excel 某列中 连续出现50个以上的空格 染色

还是针对楼主最初染色的需求来说吧：

我虽然用VBA基本上达到了这个效果，但是始终感觉还是比较麻烦。不知道有没有更简便的办法，比如用公式？我对Excel公式不是很熟，熟悉的朋友可以再琢磨下。

用VBA实现的步骤如下：

1、新建一个Excel文件；

2、键入Alt+F11打开VBA编辑环境，然后选择菜单“插入 - 模块”，在代码编辑区粘贴如下代码：

Option Explicit

Private Sub Worksheet_Change(ByVal Target As Range)

UpdateSelection Target

End Sub

Private Sub UpdateSelection(oSelection As Range)

Dim oArea As Range

Dim nColumnIndex As Long, nMaxColumn As Long, nMaxRow As Long

Dim oColumnDict As Object

Dim vKey As Variant

Set oColumnDict = CreateObject("ScriptingDictionary")

' Collect all columns that need to be updated

For Each oArea In oSelectionAreas

nMaxColumn = Min(ActiveSheetUsedRangeColumn + ActiveSheetUsedRangeColumnsCount, oAreaColumn + oAreaColumnsCount - 1)

nMaxRow = Min(ActiveSheetUsedRangeRow + ActiveSheetUsedRangeRowsCount, oAreaRow + oAreaRowsCount - 1)

For nColumnIndex = oAreaColumn To nMaxColumn

oColumnDict(nColumnIndex) = nColumnIndex

Next

Next

For Each vKey In oColumnDictKeys

UpdateColumn CInt(vKey)

Next

End Sub

Private Sub UpdateColumn(nColumnIndex As Long)

Dim oFirstCell As Range, oLastCell As Range, oNextCell As Range, oCalculateBand As Range

Dim nBlankCellsCount As Long

Dim vCellColor As Variant

Set oFirstCell = Cells(1, nColumnIndex)

Set oLastCell = Cells(ActiveSheetUsedRangeRow + ActiveSheetUsedRangeRowsCount - 1, nColumnIndex)

' Firstly clear the interior color of the existing cells

With Range(oFirstCell, oLastCell)Interior

Pattern = xlNone

End With

Do While True

' Find the end cell of one single band (the next nonblank cell after the band start cell)

Set oNextCell = CellsFind(What:=nColumnIndex - 1, After:=Cells(oFirstCellRow, nColumnIndex), LookIn:=xlValues, LookAt:= _

xlWhole, SearchOrder:=xlByColumns, SearchDirection:=xlNext, MatchCase:=False, SearchFormat:=False)

If oNextCell Is Nothing Then

' Not found, move to the end cell

Set oNextCell = oLastCell

ElseIf (oNextCellColumn <> nColumnIndex) Or (oNextCellRow <= oFirstCellRow) Then

' Not found after the band end cell in this column, also move to the end cell

Set oNextCell = oLastCell

Else

' Found, move to the cell right above it

Set oNextCell = Cells(oNextCellRow - 1, nColumnIndex)

End If

' Check to see if the start cell in the band needs to be included

If oFirstCellText = "" Then

' First cell is empty, should be counted

Set oCalculateBand = Range(oFirstCell, oNextCell)

Else

' First cell is not empty, skip it

Set oCalculateBand = Range(Cells(oFirstCellRow + 1, nColumnIndex), oNextCell)

End If

' Calculate the band size

nBlankCellsCount = oCalculateBandRowsCount

With oCalculateBandInterior

If nBlankCellsCount < 40 Then

Pattern = xlNone

ElseIf (nBlankCellsCount >= 40) And (nBlankCellsCount < 50) Then

Color = vbYellow

Else

Color = vbRed

End If

End With

' Move to the next band in this column

Set oFirstCell = Cells(oNextCellRow + 1, nColumnIndex)

' Check to see if reached the last cell

If oFirstCellRow >= oLastCellRow Then Exit Do

Loop

End Sub

Private Function Min(x As Long, y As Long)

Min = (x + y - Abs(x - y)) / 2

End Function

3、键入Alt+Q返回Excel主窗口，保存；

4、现在可以在当前工作簿里面试验一下，比如在第一列随机间隔输入若干0，检查两个相邻的0之间空格数量分别为小于40、40-50、50以上三种情况时，空格染色是否正确。在第二列、第三列、第四列……分别测试输入数字1、2、3、……的情况。

请注意，因为启用了宏，所以需要在“工具 - 宏 - 安全性”里面选择“中”或者“低”，并且在下次打开这个文档时要确认启用宏。

请楼主看看是不是自己想要的效果，如果有问题可以补充提问或者和我联系。

以下是一个可能的例子代码，其中假设条件工序代码在第1列，类产品在第2列，供应商级别在第3列，PPV值在第4列，并且数据的起始行为第2行。您可以根据您的实际情况进行相应的调整和修改。

```VBA

Sub sort_suppliers()

Dim ws As Worksheet

Dim lRow As Long

Dim FoundCell As Range

Dim strSearch As String

Dim sortRange As Range

'设置需要操作的工作表

Set ws = ThisWorkbookSheets("Sheet1")

'获取最后一行

lRow = wsCells(RowsCount, 1)End(xlUp)Row

'设置查找参数，如果需要可以将其改动为输入框让用户输入。

Dim cond_GXDM As String

cond_GXDM = "111" '条件工序代码

Dim cond_CPMC As String

cond_CPMC = "产品AB" '类产品

Dim cond_GYSJB As String

cond_GYSJB = "级别A" '供应商级别

'在第一图查找符合条件的单元格，将查找范围限制在前三列中

Set FoundCell = wsRange("A2:A" & lRow)Find(what:=cond_GXDM)

If Not FoundCell Is Nothing Then

Set FoundCell = wsRange("B" & FoundCellRow & ":D" & lRow)Find(what:=cond_CPMC & "," & cond_GYSJB)

If Not FoundCell Is Nothing Then

'找到相应行之后，利用Offset函数获取该供应商的PPV值

Set sortRange = FoundCellOffset(0, 1)Resize(1, 1)

'向下查找并选取符合条件的单元格，将其合并为一区域

Do Until IsEmpty(FoundCell) Or FoundCellOffset(0, -1) <> cond_GXDM

If FoundCellOffset(0, 1) = cond_CPMC And FoundCellOffset(0, 2) = cond_GYSJB Then

Set sortRange = ApplicationUnion(sortRange, FoundCellOffset(0, 3)Resize(1, 1))

End If

Set FoundCell = wsRange("B" & FoundCellRow + 1 & ":D" & lRow)Find(what:=cond_CPMC & "," & cond_GYSJB)

Loop

'按照PPV值从小到大排序

sortRangeSort key1:=sortRange, order1:=xlAscending, Header:=xlNo

Else

MsgBox "无符合条件的供应商。"

End If

Else

MsgBox "无符合条件的记录。"

End If

End Sub

```

此代码仅供参考，具体操作需要根据您的实际需求进行调整和修改。

Cell 179 , October 31, 2019 a 2019 

Cellular Senescence: Defining a Path Forward

Definition and Characteristics of Cellular Senescence 

Cellular senescence is a cell state 

triggered by ：stressful insults and certain physiological processes,

characterized by ：aprolongedand generally irreversible cell-cycle arrest with secretory features, macromolecular damage , and altered metabolism 

These features can be inter-dependent 

Cell-Cycle Arrest 

mammalian cells 

retinoblastoma (RB) family and p53 proteins are important for establishing senescent cell-cycle arrest 

RB1 and its family members p107 (RBL1) and p130 (RBL2) are phosphorylated by specific cyclin-dependent kinases (CDKs; CDK4, CDK6, CDK2) 

This phosphorylation reduces the ability of the RB family members torepressE2F family transcription factor activity, which is required for cell-cycle progression 

CDK2 inhibitor p21WAF1/Cip1 ( CDKN1A ) and CDK4/6 inhibitor p16INK4A ( CDKN2A ) accumulate 

Secretion 

SASP的功能

the SASP reinforces and spreads senescence in autocrineandparacrinefashions 

activates immune responses that eliminate senescent cells 

SASP factors mediate developmental senescence 

tissue plasticity 

 contribute to persistent chronic inflammation (known as inflammaging) 

the SASP can recruit immature immune-suppressive myeloid cells to prostate and liver tumors （肝脏肿瘤！！！看一下Distinct Functions of Senescence-Associated Immune Responses in Liver Tumor Surveillance and Tumor Progression 

）

控制SASP的相关通路

enhancer remodeling 

activation of transcription factors, such as NF-kB, C/EBPb, GATA4 

mammalian target of rapamycin (mTOR)  

p38MAPK signaling pathways 

上游因子控制SASP的方式不同并且和老化诱导的途径有关

type 1 interferon response：DNA damage, cytoplasmic chromatin fragments (CCFs) 

inflammasome ：damage-associated molecular patterns (DAMPs) 

SASP的成分和强度不同决定于：duration of senescence, origin of the prosenescence stimulus, and cell type 

SASP可以和外界的微环境通过：juxtacrine NOTCH/JAG1 signaling；release of ROS；cytoplasmic bridges；extracellular vesicles （egexosomes）

）

Macromolecular Damage 

DNA Damage ：The first molecular feature associated with senescence wastelomere shortening, a result of the DNA end-replication problem , during serial passages 

端粒导致DDR的过程

Type1

Telomere shortening during proliferation 

telomeric DNA loop destabilization &telomere uncapping 

generating telomere dysfunction-induced foci (TIFs) 

ctivate the DDR 

cell-cycle arrest 

（This response can also be elicited by inhibiting or altering genes involved in telomere maintenance ）

Type2

oxidative DNA damage at telomeric G-reach repeats 

telomere-associated foci (TAFs), can exist at telomeres （irrespective of telomere length or shelterin loss ）

DNA损伤种类

half of the persistent DNA damage foci in senescent cells localize to telomeres

other stressful subcytotoxic insults can trigger senescence by inducing irreparable DNA damage 

genotoxic agents： radiation (ionizing and UV),

                                 pharmacological agents (eg, certain chemotherapeutics),

                                 oxidative stress 

activated oncogenes can induce senescence (known as OIS) as a tumor-suppressive response, restricting the uncontrolled proliferation of potentially oncogenic cells 

——OIS is often mediated by the tumor suppressors p16INK4 A and ARF , both encoded by theC DKN2A locus, imposing a cell-cycle arrest 

DDR也可以产生OIS的激活

oncogene-driven hyperproliferation→damage signal originates at collapsed replication forks 

DNA-SCARSs (DNA segments with chromatin alter- ations reinforcing senescence) ：Senescent cells harbor persistent nuclear DNA damage foci 

特点：associate with promyelocytic leukemian (PML) nuclear bodies （？？？）

           lack theDNA repair proteins RPA and RAD51 as well as single- stranded DNA ( ssDNA ) 

           contain activated forms of the DDR mediators CHK2 and p53  

DNA-SCARSs 可以调节细胞生长停滞和SASP，但是并不是一个老化细胞的特征

Protein Damage 

Proteotoxicity is a hallmark of aging and cellular senescence 

damaged proteins help identify senescent cells 

蛋白质损伤的途径

ROS 

↓

oxidize both methionine and cysteine residues 

↓

alter protein folding and function 

eg

（蛋氨酸和半胱氨酸，很多络氨酸磷酸酶都含有cys，因此他们所去磷酸化的部位就会被inactivate）PTPs：protein tyrosine phosphatases 

↓

hyperactivating ERK signaling （similar to the effect of activated oncogenes ）

↓

trigger senescence 

在肿瘤前期的病变处可以发现高磷酸化的ERK

Most protein oxidative damage：degradation by the ubiquitin proteasome system(UPS) orautophagy因此这两个特点可以作为检测老化情况的指标

promyelocytic leukemian (PML) 小体可以作为ROS和氧化损伤的sensor；同样也可以作为细胞老化的一个非特异性指标

Lipid Damage 

老化细胞的清除可以减少老年小鼠肝脏和大脑中脂肪的沉积

（特定的脂代谢和老化相关知之甚少）

虽然很多方法可以检测脂肪在组织和细胞之前的变化，但是作为老化的biomarker还是未知的，因为不同的老化相关的脂肪十分不同。

比如在原癌基因激活的老化和复制性老化中脂肪代谢非常不同

Deregulated Metabolic Profile 

Mitochondria 

Mitochondria in senescent cells are less functional, showingdecreased membrane potential,increased proton leak, reduced fusion and fission rates, increased mass, andabundance of tricarboxylic acid (TCA) cycle metabolites 

Altered AMP:ATP and ADP:ATP ratios during senescence 

↓

activating AMPK (AMP-activated protein kinase), a main sensor of energy deprivation 

↓

contribute to cell-cycle withdrawal 

线粒体的功能失调和SASP的调节也相关

Mitophagy (mitochondrial clearance) in senescent cells appears tosuppressthe SASP 

genetic or pharmacological inhibition of the ETC（electron transport chain ） can induce senescence even though cells lack expression of key pro-inflammatory SASP factors

 NAD+/NADH ratios are reduced n senescent cells →alter the activity of poly-ADP ribose polymerase (PARP) and sirtuins （乙酰化酶）——both involved in activation of the SASP regulatorNF-kB 

lysosomes

  溶酶体的代谢是有细胞的代谢或者降解需要决定的

当 AA 在溶酶体的腔内含量比较高的时候，mTOR1 is recruited and activated 

并且溶酶体可以和线粒相互关联

老化的细胞中溶酶体的数量和大小都有所增加，但是活性并没有增加

↓

lysosome-mitochondrial axis degrades 

↓

decreased mitochondrial 

↓

ncreases ROS production 

↓

ROS targets cellular structures, including lysosomes, which forms a vicious feedback loop that induces more damage

溶酶体的数量和SA-b-gal 的活性有关

从治疗角度来讲，溶酶体增大的三部分可以为捕捉药物增加空间，比如CDK4/6 in- hibitors palbociclib哌柏西利, ribociclib, and abemaciclib 

Senescence-Associated (Epi-)genetic and Gene Expression Changes

上述的表型变化大多是由于基因的表达所导致，这里我们解释下相关基因的情况

老化相关基因查询网址(http://Senequestnet) 

Chromatin Landscape 

表关遗传的变化大多和环境相关。replicative senescence has been correlated with global loss of DNA methylation at CpG sites ；Cells undergoing OIS fail to show such alterations in DNA methylation 

老化的细胞呈现普遍的increase in chromatin accessibility, but the genome-wide profile varies depending on the stimulus 

大多是组蛋白的变化individual histone modifications and variants

H4K16ac is often enriched at active pro- moters in senescent, but not proliferating, cells 

N terminus proteolytic cleavage of H33 correlates with gene repression in a different subset of genes during senescence 

Certain histone modifications are crucial for senescence, such as elevatedH4K20me3andH3K9me3,which contribute to the proliferation arrest ； elevatedH3K27acat gene enhancers promotes a SASP  

Senescence is also associated with chromatinmorphological changes 

Senescence-associated heterochromatin foci ( SAHF s ), visualized as DAPI-dense foci, are enriched in heterochromatin protein (HP) 1 

 SAHFs derive from chromatin factors—

 including RB,

  histone variant macroH2A, 

 high mobility group A proteins, 

 the HIRA/UBN1/CABIN1, a

 ASF1a chaperones—and increased nuclear pore density 

SAHF主要组成复制后基因的poor eterochromatic 部分，因此和细胞老化的相关性很小

细胞的老化同时也和大面积的H1丢失有关

enescence-associated distension of satellites ( SADSs ) ——先于SAHF，并且和细胞老化相关

Retrotransposable elements

repressed LINE-1 (L1) retrotransposons are activated, stimulating the cGAS-STING pathway that elicits a type 1 interferon response ，从而和SASP相关

Downregulation of lamin B1 （a major component of the nuclear lamina,）——也是老化细胞的一个主要特点

Lamin B1 和表观基因、enescence-associated chromatin structures (SAHFs and SADSs) 相关

主要发生在H3K9me3-rich regions：liberate H3K9me3 from the nuclear lamina promoting spatial rearrangement of H3K9me3 heterochromatin to form SAHFs 尤其是在OIS中发挥作用，然而复制性老化并没有什么相互作用

lamin B1 loss and reduced nuclear integrity 也可以促进SASP的形成

Transcriptional Signatures 

genes linked to thecell-cycle arrestand SASPare frequently interrogated in combination with other biomarkers to validate the senescence phenotype or type of senescence 

eg：CDKN1A ( p21WAF1/Cip1 ), CDKN2A ( p16INK4A ), and CDK2B (p15INK4B), and a subset of SASP genes, along with decreased expression of cyclins CCNA2 and CCNE2 and LMNB1 should be determined

为了更好研究转录情况——Whole-transcriptome studies，可以预测药物靶向；

但是现在的转录因子数据还是不足，因此相关转录因子的发现还是很重要的

 miRNAs and Non-coding RNAs （）

尤其是miRNA和细胞老化的关联更大；可以直接或者间接的调节老化关键因子，

「p53, p21WAF1/Cip1, and SIRT1 」

negative：miR-504 targets the p53 30UTR, reducing p53 abundance and activity 

                  Gld2-mediated stabilization of miR-122 enables its binding to the CBEP 30 UTR, resulting in decreased p53 mRNA polyadenylation and translation 

                  multiple miRNAs downregu- late p21WAF1/Cip1, including 28 miRNAs that block OIS 

                  miR-24 suppresses p16INK4a 

positive：miR-605 targets MDM2, triggering p53-mediated senescence 

miRNA feedback loops can modulate senescence programs 

——For example, a p53/ miRNA/CCNA2 pathway drives senescence independently of the p53/p21WAF1/Cip1 axis ；p53- dependent upregulation of miR-34a/b/c downregulates cell proliferation and survival factors 

「regulate the SASP 」

MiR-146a/b ：dampens a proinflammatory arm of the SAS 

miRNAs also downregulate repressors of senescence, including polycomb group (PcG) members CBX7, EED, EZH2, and SUZ12 (miR-26b, 181a, 210, and 424), leading to p16INK4a derepression and senescence initiation 

「the role of miRNAs in senes- cence extends beyond their classical functions」

Argonaute 2 ( AGO2 ) binds let-7f in the nucleus, forming a complex with RB1 (pRB ), resulting inrepressivechromatin at CDC2 and CDCA8 promoters Silencing these E2F target genes is required for senescence initiation 

Long non-coding RNAs (lncRNAs) (>200 nt) canbind RNA, DNA, or proteinsto regulate senescence 

ANRIL , a 30-40kb antisense transcript encoded by the CDKN2A locus, binds CBX7 torepress I NK4b/ARF/INK4a expression 

lncRNA PANDA recruits PcG com- plexes, suppressing senescence-promoting genes 

silencing of GUARDIN , a p53-responsive lncRNA, causes senescence or apoptosis 

following OIS induced by RAF, the l ncRNA VAD preserves senescence by decreasing repressive H2AZ deposition at INK promoters 

lncRNA UCA1 disrupts association of the RNA-binding protein hnRNP A1 with p16INK4A

Immune-Regulation and Anti-apoptotic Proteins 

虽然细胞老化的诱导环境可以激活一些炎症反应因子，尤其是一些细胞表面的marker，可以作为研究从单个细胞到组织的方式，但是DCR2 and NKG2D ligands are not conserved among species, making mouse-to-human comparisons not possible 

Notch1 in OIS and DPP4 in replicative and OIS：upregulated cell surface markers, 并且对于调节SASP有着一定的作用

increased expression of anti-apoptotic BCL-2 family members 也可以，因为老化的细胞是有凋亡抵抗的。

in Vivo Models to Study Cellular Senescence 

Senescence Reporter Mice

通过报告基因estimate p16Ink4a expression 

Murine Models of Accelerated Senescence and Aging 

（各种早衰小鼠模型的建立方法）

Identification of Cellular Senescence In Vivo

A Simplified Algorithm for Detecting Senescent Cells In Situ

实验室免疫染色/WB+用显微镜观察下

不同方法联合检测

Challenges to Detect Senescent Cells in Humans 

将细胞的老化和人类的疾病联系起来的

neurodegenerative disorders, glaucoma青光眼, cataract白内障， atherosclerosis and cardiovascular disease, diabetes, osteoarthritis, pulmonary, and renal and liver fibrosis 

组织的检测可以：fresh samplesby SA-b-gal staining 

 or indirect markers in formalin-fixed tissues 

histochemical dye SBB interacts with lipofuscin, another hallmark of senescent cells 

Lipofuscin is preserved in fixed material 

reagent (GL13) is amenable to immunohistochemistry （identified senescent Hodgkin and Reed-Sternberg (HRS) cells in Hodgkin lymphomas (cHL) where they predicted poor prognosis ）

Another method for identi- fying and quantifying senescent cells in vivo is SA-b-gal staining combined with ImageStream X analysis 

We recommendcombining cytoplasmic (eg, SA-b-gal, lipofuscin), nuclear (eg, p16INK4A, p21WAF1/Cip1, Ki67) and SASP, context and/or cell-type-specific markers 

老化相关仍然存在的问题

不可逆的细胞周期停滞并不一定存在所有的老化细胞中！

遗传学和表观遗传学在细胞老化中的关联？

在不同的老化诱导条件下细胞的修复方式又是什么？

抗衰老治疗的应用？

（我个人觉得mirNA&Non-coding RNAs是不是也挺热门的）

FunctionSumcolor(colAsRange,sumrangeAsRange)

DimicellAsRange

ApplicationVolatile

ForEachicellInsumrange

IficellInteriorColorIndex=colInteriorColorIndexThen

Sumcolor=ApplicationSum(icell)Sumcolor

EndIf

Nexticell

EndFunction