Transdermal microarrayed electroporation for enhanced cancer immunotherapy based on DNA vaccination.

Despite the tremendous clinical potential of nucleic acid-based vaccines, their efficacy to induce therapeutic immune response has been limited by the lack of efficient local gene delivery techniques in the human body. In this study, we develop a hydrogel-based organic electronic device (µEPO) for both transdermal delivery of nucleic acids and in vivo microarrayed cell electroporation, which is specifically oriented toward one-step transfection of DNAs in subcutaneous antigen-presenting cells (APCs) for cancer immunotherapy. The µEPO device contains an array of microneedle-shaped electrodes with pre-encapsulated dry DNAs. Upon a pressurized contact with skin tissue, the electrodes are rehydrated, electrically triggered to release DNAs, and then electroporate nearby cells, which can achieve in vivo transfection of more than 50% of the cells in the epidermal and upper dermal layer. As a proof-of-concept, the µEPO technique is employed to facilitate transdermal delivery of neoantigen genes to activate antigen-specific immune response for enhanced cancer immunotherapy based on a DNA vaccination strategy. In an ovalbumin (OVA) cancer vaccine model, we show that high-efficiency transdermal transfection of APCs with OVA-DNAs induces robust cellular and humoral immune responses, including antigen presentation and generation of IFN-γ+ cytotoxic T lymphocytes with a more than 10-fold dose sparing over existing intramuscular injection (IM) approach, and effectively inhibits tumor growth in rodent animals.

Research progress of early screening and clinical prevention services for high-risk population with cardiovascular diseases / 公共卫生与预防医学

Cardiovascular diseases are preventable and controllable, and the disease burden caused by them can be reduced after preventive intervention. Attentions should be paid to the prevention of disease causes. For high-risk population, it is necessary to conduct early screening of cardiovascular diseases, control risk factors, reduce exposure level, prevent and control the occurrence or progression of diseases. Clinical prevention services are to evaluate risk factors of health in clinical sites, which can prevent diseases by personalized intervention measures. Clinical prevention services for high-risk population with cardiovascular diseases are generally at a low level in China. This article reviews the early screening, risk factors and clinical prevention services for high-risk population with cardiovascular diseases.

Research progress on overweight/obesity and atherosclerosis / 公共卫生与预防医学

Overweight/obesity has become an increasingly serious global public health problem. Studies have shown that many factors caused by overweight/obesity are involved in the occurrence of atherosclerosis, including adipokines, inflammatory factors and overweight/obesity related metabolic syndrome. This paper reviews the research progress on overweight/obesity and atherosclerosis from the above perspectives, aiming to provide reference for the prevention of overweight/obesity-related atherosclerosis.

Observation on the distribution of macular cone in healthy adult using adaptive optics scanning laser ophthalmoscope system / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the distribution of cone in the macular of healthy adult in different ages using adaptive optics scanning laser ophthalmoscope(AO-SLO)system, and analyze its relationship with age.METHODS: A total of 100 healthy examinees(200 eyes)in our hospital from June to July 2023 were selected, and they were divided into four groups according to their age, with 25 cases(50 eyes)in each group, including 18-30 years in group A, 31-40 years in group B, 41-50 years in group C, 51-65 years in group D. AO-SLO was performed in both eyes and cone density was measured.RESULTS: The density of cone in the foveal eccentricity of 3° and 2.4°×2.4° in each group was different(P<0.001), and the cone density in each area showed a relatively regular distribution characteristics, with the highest density in the temporal side, and the temporal>nasal>inferior>superior sides from high to low. The mean cone density in the macular area of both eyes was 14 144.38±1 082.40, 13 241.24±535.32, 12 930.29±727.73, and 10 907.50±490.86 cell/mm2, respectively(P<0.001), indicating that the cone density decreased with age. The correlation analysis showed that the mean cone density in the macular area was negatively correlated with age(r=-0.578, P<0.001).CONCLUSION: AO-SLO is a quantitative non-invasive detection of cones, and there is a negative correlation between cone density and age in healthy human. Furthermore, density of cone in healthy people over 50 years was significantly decreased.

Multicopy Chromosome Integration and Deletion of Negative Global Regulators Significantly Increased the Heterologous Production of Aborycin in Streptomyces coelicolor.

Aborycin is a type I lasso peptide with a stable interlocked structure, offering a favorable framework for drug development. The aborycin biosynthetic gene cluster gul from marine sponge-associated Streptomyces sp. HNS054 was cloned and integrated into the chromosome of S. coelicolor hosts with different copies. The three-copy gul-integration strain S. coelicolor M1346::3gul showed superior production compared to the one-copy or two-copy gul-integration strains, and the total titer reached approximately 10.4 mg/L, i.e., 2.1 times that of the native strain. Then, five regulatory genes, phoU (SCO4228), wblA (SCO3579), SCO1712, orrA (SCO3008) and gntR (SCO1678), which reportedly have negative effects on secondary metabolism, were further knocked out from the M1346::3gul genome by CRISPR/Cas9 technology. While the ΔSCO1712 mutant showed a significant decrease (4.6 mg/L) and the ΔphoU mutant showed no significant improvement (12.1 mg/L) in aborycin production, the ΔwblA, ΔorrA and ΔgntR mutations significantly improved the aborycin titers to approximately 23.6 mg/L, 56.3 mg/L and 48.2 mg/L, respectively, which were among the highest heterologous yields for lasso peptides in both Escherichia coli systems and Streptomyces systems. Thus, this study provides important clues for future studies on enhancing antibiotic production in Streptomyces systems.

CdSe/TiO2NTs Heterojunction-Based Nonenzymatic Photoelectrochemical Sensor for Glucose Detection.

Compared with a single semiconductor, the heterojunction formed by two different semiconductors usually has higher light utilization and better photoelectric performance. By using stable TiO2 nanotubes as the main subject, CdSe/TiO2NTs heterojunctions were synthesized by a hydrothermal method. XRD, TEM, SEM, PL, UV-vis, and EIS were used to characterize the fabricated CdSe/TiO2NTs. Under visible light irradiation, CdSe/TiO2NTs heterojunctions exhibited a higher absorption intensity and lower degree of photogenerated carrier recombination than TiO2. The electrons and holes were proven to be effectively separated in this heterojunction via theoretical calculation. Under CdSe/TiO2NTs' optimal conditions, the glucose concentrations (10-90 µM) had a linear relationship with the photocurrent value, and the detection limit was 3.1 µM. Moreover, the CdSe/TiO2NTs sensor exhibited good selectivity and stability. Based on the experimental data and theoretical calculations, its PEC sensing mechanism was also illuminated.

The tendency of anemia of inflammation in periodontal diseases.

Anemia of inflammation (AI) is associated with inflammatory diseases, and inflammation-induced iron metabolism disorder is the major pathogenic factor. Earlier studies have reported a tendency of AI in periodontitis patients, but the explicit relationship and possible pathological mechanisms remain unclear. Here, the analyses of both periodontitis patients and a mouse model of ligature-induced experimental periodontitis showed that periodontitis was associated with lower levels of hemoglobin and hematocrit with evidence of systemic inflammation (increased white blood cell levels) and evidence of iron restriction (low serum iron along with a high serum hepcidin and ferritin levels), in accordance with the current diagnosis criteria for AI. Moreover, periodontal therapy improved the anemia status and iron metabolism disorders. Furthermore, the increased level of hepcidin and significant correlation between hepcidin and key indicators of iron metabolism emphasized the pivotal role of hepcidin in the pathogenesis of periodontitis-related AI. Administration of the signal transducer and activator of transcription 3 (STAT3) inhibitors Stattic suggested that the IL-6-STAT3-hepcidin signaling pathway participated in this regulatory process. Together, these findings demonstrated that periodontitis should be considered an inflammatory disease that contributes to the development of AI; furthermore, IL-6-STAT3-hepcidin signaling pathway plays a key regulatory role in the pathogenesis of periodontitis-related AI. Our study will provide new insights into the systemic effects of periodontitis, while meaningfully expanding the spectrum of inflammatory diseases that contribute to AI.

Fluorine-thiol displacement probes for acetaminophen's hepatotoxicity

Chemicals possessing reactive electrophiles can denature innate proteins leading to undesired toxicity, and the overdose-induced liver injury by drugs containing electrophiles has been one of the major causes of non-approval and withdraw by the US Food and Drug Administration (FDA). Elucidating the associated proteins could guide the future development of therapeutics to circumvent these drugs' toxicities, but was largely limited by the current probing tools due to the steric hindrance of chemical tags including the common "click chemistry" labels. Taking the widely used non-steroidal anti-inflammatory drug acetaminophen (APAP) as an example, we hereby designed and synthesized an APAP analogue using fluorine as a steric-free label. Cell toxicity studies indicated our analogue has similar activity to the parent drug. This analogue was applied to the mouse hepatocellular proteome together with the corresponding desthiobiotin-SH probe for subsequent fluorine-thiol displacement reactions (FTDRs). This set of probes has enabled the labeling and pull-down of hepatocellular target proteins of the APAP metabolite as validated by Western blotting. Our preliminary validation results supported the interaction of APAP with the thioredoxin protein, which is an important redox protein for normal liver function. These results demonstrated that our probes confer minimal steric perturbation and mimic the compounds of interest, allowing for global profiling of interacting proteins. The fluorine-thiol displacement probing system could emerge as a powerful tool to enable the investigation of drug-protein interactions in complex biological environments.

Analysis of a child with X-linked intellectual disability due to a maternal de novo splicing variant of the PAK3 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic etiology for a child with profound intellectual disabilities and obvious behavioral abnormalities.@*METHODS@#A male child who had presented at the Zhongnan Hospital of Wuhan University on December 2, 2020 was selected as the study subject. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. Short tandem repeat (STR) analysis was carried out to determine its parental origin. The splicing variant was also validated in vitro with a minigene assay.@*RESULTS@#WES results revealed that the child had harbored a novel splicing variant of c.176-2A>G in the PAK3 gene, which was inherited from his mother. The results of minigene assay have confirmed aberrant splicing of exon 2. According to the guidelines from the American College of Medical Genetics and Genomics, it was classified as a pathogenic variant (PVS1+PM2_Supporting+PP3).@*CONCLUSION@#The novel splicing variant c.176-2A>G of the PAK3 gene probably underlay the disorder in this child. Above finding has expanded the variation spectrum of the PAK3 gene and provided a basis for genetic counseling and prenatal diagnosis for this family.

Research progress about TyK2 inhibitor deucravacitinib for the treatment of systemic lupus erythematosus / 中国药房

Deucravacitinib is a selective tyrosine kinase 2 inhibitor. It has shown certain therapeutic potential for various immune system diseases， and its use in systemic lupus erythematosus （SLE） is currently in the clinical trial stage. Deucavacitinib is easily absorbed by oral administration and can cause pharmacological effects within 24 hours. Compared with placebo， after 32 weeks of treatment， patients in the deucravacitinib group who meet the SLE response index 4 have a higher proportion， and a higher response rate in the British Isles Lupus Assessment Group’s comprehensive lupus assessment， cutaneous lupus erythematosus disease area and severity index of 50， low disease activity status， and activity， swelling， and tenderness joint counts. In terms of safety， the incidence of adverse events such as rash and acne is higher in the deucravacitinib group than placebo group， but further observation was still needed. At present， more studies are evaluating the cost-effectiveness and safety of deucravatinib in the treatment of SLE， with the expectation of more data validation of deucravatinib’s therapeutic potential.

Macular microvasculature in central retinal artery occlusion with paracentral acute middle maculopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To investigate the changes in the macular microvasculature in eyes with central retinal artery occlusion(CRAO)and paracentral acute middle maculopathy(PAMM).METHODS: Retrospective study. A total of 27 cases(27 eyes)who diagnosed with CRAO-PAMM and 29 patients(29 eyes)diagnosed as CRAO but with no PAMM were hospitalized in our hospital from January 2020 to December 2021. There were 33 normal people(33 eyes)who underwent physical examination in our hospital selected as control group. Optical coherence tomography angiography(OCTA)was used to measure retinal blood flow and thickness parameters in the 3 mm×3 mm area of the macula. The correlation among macular retinal blood flow density, retinal thickness, foveal avascular zone(FAZ)area, FAZ perimeter, acircularity index(AI), flow density in a 300-μm-wide region around the FAZ(FD-300)and lesion area, best corrected visual acuity(BCVA)in the CRAO-PAMM group was analyzed.RESULTS: Among the three groups, there were significant differences in the overall and parafoveal blood flow density of superficial capillary layer(SCP)and deep capillary layer(DCP), foveal thickness, FAZ area, FAZ perimeter, AI and FD-300(all P<0.05). In the CRAO-PAMM group, the lesion area was negatively correlated with DCP overall and parafoveal blood flow density(r=-0.569, P=0.002; r=-0.543, P=0.004), and positively correlated with the parafoveal thickness(r=0.606, P=0.001); BCVA(LogMAR)was negatively correlated with DCP foveal and parafoveal blood flow density(r=-0.433, P=0.024; r=-0.515, P=0.006), and positively correlated with FAZ area, perimeter and lesion area(r=0.484, P=0.011; r=0.531, P=0.004; r=0.417, P=0.030).CONCLUSION:Patients with CRAO and PAMM have lower macular blood flow density, heavier macular edema and poorer visual acuity, and BCVA may be influenced by both lesion area and FAZ area.

Hotspots and difficulties of biliary surgery in older patients / 中华医学杂志(英文版)

With the accelerated aging society in China, the incidence of biliary surgical diseases in the elderly has increased significantly. The clinical characteristics of these patients indicate that improving treatment outcomes and realizing healthy aging are worthy of attention. How to effectively improve the treatment effect of geriatric biliary surgical diseases has attracted widespread attention. This paper reviews and comments on the hotspots and difficulties of biliary surgery in older patients from six aspects: (1) higher morbidity associated with an aging society, (2) prevention and control of pre-operative risks, (3) extending the indications of laparoscopic surgery, (4) urgent standardization of minimally invasive surgery, (5) precise technological progress in hepatobiliary surgery, and (6) guarantee of peri-operative safety. It is of great significance to fully understand the focus of controversy, actively make use of its favorable factors, and effectively avoid its unfavorable factors, for further improving the therapeutic effects of geriatric biliary surgical diseases, and thus benefits the vast older patients with biliary surgical diseases. Accordingly, a historical record with the highest age of 93 years for laparoscopic transcystic common bile duct exploration has been created by us recently.

Endogenous corticotropin-releasing factor potentiates the excitability of presympathetic neurons in paraventricular nucleus via activation of its receptor 1 in spontaneously hypertensive rats / 生理学报

It is well established that increased excitability of the presympathetic neurons in the hypothalamic paraventricular nucleus (PVN) during hypertension leads to heightened sympathetic outflow and hypertension. However, the mechanism underlying the overactivation of PVN presympathetic neurons remains unclear. This study aimed to investigate the role of endogenous corticotropin-releasing factor (CRF) on the excitability of presympathetic neurons in PVN using Western blot, arterial blood pressure (ABP) and renal sympathetic nerve activity (RSNA) recording, CRISPR/Cas9 technique and patch-clamp technique. The results showed that CRF protein expression in PVN was significantly upregulated in spontaneously hypertensive rats (SHRs) compared with normotensive Wistar-Kyoto (WKY) rats. Besides, PVN administration of exogenous CRF significantly increased RSNA, heart rate and ABP in WKY rats. In contrast, knockdown of upregulated CRF in PVN of SHRs inhibited CRF expression, led to membrane potential hyperpolarization, and decreased the frequency of current-evoked firings of PVN presympathetic neurons, which were reversed by incubation of exogenous CRF. Perfusion of rat brain slices with artificial cerebrospinal fluid containing CRF receptor 1 (CRFR1) blocker, NBI-35965, or CRF receptor 2 (CRFR2) blocker, Antisauvagine-30, showed that blocking CRFR1, but not CRFR2, hyperpolarized the membrane potential and inhibited the current-evoked firing of PVN presympathetic neurons in SHRs. However, blocking CRFR1 or CRFR2 did not affect the membrane potential and current-evoked firing of presympathetic neurons in WKY rats. Overall, these findings indicate that increased endogenous CRF release from PVN CRF neurons enhances the excitability of presympathetic neurons via activation of CRFR1 in SHRs.

Morin induces autophagy and apoptosis in hepatocellular carcinoma cells through Akt/mTOR/STAT3 pathway / 中国中药杂志

This study investigated the effect and mechanism of morin in inducing autophagy and apoptosis in hepatocellular carcinoma cells through the protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/signal transducer and activator of transcription protein 3(STAT3) pathway. Human hepatocellular carcinoma SK-HEP-1 cells were stimulated with different concentrations of morin(0, 50, 100, 125, 200, and 250 μmol·L~(-1)). The effect of morin on the viability of SK-HEP-1 cells was detected by Cell Counting Kit-8(CCK-8). The effect of morin on the proliferation and apoptosis of SK-HEP-1 cells was investigated using colony formation assay, flow cytometry, and BeyoClick~(TM) EdU-488 with different concentrations of morin(0, 125, and 250 μmol·L~(-1)). The changes in the autophagy level of cells treated with morin were examined by transmission electron microscopy and autophagy inhibitors. The impact of morin on the expression levels of proteins related to the Akt/mTOR/STAT3 pathway was verified by Western blot. Compared with the control group, the morin groups showed decreased viability of SK-HEP-1 cells in a time-and concentration-dependent manner, increased number of apoptotic cells, up-regulated expression level of apoptosis marker PARP, up-regulated phosphorylation level of apoptosis-regulating protein H2AX, decreased number of positive cells and the colony formation rate, an upward trend of expression levels of autophagy-related proteins LC3-Ⅱ, Atg5, and Atg7, and decreased phosphorylation levels of Akt, mTOR, and STAT3. These results suggest that morin can promote apoptosis, inhibit proliferation, and induce autophagy in hepatocellular carcinoma cells, and its mechanism of action may be related to the Akt/mTOR/STAT3 pathway.

Effects of electroacupuncture at "Jiaji" (EX-B 2) combined with neurodynamic mobilization on gastrocnemius muscle atrophy and expression of NF-κB and MuRF1 in rabbits after sciatic nerve injury / 中国针灸

OBJECTIVES@#To observe the effects of electroacupuncture (EA) at "Jiaji" (EX-B 2) combined with neurodynamic mobilization (NM) on the cross-sectional area of the gastrocnemius muscle fibers after sciatic nerve injury in rabbits, and the expression of nuclear factor κB (NF-κB) and muscle-specific ring-finger protein 1 (MuRF1).@*METHODS@#A total of 180 common-grade New Zealand rabbits (half male and half female) were randomly divided into five groups, i.e. a normal control group, a model control group, a NM group, an EA group and a combined intervention group, 36 rabbits in each group. Except in the normal control group, clipping method was used to prepare the model of sciatic nerve injury in the rest groups. On the 3rd day of successful modeling, NM was delivered in the NM group. In the EA group, EA was exerted at bilateral "Jiaji" (EX-B 2) of L4 to L6, stimulated with disperse-dense wave and the frequency of 2 Hz/100 Hz. In the combined intervention group, after EA delivered at bilateral "Jiaji" (EX-B 2) of L4 to L6 , NM was operated. The intervention in each group was delivered once daily, for 6 days a week, and lasted 1, 2 or 4 weeks according to the collection time of sample tissue. After 1, 2 and 4 weeks of intervention, in each group, the toe tension reflex score and the modified Tarlov test score were observed; the morphology of the gastrocnemius muscle was observed by HE staining and the cross-sectional area of muscular fiber was measured; using Western blot method, the expression of NF-κB and MuRF1 of the gastrocnemius muscle was detected.@*RESULTS@#After 1, 2 and 4 weeks of intervention, the toe tension reflex scores and the modified Tarlov scores in the model control group were lower than those of the normal control group (P<0.05), and these two scores in the NM group, the EA group and the combined intervention group were all higher than those of the model control group (P<0.05); the scores in the combined intervention group were higher than those in the EA group and the NM group (P<0.05). The gastrocnemius fibers were well arranged and the myocyte morphology was normal in the normal control group. In the model control group, the gastrocnemius fibers were disarranged, the myocytes were irregular in morphology and the inflammatory cells were infiltrated in the local. In the NM group, the EA group and the combined intervention group, the muscle fibers were regularly arranged when compared with the model control group. After 1, 2 and 4 weeks of intervention, the cross-sectional areas of the gastrocnemius muscle fibers in the model control group were smaller than those of the normal control group (P<0.05). The cross-sectional areas in the NM group, the EA group and the combined intervention group were larger than those of the model control group (P<0.05), and the cross-sectional areas in the combined intervention group were larger than those in the NM group and the EA group (P<0.05). After intervention for 1, 2 and 4 weeks, the protein expressions of NF-κB and MuRF1 in the gastrocnemius muscle were higher in the model control group in comparison of those in the normal control group (P<0.05). In the NM group, the EA group and the combined intervention group, the expressions of NF-κB after intervention for 1, 2 and 4 weeks and the expressions of MuRF1 after 2 and 4 weeks of intervention were lower when compared with those in the model control group (P<0.05). In the combined intervention group, the protein expressions of NF-κB after intervention for 1, 2 and 4 weeks and the expressions of MuRF1 after 2 and 4 weeks of intervention were decreased when compared with those in the NM group and the EA group (P<0.05).@*CONCLUSIONS@#Electroacupuncture at "Jiaji" (EX-B 2) combined with NM may increase the muscle strength and sciatic function and alleviate gastrocnemius muscle atrophy in the rabbits with sciatic nerve injury. The underlying mechanism is related to the inhibition of NF-κB and MuRF1 expression.

Research progress of FAPI PET/CT in the diagnosis of malignant liver tumors / 中华肝脏病杂志

Malignant liver tumors have a high incidence and mortality rate. Therefore, it is of great significance to promptly learn about tumor advancement status through relevant examinations for patients' follow-up, diagnosis, and therapy as well as the improvement of the five-year survival rate. The primary lesions and intrahepatic metastases of malignant liver tumors have been better demonstrated in the clinical study with the use of various isotope-labeled fibroblast activating protein inhibitors because of their low uptake in liver tissues and high tumor/background ratio, which provides a new method for early diagnosis, precise staging, and radionuclide therapy. In light of this context, a review of the research progress of fibroblast-activating protein inhibitors for the diagnosis of liver malignant tumors is presented.

Inhibitory effect and molecular mechanism of sinomenine on human hepatocellular carcinoma HepG2 and SK-HEP-1 cells / 中国中药杂志

This study aimed to investigate the effect and molecular mechanism of sinomenine on proliferation, apoptosis, metastasis, and combination with inhibitors in human hepatocellular carcinoma HepG2 cells and SK-HEP-1 cells. The effect of sinomenine on the growth ability of HepG2 and SK-HEP-1 cells were investigated by CCK-8 assay, colony formation assay, and BeyoClick~(TM) EdU-488 staining. The effect of sinomenine on DNA damage was detected by immunofluorescence assay, and the effect of sinomenine on apoptosis of human hepatocellular carcinoma cells was clarified by Hoechst 33258 staining and CellEvent~(TM) Cystein-3/7Green ReadyProbes~(TM) reagent assay. Cell invasion assay and 3D tumor cell spheroid invasion assay were performed to investigate the effect of sinomenine on the invasion ability of human hepatocellular carcinoma cells in vitro. The effect of sinomenine on the regulation of protein expression related to the protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/signal transducer and activator of transcription 3(STAT3) signaling pathway in HepG2 and SK-HEP-1 cells was examined by Western blot. Molecular docking was used to evaluate the strength of affinity of sinomenine to the target cysteinyl aspartate specific proteinase-3(caspase-3) and STAT3, and combined with CCK-8 assay to detect the changes in cell viability after combination with STAT3 inhibitor JSI-124 in combination with CCK-8 assay. The results showed that sinomenine could significantly reduce the cell viability of human hepatocellular carcinoma cells in a concentration-and time-dependent manner, significantly inhibit the clonogenic ability of human hepatocellular carcinoma cells, and weaken the invasive ability of human hepatocellular carcinoma cells in vitro. In addition, sinomenine could up-regulate the cleaved level of poly ADP-ribose polymerase(PARP), a marker of apoptosis, and down-regulate the protein levels of p-Akt, p-mTOR, and p-STAT3 in human hepatocellular carcinoma cells. Molecular docking results showed that sinomenine had good affinity with the targets caspase-3 and STAT3, and the sensitivity of sinomenine to hepatocellular carcinoma cells was diminished after STAT3 was inhibited. Therefore, sinomenine can inhibit the proliferation and invasion of human hepatocellular carcinoma cells and induce apoptosis, and the mechanism may be attributed to the activation of caspase-3 signaling and inhibition of the Akt/mTOR/STAT3 pathway. This study can provide a new reference for the in-depth research and clinical application of sinomenine and is of great significance to further promote the scientific development and utilization of sinomenine.

Influence of COVID-19 prevention and control on the epidemic trend of notifiable infectious diseases in the first quarters， Zhejiang Province / 上海预防医学

ObjectiveTo determine the influence of COVID-19 prevention and control on the epidemic characteristics and dynamics of notifiable infectious diseases in the first quarters， Zhejiang Province， and to explore more effective countermeasures against infectious diseases. MethodsDescriptive epidemiology was conducted to determine the change in notifiable infectious diseases during the prevention and control of COVID-19 in Zhejiang Province by retrieving the data of notifiable infectious diseases from 2017 to 2022 in the Chinese information system for disease control and prevention. Cumulative reported new cases of notifiable infectious diseases in the first quarters of 2017‒2019 were compared with that of 2020‒2022. ResultsA total of 546 753 cases of notifiable infectious diseases were newly reported in the first quarters of 2017‒2019， with an average incidence of 321.92/105. In contrast， a total of 509 908 cases of notifiable infectious diseases were newly reported in the first quarters of 2020‒2022， during which the COVID-19 epidemic occurred， with an average incidence of 270.39/105. The incidence in 2020‒2022 significantly declined by 51.53/105， compared with that in 2017‒2019 （χ²=8 072.06， P<0.001）. In the first quarters of 2020‒2022， the average incidence of zoonotic diseases and vector-borne diseases decreased by more than 50%. In addition， the incidence of respiratory， enteric， blood-borne， and sexually transmitted diseases declined to certain degree. ConclusionThe decline in the newly reported cases of non-COVID-19 notifiable infectious diseases in the first quarters of 2020‒2022 indicates that the countermeasures against COVID-19 epidemic， such as multi-disease co-prevention， multi-sectoral collaboration， societal mobilization and personal hygiene and protection， may also decrease the incidence of multiple infectious diseases. It suggests the countermeasures are effective， which would provide evidence for routine prevention and control of infectious diseases in future.

A preliminary study on the effect of rapid recovery model in older adults with acute clinical conditions / 中华老年医学杂志

Objective:To explore the effectiveness of Acute Care of the Elderly(ACE)model and its existing problems in the clinical practice for older adults with acute clinical conditions.Methods:Using the random number table method, a random number sequence was generated, and the patients admitted to the Department of Geriatrics of Shenzhen Nanshan Hospital due to acute diseases From January 2019 to September 2021 were enrolled in the ACE model intervention group(160 cases)and the control group(77 cases)in a 2: 1 ratio.The inclusion criteria were based on disease severity, frailty assessment, and activity of daily living(ADL)assessment.The intervention time was 1-3 weeks.Outcomes of the patients include ADL, hospitalization days, hospitalization expenses, drug proportion, human resource investments, adverse events, 30-day readmission rate, and 1-year mortality.Results:There were no significant difference in baseline indicators such as frailty index and ADL score between the two groups at admission.The ADL score(Barthel index)of the ACE group was significantly improved compared with the control group at discharge(81.71±14.23 vs.70.9±23.89, P<0.001)and at 30 days after discharge(85.84±15.25 vs.68.29±30.91, P<0.001). The hospital cost[(12 735.81±6 541.41)￥ vs.(16 391.54±12 962.34)￥, P=0.002], drug proportion(21.34% vs.28.93 %, P=0.036)and 30-day readmission rate(13.1% vs.23.4%, P=0.037)of the ACE group were significantly lower compared to the control group.The human resource input(32.97±6.72 vs.25.03±5.31, P=0.008)and patient satisfaction(98.23% vs.90.66%, P=0.031)in the ACE group were significantly higher than those of the control group.(4)The incidence of adverse events during hospitalization was significantly lower in the ACE group than in the control group in terms of aspiration(0.63% vs.20.8%, P<0.001), falls(0 vs.10.4%, P<0.001), incontinence dermatitis(0 vs.3.9%, P=0.033), and 1-year mortality(6.3% vs.24.7%, P<0.001). There was no significant difference in the average length of stay(8.98±4.25 vs.10.03±5.32, P=0.101), pressure sores(13.01±4.77 vs.13.27±4.89, P=0.364), DVT risk score(8.53±2.79 vs.8.89±2.76, P=0.340)and medical staff satisfaction(73% vs.80%, P=0.240)between the two groups. Conclusions:The ACE model helps to reduce the disability rate of elderly patients with frailty, adverse events during hospitalization, save drug costs, and improve patient satisfaction.It is worth promoting in geriatric practice, but its localization management details and processes still face many challenges.

Exploration of critical values of monitoring indexes for perioperative major adverse cardiac events in elderly patients with biliary diseases / 中华老年医学杂志

Objective:The purpose of this study was to explore the critical values of monitored indexes of perioperative major adverse cardiac events(MACE), so as to take effective prevention and treatment measures in time to maintain the stability of perioperative cardiac function to further improve the perioperative safety of elderly patients with biliary diseases.Methods:The clinical data of 246 elderly patients with biliary diseases in our hospital from May 2016 to February 2022 were collected.According to whether MACE occurred during the perioperative period, they were divided into the MACE group and the non-MACE group.The differences of clinical data, the monitoring indexes of postoperative cardiac function, and the coagulation function between the two groups were compared and analyzed.Logistic regression was used to analyze the independent risk factors of perioperative MACE, the cut-off value of the receiver operating characteristic(ROC)curve was calculated, and the Logistic multivariate prediction model was established.Results:In the MACE compared with the non-MACE group, age, postoperative complications and mortality, postoperative hospital stay, and the levels of postoperative high sensitivity troponin-I(Hs-TnI), creatine kinase isoenzyme(CK-MB), myoglobin(MYO), B-type natriuretic peptide(BNP), and D-dimer(D-D)were significantly increased(all P<0.05). Multivariate Logistic regression showed that postoperative BNP and D-D were two independent risk factors for perioperative MACE, and their cut-off values in the ROC curve were 382.65 pg/mL and 0.975mg/L respectively.The Logistic multivariate prediction model established by the Logistic regression equation was P= ex/(1+ ex), X=-5.710+ 0.003X 1+ 0.811X 2, where X 1 was the postoperative BNP level and X 2 was the postoperative D-D level.The accuracy, specificity and sensitivity of this prediction model for predicting perioperative MACE were 96.3%(237/246), 100.0%(235/235), and 18.2%(2/11). Conclusions:The Logistic multivariate prediction model established in this study can effectively predict the occurrence of perioperative MACE in elderly patients.Postoperative BNP and D-D were two independent risk factors for perioperative MACE.The cut-off values of BNP and D-D in the ROC curve could be used as critical values for monitoring perioperative MACE.Therefore, it is of great clinical significance to take effective prevention and treatment measures in time to maintain the stability of perioperative cardiac function, and further improve the perioperative safety of elderly patients with biliary diseases.