This article was to elucidate that the needling depth is closely related to the meridian qi, disease location, disease nature and needled area based on the records of needling depth in Nei Jing (Canon of Internal Medicine). Moreover, different depths will produce different therapeutic efficacies;meanwhile, improper depth may lead to grave consequences.

AIM: To investigate the relationship between the intracellular expression of Th1 and Th2 type cytokines in placental lymphocytes and the pregnancy outcomes in NOD/SCID mice. METHODS: The resorption rate of embryos (RR) was compared between BALB/c and NOD/SCID mice. In addition, the expression rates of Th1 type (TNF-? and IL-2) and Th2 type (IL-10) cytokines were detected intracellularlly in placental lymphocytes by four-color flow cytometry. RESULTS: Although multiple-immunodeficiency was confirmed in the NOD/SCID, no significant difference was observed in RR between BALB/c and NOD/SCID mice. At the same time, a dramatically elevated level of CD8+IL-10+/CD8+ cell percentage was found at the feto-maternal interface in NOD/SCID?NOD/SCID, as compared with BALB/c?BALB/c mice, while no significant difference was observed for TNF-? and IL-2 expression in CD4+ and CD8+ cell subsets isolated from these mice. CONCLUSION: The spontaneous elevation of CD8+IL-10+/CD8+ cell percentage at the feto-maternal interface may be related to the roughly normal fertility in NOD/SCID mice.

Objective To investigate the microbiological trends and antibiotic susceptibility of peritoneal dialysis(PD)-related peritonitis (PDAP).Methods All patients who developed PDAP between 2004 and 2015 in Renji Hospital,Shanghai Jiao Tong University School of Medicine were enrolled.Demographic data,results of dialysate pathogen culture and drug susceptibility test were recorded.The trend of peritonitis incidence was measured by Poisson regression and the chi-square test or Fisher exact test method was used to compare the composition of causative organisms and their antimicrobial susceptibilities over time.Results During the study period,a total of 711 episodes of PDAP were occurred in 386 patients.The culture positive rate of pathogens rose from 52.0％ in 2004 to 77.0％ in 2015 (P ＜ 0.001).The distribution of causative organisms of the culture positive peritonitis was gram-positive bacteria (270,59.5％),followed by gram-negative bacteria (129,28.4％),polymicrobial(39,8.6％),fungi (15,3.3％) and mycobacteria (1,0.2％).From 2004 to 2015,the incidence of peritonitis decreased from 0.214 to 0.160 episodes/patient·year (P=0.034).The incidence of coagulase-negative staphylococcus peritonitis decreased from 0.049 to 0.027 episodes/patient · year (P=0.025),while others had no significant change;A significant decline was observed in the sensitivity of Gram-positive strains to the first generation cephalosporin and ampicillin/sulbactam in 2010-2015 group compared with those in 2001-2009 group (61.3％ vs 88.2％,P ＜ 0.001;61.7％ vs 85.5％,P=0,001),whereas the sensitivity to vancomycin remained the same.The sensitivity of Gram-negative strains to ceftazidime and amikacin showed no significant change.As for the gram-positive peritonitis treated with cefradine as empirical treatment,compared with those in 2004-2009 group,in 2010-2015group the proportion of patients requiring to change their treatment regime was significantly higher,and the treatment course was longer.Conclusions A gradual decline is observed in the incidence of PDAP and the culture positive rate of pathogens improves.Peritonitis caused by coagulase-negative staphylococcus decreases overtime.The present empirical treatment protocols may need re-evaluation considering the decreased rate of the first generation cephalosporin sensitivity in recent years.

ObjectiveTo explore the association between total iron， iron supplements， dietary total iron， heme iron intake and the risk of gestational diabetes mellitus（GDM）. MethodsA total of 668 pregnant women who gave birth in one hospital in Shanghai during January 2020 to July 2021 were included in a retrospective cohort study. Baseline characteristics and data of iron supplements in second trimester were collected through a questionnaire. A simplified dietary frequency questionnaire was used to quantify the food intake in second trimester. Total iron， iron supplements， dietary total iron， and heme iron intake was classified into groups by quintile and median. The association between iron intake from different sources and risk of GDM was determined using logistic regression analysis. ResultsAfter correction for age， family history of diabetes， overweight / obesity before pregnancy， hemoglobin（Hb）in first trimester， energy， carbohydrate energy， protein， and free sugar， it showed no association between total iron intake and risk of GDM （P>0.05）， while elevated risk of GDM among women with high iron supplements intake （OR=1.65； 95%CI： 1.14‒2.39）， and decreased risk of GDM among those with high dietary total iron intake （OR=0.53； 95%CI： 0.35‒0.81）. However， no association was found between heme iron intake and risk of GDM （P>0.05）. ConclusionHigh dietary total iron intake may be a protective factor， while high iron supplements may be a risk factor for GDM. It suggests that pregnant women should carefully choose high-dose iron-containing supplements in the absence of iron deficiency， as dietary iron intake should be the priority.

Objective: To investigate the efficacy and the prognostic factors in pediatric hepatoblastoma according to the standard diagnostic and therapeutic regimen. Method: Eighty-four consecutive patients were enrolled in this study between June 2000 and June 2015. Diagnosis and staging was decided by the multi-disciplinary team including oncologists, surgeons, pathologists and sub-specialized radiologists refering to protocol of Children′s Oncology Group(COG) and International Society of Pediatric Oncology Liver Tumor Study Group (SIOPEL) in a case observational study. Univariate analysis was tested by the log-rank and multivariate analysis by COX regression. All consecutive cases were divided into low risk group and high risk group according to grouping criteria. Complete remission was defined as both imaging negative and α fetoprotein (AFP) normalization. Retrospective analysis was performed in clinical features, long-term outcomes and prognostic factors. Result: Ten patients were excluded because of giving up after less than or equal to three cycles of treatment. A total of 74 cases were included in this study; 45 males and 29 females. The median age at diagnosis was 1.7 years(range 0.2-14.8 years). Untill August 30, 2016, the median follow-up time was 24.2 months (range 4.1-135.3 months); 59 cases achieved complete remission.The estimated five years overall survival (OS) and event free survival(EFS) were 90%(68/74)and 72%(58/74). AFP could be normalized after 5 circles of treatment or 2 circles of postoperation.In univariate analysis , the five years OS and EFS in low risk group were both 100%(18/18), and those in high risk group were 88%(50/56)and 68%(40/56), respectively. The five years OS rates were 75%(15/19) and 95%(53/55) in patients with or without distant metastasis (P=0.016). After 3 cycles of chemotherapy post tumor resection, we divided these patients into 2 groups according to AFP recover or not, the five years OS were 100%(43/43)and 81%(22/26), respectively (P=0.011). Conclusion The result of this protocol is reasonable when comparing with other worldwide research. Except for staging, metastasis, pathological subtypes, postoperative AFP recover or not is a prognostic factor after 3 cycles of chemotherapy.

OBJECTIVETo observe the regulatory effects of acupoint electric stimulation on the analgesic substances and the relevant indices of nerve-immunity-endocrine system in the patients undergoing general anesthesia anorectal operation.

METHODSOne hundred and fifty-six patients undergoing hemorrhoids and anal fistula operation were randomized into three groups, 146 cases were included in the analysis. In the No.1 group (48 cases), the conventional intravenous general anesthesia was applied. In the No.2 group (50 cases), besides the conventional intravenous general anesthesia, the acupoint transcutaneous electric stimulation was combined at Neiguan (PC 6), Shenmen (HT 7), Shangliao (BL 31) and Ciliao (BL 32). operation in the No.2 and No.3 groups were lower apparently than that in the No.1 group (<0.05,<0.01).

CONCLUSIONSDuring the general anesthesia anorectal operation, the acupoint transcutaneous electric stimulation achieves analgesic anesthesia through effectively promoting the release of body analgesic substance and reducing the stress level in the operation. With the comprehensive acupoint selection as Neiguan (PC 6) and Shenmen (HT 7) and the local acupoints, the therapeutic effects are better in comparison with the simple selection of local acupoints. In the No.3 group (48 cases), besides the conventional intravenous general anesthesia, the acupoint transcutaneous electric stimulation was combined at Shangliao (BL 31) and Ciliao (BL 32). The electric stimulation was maintained till the end of operation. The patients' saliva was collected 0.5 h before operation and 1 h after operation separately. The indices that reflect the body pain regulation and nerve-immune-endocrine secretion were detected, such as opiophin protein (OPI), secretory immunoglobulin A (SIgA), saliva amylase (sAA), cortisol (Cor) and tumor necrosis factor α (TNF-α). The pain degree was observed 1 h after operation.

RESULTSIn the No.2 group, OPI after operation was higher than that before operation (<0.05). The difference value of OPI in the No.2 group was higher apparently than that in the No.1 group and the No.3 group (both<0.05). SIgA after operation was higher than that before operation in the No.1 group (<0.05). The difference values of SIgA, sAA, Cor in the No.2 group were lower apparently than those in the No.1 group (<0.05,<0.01). TNF-αbefore and after operation and its difference value among the groups were not significant statistically (all>0.05). The pain degrees in 1 h after.

Objective To analyze the current status of anti-bacterial activity of carbapenem-resistant Klebsiella pneumoniae and Escherichia coli clinically isolated from hospitalized patients, detect their related resistance genes, and provide reference for the clinical treatment of carbapenem resistant Enterobacteria （CRE） infections and the rational use of antibiotics. Methods A total of 400 non-repetitive isolates of Klebsiella pneumoniae and Escherichia coli isolated from clinical specimens of Punan Branch of Renji Hospital, Shanghai Jiao Tong University School of Medicine from January 2022 to December were collected. The minimum inhibitory concentrations of these strains against commonly used antibiotics were determined by the broth microdilution method. The carbapenemase and related resistance genes of CRE were detected by drug resistance phenotype testing and PCR. Results Among the 400 strains, 51 strains were identified as CRE, accounting for 12.75%. Among these, 49 strains produced carbapenemases, with 41 strains （80.39%） being CR Klebsiella pneumoniae and 10 strains （19.61%） being CR Escherichia coli. Among the CRE strains, 34 strains （66.67%） carried bla_KPC, 13 strains （25.49%） carried bla_NDM, and 2 strains （3.92%） carried bla_OXA-48. Conclusion Compared with other commonly used antibiotics, colistin and tigecycline exhibited good in vitro antibacterial activity against carbapenemase-producing Klebsiella pneumoniae and Escherichia coli. In addition, there was good concordance between drug resistance phenotype testing and genotyping. Clinical microbiology laboratories could continuously monitor the drug resistance phenotype and genotype of CRE and develop appropriate treatment plans based on actual conditions.

SUMOylation is recently found to function as a targeting signal for the degradation of substrates through the ubiquitin-proteasome system. RNF4 is the most studied human SUMO-targeted ubiquitin E3 ligase. However, the relationship between SUMO proteases, SENPs, and RNF4 remains obscure. There are limited examples of the SENP regulation of SUMO2/3-targeted proteolysis mediated by RNF4. The present study investigated the role of SENP3 in the global protein turnover related to SUMO2/3-targeted ubiquitination and focused in particular on the SENP3 regulation of the stability of Sp1. Our data demonstrated that SENP3 impaired the global ubiquitination profile and promoted the accumulation of many proteins. Sp1, a cancer-associated transcription factor, was among these proteins. SENP3 increased the level of Sp1 protein via antagonizing the SUMO2/3-targeted ubiquitination and the consequent proteasome-dependent degradation that was mediated by RNF4. De-conjugation of SUMO2/3 by SENP3 attenuated the interaction of Sp1 with RNF4. In gastric cancer cell lines and specimens derived from patients and nude mice, the level of Sp1 was generally increased in parallel to the level of SENP3. These results provided a new explanation for the enrichment of the Sp1 protein in various cancers, and revealed a regulation of SUMO2/3 conjugated proteins whose levels may be tightly controlled by SENP3 and RNF4.
Animals ; Cysteine Endopeptidases ; genetics ; metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Immunoenzyme Techniques ; Immunoprecipitation ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Prognosis ; Protein Processing, Post-Translational ; Proteolysis ; RNA, Messenger ; genetics ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Small Ubiquitin-Related Modifier Proteins ; antagonists & inhibitors ; genetics ; metabolism ; Sp1 Transcription Factor ; genetics ; metabolism ; Stomach Neoplasms ; genetics ; metabolism ; pathology ; Sumoylation ; Tumor Cells, Cultured ; Ubiquitination ; Ubiquitins ; antagonists & inhibitors ; genetics ; metabolism ; Xenograft Model Antitumor Assays

Background Lead (Pb) exposure impairs cognitive functions of children. Whether Pb exposure in different developmental stages induces long-term cognitive impairment, and whether chelation therapy could mitigate the cognitive impairment is rarely reported. Objective This experiment is designed to investigate effects of Pb exposure and chelation therapy during different developmental stages (breastfeeding, weaning, and early puberty periods) on mouse short-term and long-term cognitive functions. Methods C57BL/6 male mice in breastfeeding period, weaning period, and early puberty period (postnatal day 2, 21, and 41; PND 2, PND 21, and PND 41, n=30, respectively) were randomly divided into control, Pb exposure, and Pb+dimercaptosuccinic acid (DMSA) treatment groups (n=10 in each group). The control groups received standard food and deionized water. The Pb exposure mice received standard food and free drinking water containing Pb acetate (0.1% for dams, and 0.05% for pups). After receiving Pb acetate for 19 d, the Pb+DMSA treatment groups were given 1 mmol·kg⁻¹·d⁻¹ DMSA for 6 d with gastric infusion. Whole blood Pb levels were measured after DMSA treatment on experimental day 25. The effects on short-term cognitive function were tested in the Morris Water Maze task by the analyses of escape latency on PND 75−79, as well as target quadrant time and times of platform-crossing on PND 80. Hippocampal long-term potentiation of field excitatory postsynaptic potential (fEPSP) of mice on PND 365 was induced to demonstrate the effects on long-term cognitive function. Results The blood Pb levels among the Pb, Pb+DMSA, and control groups were statistically different for each developmental stage (F_{breastfeeding period}=43.47, F_{weaning period}=228.6, F_{early period of puberty}=274.2, all P<0.001). Compared to the counterpart control groups, blood Pb levels of the pb exposure groups (386.4, 265.0, and 178.1 μg·L⁻¹ in breastfeeding period, weaning period, and early puberty period, respectively) were significantly higher for all stages. After the chelation therapy, the blood Pb significantly decreased for all stages (28.68, 47.29, and 20.93 μg·L⁻¹ in the three periods, respectively, all P<0.001) and the Pb levels of the mice exposed in the breastfeeding period decreased most (by 92.58%, 82.15%, and 88.25% in the three periods, respectively, P<0.01). In the water maze task, the mice exposed to Pb in the breastfeeding period had a gentler decrease in escape latency (from 54.20 s on day 1 to 30.54 s on day 5, by 43.65 % decrease) than the control group (from 32.44 s on day 1 to 15.20 s on day 5, by 53.14 % decrease) (P<0.01) and a significant decrease in target quadrant time (P<0.05). After the chelation therapy, the escape latency of the DMSA-treated mice in the breastfeeding period (from 40.94 s on day 1 to 20.87 s on day 5, by 48.99 % decrease) was steeper than that of the Pb-exposed mice (P<0.05). The differences in the escape latency, target quadrant time, and times of platform-crossing were not significant between the Pb-exposed mice and the control mice in the weaning period and early period of puberty (all P>0.05). After the chelation therapy, such differences were also not significant compared with before therapy. Due to the small sample size, data were merged for different developmental stages in the long-term potentiation test. The amplitudes of fEPSP induced in the control, Pb-exposed, and DMSA treatment groups were significantly different (F_groups=212.2, F_time=11.36. P<0.001). The average fEPSP amplitude induced in the last 10 min recorded in the hippocampal slices in the Pb exposure group was significantly lower than that in the control group (P<0.05). After the DMSA treatment, no significant differences were observed in the fEPSP amplitudes between the Pb exposure group and the DMSA treatment group (P>0.05). When observing the fEPSP data by developmental stages, the fEPSP amplitude in the breastfeeding Pb-exposure group was 27.2% lower than that of the breastfeeding control group, while such changes were not obvious in the weaning period or in the early period of puberty. The fEPSP amplitude in breastfeeding DMSA treatment group was 44.3% higher than that of the breastfeeding Pb exposure group, while such changes were not observed in the weaning period or in early period of puberty. Conclusion Pb exposure during different developmental stages, especially in breastfeeding period, could affect short-term and long-term cognitive functions of mice. The harmful effects may be partially reversed by DMSA chelation therapy, especially being treated in breastfeeding period.