Analysis of the Human Kinome and Phosphatome by Mass Cytometry Reveals Overexpression-Induced Effects on Cancer-Related Signaling.

Kinase and phosphatase overexpression drives tumorigenesis and drug resistance. We previously developed a mass-cytometry-based single-cell proteomics approach that enables quantitative assessment of overexpression effects on cell signaling. Here, we applied this approach in a human kinome- and phosphatome-wide study to assess how 649 individually overexpressed proteins modulated cancer-related signaling in HEK293T cells in an abundance-dependent manner. Based on these data, we expanded the functional classification of human kinases and phosphatases and showed that the overexpression effects include non-catalytic roles. We detected 208 previously unreported signaling relationships. The signaling dynamics analysis indicated that the overexpression of ERK-specific phosphatases sustains proliferative signaling. This suggests a phosphatase-driven mechanism of cancer progression. Moreover, our analysis revealed a drug-resistant mechanism through which overexpression of tyrosine kinases, including SRC, FES, YES1, and BLK, induced MEK-independent ERK activation in melanoma A375 cells. These proteins could predict drug sensitivity to BRAF-MEK concurrent inhibition in cells carrying BRAF mutations.

Profiling Cell Signaling Networks at Single-cell Resolution.

Signaling networks process intra- and extracellular information to modulate the functions of a cell. Deregulation of signaling networks results in abnormal cellular physiological states and often drives diseases. Network responses to a stimulus or a drug treatment can be highly heterogeneous across cells in a tissue because of many sources of cellular genetic and non-genetic variance. Signaling network heterogeneity is the key to many biological processes, such as cell differentiation and drug resistance. Only recently, the emergence of multiplexed single-cell measurement technologies has made it possible to evaluate this heterogeneity. In this review, we categorize currently established single-cell signaling network profiling approaches by their methodology, coverage, and application, and we discuss the advantages and limitations of each type of technology. We also describe the available computational tools for network characterization using single-cell data and discuss potential confounding factors that need to be considered in single-cell signaling network analyses.

A quantitative analysis of the interplay of environment, neighborhood, and cell state in 3D spheroids.

Cells react to their microenvironment by integrating external stimuli into phenotypic decisions via an intracellular signaling network. To analyze the interplay of environment, local neighborhood, and internal cell state effects on phenotypic variability, we developed an experimental approach that enables multiplexed mass cytometric imaging analysis of up to 240 pooled spheroid microtissues. We quantified the contributions of environment, neighborhood, and intracellular state to marker variability in single cells of the spheroids. A linear model explained on average more than half of the variability of 34 markers across four cell lines and six growth conditions. The contributions of cell-intrinsic and environmental factors to marker variability are hierarchically interdependent, a finding that we propose has general implications for systems-level studies of single-cell phenotypic variability. By the overexpression of 51 signaling protein constructs in subsets of cells, we also identified proteins that have cell-intrinsic and cell-extrinsic effects. Our study deconvolves factors influencing cellular phenotype in a 3D tissue and provides a scalable experimental system, analytical principles, and rich multiplexed imaging datasets for future studies.

[Expression of TGF-ß in bladder neck contracture after transurethral enucleation and resection of the prostate].

OBJECTIVE: To explore the role of transforming growth factor-ß (TGF-ß) in bladder neck contracture (BNC) after transurethral enucleation and resection of the prostate (TUERP). METHODS: This study included 300 BPH patients undergoing TUERP, aged 51－89 (69.19 ± 8.43) years, with the prostate volume of 14.4－355.8 (63.18 ± 47.63) ml and preoperative IPSS of 15－35 (26.07 ± 5.9), QOL score of 3－6 (4.43 ± 0.67), PSA content of 0.17－23.16 (2.94 ± 3.77) ug/L, urinary leukocyte increase in 50 cases, post-void residual urine volume (PVR) of 0－440 (83.53 ± 86.85) ml, and maximum urinary flow rate (Qmax) of 2.3－14.5 (7.77 ± 3.47) ml/s. During TUERP, we collected the tissues from the bladder neck at 5 and 7 o'clock as well as the BPH tissue and the tissue from the residual prostate for HE staining, immunohistochemistry (the SP method) and examination of the infiltration degree of inflammatory cells and expressions of TGF-ß1 and TGF-ß3. During the 6－24 months follow-up, 6 of the patients were confirmed with BNC based on the clinical symptoms and the results of uroflowmetry and cystoscopy, and underwent transurethral bladder neck incision and detection of the expressions of TGF-ß1 and TGF-ß3 in the bladder neck tissue with BNC. RESULTS: The bladder neck tissue without BNC was mainly composed of smooth muscle and fibrous tissues with local infiltration of inflammatory cells, and the residual prostate tissue primarily comprised fibrous and muscle tissues, mixed with a little prostatic epithelial tissue. The bladder neck tissue with BNC, compared with that harvested during the initial TUERP, exhibited significantly increased expression of TGF-ß1 (ï¼»68.20 ± 10.88ï¼½% vs ï¼»36.14 ± 7.62ï¼½%, P < 0.05), decreased expression of TGF-ß3 (ï¼»8.55 ± 4.73ï¼½% vs ï¼»20.77 ± 8.69ï¼½%, P < 0.05), and enhanced infiltration of inflammatory cells (P < 0.05). The bladder neck tissue without BNC, in comparison with the BPH tissue, showed dramatically up-regulated expressions of TGF-ß1 (ï¼»27.05 ± 8.21ï¼½% vs ï¼»1.61 ± 0.69ï¼½%, P < 0.001) and TGF-ß3 (ï¼»14.09 ± 4.19ï¼½% vs ï¼»0.32 ± 0.11ï¼½%, P < 0.001) and increased infiltration of inflammatory cells (P < 0.05). CONCLUSIONS: After TUERP, the expression of TGF-ß1 is increased, that of TGF-ß3 decreased and the infiltration of inflammatory cells enhanced in the bladder neck tissue with BNC, which suggests that BNC may be related to the expression of TGF-ß and that BNC after TUERP could be prevented by regulating the expression of TGF-ß.

Approximating mutual information of high-dimensional variables using learned representations.

Mutual information (MI) is a general measure of statistical dependence with widespread application across the sciences. However, estimating MI between multi-dimensional variables is challenging because the number of samples necessary to converge to an accurate estimate scales unfavorably with dimensionality. In practice, existing techniques can reliably estimate MI in up to tens of dimensions, but fail in higher dimensions, where sufficient sample sizes are infeasible. Here, we explore the idea that underlying low-dimensional structure in high-dimensional data can be exploited to faithfully approximate MI in high-dimensional settings with realistic sample sizes. We develop a method that we call latent MI (LMI) approximation, which applies a nonparametric MI estimator to low-dimensional representations learned by a simple, theoretically-motivated model architecture. Using several benchmarks, we show that unlike existing techniques, LMI can approximate MI well for variables with $> 10^3$ dimensions if their dependence structure has low intrinsic dimensionality. Finally, we showcase LMI on two open problems in biology. First, we approximate MI between protein language model (pLM) representations of interacting proteins, and find that pLMs encode non-trivial information about protein-protein interactions. Second, we quantify cell fate information contained in single-cell RNA-seq (scRNA-seq) measurements of hematopoietic stem cells, and find a sharp transition during neutrophil differentiation when fate information captured by scRNA-seq increases dramatically.

Signal amplification by cyclic extension enables high-sensitivity single-cell mass cytometry.

Mass cytometry uses metal-isotope-tagged antibodies to label targets of interest, which enables simultaneous measurements of ~50 proteins or protein modifications in millions of single cells, but its sensitivity is limited. Here, we present a signal amplification technology, termed Amplification by Cyclic Extension (ACE), implementing thermal-cycling-based DNA in situ concatenation in combination with 3-cyanovinylcarbazole phosphoramidite-based DNA crosslinking to enable signal amplification simultaneously on >30 protein epitopes. We demonstrate the utility of ACE in low-abundance protein quantification with suspension mass cytometry to characterize molecular reprogramming during the epithelial-to-mesenchymal transition as well as the mesenchymal-to-epithelial transition. We show the capability of ACE to quantify the dynamics of signaling network responses in human T lymphocytes. We further present the application of ACE in imaging mass cytometry-based multiparametric tissue imaging to identify tissue compartments and profile spatial aspects related to pathological states in polycystic kidney tissues.

Meta-analysis of the survival rate and postoperative infection rate of primary and secondary implants after vascularized fibula transplantation for reconstruction of jaw defects.

OBJECTIVES: Vascularized fibula flap transplantation is the most effective and common method to repair the jaw defects. In addition, implantation is the first choice to restore dentition on the graft fibula. Implants are usually implanted at least 6 months after fibula transplantation. Primary implantation of implants during surgery can restore the dentition earlier, but whether this method can achieve the same restorative effect as secondary implantation is still uncertain. This article aims to compare the survival rate and complications between primary and secondary implantation through meta-analysis. METHODS: This meta-analysis was conducted according to PRISMA protocol and the Cochrane Handbook of Systematic Reviews of Interventions. According to the inclusion and exclusion criteria, we selected the PubMed, Embase, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Chinese BioMedical Literature Database (CBM) according to established inclusion and exclusion criteria. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the included studies. Meta-analysis was conducted to compare the survival rate and postoperative infection rate of primary and secondary implantation. RESULTS: Seven studies were involved in our research, involving 186 patients. Five of the studies detailed implant success in 106 patients (primary implantation 50, secondary implantation 56), and four studies documented infection after implantation in 117 patients (primary implantation 52, secondary implantation 65); the survival rate of the primary implantation was 93.3%, and the incidence of postoperative infection was 17.3%. The survival rate of the secondary implantation was 93.4%, and 23.1% had postoperative infection. Meta-analysis showed that there was no significant difference in the survival rate between primary implantation and secondary implantation, OR = 0.813 (95% CI 0.383-1.725, P = 0.589 > 0.05), and there was no significant difference in the incidence of postoperative infection, OR = 0.614 (95% CI 0.239-1.581, P = 0.312 > 0.05). CONCLUSIONS: Based on the results of this study, the research found no significant difference in the survival rate or infection rates between primary and secondary implantation. After appropriate indications selection, primary implantation can be used to reconstruct the dentition with less waiting time, reduce the impact of radiotherapy, and bring a higher quality of life for patients.

[Pollution Characteristics and Source Apportionment of VOCs in Urban Areas of Liaocheng in Summer].

Based on the online monitoring data of volatile organic compounds(VOCs) and ozone(O3) in Liaocheng in June 2021, the concentration levels, compositional characteristics, daily variation characteristics, and ozone formation potential(OFP) of VOCs on polluted days and clean days were systematically analyzed. Potential source areas of VOCs were identified by the potential source contribution function(PSCF) and concentration-weighted trajectory(CWT). The sources of VOCs in Liaocheng were analyzed using the characteristic species ratio and positive matrix factorization(PMF). The results showed that the hourly mean values of VOCs concentrations on polluted days and clean days in Liaocheng in June 2021 were(115.38±59.12) µg·m-3 and(88.10±33.04) µg·m-3, respectively, and the concentration levels of VOCs in each category showed that oxygenated volatile organic compounds(OVOCs)>alkanes>halogenated hydrocarbons>aromatic hydrocarbons>alkenes>alkynes>organosulfur. VOCs species with large differences in concentrations between polluted and clean days were among the top ten species of the hourly mean VOCs concentrations. The daily trends of concentrations of total VOCs, alkanes, alkynes, aromatic hydrocarbons, halogenated hydrocarbons, and organosulfur showed that the daytime concentrations were lower than the nighttime concentrations, and the daily changes in OVOCs concentrations showed the characteristics of high in the daytime and low at nighttime. The OFP was 285.29 µg·m-3 on polluted days and 212.00 µg·m-3 on clean days, and OVOCs, alkenes, and aromatic hydrocarbons contributed significantly to ozone formation. The PSCF and CWT results found that the potential source areas of VOCs in Liaocheng were concentrated in the northern and northeastern part of Dongchangfu District and the central and southwestern part of Chiping District. The results of the characteristic species ratio indicated that the VOCs in Liaocheng might have been more from coal combustion, gasoline volatilization, and motor vehicle exhaust. The results of PMF showed that industrial emission sources(30.57%), motor vehicle exhaust and oil and gas volatilization sources(19.44%), combustion sources(17.23%), air aging and secondary generation sources(13.69%), solvent usage sources(12.75%), and natural sources(6.32%) were the main sources of VOCs in Liaocheng.

[Predictors of peri-operative mortality in patients with aortic dissection].

OBJECTIVE: To analyze the peri-operative risk factors of mortality in patients with aortic dissection (AD). METHODS: Between January 2003 and June 2008, 361 AD patients at our hospital were enrolled. Their demographics, history, clinical characteristics and laboratory examinations were retrospectively analyzed. Twenty pre-operative variables were analyzed to identify the predictors of perioperative mortality of AD patients by the analyses of univariate and multivariate logistic regression. RESULTS: The analysis of univariate logistic regression showed that history of hypertension [odds ratio (OR) 0.465, 95% confidence interval (CI) 0.229 - 0.947, P = 0.035], Stanford type A (OR 2.758, 95%CI 1.054 - 7.213 P = 0.039), acute course (OR 7.897, 95%CI 1.874 - 33.275 P = 0.005), neurological symptoms (OR 0.275, 95%CI 0.140 - 0.541, P < 0.001) and operation or not (OR 8.206, 95%CI 4.205 - 16.012, P < 0.001) had a higher mortality in AD patients. The multivariate analysis revealed that acute course (OR 8.178, 95%CI 1.796 - 37.242, P = 0.007), Stanford type A (OR 3.236, 95%CI 1.104-9.487 P = 0.032), neurological symptoms (OR 0.350, 95%CI 0.159 - 0.770, P = 0.009) and operation or not (OR 9.429, 95%CI 4.456 - 19.952, P < 0.001) were significant independent predictors of perioperative mortality in AD patients. CONCLUSION: History of hypertension, acute course, Stanford A and positive neurological symptoms are the independent predictors of perioperative mortality in AD patients. Operation or not is a determinant of patient outcome.

Stabilized Reconstruction of Signaling Networks from Single-Cell Cue-Response Data.

Inferring cell-signaling networks from high-throughput data is a challenging problem in systems biology. Recent advances in cytometric technology enable us to measure the abundance of a large number of proteins at the single-cell level across time. Traditional network reconstruction approaches usually consider each time point separately, resulting thus in inferred networks that strongly vary across time. To account for the possibly time-invariant physical couplings within the signaling network, we extend the traditional graphical lasso with an additional regularizer that penalizes network variations over time. ROC evaluation of the method on in silico data showed higher reconstruction accuracy than standard graphical lasso. We also tested our approach on single-cell mass cytometry data of IFNγ-stimulated THP1 cells with 26 phospho-proteins simultaneously measured. Our approach recapitulated known signaling relationships, such as connection within the JAK/STAT pathway, and was further validated in characterizing perturbed signaling network with PI3K, MEK1/2 and AMPK inhibitors.

Mechanistic Model of Signaling Dynamics Across an Epithelial Mesenchymal Transition.

Intracellular signaling pathways are at the core of cellular information processing. The states of these pathways and their inputs determine signaling dynamics and drive cell function. Within a cancerous tumor, many combinations of cell states and microenvironments can lead to dramatic variations in responses to treatment. Network rewiring has been thought to underlie these context-dependent differences in signaling; however, from a biochemical standpoint, rewiring of signaling networks should not be a prerequisite for heterogeneity in responses to stimuli. Here we address this conundrum by analyzing an in vitro model of the epithelial mesenchymal transition (EMT), a biological program implicated in increased tumor invasiveness, heterogeneity, and drug resistance. We used mass cytometry to measure EGF signaling dynamics in the ERK and AKT signaling pathways before and after induction of EMT in Py2T murine breast cancer cells. Analysis of the data with standard network inference methods suggested EMT-dependent network rewiring. In contrast, use of a modeling approach that adequately accounts for single-cell variation demonstrated that a single reaction-based pathway model with constant structure and near-constant parameters is sufficient to represent differences in EGF signaling across EMT. This result indicates that rewiring of the signaling network is not necessary for heterogeneous responses to a signal and that unifying reaction-based models should be employed for characterization of signaling in heterogeneous environments, such as cancer.

CellCycleTRACER accounts for cell cycle and volume in mass cytometry data.

Recent studies have shown that cell cycle and cell volume are confounding factors when studying biological phenomena in single cells. Here we present a combined experimental and computational method, CellCycleTRACER, to account for these factors in mass cytometry data. CellCycleTRACER is applied to mass cytometry data collected on three different cell types during a TNFα stimulation time-course. CellCycleTRACER reveals signaling relationships and cell heterogeneity that were otherwise masked.

Simultaneous Multiplexed Imaging of mRNA and Proteins with Subcellular Resolution in Breast Cancer Tissue Samples by Mass Cytometry.

To build comprehensive models of cellular states and interactions in normal and diseased tissue, genetic and proteomic information must be extracted with single-cell and spatial resolution. Here, we extended imaging mass cytometry to enable multiplexed detection of mRNA and proteins in tissues. Three mRNA target species were detected by RNAscope-based metal in situ hybridization with simultaneous antibody detection of 16 proteins. Analysis of 70 breast cancer samples showed that HER2 and CK19 mRNA and protein levels are moderately correlated on the single-cell level, but that only HER2, and not CK19, has strong mRNA-to-protein correlation on the cell population level. The chemoattractant CXCL10 was expressed in stromal cell clusters, and the frequency of CXCL10-expressing cells correlated with T cell presence. Our flexible and expandable method will allow an increase in the information content retrieved from patient samples for biomedical purposes, enable detailed studies of tumor biology, and serve as a tool to bridge comprehensive genomic and proteomic tissue analysis.

Protective effect of melatonin against oxygen-induced retinopathy: a study based on the HMGB1/NF-κB/NLRP3 axis / 中国当代儿科杂志

OBJECTIVES@#To study the protective effect of melatonin (Mel) against oxygen-induced retinopathy (OIR) in neonatal mice and the role of the HMGB1/NF-κB/NLRP3 axis.@*METHODS@#Neonatal C57BL/6J mice, aged 7 days, were randomly divided into a control group, a model group (OIR group), and a Mel treatment group (OIR+Mel group), with 9 mice in each group. The hyperoxia induction method was used to establish a model of OIR. Hematoxylin and eosin staining and retinal flat-mount preparation were used to observe retinal structure and neovascularization. Immunofluorescent staining was used to measure the expression of proteins and inflammatory factors associated with the HMGB1/NF-κB/NLRP3 axis and lymphocyte antigen 6G. Colorimetry was used to measure the activity of myeloperoxidase.@*RESULTS@#The OIR group had destruction of retinal structure with a large perfusion-free area and neovascularization, while the OIR+Mel group had improvement in destruction of retinal structure with reductions in neovascularization and perfusion-free area. Compared with the control group, the OIR group had significant increases in the expression of proteins and inflammatory factors associated with the HMGB1/NF-κB/NLRP3 axis, the expression of lymphocyte antigen 6G, and the activity of myeloperoxidase (P<0.05). Compared with the OIR group, the OIR+Mel group had significant reductions in the above indices (P<0.05). Compared with the control group, the OIR group had significant reductions in the expression of melatonin receptors in the retina (P<0.05). Compared with the OIR group, the OIR+Mel group had significant increases in the expression of melatonin receptors (P<0.05).@*CONCLUSIONS@#Mel can alleviate OIR-induced retinal damage in neonatal mice by inhibiting the HMGB1/NF-κB/NLRP3 axis and may exert an effect through the melatonin receptor pathway.

Influence of node abundance on signaling network state and dynamics analyzed by mass cytometry.

Signaling networks are key regulators of cellular function. Although the concentrations of signaling proteins are perturbed in disease states, such as cancer, and are modulated by drug therapies, our understanding of how such changes shape the properties of signaling networks is limited. Here we couple mass-cytometry-based single-cell analysis with overexpression of tagged signaling proteins to study the dependence of signaling relationships and dynamics on protein node abundance. Focusing on the epidermal growth factor receptor (EGFR) signaling network in HEK293T cells, we analyze 20 signaling proteins during a 1-h EGF stimulation time course using a panel of 35 antibodies. Data analysis with BP-R2, a measure that quantifies complex signaling relationships, reveals abundance-dependent network states and identifies novel signaling relationships. Further, we show that upstream signaling proteins have abundance-dependent effects on downstream signaling dynamics. Our approach elucidates the influence of node abundance on signal transduction networks and will further our understanding of signaling in health and disease.

Butorphanol suppresses fentanyl-induced cough during general anesthesia induction: A randomized, double-blinded, placebo-controlled clinical trial.

Fentanyl-induced cough (FIC) is unwanted in the patients requiring stable induction of general anesthesia. This study was designed to evaluate the suppressive effects of butorphanol pretreatment on the incidence and severity of FIC during the induction of general anesthesia. A total of 315 patients of American Society of Anesthesiologists physical status I and II, scheduled for elective surgery under general anesthesia were randomized into 3 equally sized groups (n = 0105). Two minutes before fentanyl bolus, group I received intravenously 5 mL normal saline, groups II and III received butorphanol 0.015 and 0.03 mg/kg (diluted with saline to 5 mL), respectively. Patients were then administrated with fentanyl 2.5 µg/kg within 5 s. The incidence and severity of FIC was recorded for 2 minutes after fentanyl bolus. During experimental period, the mean arterial pressure, heart rate, and peripheral capillary oxygen saturation (SpO2) were recorded before the administration of butorphanol or normal saline (T0), 2 minutes (T1) after butorphanol injection, and 2 minutes (T2) after fentanyl injection. The incidence of FIC was 31.4% in group I, 11.4% in group II, and 3.8% in group III. Group III had a lowest incidence of FIC among 3 groups (P < 0.001, vs group I; P < 0.05, vs group II). The severe FIC was not observed in groups II and III, but was recoded from 6 patients in group I. At 2 minutes after fentanyl injection (T2), the mean arterial pressure was significantly higher in group I than that in groups II and III (P < 0.01, vs group II; P < 0.05, vs group III), but the values remained within safe limits. In conclusion, pretreatment with butorphanol could effectively and safely suppress FIC during anesthesia induction.

[N2O exchange fluxes from wheat-maize crop rotation system in the North China Plain].

N2O exchange fluxes from the intensively cultivated winter wheat-summer maize crop rotation system in the North China Plain were measured by the static chamber technique under normal fertilization treatment and normal fertilization combined with straw returning treatment. The results indicated that the cumulative emissions of N2O from normal fertilization treatment and normal fertilization combined with straw returning treatment were 7.61 kg x hm(-2) and 12.6 kg x hm(-2), respectively. The increased N2O from the straw returning mainly occurred during the maize growing season. The N2O emission during the maize growing season from the two fertilization treatments accounted for 57% - 86% of the annual N2O cumulative emission, which indicated that the annual emission of N2O mainly occurred during the maize growing season. Total N2O emission after 10 days of each fertilization accounted for about 71% - 88% of the annual emission. It is obvious that the application of existing chemical fertilizers greatly promoted the N2O emissions in the North China Plain.

Standardized management of hypertension in communities / 中华健康管理学杂志

Objective To confirm whether community management of hypertension could improve blood pressure control in Chongqing.Methods Cluster sampling method was used to select 5283 adults from 20 community healthcare centers in Chongqing.Matched t test was used to analyze the changes of blood pressure before and after the intervention.x2 test analysis was performed to compare the rate of normal blood pressure.Results The average age of 5283 participants was (60.5 ± 11.0) years old.Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were significantly decreased after intervention (total population:t values were 16.98 and 13.80,respectively; male:t values were 12.58 and 10.66,respectively; female:t values were 11.60 and 9.10,respectively; all P ＜ 0.05).The most significant decrease in SBP was found in 50-59 y age group (t =15.29,P ＜0.05),followed by 40-49 y age group (t =9.22,P ＜0.05).The control rate of hypertension was increased by 5.3％ after 1 year's intervention (x2 =134.5,P＜0.05),except for 60-69 y age group and ≥70 y age group (x2 values were 2.5 and 1.7,respectively ; both P ＞ 0.05).Conclusion Our results show that standardized management of hypertension in communities can decrease the level of blood pressure and increase the control rate of hypertension.

Standard operation procedure and cost of primary public healthcare services / 中华健康管理学杂志

Objective To explore cost of standard operation procedure of primary public healthcare services.Methods Standard operation procedure of primary public healthcare services was put forward according to national basic public healthcare service standards (2011 edition) in 2012.Random sampling method was used to choose participants from two community sanitary service centers,two township heahhcare centers and one maternity and child heahhcare hospital.Service standard operation procedure was used to measure human cost and supportive cost of public healthcare services.Results Management of 10 thousand patients who had different diseases needed various numbers of medical staff (MS),such as health profile needed 3.4 MS,hypertension management needed 10.8 MS,diabetes management needed 10.6 MS,elderly people care needed 9.2 MS,child care needed 4.6 MS,maternal care needed 24.3 MS,psychosis management needed 13.3 MS,and planned immunity for children needed 4.6 MS.Besides,the people whole covered service projects need 2.4 MS per 100 thousand people.The research showed that managing 1 sample of different kind people needed different human cost,such as health profile needed 22.67 yuan,hypertension management needed 72.69 yuan,planned immunity for children needed 30.68 yuan,diabetes management needed 71.34 yuan,old people management needed 61.50 yuan,child care needed 30.88 yuan,maternal care needed 157.15 yuan,psychosis management needed 74.25 yuan.Besides,the people whole covered service projects needed 124.9 thousand yuan per 100 thousand people.Conclusion For primary public healthcare service project,it should be critical to modify manning regulation and labor costs.