[Progress in the diagnose and treatment of pulmonary arterial thrombosis in situ].

In situ pulmonary arterial thrombosis (ISPAT) refers to the formation of new blood clots in the pulmonary arterial system in the absence of pre-existing clots in the peripheral venous system. With the emergence and prevalence of COVID-19, ISPAT has become an increasingly important cause of pulmonary arterial thrombosis (PAT) alongside thromboembolism. Several factors such as hypoxia, inflammation, endothelial dysfunction, and hypercoagulable state can lead to ISPAT, which is associated with a number of conditions such as thoracic trauma, partial lung resection, pulmonary infectious disease, pulmonary vasculitis, connective tissue diseases, severe pulmonary hypertension, radiation pneumonitis, and acute chest syndrome in sickle cell disease. It is important to differentiate between pulmonary thromboembolism (PTE) and ISPAT for proper disease management and prognosis. In this review, we summarized the characteristics of ISPAT under different disease conditions, the methods to distinguish ISPAT from PTE, and the best treatment strategies. We hoped that this review could improve clinicians' understanding of this independent disease and provide guidance for the refined treatment of patients with PAT.

[A prospective cohort study of long-term fasting blood glucose variability and risk of mortality in patients with type 2 diabetes].

Objective: To investigate the association between long-term fasting blood glucose (FPG) variability and all-cause mortality in patients with type 2 diabetes. Methods: A total of 7 174 type 2 diabetic patients included in National Basic Public Health Service Program in Changshu of Jiangsu Province were recruited as participants. Long-term glucose variability was assessed using standard deviation (SD), coefficient of variation (CV), average real variability (ARV), and variability independent of the mean (VIM) across FPG measurements at the more than three visits. Death information were mainly obtained from the death registry system in Jiangsu. Then Cox proportional hazards regression models were used to estimate the associations of four variability indicators and all-cause mortality's hazard ratios (HRs) and their 95%CIs. Results: Among 55 058.50 person-years of the follow-up, the mean follow-up time was 7.67 years, and 898 deaths occurred during the follow-up period. After adjustment, compared with T1 group, the Cox regression model showed that HRs of T3 group in SD, CV, ARV and VIM were 1.24 (95%CI: 1.03-1.49), 1.20 (95%CI: 1.01-1.43), 1.28 (95%CI: 1.07-1.55) and 1.20 (95%CI:1.01-1.41), respectively. HRs of per 1 SD higher SD, CV, ARV and VIM were 1.13 (95%CI: 1.06-1.21), 1.08 (95%CI: 1.01-1.15), 1.05 (95%CI: 1.00-1.12) and 1.09 (95%CI: 1.02-1.16) for all-cause mortality, respectively. In the stratified analysis, age, gender, hypoglycemic agent and insulin uses had no effect on the above associations (all P for interaction >0.05). Conclusion: Long-term FPG glycemic variability was positively associated with the risk of all-cause mortality in type 2 diabetes patients.

[The distribution of blood pressure and associated factors of the elderly with type 2 diabetes in Jiangsu Province].

Objective: To investigate the distribution of blood pressure and analyze the associated factors of blood pressure of the elderly with type 2 diabetes in Jiangsu Province. Methods: The elderly over 60 years old participants with type 2 diabetes in the communities of Huai'an City and Changshu City, Jiangsu Province were selected in this study. They were divided into two groups: taking antihypertensive drugs and not taking antihypertensive drugs. The demographic characteristics, such as age and sex, and relevant factors were collected by questionnaire. The systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured by physical examination. The percentile of SBP and DBP in each age group of men and women were described. The kernel density estimation curve was used to show the blood pressure distribution. The trend of blood pressure with age was fitted by locally weighted regression. The logistic regression model was used to analyze relevant factors of blood pressure. Results: A total of 12 949 participants were included in this study, including 7 775 patients in the antihypertensive drug group and 5 174 patients in the group without antihypertensive drugs. The SBP of participants was concentrated at 140-160 mmHg, and their DBP was concentrated at 75-85 mmHg. There were significant differences in the distribution of blood pressure among the subgroups of body mass index (BMI) and rural areas whether taking antihypertensive drugs and not. For participants aged under 80 years old, the SBP showed an increasing trend with age and the DBP showed a decreasing trend with age. Age, BMI ≥24 kg/m2, fasting blood glucose ≥7.0 mmol/L, living in rural areas and no smoking were influencing factors of the elevated SBP; BMI ≥24 kg/m2, male, living in rural areas, no smoking, drinking alcohol and not receiving drug hypoglycemic treatment were influencing factors of the elevated DBP. Conclusion: The SBP of older diabetic adults in Jiangsu Province is at a high level, and the distribution of blood pressure is significantly different between men and women in taking antihypertensive drugs group. The SBP presents a rising trend and the DBP is decreasing at the age of 60-80 years. The blood pressure level of this population are mainly affected by age, BMI, urban and rural areas, smoking.

[Progress in clinical diagnosis and treatment of multiple primary lung cancer].

With the application of high-resolution chest imaging system and lung cancer screening program, patients with multiple primary lung cancer (MPLC) are becoming a growing population in clinical practice. However, the diagnostic criteria of MPLC and its differentiation from intrapulmonary metastasis of lung cancer (IM) are still controversial, especially in cases with similar histology. On the basis of reviewing the existing literature, this paper discusses the changes of the diagnostic criteria of MPLC and the differential diagnosis methods of imaging, histology and molecular genetics of MPLC and IM, and briefly introduces the application of multidisciplinary diagnosis, algorithm, predictive model and artificial intelligence in the differential diagnosis of MPLC. In addition, we also discuss the latest progress in the treatment of MPLC. Radical surgery is the main method for the treatment of MPLC. Stereotactic body radiation therapy (SBRT) is safe and feasible for inoperable MPLC patients, and targeted therapy and immunotherapy can also be used in MPLC after appropriate patient selection.

[Association and effects of gene-gene interactions between peroxisome proliferator-activated receptor and pulse pressure].

Objective: To investigate the association between ten single nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptors and pulse pressure (PP) as well as the relationships between gene-gene interaction between PPARα/δ/γ genes and PP. Methods: A total of 820 subjects, with 550 females and 270 males, were recruited from a cohort study of "Prevention of Metabolic Syndrome and Multi-metabolic Disorders in Jiangsu Province of China Study (PMMJS)" . Ten SNPs of PPARα/δ/γ genes were selected. GMDR software (version 1.0.1) was used to evaluate the gene-gene interactions among PPARs SNPs associated with PP. Results: The mean levels of PP in people with mutant genotype of rs1805192 in PPARγ genes (PA+AA) showed a significant increase by 1.341 mmHg (95%CI: 0.431-2.252 mmHg) when compared to the persons with wild genotype (PP). In the subgroup of subjects with more than 30 mmHg levels of PP, a six-locus model comprised rs135539 of PPARα, rs2016520 of PPARδ, rs10865710, rs1805192, rs709158 and rs3856806 of PPARγ showed a highest level of prediction accuracy (0.577) and displayed a better cross-validation consistency (10/10). In the subgroup of subjects with less than 40 mmHg levels of PP, a two-locus model was statistically associated with PP with 0.628 of prediction accuracy and 10/10 of cross-validation consistency. Conclusion: PPARγ rs1805192 was associated with the occurrence of PP. Gene-gene interactions among rs135539 of PPARα, rs2016520 of PPARδ, rs10865710, rs1805192, rs709158 and rs3856806 of PPARγ were all significantly related to PP.

Overexpression of zinc finger protein 687 enhances tumorigenic capability and promotes recurrence of hepatocellular carcinoma.

Zinc finger protein 687 (ZNF687), identified as a C2H2 zinc finger protein, has been found to be mutated and upregulated in giant cell tumor of bone and acute myeloid leukemia, suggesting an oncogenic role for ZNF687 in cancer. However, the clinical significance and precise role of ZNF687 in cancer progression are largely unknown. Herein, we report that ZNF687 was markedly upregulated in hepatocellular carcinoma (HCC) cell lines and HCC tissues, and was significantly correlated with relapse-free survival in HCC. ZNF687 overexpression greatly enhanced HCC cell capability for tumorsphere formation, invasion and chemoresistance in vitro, whereas inhibiting ZNF687 reduced these capabilities and inhibited HCC cell tumorigenic capability in vivo. Importantly, extreme limiting dilution analysis revealed that even 1 × 102 ZNF687-transduced cells could form tumors in vivo, indicating that ZNF687 contributes to HCC recurrence. Moreover, we demonstrate that ZNF687 transcriptionally upregulated the expression of the pluripotency-associated factors BMI1, OCT4 and NANOG by directly targeting their promoters. Therefore, our results suggest that ZNF687 has a promoter role in regulating HCC progression, which provides a potential therapeutic target for HCC in humans.

A 5-year evaluation of NORPLANT contraceptive implants in China.

OBJECTIVE: To assess the efficacy, safety, and acceptability of NORPLANT implants when used by Chinese women. METHODS: In a prospective, multicenter clinical trial, 10,718 women selecting NORPLANT implants were monitored semiannually for the first 2 study years and then annually through 5 years. Life table rates of pregnancy and other terminations were calculated, as were incidence rates of serious conditions leading to termination. RESULTS: The 5-year average annual pregnancy rate was 0.3 per 100 and the ectopic pregnancy rate was minimal, 0.09 per 1000 woman-years. Pregnancy rates correlated significantly with weight, but regardless of weight group, annual average pregnancy rates were less than one per 100. Younger women experienced higher pregnancy rates than did older users. Headache, myoma, dizziness, and weight gain led more frequently to termination than did other adverse events apart from menstrual disturbances. Mortality during use was 2.0 per 10,000 years, based on 44,954 years of experience. There were no cardiovascular or cerebrovascular deaths, and no deaths were attributable to NORPLANT use. Seventy-two per 100 initial acceptors used the implants continuously for 5 years. CONCLUSION: NORPLANT implants proved highly effective, safe, and acceptable among Chinese women regardless of province, age, or weight at admission.

NORPLANT and the levonorgestrel IUD in Chinese family planning programmes.

NORPLANT was introduced into the Chinese family planning programmes in 1984 by the Population Council. After a pilot study of 1200 cases in four centres in China, the study was expanded to 12 centres with 10,718 cases of NORPLANT and 1208 cases of NORPLANT-2 followed up for more than 6 years. The 5 years net cumulative pregnancy rates were 0.5-1.2 and the net cumulative continuation rates were around 65-72 per 100 users. There were significant differences in pregnancy rates between different groups of body weight and age, i.e. the pregnancy rates were higher in groups with body weight over 70 kg and those aged below 25 years. The age, body weight and dependence on contraceptive effectiveness of NORPLANT should be taken into account in the selection of users. Nationwide large-scale studies in provincial and country rural areas and postmarketing surveillance are being carried out. Changes in ovarian function and endometrium have been studied. Levonorgestrel IUD (LNg-IUD) was introduced into China in 1985. Comparative clinical studies on NORPLANT and LNg-IUD, pharmacokinetic and pharmacodynamic studies and endometrial studies of LNg-IUD were performed. The higher percentage (55.1%) of ovarian suppression in Chinese users of LNg-IUD may be attributed to ethnic differences among Caucasian women in their susceptibility to steroid hormones. Results showed favourable acceptance of both devices among Chinese women. The studies promoted the incorporation of new long-acting contraceptive methods into the Chinese family planning programmes.

[Bioavailability studies on the preparations of biphenyl dimethyl dicarboxylate(DDB)].

Since the bioavailability of the suspension and the tablet of DDB given orally is only 20-30%, we have prepared four kinds of DDB solid dispersion preparations (DDB pilule I with polyethylene glycol 6000 as the vehicle, DDB pilule II with polyethylene glycol 6000 and absorption accelerator as the vehicle, capsule of DDB-urea fusing mixture and DDB-polyvinyl pyrrolidone coprecipitate), and the bioavailability of these preparations were studied in rabbits, rats and human volunteers by HPLC method. All four preparations showed better absorption than the DDB tablet, and the area under serum DDB concentration-time curve of pilule II was 19 fold that of the tablet in rabbits, meaning that the absorption of pilule II is the best of the four preparations. After administration of the four solid dispersion preparations, the fecal excretion of DDB were all lower than the tablet in both animals and human volunteers. The protective action of pilule II against CCl4 hepatotoxicity was about six times stronger than that of the suspensions. Therefore, there are good reasons to use DDB pilule II instead of the tablets of suspension in the clinic.

[Mucus histochemical study of bilirubin cholangiolithiasis in rabbit model].

Sulfated mucopolysaccharides have an important role in pigment gallstone formation. In this experiment, the animal model of bilirubin cholangiolithiasis was made with Japanese hybrid big-ear white rabbits. The source, nature, quantity and distribution of sulfated mucopolysaccharides in the cause of bilirubin cholangiolithiasis were observed by means of mucous histochemical study. There were three characteristic pathologic changes observed in this experiment: 1. In normal condition, the sulfated mucopolysaccharides were secreted by epithelium of biliary tracts and the quantity was minimum. When bacterial infection was present in the biliary tracts, they were secreted mainly by the proliferative glands in submucosa of the bile duct; 2. In 26 rabbits where the bilirubin cholangiolithiasis developed, there were many proliferative glands in submucosa of the bile duct. Most of the glands produced sulfonated acid mucin. In 5 rabbits where the gallstones did not develop in the stone growing stage, the proliferative glands were not present in the bile duct. It was suggested that there was a close relationship between the proliferative glands and the formation of bilirubin cholangiolithiasis, and 3. The glands in submucosa of the biliary tract provided the refuge where the bacteria could not be cleaned out easily and so it was difficult to control the infection of the biliary tract.

[Acceptability of norplant implantation in China].

The results of Norplant subdermal implants in 10,718 women receiving Norplant-6 and 1,208 women accepted Norplant-2 were analyzed. Up to May 31, 1988, the 3-year cumulative pregnancy rate was 0.2 per 100 acceptor for Norplant-6 and 0.1 per 100 acceptor for Norplant-2 and the continuation rate was 78.6 and 73.1 per 100 acceptor respectively. Menstrual disturbance constituted the majority (70%) of terminations. Cumulative termination rate for medical reasons was only 4.2 and 6.3 per 100 acceptor for Norplant-6 and Norplant-2 respectively. It is concluded preliminarily that the Norplant subdermal implantable contraceptive system is a safe and acceptable to the Chinese women.

[The dissolution rate and physical dispersion state of preparations of biphenyl dimethyl dicarboxylate (DDB)].

DDB is poorly soluble in water. The solid dispersions of DDB with easily soluble carriers such as polyethylene glycol 6000 (PEG 6000), polyvinyl pyrrolidone (PVP) and urea were prepared by melting and solvent methods. The two DDB-PEG 6000 systems are thermodynamically stable interstitial solid solutions. The DDB-PVP system is an amorphous precipitate and the DDB-urea system is a simple eutectic physical mixture judged by X-ray diffraction and thermal analysis methods. The dissolution rate of DDB-PEG 6000 pilule and two kinds of DDB tablets were determined. The dissolution rate of DDB-PEG 6000 pilule was found to be faster. The physical dispersion state is an important factor in relation to the dissolution rate of DDB preparations.

A two-year study of acceptability, side effects, and effectiveness of Norplant and Norplant-2 implants in the People's Republic of China.

A large scale, phased investigation of NORPLANT contraceptive systems was conducted in the People's Republic of China. The first phase comprehended 1,200 women in four cities. Expanded trials included 11,918 women at 12 major centers and at sub-centers by 31 May 1987. At that date 4,676 NORPLANT capsule subjects and 1,089 rod subjects had completed one year of use, 1,381 capsule acceptors had completed two years as had 197 rod users. Gross pregnancy rates were less than 0.1 per 100 for each implant type both at one and at two years. Continuation rates were 94 per 100 for each implant type at one year, and were 82.0 and 83.6 per 100 among users of NORPLANT capsule and rod implants, respectively, at two years. Disruption of menstrual function was the dominant reason for termination, but mean hemoglobin levels increased in each of the nine centers reporting values at admission and at one year. First year gross cumulative termination rates for medical reasons were 1.2 to 1.3 per 100, reaching 3.8 and 5.6 per 100 for capsule and rod implants, respectively, at two years. Microdose contraception with these levonorgestrel-releasing implants appears to be a highly acceptable and effective modality suitable for Chinese women. NORPLANT implants are now approved by the national drug regulatory agency for general use in China.