Investigation of Antigen and Gene Frequency of Kell(K) and Rh(D) Blood Groups in Xinjiang / 中国实验血液学杂志

OBJECTIVE@#To investigate the phenotypes and gene frequencies of Kell blood group system K antigen and Rh blood group system D antigen in Xinjiang, and summarize and understand the distribution of Kell(K) blood type and Rh(D) blood type in this area.@*METHODS@#A total of 12 840 patients who met the inclusion criteria during physical examination and treatment in our hospital and 18 medical institutions in our district from January 1, 2019 to December 31, 2019 were collected for identification of Kell blood group system K antigen and Rh blood group System D antigen, and the distribution of K and D blood groups in different regions, genders and nationalities were investigated and statistically analyzed.@*RESULTS@#The proportion of K positive in the samples was 1.39%, the highest was 1.91% in southern Xinjiang, and the lowest was 1.03% in northern Xinjiang(P<0.01). The proportion of Rh(D) negative samples was 2.75% and the gene frequency was 16.64%. The proportion of Rh(D) negative samples was 4.03% and the gene frequency was 20.10% in southern Xinjiang, followed by eastern Xinjiang and the lowest in northern Xinjiang (P<0.01). The frequency of K antigen in Uygur nationality was the highest, reaching 2.16%, Kirgiz 1.54%, and the distribution trend of D/d antigen was similar to that of K antigen. Among women, the K positive frequency of Kazak nationality was slightly higher than that of Mongolian nationality. The highest proportion of K positive in Uygur women was 2.38%, which was higher than that in Uygur men (1.86%). The frequency of d phenotype in Kazak women was 3.15%, which was higher than that in Kirgiz （2.89%） (P<0.01).@*CONCLUSION@#The distributions of Kell(K) and Rh(D) blood groups in northern and southern Xinjiang and eastern Xinjiang had its own unique characteristics and differences. There are significant differences in blood group distribution among different ethnic groups and gender groups. In the future, k antigen detection can be included to further improve the investigation on the distribution of Kell blood group system in this region.

Diquafosol sodium combined with intense pulsed light in the treatment of meibomian gland dysfunction dry eye after corneal refractive surgery / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the therapeutic effect of the diquafosol sodium combined with intense pulsed light(IPL)on meibomian gland dysfunction(MGD)dry eye after refractive surgery.METHODS:A total of 64 patients(128 eyes)with MGD dry eye diagnosed within 6mo after laser corneal refractive surgery in our hospital from March 2021 to December 2021 were selected. They were randomly divided into control group and experimental group. A total of 33 patients(66 eyes)in the control group were treated with sodium hyaluronate combined with IPL, and 31 patients(62 eyes)in the experimental group were treated with diquafosol sodium combined with IPL. Ocular symptom scores were performed before each IPL treatment in both groups to examine non-invasive tear breakup time(NIBUT), tear meniscus height, lipid layer grade of tear film, meibomian gland deletion rate and uncorrected visual acuity.RESULTS:After IPL treatment, ocular symptom scores and meibomian gland deletion rate score of two groups were decreased continuously. NIBUT, tear meniscus height and lipid layer grade of tear film were increased continuously, and there was no significant change in uncorrected visual acuity. NIBUT of patients in the experimental group was better than that in the control group before the third IPL treatment(6.24±0.27s vs. 5.51±0.24s, P=0.046).CONCLUSIONS:Both diquafosol sodium and sodium hyaluronate combined with IPL showed good therapeutic effect on MGD dry eye, but there was no significant difference in the short-term efficacy between the two groups.

Varieties systematization and standards status analysis of fermented Chinese medicine / 中国中药杂志

Fermented Chinese medicine has long been used. Amid the advance for preservation of experience, the connotation of fermented Chinese medicine has been enriched and improved. However, fermented Chinese medicine prescriptions generally contain a lot of medicinals. The fermentation process is complicated and the conventional fermentation conditions fail to be strictly controlled. In addition, the judgment of the fermentation end point is highly subjective. As a result, quality of fermented Chinese medicine is of great difference among regions and unstable. At the moment, the quality standards of fermented Chinese medicine are generally outdated and different among regions, with simple quality control methods and lacking objective safe fermentation-specific evaluation indictors. It is difficult to comprehensively evaluate and control the quality of fermented medicine. These problems have aroused concern in the industry and also affected the clinical application of fermented Chinese medicine. This article summarized and analyzed the application, quality standards, and the modernization of fermentation technology and quality control methods of fermented Chinese medicine and proposed suggestions for improving the quality standards of the medicine, with a view to improving the overall quality of it.

Effect of eccentricity of optical treatment zone on retinal defocus after wearing orthokeratology lens / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the effect of eccentricity of the optical treatment zone on retinal defocus after wearing orthokeratology lens for 12mo.METHODS: In this case-control study, a total of 120 myopic patients(120 eyes)who completed the fitting in our hospital from March 2021 to September 2021 and insisted on wearing orthokeratology lenses for 12mo were selected. According to the eccentricity after wearing lenses for 12mo, they were divided into the low eccentricity group(&#x003C;0.5mm, 58 cases, 58 eyes)and the moderate and high eccentricity group(≥0.5mm, 62 cases, 62 eyes). The optical treatment zone diameter(OTZD), eccentricity, axial length(AL), pupil diameter(PD)and refraction difference value(RDV)were evaluated after 12mo of wearing orthokeratology lenses, and the correlation between RDV and eccentricity was analyzed.RESULTS: After wearing orthokeratology lenses for 12mo, AL growth and RDV at 30°～40° and 40°～53° from the fovea were significantly lower in the moderate and high eccentricity group than in the low eccentricity group(all P&#x003C;0.05). In all patients, RDV at 40°～53° from the fovea was positively correlated with AL growth and OTZD(rs=0.544, 0.333, both P&#x003C;0.01), and negatively correlated with eccentricity(rs=-0.224, P=0.014).CONCLUSION: Peripheral retinal defocus is related to eccentricity and OTZD after wearing orthokeratology lenses. The greater eccentricity and the smaller OTZD within a certain range can induce more peripheral retinal myopic defocus, leading to a better control of AL growth.

Laboratory diagnosis of hepatitis type E / 中华肝脏病杂志

Hepatitis type E virus (HEV) infection is a common cause of acute viral hepatitis in China, and its etiological diagnosis relies on laboratory detection. Therefore, this article introduces the HEV RNA, HEV antigen, anti-HEV IgM, and IgG detection methods and their diagnostic application value. In addition, it also discusses the current international diagnostic standard and HEV infection presentation.

A new form of familial platelet disorder caused by germline mutations in RUNX1 in a pedigree / 中华内科杂志

Objective: To investigate the clinical and biological characteristics of familial platelet disorder (FPD) with germline Runt-related transcription factor (RUNX) 1 mutations. Methods: Patients diagnosed with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) with RUNX1 mutations from February 2016 to December 2021 in Wuhan No.1 Hospital underwent pedigree analysis and were screened for gene mutations (somatic and germline). Patients diagnosed with FPD with germline RUNX1 mutations were enrolled and evaluated in terms of clinical characteristics and biological evolution. Bioinformatics analysis was used to assess the pathogenicity of mutations and to analyze the effect of mutated genes on the function of the corresponding protein. Results: Germline RUNX1 mutations were detected in three out of 34 patients suffering from MDS/AML who had RUNX1 mutations. A pedigree of FPD with RUNX1 (RUNX1-FPD) c.562A>C and RUNX1 c.1415T>C mutations was diagnosed, and the mutations were of patrilineal origin. Bioinformatics analysis indicated that the locus at positions 188 and 472 in the AML-1G type of RUNX1 was highly conserved across different species, and that variations might influence functions of the proteins. The mutations were evaluated to be highly pathogenic. Of the nine cases with germline RUNX1 mutations: two patients died due AML progression; one case with AML survived without leukemia after transplantation of hemopoietic stem cells; four patients showed mild-to-moderate thrombocytopenia; two cases had no thrombocytopenia. During the disease course of the proband and her son, mutations in RUNX1, NRAS and/or CEBPA and KIT appeared in succession, and expression of cluster of differentiation-7 on tumor cells was enhanced gradually. None of the gene mutations correlated with the tumor were detected in the four cases not suffering from MDS/AML, and they survived until the end of follow-up. Conclusions: RUNX1-FPD was rare. The mutations c.562A>C and c.1415T>C of RUNX1 could be the disease-causing genes for the family with RUNX1-FPD, and these mutations could promote malignant transformation. Biological monitoring should be carried out regularly to aid early intervention for family members with RUNX1-FPD.

Comparison of visual quality after refractive surgery between smart pulse technology-assisted transepithelial photorefractive keratectomy of 1 050Hz ablation frequency and small incision lenticule extraction / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To compare the visual quality between smart pulse technology-assisted(SPT)transepithelial photorefractive keratectomy(TransPRK)of 1 050Hz ablation frequency and small incision lenticule extraction(SMILE)for myopia and astigmatism.METHODS: A total of 138 cases(248 eyes)who received corneal refractive surgery in the Eye Hospital of Chengdu University of TCM were enrolled from July 2020 to January 2021. The patients were divided into TransPRK group(64 cases, 123 eyes)and SMILE group(74 cases, 125 eyes)according to the surgical method. The follow-up duration was 6mo. Strehl ratio(SR)and high-order aberration at 6mm pupil diameter measured by Sirius anterior segment integrated analyzer and LogMAR visual acuity were recorded at different preoperative and postoperative time points.RESULTS: The uncorrected visual acuity(UCVA)of TransPRK group was worse than SMILE group at 1wk and 1mo after surgery(all P<0.05), but UCVA was better in TransPRK group at 6mo after surgery(P<0.05). SR in TransPRK group was lower than that in SMILE group at 1wk and 1mo after surgery(all P<0.05). There was no significant difference in SR between the two groups at 3 and 6mo after surgery(P=0.968, 0.433). At 1wk after surgery, there was no significant difference in coma between the two groups(P=0.554). At 1, 3, and 6mo after surgery, coma in the TransPRK group was lower than that in SMILE group(all P<0.05). At 1wk, 1 and 3mo after surgery, the trefoil aberration in TransPRK group was higher than that in SMILE group(all P<0.05). At 6mo after surgery, there was no significant difference in trefoil aberration between the two groups(P=0.167). At 6mo after surgery, UCVA of TransPRK group and SMILE group were -0.13±0.05 and -0.11±0.08, respectively, which were better than the best corrected visual acuity(BCVA)before surgery(-0.07±0.05 and -0.07±0.05; all P<0.05). Furthermore, the SR of both groups was higher than that before surgery(all P<0.05).CONCLUSION: Both SPT-assisted TransPRK of 1 050Hz ablation frequency and SMILE can achieve better visual acuity after refractive surgery, while SMILE has better visual quality at 1wk and 1mo after surgery. However, SPT-assisted TransPRK of 1 050Hz ablation frequency has better visual acuity at 6mo after surgery than SMILE, and the coma is smaller.

Domestic and international research status and trend of adolescent myopia: A bibliometrics based analysis / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore the current research progress, hot spots and future development trends of myopia in children and adolescents at home and abroad, thus providing references for the further research on the field.METHODS: Using China National Knowledge Infrastructure(CNKI)and Web of Science(WOS)as data sources, the literature on myopia in children and adolescents from January 1, 2003 to December 31, 2022 was collected. Visual analyses were conducted based on the quantity of the published articles, authors, publishing institutions, journals as well as keyword co-occurrence, clustering, timeline graph and emergence by using the VOSviewer and CiteSpace.RESULT: The number of publications on myopia research has increased steadily both articles in Chinese and English. Xian-Gui He and Saw, Seang-Mei have published the most papers, and the Chinese Journal of School Health and Investigative Ophthalmology &#x0026; Visual Science published the most related articles. Shanghai Eye Disease Prevention and Treatment Center, and Sun Yat-sen University are the institutions with the most publications in the area. Clinical observation is the main focus of research both domestically and internationally, with orthokeratology, outdoor activities, axial length, prevalence, and influencing factors attracting much attention.CONCLUSION: Current research on myopia in children and adolescents focuses on the epidemiology, intervention measures, and biological parameters of the condition. Future research on myopia epidemiology is likely to become a major focus of research in this area.

Clinical tolerability and pharmacokinetics of troxacitabine / 中华肿瘤杂志

Objective: To investigate the safety and efficacy of troxatabine in advanced or relapsed malignant tumors resistant to standard therapy in China. Methods: This is a phase Ⅰ prospective study. During dose escalation, patients in Cancer Hospital, Chinese Academy of Medical Sciences received a single-dose intravenous infusion of troxacitabine. The planned dosing groups were 1.8, 3.6, 4.8, 6.4 and 8.0 mg/m(2) on days 1 and 8 every 3 weeks. The data of all patients were collected for safety analyses. Safety and tolerability were evaluated by monitoring adverse events. Results: Nineteen patients were enrolled from April 2018 to May 2019. The major adverse events were fatigue (89.5%, 17/19), leukopenia (84.2%, 16/19) and neutropenia (78.9%, 15/19). The dose limiting toxicity was neutropenia. The maximum tolerated dose was 6.4 mg/m(2). The best effect was stable disease (43.8%). The half-life of elimination phase from 15.91 hours to 76.63 hours in each dose group. Conclusions: The toxicity of troxacitabine is well tolerant. We recommend that the dose for Phase Ⅱ clinical trial should be 6.4 mg/m(2).

Changes in retinal peripheral refractive status and aberrations before and after femtosecond laser-assisted laser in situ keratomileusis and small incision lenticule extraction / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe and compare the changes in retinal peripheral refraction and aberrations after femtosecond laser-assisted laser in situ keratomileusis(FS-LASIK)versus small incision lenticule extraction(SMILE)for myopia correction.METHODS: A total of 71 patients(71 eyes)with myopia who underwent FS-LASIK from October 2022 to April 2023 in our hospital were selected as the FS-LASIK group, and 80 patients(80 eyes)with myopia who underwent SMILE were selected as the SMILE group. All patients underwent corneal wavefront aberration measurement and multispectral refractive topography preoperatively and 3mo postoperatively, as well as refraction difference value(RDV)in the range of 0°～10°, 10°～20°, 20°～30°, 30°～40°, and 40°～53° in the annulus of the retina, which were recorded as RDV-(0°～10°), RDV-(10°～20°), RDV-(20°～30°), RDV-(30°～40°), and RDV-(40°～53°). The results of two groups of patients were compared.RESULTS: No significant differences were observed in RDV-(0°～10°), RDV-(10°～20°), RDV-(20°～30°), RDV-(30°～40°), RDV-(40°～53°)between the two groups at 3mo post-operation(all P&#x003E;0.05). Furthermore, the RDV-(20°～30°), RDV-(30°～40°)and RDV-(40°～53°)of the two groups at 3mo postoperatively were all significantly lower than those preoperatively(all P&#x003C;0.05). The changes in coma(horizontal)and spherical aberration(SA)at 3mo postoperatively were smaller in the SMILE group [0.106(0.056, 0.171)and 0.115(0.081, 0.182)μm] than in the FS-LASIK group [0.206(0.104, 0.355)and 0.197(0.128, 0.254)μm](Z=-4.170, -5.016, all P&#x003C;0.05). A negative correlation was found between postoperative SA and postoperative RDV-(10°～53°)(rs=-0.205, -0.181, -0.226, -0.244, all P&#x003C;0.05).CONCLUSION: Both FS-LASIK and SMILE reduced retinal hyperopic defocus in the peripapillary macular range of 20°～53° eccentricity, and the postoperative changes in coma(horizontal)and SA were smaller with SMILE than with FS-LASIK. There was a certain correlation between postoperative SA and postoperative retinal peripheral defocus.

Risks and suggestions of Investigator-Initiated Clinical Trial approvals based on drug supply and security / 中华医学科研管理杂志

Objective:To improve the standard and quality of clinical trials, the possible risks of Investigator-Initiated Clinical Trial(IIT) approvals based on drug supply and security were discussed and suggestions were put forward.Methods:According to the laws and regulations and literature review, concerning experimental drug supply and security during project negotiation, the risk points of IIT approvals were comprehensively analyzed and suggestions were put forward.Results:There are four main types of risks in assessing IIT approvals in terms of drug supply and security: drug entry and sales, drug promotion, discounts of observation fees, and concept confusion. Healthcare institutions should pay attention to and coordinate the IIT approvals.Conclusions:IIT is a supplement and extension of Industry Sponsored Trial(IST), which should be actively carried out by healthcare institutions while also paying attention to the security and risk prevention of drug supply, ensuring a standardized and orderly manner.

Renal thrombotic microangiopathy induced by targeted therapy combined with immunotherapy: a case report / 中华肾脏病杂志

Targeted therapy and immunotherapy have achieved great success in treating various solid and non-solid tumors, but the incidence of drugs-related adverse events is relatively high. The paper reports a case of renal thrombotic microangiopathy in an intrahepatic cholangiocarcinoma patient who underwent targeted therapy combined with immunotherapy. During the treatment, the tumor burden relieved continuously, but the patient developed proteinuria, edema and hypertension. The ADAMTS13 activity and inhibitors were normal, while the antiphospholipid antibody was positive. The patient was finally diagnosed as glomerular thrombotic microangiopathy with immune complex deposition by renal biopsy. After the cease of the antineoplastic agents and treatment with "cordyceps preparations" and "α-keto acids", the patient's blood pressure dropped to normal, her urine protein turnned to weakly positive, and her renal function remained stable.

Relationship between adverse childhood experiences and depression and anxiety among students in middle school / 中国学校卫生

Objective@#To investigate the relationship between adverse childhood experiences with depression and anxiety prevention and intervention among middle school students, so as to provide evidence for preventing and intervening in depression and anxiety among adolescents.@*Methods@#From October to November 2020, a total of 4 861 middle school students from 12 schools in a province in central China, including junior high schools, senior high schools, secondary vocational schools, and vocational high school selected by using convenient sampling method. Demographic information, adverse childhood experiences, depression and anxiety symptoms were collected. The Chi square test and multivariate Logistic regression analysis were used to analyze the data.@*Results@#The detection rates of depression and anxiety of students in middle school were 39.0% and 52.3%, respectively. Univariate analysis showed that the total scores of adverse childhood experiences and dimensions of childhood maltreatment and neglect, family dysfunction, parent absence, and violence outside the home were significantly associated with depressive and anxiety symptoms ( χ 2=105.36, 147.12, 43.69, 46.61, 196.48; 100.06, 132.28, 26.53, 24.32, 169.94, P <0.01). After controlling variables such as age, only child, sex and economic status of family, Logistic regression showed that childhood maltreatment and neglect, family dysfunction,family absence and violence outside the home were positively associated with depressive symptoms ( OR =1.61, 1.62, 1.06,2.08, P <0.01) and anxiety symptoms ( OR =1.66, 1.50, 1.98, P <0.05).@*Conclusion@#Depressive and anxiety symptoms among middle school students are associated with adverse childhood experiences, and those who experienced childhood maltreatment and neglect and violence outside the home are at higher risk.

3D-printed vertebral body in anterior spinal reconstruction after total spondylectomy for patients with cervical chordoma / 北京大学学报(医学版)

OBJECTIVE@#To investigate whether 3D-printed artificial vertebral body can reduce prosthesis subsidence rate for patients with cervical chordomas, through comparing the rates of prosthesis subsidence between 3D printing artificial vertebral body and titanium mesh for anterior spinal reconstruction after total spondylectomy.@*METHODS@#This was a retrospective analysis of patients who underwent surgical treatment for cervical chordoma at our hospital from March 2005 to September 2019. There were nine patients in the group of 3D artificial vertebral body (3D group), and 15 patients in the group of titanium mesh cage (Mesh group). The patients' characteristics and treatment data were extracted from the medical records, including age, gender, CT hounsfield unit of cervical vertebra and surgical information, such as the surgical segments, time and blood loss of surgery, frequency and degree of prosthesis subsidence after surgery. Radiographic observations of prosthesis subsidence during the follow-up, including X-rays, CT, and magnetic resonance imaging were also collected. SPSS 22.0 was used to analysis the data.@*RESULTS@#There was no significant difference between the two groups in gender, age, CT hounsfield unit, surgical segments, time of surgery, blood loss of posterior surgery and total blood loss. Blood loss of anterior surgery was 700 (300, 825) mL in 3D group and 1 500 (750, 2 800) mL in Mesh group (P < 0.05). The prosthesis subsidence during the follow-up, 3 months after surgery, there was significant difference between the two groups in mild prosthesis subsidence (P < 0.05). The vertebral height of the 3D group decreased less than 1 mm in eight cases (no prosthesis subsidence) and more than 1 mm in one case (mild prosthesis subsidence). The vertebral height of the Mesh group decreased less than 1 mm in five cases (no prosthesis subsidence), and more than 1 mm in eight cases (mild prosthesis subsidence). Two patients did not have X-rays in 3 months after surgery. There was a statistically significant difference between the two groups in the prosthesis subsidence rate at the end of 12 months (P < 0.01). The vertebral height of eight cases in the 3D group decreased less than 1 mm (no prosthesis subsidence) and one case more than 3 mm (severe prosthesis subsidence). Four of the 15 cases in the Mesh group decreased less than 1 mm (no prosthesis subsidence), two cases more than 1 mm (mild prosthesis subsidence), and nine cases more than 3 mm (severe prosthesis subsidence). There was a statistically significant difference between the two groups in the prosthesis subsidence rate at the end of 24 months (P < 0.01). The vertebral height of seven cases in the 3D group decreased less than 1 mm (no prosthesis subsidence), one case more than 3 mm (severe prosthesis subsidence), and one case died with tumor. One case in the Mesh group decreased less than 1 mm (no prosthesis subsidence), one case more than 1 mm (mild prosthesis subsidence), 11 case more than 3 mm (severe prosthesis subsidence), one case died with tumor and one lost the follow-up. Moreover, at the end of 12 months and 24 months, there was significant difference between the two groups in severe prosthesis subsidence rate (P < 0.01).@*CONCLUSION@#3D-printed artificial vertebral body for anterior spinal reconstruction after total spondylectomy for patients with cervical chordoma can provide reliable spinal stability, and reduce the incidence of prosthesis subsidence after 2-year follow-up.

Application and prospect of drug discrimination in field of drug abuse / 中国药理学通报

Drug discrimination is a behavioral pharmacological technique to study the discriminative stimulus effects of drug. Currently drug discrimination has been widely used in preclinical drug development of CNS drugs, the most extensive of which is psychodependent research in the field of drug abuse. This review describes in general the basic principles of drug discrimination, preliminarily elaborates on the relevant characteristics and applications of the subjective effects, time-course effect, stereo specificity, individual differences, and receptor mechanisms, and its development prospects for hallucinogens and cannabis drugs are also presented.

Clinical analysis of 86 cases of acute fatty liver of pregnancy / 中华妇产科杂志

Objective: To investigate the clinical characteristics and maternal and fetal prognosis of pregnant women with acute fatty liver of pregnancy (AFLP). Methods: The clinical data of 86 AFLP pregnant women admitted to the Third Affiliated Hospital of Guangzhou Medical University from September 2017 to August 2022 were collected, and their general data, clinical characteristics, laboratory tests and maternal and fetal outcomes were retrospectively analyzed. Results: (1) General information: the age of the 86 pregnant women with AFLP was (30.8±5.4) years, and the body mass index was (21.0±2.5) kg/m2. There were 50 primiparas (58.1%, 50/86) and 36 multiparas (41.9%, 36/86). There were 64 singleton pregnancies (74.4%, 64/86) and 22 twin pregnancies (25.6%, 22/86). (2) Clinical characteristics: the main complaints of AFLP pregnant women were gastrointestinal symptoms, including epigastric pain (68.6%, 59/86), nausea (47.7%, 41/86), anorexia (46.5%, 40/86), vomiting (39.5%, 34/86). The main non-gastrointestinal symptoms were jaundice of skin and/or scleral (54.7%, 47/86), edema (38.4%, 33/86), fatigue (19.8%, 17/86), bleeding tendency (16.3%, 14/86), polydipsia or polyuria (14.0%, 12/86), skin itching (8.1%, 7/86), and 17.4% (15/86) AFLP pregnant women had no obvious symptoms. (3) Laboratory tests: the incidence of liver and kidney dysfunction and abnormal coagulation function in AFLP pregnant women was high, and the levels of blood ammonia, lactate dehydrogenase and lactic acid were increased, and the levels of hemoglobin, platelet and albumin decreased. However, only 24 cases (27.9%, 24/86) of AFLP pregnant women showed fatty liver by imageology examination. (4) Pregnancy outcomes: ① AFLP pregnant women had a high incidence of pregnancy complications, mainly including renal insufficiency (95.3%, 82/86), preterm birth (46.5%, 40/86), hypertensive disorders in pregnancy (30.2%, 26/86), gestational diabetes mellitus (36.0%, 31/86), fetal distress (24.4%, 21/86), pulmonary infection (23.3%, 20/86), disseminated intravascular coagulation (16.3%, 14/86), multiple organ dysfunction syndrome (16.3%, 14/86), hepatic encephalopathy (9.3%, 8/86), and intrauterine fetal death (2.3%, 2/86). ② Treatment and outcome of AFLP pregnant women: the intensive care unit transfer rate of AFLP pregnant women was 66.3% (57/86). 82 cases were improved and discharged after treatment, 2 cases were transferred to other hospitals for follow-up treatment, and 2 cases (2.3%, 2/86) died. ③ Neonatal outcomes: except for 2 cases of intrauterine death, a total of 106 neonates were delivered, including 39 cases (36.8%, 39/106) of neonatal asphyxia, 63 cases (59.4%, 63/106) of neonatal intensive care unit admission, and 3 cases (2.8%, 3/106) of neonatal death. Conclusions: AFLP is a severe obstetric complication, which is harmful to mother and fetus. In the process of clinical diagnosis and treatment, attention should be paid to the clinical manifestations and laboratory tests of pregnant women, early diagnosis and active treatment, so as to improve maternal and fetal outcomes.

Gut microbiota controls the development of chronic pancreatitis: A critical role of short-chain fatty acids-producing Gram-positive bacteria

Chronic pancreatitis (CP) is a progressive and irreversible fibroinflammatory disorder, accompanied by pancreatic exocrine insufficiency and dysregulated gut microbiota. Recently, accumulating evidence has supported a correlation between gut dysbiosis and CP development. However, whether gut microbiota dysbiosis contributes to CP pathogenesis remains unclear. Herein, an experimental CP was induced by repeated high-dose caerulein injections. The broad-spectrum antibiotics (ABX) and ABX targeting Gram-positive (G+) or Gram-negative bacteria (G-) were applied to explore the specific roles of these bacteria. Gut dysbiosis was observed in both mice and in CP patients, which was accompanied by a sharply reduced abundance for short-chain fatty acids (SCFAs)-producers, especially G+ bacteria. Broad-spectrum ABX exacerbated the severity of CP, as evidenced by aggravated pancreatic fibrosis and gut dysbiosis, especially the depletion of SCFAs-producing G+ bacteria. Additionally, depletion of SCFAs-producing G+ bacteria rather than G- bacteria intensified CP progression independent of TLR4, which was attenuated by supplementation with exogenous SCFAs. Finally, SCFAs modulated pancreatic fibrosis through inhibition of macrophage infiltration and M2 phenotype switching. The study supports a critical role for SCFAs-producing G+ bacteria in CP. Therefore, modulation of dietary-derived SCFAs or G+ SCFAs-producing bacteria may be considered a novel interventive approach for the management of CP.

Qiling Tongluo Prescription Improves Renal Injury in Rats with Idiopathic Membranous Nephropathy by Inhibiting TLR4/MyD88/NF-κB Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the therapeutic effect and mechanism of Qiling Tongluo prescription against idiopathic membranous nephropathy （IMN） in rats based on Toll-like receptor 4/myeloid differentiation factor 88/nuclear transcription factor-κB （TLR4/MyD88/NF-κB） signaling pathway. MethodSixty male SD rats were randomly divided into the normal group， model group， benazepril hydrochloride （10 mg·kg-1） group， and low-，medium-， and high-dose （6.48， 12.95， and 25.9 g·kg-1） Qiling Tongluo prescription groups. The IMN rat model was established by injection of cationized bovine serum albumin （C-BSA） into the tail vein. After the model was successfully prepared， the rats were gavaged with the corresponding drugs， once a day， for four consecutive weeks. After the treatment， the pathological changes in rat kidneys were observed by hematoxylin-eosin （HE） staining， Masson staining， and periodic acid-silver metheramine （PASM） staining， followed by the detection of 24 h urinary total protein （24 h UTP）， plasma albumin （ALB）， total serum protein （TP）， serum creatinine （SCr）， urea nitrogen （BUN）， and uric acid （UA） levels. The levels of interleukin-1β （IL-1β） and interleukin-6 （IL-6） were determined by enzyme-linked immunosorbent assay （ELISA）， and the mRNA and protein expression levels of TLR4， MyD88， and NF-κB in the kidney tissue were assayed by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）， immunohistochemistry （IHC）， and Western blot. ResultCompared with the normal group， the model group exhibited elevated 24 h UTP and serum SCr， BUN， UA， IL-1β， and IL-6 （P<0.05， P<0.01）， decreased ALB and TP （P<0.01）， up-regulated TLR4， MyD88， and NF-κB p65 mRNA and protein expression in kidney tissue （P<0.05， P<0.01）， obvious inflammation， disordered glomerular structure with enlarged volume， irregularly thickened basement membrane， inflammatory cell infiltration in the renal interstitium， reduced renal tubular epithelial cells due to shedding and apoptosis， and some vacuolar degeneration. Compared with the model group， benazepril hydrochloride and Qiling Tongluo prescription at the high dose remarkably lowered the serum SCr and UA （P<0.05） and increased ALB and TP （P<0.05）. Benazepril hydrochloride and Qiling Tongluo prescription at the low， medium， and high doses down-regulated the 24 h UTP， serum IL-1β and IL-6 levels， and renal TLR4， MyD88， and NF-κB p65 mRNA and protein expression to varying degrees （P<0.05， P<0.01）， alleviated IMN inflammatory reaction， glomerular swelling， and volume increase， slightly dilated glomerular capillaries， proliferated mesangial matrix， and relieved pathological and morphological damages in rat kidney， with inflammatory cell infiltration occasionally observed. ConclusionQiling Tongluo prescription may reduce the release and expression of inflammatory factors by regulating the TLR4/MyD88/NF-κB signaling pathway to inhibit the inflammatory response in IMN rats， ameliorate proteinuria and kidney damage， and protect kidney function.

Effects of Dasatinib on the Maturation of Monocyte-Derived Dendritic Cells Derived from Healthy Donors and Chronic Myelogenous Leukemia Patients / 中国实验血液学杂志

OBJECTIVE@#To investigate the effects of dasatinib on the maturation of monocyte-derived dendritic cells (moDCs) derived from healthy donors (HDs) and chronic myelogenous leukemia (CML) patients.@*METHODS@#Peripheral blood mononuclear cells (PBMCs) were isolated from HDs (n=10) and CML patients (n=10) who had got the remission of MR4.5 with imatinib treatment. The generation of moDCs from PBMCs was completed after 7 days of incubation in DC I culture medium, and another 3 days of incubation in DC II culture medium with or without 25 nmol/L dasatinib. On the 10th day, cells were harvested and expression of molecules of maturation related marker were assessed by flow cytometry. The CD80+CD86+ cell population in total cells was gated as DCs in the fluorescence-activated cell storting (FACS) analyzing system, then the expression of CD83, CD40 or HLA-DR in this population was analyzed respectively.@*RESULTS@#The proportion of CD80+CD86+ cells in total cells didn't show a statistical difference between HD group and patient group (89.46%±9.70% vs 87.39%±9.34%, P=0.690). Dasatinib significantly enhanced the expression of the surface marker CD40 (P=0.008) and HLA-DR (P=0.028) on moDCs derived from HDs compared with the control group, while the expression of CD83 on moDCs didn't show a significant difference between dasatinib group and the control group (P=0.428). Meanwhile, dasatinib significantly enhanced the expression of the surface marker CD40 (P=0.023), CD83 (P=0.038) and HLA-DR (P=0.001) on moDCs derived from patients compared with the control group.@*CONCLUSION@#For CML patients, the same high proportion of moDCs as HDs can be induced in vitro, which provides a basis for the application of DC-based immunotherapy strategy. Dasatinib at the concentration of 25 nmol/L can efficiently promote the maturation of moDCs derived from HDs and CML patients in vitro. Dasatinib shows potential as a DC adjuvant to be applied in DC-based immunotherapy strategies, such as DC vaccine and DC cell-therapy.

Advances in the study of peptide drugs in oral drug delivery system / 药学学报

Peptide drugs exhibit an irreplaceable role in clinics due to their high specificity, efficiency and low toxicity. At present, more than 80 peptide drugs have been approved for marketing with global sales exceeding $50 billion in 2019. However, with large molecular weights, high hydrophilicity and instability in digestive tract, oral peptide drugs encounter substantial physiological barriers leading to low oral bioavailability. Therefore, peptide drugs are mostly administered by parenteral routes. Although parenteral delivery of peptide drugs achieves high bioavailability, this is associated with inconvenience and discomfort, even causing severe side effects compared with the oral route possessing a high degree of patient compliance. Therefore, numerous studies concentrate on novel strategies to improve the oral bioavailability of peptide drugs. Some delivery technologies such as Eligen™ and Axcess™ have been successfully applied to the oral dosage form of therapeutic peptides and have accelerated relevant oral formulations for Food and Drug Administration (FDA) approval and clinical treatment. In this review, we focus on the oral peptide delivery, mainly summarizing the progress of recent strategies used to overcome oral barriers and the commercialization applications of related patents, which could facilitate the research and development (R&D) of clinical applications of oral delivery techniques for peptide drugs.