ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

To formulate an expert consensus on the principles of preoperative hair removal and provide scientific guidance for standardized removal of hair before surgical procedures so as to reduce the incidence of surgical site infections.METHODS Led by the Hospital Management Institute of National Health Commission of the People's Republic of China,this consensus was reached with the joint efforts from the expects of relevant fields such as surgeries,interventional therapies,nursing,and infection prevention and control.The consensus facilitates the classification and evaluation of literatures by following the evidence grade formulated by Oxford Evidence-based Medicine Center and focuses on the association of preoperative hair removal with surgical site infection,it reaches the evidence grade of expert consensus and recommendation intensity by integrating with discussions on meetings and clinical experience of the expects from relevant fields.RESULTS A total of 6 items of consensus were reached by summarizing the latest evidence on the aspects including the indications for preoperative hair removal,tools,range,timing and places.CONCLUSION The consensus,to some extent,make supplements to and complete the exiting regulations and standards.It provides guidance for the medical institutions to carry out the preoperative hair removal.

Objective To explore the value of MRI subtraction technique(ST)for evaluating the efficacy of systemic therapy for advanced hepatocellular carcinoma(HCC)and predicting prognosis after combining with surgery.Methods Totally 35 patients with 39 HCC lesions who received systemic therapy+radical resection were retrospectively collected.Based on preoperative MRI,tumor activity ratio(recorded as tumor activityST)was obtained with ST,while tumor activity value(recorded as tumor activitypathology)was obtained through postoperative pathology,and their correlation was analyzed.The patients were regularly followed up after surgery,and the survival data were recorded.Receiver operating characteristic(ROC)curve was drawn to evaluate the efficacy of tumor activityST for predicting patients'survival status.Then the patients were divided into survival benefit group and no survival benefit group according to the cut-off value,and survival analysis was conducted.Results Tumor activityST was positively correlated with tumor activitypathology(r=0.900,P＜0.001).The median follow-up time was 32.93 months,during which 8 patients died,and the median survival time was 29.9 months.The area under the curve(AUC)of tumor activityST for predicting patients'survival status was 0.67,and the cut-off value was 0.36.Thirty patients with tumor activityST＜0.36 were enrolled in survival benefit group,while 5 patients≥0.36 were collected in no survival benefit group.The overall survival in survival benefit group was longer than that in no survival benefit group(P＜0.001).Conclusion MRI ST could be used to non-invasively evaluate the efficacy of systemic therapy for advanced HCC and predict prognosis after combining with surgery.

To formulate an expert consensus on the principles of preoperative hair removal and provide scientific guidance for standardized removal of hair before surgical procedures so as to reduce the incidence of surgical site infections.METHODS Led by the Hospital Management Institute of National Health Commission of the People's Republic of China,this consensus was reached with the joint efforts from the expects of relevant fields such as surgeries,interventional therapies,nursing,and infection prevention and control.The consensus facilitates the classification and evaluation of literatures by following the evidence grade formulated by Oxford Evidence-based Medicine Center and focuses on the association of preoperative hair removal with surgical site infection,it reaches the evidence grade of expert consensus and recommendation intensity by integrating with discussions on meetings and clinical experience of the expects from relevant fields.RESULTS A total of 6 items of consensus were reached by summarizing the latest evidence on the aspects including the indications for preoperative hair removal,tools,range,timing and places.CONCLUSION The consensus,to some extent,make supplements to and complete the exiting regulations and standards.It provides guidance for the medical institutions to carry out the preoperative hair removal.

Objective To explore the value of MRI subtraction technique(ST)for evaluating the efficacy of systemic therapy for advanced hepatocellular carcinoma(HCC)and predicting prognosis after combining with surgery.Methods Totally 35 patients with 39 HCC lesions who received systemic therapy+radical resection were retrospectively collected.Based on preoperative MRI,tumor activity ratio(recorded as tumor activityST)was obtained with ST,while tumor activity value(recorded as tumor activitypathology)was obtained through postoperative pathology,and their correlation was analyzed.The patients were regularly followed up after surgery,and the survival data were recorded.Receiver operating characteristic(ROC)curve was drawn to evaluate the efficacy of tumor activityST for predicting patients'survival status.Then the patients were divided into survival benefit group and no survival benefit group according to the cut-off value,and survival analysis was conducted.Results Tumor activityST was positively correlated with tumor activitypathology(r=0.900,P＜0.001).The median follow-up time was 32.93 months,during which 8 patients died,and the median survival time was 29.9 months.The area under the curve(AUC)of tumor activityST for predicting patients'survival status was 0.67,and the cut-off value was 0.36.Thirty patients with tumor activityST＜0.36 were enrolled in survival benefit group,while 5 patients≥0.36 were collected in no survival benefit group.The overall survival in survival benefit group was longer than that in no survival benefit group(P＜0.001).Conclusion MRI ST could be used to non-invasively evaluate the efficacy of systemic therapy for advanced HCC and predict prognosis after combining with surgery.

Objective:To compare the medical costs of using standard fortified donor human milk (DHM) or preterm formula (PF) to supply very low birth weight [VLBW, defined as birth weight (BW) ≥1 000 g but <1 500 g] and extremely low birth weight (ELBW, defined as BW <1 000 g) premature infants with insufficient maternal breast milk.Methods:VLBW and ELBW preterm infants hospitalized in Peking Union Medical College Hospital from September 2017 to October 2020 were retrospectively enrolled and assigned into DHM group and PF group based on complementary feeding methods. The cost of parenteral nutrition (PN), cost of antibiotics, and total medical expenses during hospitalization were compared between the two groups.Results:A total of 89 infants were enrolled in this study, out of whom 50 was in the DHM group and 39 the PF group. The gestational age in DHM group and PF group were both (29±2) weeks. The BW of DHM group was 1 170 (919, 1 380)?g and that of PF group was 1 170 (1 010, 1 360) g. There were no significant differences in gestational age, BW, maternal age at delivery, delivery mode, gender ratio, proportion of small-for-gestational-age infants and length of hospital stay between the two groups (all P>0.05). The cost of parenteral nutrition in DHM group was significantly lower than that in PF group [3 500 (1 922, 5 704) Chinese yuan vs 7 995 (5 579, 10 788) Chinese Yuan, P<0.01]. The cost of antibiotics in DHM group was significantly lower than that in PF group [6 529 (2 265, 10 860) Chinese Yuan vs 13 676 (10 480, 18 506) Chinese Yuan, P<0.01]. The difference in total medical expense during hospitalization showed no statistical significance between two groups ( P>0.05). Amorg VLBW preterm infants, the cost of PN, cost of antibiotics, total cost of hospitalization, and daily cost of hospitalization in HDM group was significantly lower than that in PF group (all P<0.05). In ELBW preterm infants, the cost of PN and the cost of antibiotics in HDM group were significantly lower than that in PF group (both P<0.05), but the total cost of hospitalization and the daily cost of hospitalization between two groups showed no significant difference (all P>0.05). Conclusions:When mother's own milk is insufficient, using donor human milk reduces the costs of PN and antibiotics in VLBW and ELBW preterm infants compared with using PF. In VLBW preterm infants, using DHM can also reduce the total and daily cost of hospitalization.

AIM:This study aims to investigate the role of histone methyltransferase SET and MYND domain containing 2(SMYD2)in facilitating renal fibrosis through the macrophage-myofibroblast transition in diabetic kidney dis-ease(DKD).METHODS:(1)C57BL/6J mice were intraperitoneally administered 55 mg/kg of streptozotocin to induce diabetes mellitus(DM).The experimental groups were categorized as follows:normal control,DM(20 weeks),DM(28 weeks),and DM(36 weeks).Blood glucose(BG),serum creatinine(SCr)and blood urea nitrogen(BUN)levels were determined using a biochemical analyzer.Hematoxylin-eosin(HE)staining and Masson staining were performed to assess morphological and fibrotic changes in renal tissues.Western blot analysis was used to measure the protein levels of SMYD2,histone H3 lysine 4 trimethylation(H3K4me3),arginase-1,matrix metalloproteinase 9(MMP9),collagen type Ⅰ(Col Ⅰ)and α-smooth muscle actin(α-SMA).Immunofluorescence staining was conducted to examine the localization and expression of F4/80,α-SMA,SMYD2,CD86,CD206 and CD163.(2)Mouse monocyte/macrophage RAW264.7 cells were cultured in vitro and assigned to groups as follows:normal glucose(NG)+negative control siRNA(siNC),high glucose(HG)+siNC,NG+SMYD2 siRNA(siSMYD2),and HG+siSMYD2.Western blot analysis was used to assess the expression of relevant proteins.RESULTS:(1)Compared with normal control group,the levels of BG,SCr and BUN were significantly elevated in DM(28 weeks)and DM(36 weeks)groups(P＜0.05).Renal tissue exhibited tubular atro-phy,dilation,and collagen fiber deposition.The levels of H3K4me3,arginase-1,MMP9,Col Ⅰ and α-SMA proteins were up-regulated(P＜0.05).The CD86,CD206,CD163 and F4/80 were primarily localized in the interstitial macrophages of the renal tubules,α-SMA was predominantly detected in the renal interstitium,and SMYD2 was mainly expressed in renal tubular epithelial cells and the renal interstitium.(2)Compared with NG+siNC group,the protein levels of SMYD2,H3K4me3,arginase-1,CD163,Col Ⅰ,α-SMA,transforming growth factor-β1(TGF-β1)and p-Smad3 in the cells of HG+siNC group were significantly increased(P＜0.05).Knockdown of SMYD2 resulted in a reduction of these indicators(P＜0.05).CONCLUSION:The SMYD2 protein appears to facilitate renal fibrosis in DKD by promoting the macrophage-myofibroblast transition,potentially through the modulation of TGF-β1/Smad3 signaling pathway.

Objective To investigate the distribution characteristics of Klebsiella pneumoniae(KP),hyperviru-lent Klebsiella pneumoniae(hvKP),carbapenem-resistant Klebsiella pneumoniae(CRKP),and hypervirulent car-bapenem-resistant Klebsiella pneumoniae(hv-CRKP/CR-hvKP)in the environment of general intensive care unit(ICU)at medical institutions,and provide reference for environment assessment as well as healthcare-associated in-fection(HAI)prevention and control in ICU.Methods A total of 3 336 environmental specimens were collected from general ICUs of medical institutions in Shanghai in 2019 and 2023.After strain isolation,antimicrobial suscep-tibility testing and whole genome sequencing were conducted.Results The detection rate of KP was 1.59％(n=53),among which hvKP,CRKP,and hv-CRKP/CR-hvKP accounted for 37.74％(20/53),52.83％(28/53),and 24.53％(13/53)of the total detected strains,respectively.The main types of hvKP were ST11-KL64 and ST11-KL25,CRKP were ST15-KL19 and ST11-KL25,hv-CRKP/CR-hvKP were ST11-KL25 and ST11-KL64.The main carried resistance genes included fosA,oqx AB,tet(A),blaTEM-1B,blaKPC-2,qnrS11,etc.All strains carried viru-lence genes fimH,iutA,ent A,entB,entC,entD,entE,and entF,with only one strain carrying rmp A gene.Conclusion KP contamination is widespread in general ICU environment of medical institutions,predominantly ST11 and ST15,presenting a polymorphic distribution.CRKP and hvKP account for a relatively high proportion,and multidrug resistance is serious.Co-evolution of drug resistance and virulence presents in KP,and poses signifi-cant infection and pathogenic risks to patients,necessitating enhanced clinical vigilance and preparedness for poten-tial outbreaks.

Objective:To compare the medical costs of using standard fortified donor human milk (DHM) or preterm formula (PF) to supply very low birth weight [VLBW, defined as birth weight (BW) ≥1 000 g but <1 500 g] and extremely low birth weight (ELBW, defined as BW <1 000 g) premature infants with insufficient maternal breast milk.Methods:VLBW and ELBW preterm infants hospitalized in Peking Union Medical College Hospital from September 2017 to October 2020 were retrospectively enrolled and assigned into DHM group and PF group based on complementary feeding methods. The cost of parenteral nutrition (PN), cost of antibiotics, and total medical expenses during hospitalization were compared between the two groups.Results:A total of 89 infants were enrolled in this study, out of whom 50 was in the DHM group and 39 the PF group. The gestational age in DHM group and PF group were both (29±2) weeks. The BW of DHM group was 1 170 (919, 1 380)?g and that of PF group was 1 170 (1 010, 1 360) g. There were no significant differences in gestational age, BW, maternal age at delivery, delivery mode, gender ratio, proportion of small-for-gestational-age infants and length of hospital stay between the two groups (all P>0.05). The cost of parenteral nutrition in DHM group was significantly lower than that in PF group [3 500 (1 922, 5 704) Chinese yuan vs 7 995 (5 579, 10 788) Chinese Yuan, P<0.01]. The cost of antibiotics in DHM group was significantly lower than that in PF group [6 529 (2 265, 10 860) Chinese Yuan vs 13 676 (10 480, 18 506) Chinese Yuan, P<0.01]. The difference in total medical expense during hospitalization showed no statistical significance between two groups ( P>0.05). Amorg VLBW preterm infants, the cost of PN, cost of antibiotics, total cost of hospitalization, and daily cost of hospitalization in HDM group was significantly lower than that in PF group (all P<0.05). In ELBW preterm infants, the cost of PN and the cost of antibiotics in HDM group were significantly lower than that in PF group (both P<0.05), but the total cost of hospitalization and the daily cost of hospitalization between two groups showed no significant difference (all P>0.05). Conclusions:When mother's own milk is insufficient, using donor human milk reduces the costs of PN and antibiotics in VLBW and ELBW preterm infants compared with using PF. In VLBW preterm infants, using DHM can also reduce the total and daily cost of hospitalization.