNKI and PubMed databases were searched for relevant literature published from 2001 to June 2024,and the search terms were"SRY-related HMG-box5,SOX5,Bone"in Chinese and English,respectively.After screening,analysis and summarization,105 articles were included in the final review.RESULTS AND CONCLUSION:(1)Role of SOX5 in bone development:SOX5 is an important member of the SOX family,which plays a central role in the regulation of skeletal development,bone metabolism and cartilage formation.In synergy with SOX6 and SOX9,SOX5 activates gene expression in osteoblasts and chondrocytes by binding to specific DNA sequences to regulate bone formation and bone remodeling.(2)Abnormal expression of SOX5 is closely related to bone and joint diseases such as chondrodysplasia,osteoporosis and osteoarthritis,suggesting that it may be a key regulator of these diseases.Currently,a variety of drugs may be used to treat bone metabolism-related diseases by regulating SOX5 and its family,and upregulation of SOX5 in mesenchymal stem cells may be effective in improving the symptoms of bone metabolism disease patients in bone tissue engineering.(3)Exercise may effectively prevent osteoporosis and related bone diseases by enhancing bone metabolism and promoting osteoblast differentiation and bone density increase.This mechanism of action may be related to the specific regulatory mechanism of SOX5,especially in different types,intensities and durations of exercise need to be further explored and studied.In conclusion,SOX5 has an important regulatory role in bone development,chondrogenesis,and prevention of bone diseases,and its activity is regulated by a variety of factors,while exercise intervention provides a new scientific basis for the treatment of bone diseases.

Objective:To evaluate the diagnostic value of MRI findings in differentiating between tophus and giant cell tumors of the tendon sheath (GCTTS) in the knee.Methods:The study was a case-control study. The clinical and MRI data of patients diagnosed with knee tophus or GCTTS was retrospectively analyzed at the Affiliated Hospital of Qingdao University from September 2018 to September 2024. The study included 23 cases of tophus and 22 cases of GCTTS. MRI sequences, including T 1WI, fat-suppressed T 2WI, and proton density weighted imaging, were evaluated. Parameters including lesion signal intensity and homogeneity, margin, maximum diameter, location (inside or outside the synovial cavity), ligament/tendon involvement, ligament/tendon parenchymal changes, adjacent bone erosion, bone marrow edema, synovial hyperplasia, joint effusion, and periarticular soft tissue swelling were recorded. Independent sample t-tests, χ2 tests, or Fisher exact tests were used to compare MRI findings between the two groups. Multivariate logistic regression was performed to identify independent predictive factors. Results:Significant differences in terms of maximum diameter, location (inside or outside the synovial cavity), ligament/tendon involvement, ligament/tendon parenchymal changes, adjacent bone erosion, bone marrow edema, and periarticular soft tissue swelling between the two groups were found (all P<0.05). No significant differences for other parameters were observed (all P>0.05). Lesion location and ligament/tendon parenchymal involvement demonstrated the highest sensitivity and specificity for distinguishing the two diseases. The sensitivity and specificity values for lesion location were 0.78 and 0.95. The sensitivity and specificity values for ligament/tendon involvement were 0.78 and 1.00. Multivariate logistic regression identified lesion location (inside or outside the synovial cavity) as an independent predictor for differentiating tophus from GCTTS ( OR=31.48, 95% CI 1.58-625.69, P=0.024). Conclusion:The location of the lesion (inside or outside the synovial cavity) and involvement of ligament/tendon parenchyma are critical factors in differentiating knee tophus from GCTTS. Additionally, lesion location serves as an independent predictor for distinguishing between the two conditions.

OBJECTIVE To observe and compare the synergistic rates of combined use of polymyxin B with 12 types of traditional antibiotics against carbapenem-resistant Klebsiella pneumoniae(CRKP)in vitro antimicrobial ac-tion.METHODS Totally 30 strains of CRKP were randomly drawn from 312 strains of CRKP that were isolated from the clinical departments of Shiyan People's Hospital between 2020 to 2023.The carbapenemases were detec-ted by Carba NP test.The six genotypes KPC,OXA-48,OXA-23,NDM,VIM and IMP were detected by means of fluorescent quantitative polymerase chain reaction(PCR),the drug resistance of the strains was detected by mi-cro broth dilution method,and the synergistic effect of polymyxin B combined with 12 types of traditional antibi-otics on in vitro antimicrobial action was detected by using micro chessboard dilution method.RESULTS All of the isolated CRKP strains produced carbapenemases,with the KPC genotype dominant.The drug resistance rates to cephalosporins,carbapenems and quinolones reached up to 100.00％,and no polymyxin B-resistant strains were detected.The synergistic rates of minocycline and rifampicin combined with polymyxin B to the in vitro antimicro-bial action were the highest,which were 73.33％and 50.00％,respectively;the synergistic rates of levofloxacin and ciprofloxacin combined with polymyxin B were the lowest,and both were 0.The synergistic rates of meropen-em and imipenem combined with polymyxin B to the in in vitro antimicrobial action were 36.67％and 30.00％,re-spectively.The synergistic rates of ceftazidime,cefepime,piperacillin-tazobactam and cefoperazone-sulbactam combined with polymyxin B to the in vitro antimicrobial action were less than 30.00％.CONCLUSIONS Polymyxin B combined with minocycline and rifampicin should be taken as the first choice for treatment of the CRKP-induced infection.The synergistic rate of the carbapenems combined with polymyxin B is higher than that of the cephalo-sporins combined with polymyxin B to the antimicrobial action.Levofloxacin and ciprofloxacin combined with pol-ymyxin B do not have synergistic effect on the in vitro antimicrobial action.

Objective To investigate the effects of electroacupuncture(EA)at"Baihui(GV 20),""Pishu(BL 20),"and"Zusanli(ST 36)"on the learning and memory functions of rats with Alzheimer's disease(AD)induced by Aβ1-42.Additionally,the mechanism of EA in treating AD was explored from the perspective of the inflammatory cascade mediated by the NF-κ B/NLRP3/Caspase-1 signaling pathway.Methods A rat model of Alzheimer's disease was established by bilateral injection of Aβ1-42 solution into the C1 region of the hippocampus.According to the random number table method,32 male SPF-grade rats were divided into four groups(n=8 per group):a sham-operated group,a model group,an electroacupuncture(EA)group,and a Western medicine group(donepezil hydrochloride).The EA group received electroacupuncture at the"Baihui","Pishu",and"Zusanli"acu-points;the Western medicine group received donepezil hydrochloride via gavage.After the treatment period,Morris water maze experiments were conducted to evaluate learning and memory abilities.Hematoxylin and eosin(HE)staining was used to examine morphological changes in hippocampal tissues.Enzyme-linked immunosorbent assay(ELISA)was employed to measure serum levels of TNF-α and IL-1β.Western blotting and immunofluorescence staining were utilized to assess the co-expression levels of NF-κB p65,NLRP3,and Caspase-1 proteins in the hippocampal region.Results Compared with the sham-operated group,rats in the post-modeling group exhibited significantly prolonged escape latency(P<0.05),reduced crossings of the original platform location,and decreased time spent in the target quadrant(P<0.05).Additionally,nuclear morphology was altered,neurons surrounding the hippocampus displayed necrosis,vacuolar degeneration,and chromatin marginalization.Serum levels of TNF-α and IL-1β were elevated(P<0.05),and protein expression levels as well as fluorescent positivity for NF-κB p65,NLRP3,and caspase-1 in the hippocampus were increased(P<0.05).Compared with the model group,rats in both the EA and Western medicine groups showed a trend toward shorter escape latency(P<0.05),increased crossings of the original platform location and time spent in the target quadrant(P<0.05).Cell structures were largely intact,with only a few nuclei showing slight irregularities and some chromatin accumulation at the edges.Serum levels of TNF-α and IL-1β were reduced(P<0.05),and protein expression levels and fluorescence positivity for NF-κB p65,NLRP3,and caspase-1 in the hippocampus were also decreased(P<0.05).Conclusion EA enhances the learning and memory capabilities of AD rats,potentially by downregulating the NF-κ B/NLRP3/Caspase-1+signaling+pathway and decreasing the release of neuroinflammatory factors,thereby alleviating cognitive dysfunction in AD rats.

ObjectiveTo investigate the efficacy of Xingpi capsules （XPC） in treating diarrhea-predominant irritable bowel syndrome （IBS-D） with spleen deficiency and elucidate its potential molecular mechanisms. MethodsA rat model of IBS-D with spleen deficiency was established by administering senna leaf in combination with restrained stress and swimming fatigue for 14 d. Ten specific pathogen free （SPF）-grade healthy rats were used as the normal control group. After successful modeling， SPF-grade rats were randomly divided into a model group， a pinaverium bromide group （1.5 mg·kg^-1）， and low- and high-dose XPC groups （0.135 and 0.54 g·kg^-1）， with 10 rats in each group. Rats in the normal control group and the model group were given distilled water by gavage， while the remaining groups were administered corresponding drug solutions by gavage once a day for 14 consecutive days. The rat body weights and fecal condition were observed every day， and the Bristol score was recorded. Enzyme-linked immunosorbent assay （ELISA） was used to determine the levels of 5-hydroxytryptamine （5-HT） in serum and colon tissue. Transmission electron microscopy was used to observe the microvilli and tight junctions in the colon. The integrity of the colonic barrier， intestinal motility， and expression of related pathway proteins were evaluated by hematoxylin-eosin （HE） staining， immunohistochemistry， and Western blot. ResultsCompared with those in the normal control group， rats in the model group showed a significantly decreased body weight and increased diarrhea rate， diarrhea grade， and Bristol score （P<0.01）. HE staining revealed incomplete colonic mucosa in the model group， with evident congestion and edema observed. Electron microscopy results indicated decreased density and integrity of the colonic barrier， shedding and disappearance of microvilli， and significant widening of tight junctions. The expression levels of colonic tight junction proteins Occludin and Claudin-5 were downregulated （P<0.01）， and the levels of 5-HT in serum and colon tissue were elevated （P<0.01）. The small intestine propulsion rate significantly increased （P<0.01）， and the expression of contractile proteins Ras homolog family member A （RhoA） and Rho-associated coiled-coil containing protein kinase 2 （ROCK2） in colon and phosphorylation of myosin light chain （MLC₂₀） were upregulated （P<0.01）. Compared with the model group， the treatment groups showed alleviated diarrhea， diarrhea-associated symptoms， and pathological manifestations of colon tissue to varying degrees. Specifically， high-dose XPC exhibited effectively relieved diarrhea， promoted recovery of colonic mucosal structure， significantly reduced congestion and edema， upregulated expression of Occludin and Claudin-5 （P<0.01）， decreased levels of 5-HT in serum and colon tissue （P<0.05，P<0.01）， significantly slowed small intestine propulsion rate （P<0.01）， and significantly downregulated expression of contractile proteins RhoA and ROCK2 in colon and phosphorylation of MLC₂₀ （P<0.05，P<0.01）. ConclusionXPC effectively alleviates symptoms of spleen deficiency and diarrhea and regulates the secretion of brain-gut peptide. The characteristics of XPC are mainly manifested in alleviating IBS-D with spleen deficiency from the aspects of protecting intestinal mucosa and inhibiting smooth muscle contraction， and the mechanism is closely related to the regulation of the 5-HT-RhoA/ROCK2 pathway expression.

OBJECTIVE To observe and compare the synergistic rates of combined use of polymyxin B with 12 types of traditional antibiotics against carbapenem-resistant Klebsiella pneumoniae(CRKP)in vitro antimicrobial ac-tion.METHODS Totally 30 strains of CRKP were randomly drawn from 312 strains of CRKP that were isolated from the clinical departments of Shiyan People's Hospital between 2020 to 2023.The carbapenemases were detec-ted by Carba NP test.The six genotypes KPC,OXA-48,OXA-23,NDM,VIM and IMP were detected by means of fluorescent quantitative polymerase chain reaction(PCR),the drug resistance of the strains was detected by mi-cro broth dilution method,and the synergistic effect of polymyxin B combined with 12 types of traditional antibi-otics on in vitro antimicrobial action was detected by using micro chessboard dilution method.RESULTS All of the isolated CRKP strains produced carbapenemases,with the KPC genotype dominant.The drug resistance rates to cephalosporins,carbapenems and quinolones reached up to 100.00％,and no polymyxin B-resistant strains were detected.The synergistic rates of minocycline and rifampicin combined with polymyxin B to the in vitro antimicro-bial action were the highest,which were 73.33％and 50.00％,respectively;the synergistic rates of levofloxacin and ciprofloxacin combined with polymyxin B were the lowest,and both were 0.The synergistic rates of meropen-em and imipenem combined with polymyxin B to the in in vitro antimicrobial action were 36.67％and 30.00％,re-spectively.The synergistic rates of ceftazidime,cefepime,piperacillin-tazobactam and cefoperazone-sulbactam combined with polymyxin B to the in vitro antimicrobial action were less than 30.00％.CONCLUSIONS Polymyxin B combined with minocycline and rifampicin should be taken as the first choice for treatment of the CRKP-induced infection.The synergistic rate of the carbapenems combined with polymyxin B is higher than that of the cephalo-sporins combined with polymyxin B to the antimicrobial action.Levofloxacin and ciprofloxacin combined with pol-ymyxin B do not have synergistic effect on the in vitro antimicrobial action.

Objective:To understand the composition of infectious pathogens and the changes in the epidemic characteristics of inpatients with acute respiratory tract infections in Pudong New Area of Shanghai, from 2018 to 2023.Methods:Specimens of inpatients with acute respiratory infection cases were collected from 14 healthcare institutions in Pudong New Area, Shanghai, from 2018-2023 and tested for eight respiratory pathogens: influenza virus, adenovirus, rhinovirus, parainfluenza virus, respiratory syncytial virus, common coronavirus, metapneumovirus, and bocavirus. The groups were divided into three periods,2018-2019, 2020-2022 and 2023, and the chi-square or Kruskal-Wallis rank sum test was used to compare the group differences. The SPSS 22.0 software was used for statistical analysis.Results:Among the 3 023 inpatients with acute respiratory infection, the positive rate of any virus was 24.25% (733/3 023). The positive rates of any virus in 2018-2019, 2020-2022, and 2023 were 33.40% (336/1 006), 12.01% (116/966), and 26.74% (281/1 051), respectively, and the differences were statistically significant ( χ2=128.20, P<0.001). Among the age groups, in 2018-2019 and 2020-2022, the positive rate of any virus was the highest in the <5 years age group (46.20% and 14.64%), while in 2023, the 15-59 years age group had the highest positive rate (32.97%). The positive rate of any virus in winter was the highest in 2018-2019 (53.21%) and 2020-2022 (17.58%), and the highest in autumn was in 2023 (31.53%). The peak positive rate of respiratory syncytial virus was in winter of 2018-2019 and 2020-2022, as well as the summer of 2023.The positive rates of influenza virus in 2018-2019, 2020-2022 and 2023 were 9.84%, 1.55% and 9.71%, respectively. Conclusions:The pathogen epidemic characteristics of inpatients with acute respiratory infection in Pudong New Area from 2018 to 2023 have shown certain changes. It is necessary to strengthen monitoring. Targeted prevention and control strategies should be developed and implemented in a timely manner.

ObjectiveTo investigate the infection characteristics of respiratory syncytial virus (RSV) in children with acute respiratory tract infection (ARI) in Pudong New Area, Shanghai, from 2013 to 2023, so as to provide an evidence for the prevention and control of RSV in Shanghai. MethodsChildren who sought medical care at sentinel healthcare facilities in Pudong New Area, Shanghai, between January 2013 and December 2023 and met the case definition of ARI were included in the study. Nasopharyngeal swab samples were collected and tested for viral pathogens using real-time fluorescene PCR, and the clinical information of whom was collected simultaneously. ResultsA total of 4 980 children were included in the ARI surveillance, among whom 231 tested positive for RSV, with an overall detection rate of 4.64%. Of these, 106 cases were type A and 125 were type B. From 2013 to 2023, the detection rate of RSV in children showed an overall trend of initial increase followed by a decline, with higher detection rates in autumn and winter and lower rates in spring and summer. The RSV detection rate gradually decreased with age, with the highest rate observed in children <1 year old, accounting for 16.33% (80/490) of RSV-detection cases. Cough was the most common clinical symptom. Among the RSV-positive cases, 36 involved co-infection with another virus, 6 co-infected with three viruses, and 1 with mixed infection of four viruses. The most frequent co-infection was RSV and human coronavirus. ConclusionChildren under 1 year of age are more susceptible to RSV infection, with cough being the predominant symptom. RSV infection in Pudong New Area, Shanghai, mainly occurs in winter. Targeted prevention and control measures should be taken for children under 1 year old during the winter season to reduce the risk of both RSV infection and co-infection with human coronavirus and influenza virus.

ObjectiveTo investigate the epidemiological characteristics of human parainfluenza virus (HPIV) in Pudong New Area, Shanghai, and to provide a basis for the prevention and control of HPIV infections in this area. MethodsA total of 8 180 cases with acute respiratory infection (ARI)/influenza-like illness (ILI) attending the fever outpatient clinics, pediatric outpatient clinics, respiratory outpatient clinics, pediatric wards, emergency departments, respiratory wards, and intensive care units (ICUs) and other monitoring departments in 9 sentinel hospitals in Pudong New Area from 2017 to 2022 were selected as the research subjects, and their nasopharyngeal/ throat swabs were collected. Polymerase chain reaction (PCR) method was performed for testing the respiratory virus such as influenza virus, human adenovirus, human parainfluenza virus, respiratory syncytial virus (RSV), human enterovirus, rhinovirus, et al. HPIV serotypes were analyzed, and the detection rates of HPIV were compared between different times, seasons, and population groups. ResultsThe overall HPIV detection rate of ARI/ILI cases in Pudong New Area was 3.73% (305/8 180) in 2017‒2022, with HPIV-3 being the predominant serotype. The detection rate of HPIV decreased significantly in 2017‒2022, peaking at 7.66% (99/1 293) in 2017 and falling to 0.80% (13/1 617) in 2021. Statistically significant differences were observed in HPIV detection rates across different years (χ²_trend=80.037, P_trend<0.001). The detection rate was higher in 2017‒2019 than that in 2020‒2022 (χ²_trend=38.990, P_trend<0.001). HPIV exhibited seasonal patterns in 2017‒2019, with higher detection rates in summer and autumn and lower in spring and winter, whereas no seasonal patterns were observed in 2020‒2022. Children aged <6 years had the highest detection rate (7.07%, 139/1 967), followed by adults aged ≥60 years (4.78%, 85/1 779). Statistically significant differences were observed in the detection rates of HPIV among different age groups (χ²=111.210, P<0.001). Symptoms of HPIV infection were predominantly cough, fever, and runny nose in pre-school children, fever, cough, and sore throat in school-age children, and adults, and cough, expectoration, and fever in the elderly. ConclusionThe HPIV detection rate in Pudong New Area was low in 2017‒2022. The seasonal pattern of HPIV circulation in Pudong New Area disappeared in 2020‒2022 due to the influence of infectious disease epidemics. Young children and the elderly should be prioritized in HPIV prevention and control efforts.