Two years of Covid-19: Excess mortality by age, region, gender, and race/ethnicity in the United States during the Covid-19 pandemic, March 1, 2020, through February 28, 2022

IntroductionExcess mortality does not depend on labeling the cause of death and is an accurate representation of the pandemic population-level effects. A comprehensive evaluation of all-cause excess mortality in the United States during the first two years of the COVID-19 pandemic, stratified by age, sex, region, and race/ethnicity can provide insight into the extent and variation in harm. MethodsWith Centers for Disease Control and Prevention (CDC)/National Center for Health Statistics (NCHS) data from 2014-2022, we use seasonal autoregressive integrated moving averages (sARIMA) to estimate excess mortality during the pandemic, defined as the difference between the number of observed and expected deaths. We continuously correct monthly expected deaths to reflect the decreased population owing to cumulative pandemic-associated excess deaths recorded. We calculate excess mortality for the total US population, and by age, sex, US census division, and race/ethnicity. ResultsFrom March 1, 2020, through February 28, 2022, there were 1.17 million excess deaths in the United States. Overall, mortality was 20% higher than expected during the study period. Of the excess deaths, 799,477 (68%) were among residents aged 65 and older. The largest relative increase in all-cause mortality was 27% among adults ages 18-49 years. Males comprised most of the excess mortality (57%), but this predominance declined with age. A higher relative mortality occurred among non-Hispanic American Indian/Alaskan Native, non-Hispanic Black, non-Hispanic Native Hawaiian and Other Pacific Islander, Hispanic people. Excess mortality differed by region; the highest rates were in the South, including in the population ages [≥]65 years. Excess mortality rose and fell contemporaneously with COVID-19 waves. ConclusionIn the first two years of the pandemic, the US experienced 1.17 million excess deaths, with greater relative increases in all-cause mortality among men, in American Indian/Alaskan Native, Black and Hispanic people, and the South.

The uncoupling of all-cause excess mortality from Covid-19 cases and associated hospitalizations in late winter and spring of 2022 in a highly vaccinated state.

IntroductionSince March 2020, all-cause excess mortality--the number of all-cause deaths exceeding the baseline number of expected deaths--has been observed in waves coinciding with Covid-19 outbreaks in the United States. We recently described high levels of excess mortality in Massachusetts during the initial 8-week Omicron wave. However, whether excess mortality continued after that period--during which an outbreak of Omicron subvariants occurred--is unknown. MethodsWe applied seasonal autoregressive integrated moving averages to five years of pre-pandemic data provided by the Massachusetts Registry of Vital Records and Statistics (MRVRS) to project the weekly populations and expected deaths for the pandemic period. Observed deaths during the pandemic were also provided by MRVRS and are >99% complete for all study weeks. ResultsDuring the 18-week Omicron subvariant period (the week ending February 27, 2022, through June 26, 2022) the incidence of all-cause excess mortality was 0.1 per 100,000-person weeks, corresponding to 148 excess deaths (95%. CI -907 to 1153), representing a 97.1% decrease from the initial Omicron period (during which all-cause excess mortality was 4.0 per 100,000-person-weeks), and a 91.9% reduction from the Delta and Delta-Omicron transition period (during which all-cause excess mortality was 1.5 per 100,000-person-weeks), despite >226,000 reported new Covid-19 cases during the subvariant/spring period. However, Covid-19-associated hospitalizations were observed during the subvariant/spring 2022 period. ConclusionIn a highly vaccinated state with a recent wave of SARS-CoV-2, all-cause excess mortality was uncoupled from new case counts, indicating the possibility of temporary protection from the most severe outcomes related to Covid-19 among high-risk individuals. However, given the possibility of waning immunity and the emerging of new variants, continued monitoring is warranted.

Absence of Excess Mortality in a Highly Vaccinated Population During the Initial Covid-19 Delta Period.

BackgroundAll-cause excess mortality (the number of deaths that exceed projections in any period) has been widely reported during the Covid-19 pandemic. Whether excess mortality has occurred during the Delta wave is less well understood. MethodsWe performed an observational study using data from the Massachusetts Department of Health. Five years of US Census population data and CDC mortality statistics were applied to a seasonal autoregressive integrated moving average (sARIMA) model to project the number of expected deaths for each week of the pandemic period, including the Delta period (starting in June 2021, extending through August 28th 2021, for which mortality data are >99% complete). Weekly Covid-19 cases, Covid-19-attributed deaths, and all-cause deaths are reported. County-level excess mortality during the vaccine campaign are also reported, with weekly rates of vaccination in each county that reported 100 or more all-cause deaths during any week included in the study period. ResultsAll-cause mortality was not observed after March 2021, by which time over 75% of persons over 65 years of age in Massachusetts had received a vaccination. Fewer deaths than expected (which we term deficit mortality) occurred both during the summer of 2020, the spring of 2021 and during the Delta wave (beginning June 13, 2021 when Delta isolates represented >10% of sequenced cases). After the initial wave in the spring of 2020, more Covid-19-attributed deaths were recorded that all-cause excess deaths, implying that Covid-19 was misattributed as the underlying cause, rather than a contributing cause of death in some cases. ConclusionIn a state with high vaccination rates, excess mortality has not been recorded during the Delta period. Deficit mortality has been recorded during this period.

Emergency Department Utilization for Emergency Conditions During COVID-19.

STUDY OBJECTIVE: We use a national emergency medicine clinical quality registry to describe recent trends in emergency department (ED) visitation overall and for select emergency conditions. METHODS: Data were drawn from the Clinical Emergency Department Registry, including 164 ED sites across 35 states participating in the registry with complete data from January 2019 through November 15, 2020. Overall ED visit counts, as well as specific emergency medical conditions identified by International Classification of Diseases, Tenth Revision, Clinical Modification code (myocardial infarction, cerebrovascular accident, cardiac arrest/ventricular fibrillation, and venous thromboembolisms), were tabulated. We plotted biweekly visit counts overall and across specific geographic regions. RESULTS: The largest declines in visit counts occurred early in the pandemic, with a nadir in April 46% lower than the 2019 monthly average. By November, overall ED visit counts had increased, but were 23% lower than prepandemic levels. The proportion of all ED visits that were for the select emergency conditions increased early in the pandemic; however, total visit counts for acute myocardial infarction and cerebrovascular disease have remained lower in 2020 compared with 2019. Despite considerable geographic and temporal variation in the trajectory of the coronavirus disease 2019 outbreak, the overall pattern of ED visits observed was similar across regions and time. CONCLUSION: The persistent decline in ED visits for these time-sensitive emergency conditions raises the concern that coronavirus disease 2019 may continue to impede patients from seeking essential care. Efforts thus far to encourage individuals with concerning signs and symptoms to seek emergency care may not have been sufficient.

Mortality from injury, overdose and suicide during the 2020 COVID-19 pandemic, March-July, 2020

Introduction The COVID-19 pandemic has been associated with substantial rates of all-cause excess mortality. The contribution of external causes of death to excess mortality including drug overdose, homicide, suicide, and unintentional injuries during the initial outbreak in the United States is less well documented. MethodsUsing public data published by the National Center for Health Statistics on February 10, 2021, we measured monthly excess mortality (the gap between observed and expected deaths) from five external causes using national-level data published by National Center for Health Statistics; assault (homicide); intentional self-harm (suicide); accidents (unintentional injuries); and motor vehicle accidents. We used seasonal autoregressive integrated moving average (sARIMA) models developed with cause-specific monthly mortality counts and US population data from 2015-2019 and estimated the contribution of individual cause-specific mortality to all-cause excess mortality from March-July 2020. ResultsFrom March-July, 2020, 212,825 (95% CI 136,236-290,776) all-cause excess deaths occurred in the US). There were 8,540 excess drug overdoses (all intents) (95% CI 5,106 to 11,975), accounting for 4% of all excess mortality; 1,455 excess homicide deaths (95% CI 708 to 2202, accounting for 0.7% of excess mortality; 5,492 excess deaths due to unintentional accidents occurred (95% CI 85 to 10,899, accounting for 2.6% of excess mortality. Though a non-significantly 135 (95% CI -1361 to 1,630) more MVA deaths were recorded during the study period, a significant decrease in April (525; 95% CI -817 to -233) and significant increases in June-July (965; 95% CI 348 to 1,587) were observed. Suicide deaths were statistically lower than projected by 2,067 (95% CI 941-3,193 fewer deaths). MeaningExcess deaths from drug overdoses, homicide, and addicents occurred during the pandemic but represented a small fraction of all-cause excess mortality. The excess external causes of death, however, still represent thousands of lives lost. Notably, deaths from suicide were lower than expected and therefore did not contribute to excess mortality.

Application of Automatic Nucleic Acid Extractor Combined with Vacuum Concentrator in Forensic Science / 法医学杂志

Objective To explore the application value of automatic nucleic acid extractor combined with vacuum concentrator in forensic DNA extraction. Methods Gradient samples of human peripheral venous blood were collected at 40, 80, 120, 160, 200, 240, 280 and 320 fold dilution. The samples of each gradient were treated with no inhibitor, black oil, rust, fruit acid, tin foil and indigo, respectively. The automatic nucleic acid extractor was used for DNA purification and extraction of the above samples. The extracted DNA eluent （6 μL） was taken for amplification directly, and the rest was concentrated by vacuum concentrator. DNA was amplified and examined using the Investigator 26plex QS kit before and after concentration. Results Only gradient samples treated with fruit acid obtained complete STR typing results at 40 fold dilution. The other 5 methods obtained complete STR typing results at 40-160 fold dilution. The results of STR typing after DNA concentration showed that the average peak height and detection rates of gene loci both increased to a certain extent, but the effect was not obvious. Conclusion The automatic nucleic acid extractor has an efficient inhibitor removal ability and high extracting efficiency of DNA. The vacuum concentrator can concentrate DNA samples to a certain extent. Combining the automatic nucleic acid extractor with the vacuum concentrator can improve the examination success rate of forensic materials.

SARS-CoV-2 Infection Hospitalization Rate and Infection Fatality Rate among the Non-Congregant Population in Connecticut

ImportanceCOVID-19 case fatality and hospitalization rates, calculated using the number of confirmed cases of COVID-19, have been described widely in the literature. However, the number of infections confirmed by testing underestimates the total infections as it is biased based on the availability of testing and because asymptomatic individuals may remain untested. The infection fatality rate (IFR) and infection hospitalization rate (IHR), calculated using the estimated total infections based on a representative sample of a population, is a better metric to assess the actual toll of the disease. ObjectiveTo determine the IHR and IFR for COVID-19 using the statewide SARS-CoV-2 seroprevalence estimates for the non-congregate population in Connecticut. DesignCross-sectional. SettingAdults residing in a non-congregate setting in Connecticut between March 1 and June 1, 2020. ParticipantsIndividuals aged 18 years or above. ExposureEstimated number of adults with SARS-CoV-2 antibodies. Main Outcome and MeasuresCOVID-19-related hospitalizations and deaths among adults residing in a non-congregate setting in Connecticut between March 1 and June 1, 2020. ResultsOf the 2.8 million individuals residing in the non-congregate settings in Connecticut through June 2020, 113,515 (90% CI 56,758-170,273) individuals had SARS-CoV-2 antibodies. There were a total of 9425 COVID-19-related hospitalizations and 4071 COVID-19-related deaths in Connecticut between March 1 and June 1, 2020, of which 7792 hospitalizations and 1079 deaths occurred among the non-congregate population. The overall COVID-19 IHR and IFR was 6.86% (90% CI, 4.58%-13.72%) and 0.95% (90% CI, 0.63%-1.90%) among the non-congregate population. Older individuals, men, non-Hispanic Black individuals and those belonging to New Haven and Litchfield counties had a higher burden of hospitalization and deaths, compared with younger individuals, women, non-Hispanic White or Hispanic individuals, and those belonging to New London county, respectively. Conclusion and RelevanceUsing representative seroprevalence estimates, the overall COVID-19 IHR and IFR were estimated to be 6.86% and 0.95% among the non-congregate population in Connecticut. Accurate estimation of IHR and IFR among community residents is important to guide public health strategies during an infectious disease outbreak.

Suicide Deaths during the Stay-at-Home Advisory in Massachusetts.

Many believe that shelter-in-place or stay-at-home policies might cause an increase in so-called deaths of despair. While increases in psychiatric stressors during the COVID-19 pandemic are anticipated, whether suicide rates changed during stay-at-home periods has not been described. This was an observational cohort study that assembled suicide death data for persons aged 10 years or older from the Massachusetts Department of Health Registry of Vital Records and Statistics from January 2015 through May 2020. Using autoregressive integrated moving average (ARIMA) and seasonal ARIMA to analyze suicide deaths in Massachusetts, we compared the observed number of suicide deaths in Massachusetts during the stay-at-home period (March through May, 2020) in Massachusetts to the projected number of expected deaths. To be conservative, we also accounted for the deaths still pending final cause determination The incident rate for suicide deaths in Massachusetts was 0.67 per 100,000 person-month (95% CI 0.56-0.79) versus 0.81 per 100,000 person-month (95% CI 0.69-0.94) during the 2019 corresponding period (incident rate ratio of 0.83; 95% CI 0.66-1.03). The addition of the 57 deaths pending cause determination occurring from March through May 2020 and the 33 cases still pending determination from the 2019 corresponding period did not change these findings. The observed number of suicide deaths during the stay-at-home period did not deviate from ARIMA projected expectations using either preliminary data or an alternate scenario in which deaths pending investigation (exceeding the average remaining number of deaths still pending investigation which occurred during the corresponding 2015-2019 period) were ascribed to suicide. Decedent age and sex demographics were unchanged during the pandemic period compared to 2015-2019. The stable rates of suicide deaths during the stay-at-home advisory in Massachusetts parallel findings following ecological disasters. As the pandemic persists, uncertainty about its scope and economic impact may increase. However, our data are reassuring that an increase in suicide deaths in Massachusetts during the stay-at-home advisory period did not occur.

Seroprevalence of SARS-CoV-2-Specific IgG Antibodies Among Adults Living in Connecticut Between March 1 and June 1, 2020: Post-Infection Prevalence (PIP) Study

BackgroundA seroprevalence study can estimate the percentage of people with SARS-CoV-2 antibodies in the general population, however, most existing reports have used a convenience sample, which may bias their estimates. MethodsWe sought a representative sample of Connecticut residents, aged [≥]18 years and residing in non-congregate settings, who completed a survey between June 4 and June 23, 2020 and underwent serology testing for SARS-CoV-2-specific IgG antibodies between June 10 and July 29, 2020. We also oversampled non-Hispanic Black and Hispanic subpopulations. We estimated the seroprevalence of SARS-CoV-2-specific IgG antibodies and the prevalence of symptomatic illness and self-reported adherence to risk mitigation behaviors among this population. ResultsOf the 567 respondents (mean age 50 [{+/-}17] years; 53% women; 75% non-Hispanic White individuals) included at the state-level, 23 respondents tested positive for SARS-CoV-2-specific antibodies, resulting in weighted seroprevalence of 4.0 (90% confidence interval [CI] 2.0-6.0). The weighted seroprevalence for the oversampled non-Hispanic Black and Hispanic populations was 6.4% (90% CI 0.9-11.9) and 19.9% (90% CI 13.2-26.6), respectively. The majority of respondents at the state-level reported following risk mitigation behaviors: 73% avoided public places, 75% avoided gatherings of families or friends, and 97% wore a facemask, at least part of the time. ConclusionsThese estimates indicate that the vast majority of people in Connecticut lack antibodies against SARS-CoV-2 and there is variation by race/ethnicity. There is a need for continued adherence to risk mitigation behaviors among Connecticut residents to prevent resurgence of COVID-19 in this region.

Effect of Shaoyaotang on Expressions of TLR4, NF-κB p65 and IL-6 in Rats with Damp-heat Ulcerative Colitis / 中国实验方剂学杂志

Objective:To explore the mechanism of Shaoyaotang in the treatment of ulcerative colitis (UC) based on toll-like receptor 4 (TLR4)/nuclear factor kappaB (NF-κB) signaling pathway. Method:A total of 50 Wistar rats were selected, including half male and half female. The damp-heat UC rat model was replicated by the methods of the combination of diseases and syndromes and the combination of 2, 4, 6-nitrobenzene sulfonic acid (TNBS) and ethanol. After the successful modeling, the model rats were randomly divided into model group, salazulesulfonate group, and low, medium and high-dose Shaoyaotang groups, and 10 rats (half male and half female) were selected as the blank control group. Low, medium and high-dose Shaoyaotang groups were given 6, 12, 24 g·kg-1 by gavage, and salazonyl arsenic group was given 1 g·kg-1 by gavage. Blank control group was given the equal volume of normal saline for 21 consecutive days. Colon samples were collected after the last administration, and the expressions of TLR4, NF-κB p65 and IL-6 mRNA in colon tissues were detected by fluorescent quantitative polymerase chain reaction (Real-time PCR）, and the expressions of TLR4, NF-κB p65 and IL-6 protein in colon tissues were detected by Western blot. Result:Compared with the blank control group, the relative expressions of TLR4, NF-κB p65, IL-6 mRNA and protein in the model group were significantly increased (P<0.05). Compared with the model group, the expression levels of TLR4, NF-κB p65 and IL-6 mRNA and protein in the salazopyridine group and Shaoyaotang groups were significantly decreased (P<0.05). Conclusion:Shaoyaotang can inhibit the development of UC by regulating the expressions of TLR4, NF-κB p65 and IL-6 mRNA and proteins in the TLR4/NF-κB pathway.

Quantitative analysis of residual ethanol content in corneal epithelium flaps in LASEK / 眼科新进展

Objective To detect and analyze of residual ethanol in abandoned flaps after laser subepithelial keratomileusis (LASEK) with ethanol infiltration methods.Methods Together 20 patients (40 eyes) undergoing LASEK were recruited in the study.After infiltrated with 20％ ethanol and rinsed in equilibration solution,the corneal epithelial free flap was isolated and removed in time for sealing,and then procedures were continuously completed.Finally,observation of the skin flap production,postoperative irritation symptoms,epithelial healing,visual recovery and postoperative haze situation was performed,and then the amount of ethanol in the epithelial flap was measured.Results There was no failure in making the intact corneal flaps.The sensory score of postoperative irritation was 2.52 ± 1.46.Neonatal epithelial with 1 grade was observed in 32 eyes,2 grade in 8 eyes 5 days after surgery,while corneal haze with 0.5 grade was occurred in 3 eyes,1 grade in 2 eyes 12 weeks after surgery.There were ethanol residues in corneal epithelium in the abandoned flaps,with the amount of ethanol residues of (0.205 2 ± 0.041 0) μL in each flap.Conclusion It is found that a certain amount of ethanol residue in the corneal epithelium after LASEK with ethanol infiltration equilibration solution rinse,which may be one reason of the corneal irritation symptoms and corneal haze.

China Patient-centered Evaluative Assessment of Cardiac Events Prospective Study of Acute Myocardial Infarction: Study Design / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Despite the rapid growth in the incidence of acute myocardial infarction (AMI) in China, there is limited information about patients' experiences after AMI hospitalization, especially on long-term adverse events and patient-reported outcomes (PROs).</p><p><b>METHODS</b>The China Patient-centered Evaluative Assessment of Cardiac Events (PEACE)-Prospective AMI Study will enroll 4000 consecutive AMI patients from 53 diverse hospitals across China and follow them longitudinally for 12 months to document their treatment, recovery, and outcomes. Details of patients' medical history, treatment, and in-hospital outcomes are abstracted from medical charts. Comprehensive baseline interviews are being conducted to characterize patient demographics, risk factors, presentation, and healthcare utilization. As part of these interviews, validated instruments are administered to measure PROs, including quality of life, symptoms, mood, cognition, and sexual activity. Follow-up interviews, measuring PROs, medication adherence, risk factor control, and collecting hospitalization events are conducted at 1, 6, and 12 months after discharge. Supporting documents for potential outcomes are collected for adjudication by clinicians at the National Coordinating Center. Blood and urine samples are also obtained at baseline, 1- and 12-month follow-up. In addition, we are conducting a survey of participating hospitals to characterize their organizational characteristics.</p><p><b>CONCLUSION</b>The China PEACE-Prospective AMI study will be uniquely positioned to generate new information regarding patient's experiences and outcomes after AMI in China and serve as a foundation for quality improvement activities.</p>

Glassy cell carcinoma of cervix: a clinicopathologic analysis of 5 cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathological characteristics, histological diagnosis, immunohistochemistry and prognosis of cervical glassy cell carcinoma (GCC).</p><p><b>METHODS</b>The clinical characteristics, cytology, histology and immunohistochemistry were analyzed in 5 cases of GCC.</p><p><b>RESULTS</b>The average age of the five patients was 34.4 years (31 - 41 years). Abnormal vaginal bleeding and/or watery discharge were clinical presentations. One case was complicated with pregnancy and another one had a seven-year history of using contraceptives. All patients had an obvious mass in the cervix. Characteristic morphological features of GCC were present in 2 cases. Morphologically, the tumors consisted of clusters of tumor cells with distinct cell bounders, a large amount of eosinophilic granules in the cytoplasm imparting ground glass appearance, and thin nuclear membrane and prominent nucleoli. Nuclear enlargement and multinucleation were frequently noted. Mitosis and apoptosis were common. Numerous eosinophils and plasma cells were present in the stroma. Immunohistochemically, GCC expressed markers for both squamous cell carcinoma (p63 and CK34βE12) and adenocarcinoma (CAM5.2, MUC1, MUC2 and CEA). Ki-67 proliferation index was high (≥ 70%). All the five patients were treated with radical hysterectomy, followed by radiation and chemotherapy. The tumor-free survival time ranged from 25 days to 33 months.</p><p><b>CONCLUSIONS</b>GCC is a distinct variant of adenosquamous carcinoma of the cervix with high proliferation index and expression of markers of both squamous cell carcinoma and adenocarcinoma. The tumor has characteristic cytological and histological features.</p>

Expression of survivin, caspase-3 in oral precancerous lesions and oral squamous-cell carcinoma / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the roles of surviving and caspase-3 in the development of oral cancer.</p><p><b>METHODS</b>Archival tissue sections of 17 oral squamous cell carcinoma (OSCC), 28 oral leukoplakia with dysplasia, 10 normal oral mucosa were obtained from Capital Medical University School of Stomatology for immunohistochemical staining of markers of survivin and caspase-3. The cell apoptosis was detected with terminal deoxynucleotidyl transferase-mediated nucleotide shift enzyme (TdT) mediated d-UTP end labeling (TUNEL). Positively stained cells were counted and analyzed statistically to determine potential relationship between survivin, caspase-3 and cell apoptosis.</p><p><b>RESULTS</b>The expression of survivin was faint or negative in normal epithelial cells. The average positive rate of survivin was (1.05 ± 1.21)% in control group and (21.89 ± 10.45)% in OSCC. Caspase-3 was expressed in all the normal mucosa,but it obviously down-regulated in dysplasia and OSCC. The apoptosis index (AI) decreased from (0.89 ± 0.46)% in normal mucosa to (0.21 ± 0.12)% in OSCC.</p><p><b>CONCLUSIONS</b>Both survivin and caspase-3 are associated with carcinogenesis of the oral mucosa. Survivin may restrain cell apoptosis by inhibiting caspase-3.</p>

Prediction of mycophenolic acid exposure in renal transplantation recipients by artificial neural network / 药学学报

The paper is aimed to establish an artificial neural network (ANN) for predicting mycophenolic acid (MPA) area under the plasma concentration-time curve (AUC) in renal transplantation recipients. 64 Chinese renal transplantation recipients receiving mycophenolate mofetil (MMF) were investigated. 10 timed samples were drawn at different days after transplantation. Plasma MPA concentration was determined by HPLC method and area under curve over the period of 0 to 12 h (AUC(0-12 h)) was calculated using the linear trapezoidal rule. ANN was established after network parameters were optimized using momentum method in combination with genetic algorithm. Furthermore, the predictive performance of ANN was compared with that of multiple linear regression (MLR). When using plasma MPA concentration of 0, 0.5, 2 h after MMF administration to predict MPA AUC(0-12 h), mean prediction error and mean absolute prediction error were -1.53% and 9.12%, respectively. Accuracy and precision of prediction by ANN were superior to that of MLR prediction, and similar results could be found when using plasma MPA concentration of 0, 0.5 h to predict MPA AUC(0-12h). The accuracy and precision of ANN prediction were superior to that of MLR prediction, and ANN can be used to predict MPA AUC(0-12 h).

Amifostine used in the treatment of patients with myelodysplastic syndrome / 中国实验血液学杂志

The study was aimed to investigate the curative effects and adverse effects of amifostine in the treatment of patients with myelodysplastic syndrome (MDS). Amifostine (AMF) was used alone (4/12) or combined with recombinant human erythropoietin (rh-EPO) (8/12) in 12 MDS patients. The therapeutic regimen was adopted with AMF 0.4 g/day for 5 days, then took a break of 2 days and then went on for 3 weeks consecutively, that was reputed as one treatment cycle. rh-EPO 6 000 U was used for 3 days per week. The results showed that 12 patients all attained hematological improvement in peripheral blood. 11 cases showed major effective response rate (91.7%), while 1 case showed minor response rate (8.3%). The effective response rate of hemoglobin, leukocytes and platelets was 100%, 75% and 58.3% respectively. The intervals of red cell transfusions (RCT) in 2 cases living on red cell transfusion before AMF treatment were prolonged after AMF treatments, and the amount of each RCT was decreased obviously. The side effect was usually discomfort of digestive system, but all patients can endure. In conclusion, Amifostine is a potential drug in the treatment of MDS patients with safety especially to those elder patients who often suffered from other multiple organ disfunctions, and the curative effect will be improved by more treatment cycles.

Immunohistochemical study of benign lymphoadenosis of oral mucosa / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To study the expression of Ki-67 and the changes of MVD and apoptosis in benign lymphoadenosis of oral mucosa (BLOM).</p><p><b>METHODS</b>The expression of Ki-67, CD34 and apoptosis were evaluated by SP immunohistochemical staining in 15 BLOM, 9 BLOM with dysplasia, 15 oral squamous cell carcinoma (OSCC).</p><p><b>RESULTS</b>The expression of Ki-67 in BOLM with dysplasia and OSCC was significantly higher than that of BLOM without dysplasia and normal oral mucosa (P < 0.05). The MVD in all BLOM and OSCC was significantly higher than that in normal mucosa (P < 0.05). Apoptosis in BLOM was higher than in normal mucosa and OSCC (P < 0.05).</p><p><b>CONCLUSIONS</b>The expression of Ki-67 and MVD in BLOM with dysplasia were between normal oral mucosa and oral carcinoma. The occurrence of apoptosis in BLOM was significantly higher than in normal oral mucosa. The results suggest that BLOM had the potentiality of malignant transformation.</p>

Correlation between neuronal injury and Caspase-3 after focal ischemia in human hippocampus / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Cerebral ischemia is a significant clinical problem, and cerebral ischemia usually causes neuron injury such as apoptosis in various brain areas, including hippocampus. Cysteinyl aspartate-specific protease (Caspases) are fundamental factors of apoptotic mechanism. Caspase-3 inhibitors show effect in attenuating brain injury after ischemia. But all the results were from animal models in research laboratories. This study aimed at investigating the correlation between the change of ischemic neuronal injury and Caspase-3 post-ischemia in human hippocampus.</p><p><b>METHODS</b>We selected and systematized 48 post-mortem specimens from 48 patients, who died of cerebral infarction. Morphological change was firstly analyzed by observing hematoxyline/eosin-staining hippocampal sections. The expression of Caspase-3 was investigated using the methods of in situ hybridization and immunohistochemistry. Terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick-end labeling (TUNEL) method was used to clarify the involvement of Caspase-3 in neuron death. The loss of MAP 2 (MAP-2) was applied to judging the damaged area and degree of neuronal injury caused by ischemia.</p><p><b>RESULTS</b>In the CA1 sector of hippocampus, Caspase-3 immunostaining modestly increased at 8 hours [8.05/high-power field (hpf)], dramatically increased at 24 hours (24.85/hpf), decreased somewhat after 72 hours. Caspase-3 mRNA was detectable at 4 hours (6.75/hpf), reached a maximum at 16 hours (17.60/hpf), faded at 72 hours. TUNEL-positive cells were detectable at 24 hours (10.76/hpf), markedly increased at 48 - 72 hours. The loss of MAP-2 was obviously detected at 4 hours, progressed significantly between 24 and 72 hours; MAP-2 immunoreactivity was barely detectable at 72 hours. Before 72 hours, the Caspase-3 evolution was related with the upregulation of TUNEL and the loss of MAP-2. The positive correlation between Caspase-3 mRNA and TUNEL was significant at the 0.05 level (correlation coefficient was 0.721); the negative correlation between Caspase-3 mRNA and MAP-2 was significant at the 0.05 level (correlation coefficient is 0.857). In the early stage (before 72 hours), the staining of Caspase-3 mRNA and immunohistochemistry was predominantly present in cytoplasm; the staining of TUNEL was predominantly localized in nucleus. At 4 - 16 hours, most neurons in hippocampal CA1 areas had relatively normal morphology; at 24 - 48 hours, neurons showed apoptotic morphology; at 72 hours, most cells showed significantly pathological morphology.</p><p><b>CONCLUSIONS</b>There exist a time-dependent evolution of neuronal damage after hippocampal ischemia in human brain, which was characterized by its close correspondence to Caspase-3.</p>