Mechanism and prevention of liver failure complicated by acute pancreatitis / 临床肝胆病杂志

Liver failure often has rapid progression， multiple complications， and dangerous conditions. Acute pancreatitis is a common comorbidity during the progression of liver failure， and since acute pancreatitis has extremely similar clinical symptoms and signs to liver failure complicated by spontaneous peritonitis， it is often neglected in clinical practice. This article elaborates on the mechanisms of liver failure complicated by acute pancreatitis from the five aspects of inflammatory response， duodenal papillary dysfunction， gut microbiota dysbiosis， oxidative stress， and microcirculatory disturbance and proposes corresponding preventive measures based on these mechanisms.

Advances in the treatment of acute hepatic porphyria / 临床肝胆病杂志

Acute hepatic porphyria （AHP） is a rare disease with abnormal heme metabolism， and breakthroughs have been made in the treatment of this disease in recent years. In addition to conventional treatment methods， this article reviews new therapies for AHP that are in the stage of initial clinical application or are still in the research stage， including RNAi therapy， enzyme replacement therapy， genetic supplementation of DNA or mRNA， drug molecular chaperones， and glycine transporter inhibitors for reducing heme synthesis. Moreover， this article also reviews the treatment of AHP-related comorbidities and complications， such as hyponatremia and posterior reversible encephalopathy syndrome. High glucose infusion is the main treatment method for AHP in China， and the improvement in diagnosis and increased attention to rare diseases in China has promoted the development of the diagnosis and treatment of AHP， and it is expected to explore more suitable treatment methods for AHP in the Chinese population in the future.

Network Meta-analysis of Oral Chinese Patent Medicine in Adjuvant Treatment of Chronic Prostatitis/Chronic Pelvic Pain Syndrome / 中国实验方剂学杂志

ObjectiveTo evaluate the efficacy and safety of various oral Chinese patent medicines in the adjuvant treatment of chronic prostatitis/chronic pelvic pain syndrome （CP/CPPS） based on network Meta-analysis. MethodRandomized controlled trials （RCTs） of oral Chinese patent medicine in the adjuvant treatment of CP/CPPS were retrieved from the databases of China National Knowledge Infrastructure （CNKI）， Wanfang， VIP， SinoMed， PubMed， Cochrane Library， EMbase， and Web of Science from database inception to November， 2022. The quality of the included literature was evaluated according to the Cochrane risk-of-bias tool， and the data were analyzed by RevMan 5.4 and Stata 16 software. ResultA total of 63 RCTs were included， with 13 kinds of oral Chinese patent medicines involved， including Qianlie Shutong capsules， Ningmitai capsules， Qianlie Beixi capsules， Sanjin tablets， etc. The results of the network Meta-analysis showed that in terms of clinical effective rate， the intervention measure ranked first was Qianlie Beixi capsules combined with conventional western medicine. In terms of reducing pain， the intervention measure ranked first was Sanjin tablets combined with conventional western medicine. In terms of reducing urination disorder， the intervention measure ranked first was Relinqing granules combined with conventional western medicine. In terms of improving quality of life， the intervention measure ranked first was Qianlie Beixi capsules combined with conventional western medicine. In terms of reducing the total National Institutes of Health Chronic Prostatitis Symptom Index （NIH-CPSI） score， the intervention measure ranked first was Yinhua Miyanling tablets combined with conventional western medicine. In terms of reducing leukocyte count in prostatic secretions， the intervention measure ranked first was Qianlie Jiedu capsules combined with conventional western medicine. In terms of safety， the intervention measure with the least adverse reactions was Qianlie Shutong capsules combined with conventional western medicine. The cluster analysis results showed that Qianlie Shutong capsules combined with conventional western medicine had outstanding efficacy and high safety. ConclusionOral Chinese patent medicine in the adjuvant treatment of CP/CPPS can improve the comprehensive efficacy， reduce the NIH-CPSI score and leukocyte count in prostatic secretions， and improve the quality of life of patients. For clinical treatment， the preferred choice is Qianlie Beixi capsules or Qianlie Shutong capsules combined with conventional western medicine. Limited by the quantity and quality of literature included in this study， the results need to be verified by high-quality studies with a larger sample size.

Clinical phenotypic and genotypic analysis of 5 pediatric patients with β-ketothiolase deficiency / 中华儿科杂志

Objective: To summarize the clinical and genetic characteristics of children with β-ketothiolase deficiency (BKTD). Methods: The clinical characteristics, biochemical, markers detected by tandem mass spectrometry (MS/MS) and gas chromatography-mass spectrometry (GC/MS), as well as the variants in ACAT1 gene among 5 children with BKTD in Children's Hospital of Chongqing Medical University between October 2018 and December 2022 were retrospectively analyzed. Results: The onset age of the disease in 5 patients (4 males and 1 female) ranged from 9.7 to 28.0 months. During the acute phase, severe metabolic acidosis was observed with a pH of 6.9-7.1, as well as hypoglycaemia (2.3-3.4 mmol/L) and positive urinary ketone bodies (+-++++). Blood levels of methylcrotonyl carnitine, methylmalonyl carnitine and malonyl carnitine were 0.03-0.42, 0.34-1.43 and 0.83-3.53 μmol/L respectively and were significantly elevated. Urinary 2-methyl-3-hydroxybutyric acid was 22-202 and 3-hydroxybutyric acid was 4-6 066, both were higher than the normal levels. Methylcrotonylglycine was mild elevated (0-29). The metabolites detected by MS/MS and GC/MS were significantly reduced after treatment. Analysis of ACAT1 gene mutation was performed in 5 children. Most variants were missense (8/9). Four previously unreported variants were identified: c.678G>T (p.Trp226Cys), c.302A>G (p.Gln101Arg), c.627_629dupTGA (p.Asn209_Glu210insAsp) and c.316C>T (p.Gln106Ter), the first 2 variants were predicted to be damaging by SIFT, PolyPhen-2 and Mutation Taster software. c.316C>T (p.Gln106Ter) is a nonsense variant. Conclusions: β-ketothiolase deficiency is relatively rare, lacks specific clinical manifestations, however severe metabolic acidosis, hypoglycemia, and ketosis during the acute onset were consistent findings. Missense mutations in the ACAT1 gene are common genetic causes of β-ketothiolase deficiency.

Xinjia Congrong Tusizi Decoction Regulates Ferroptosis of Granulosa Cells in Rat Model of Premature Ovarian Insufficiency via p53/Nrf2 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effects of Xinjia Congrong Tusizi decoction （XJCTD） on ovarian functions in the rat model of premature ovarian insufficiency （POI） and decipher the mechanism of regulating the tumor suppressor protein （p53）/nuclear factor E2-related factor 2 （Nrf2） pathway to attenuate granulosa cell ferroptosis. MethodForty-eight SPF-grade female SD rats were randomized into control， model， low-， medium-， and high-dose （1.1， 2.2， 4.4 g·kg-1） XJCTD， and Western medicine （coenzyme Q10， 0.002 7 g·kg-1） groups， with eight rats in each group. The rat model of POI was established by gavage of triptolide （TP）， and after successful modeling， each group was administrated with the corresponding drugs by gavage for 14 d. The body weight and ovarian weight of each rat were weighed and the ovarian index was calculated. The morphology of the ovarian tissue was observed by hematoxylin-eosin staining， and the proportions of growing follicles and atretic follicles were calculated. The serum levels of anti-Müllerian hormone （AMM）， estradiol （E2）， and follicle-stimulating hormone （FSH） were measured by enzyme-linked immunosorbent assay （ELISA）. The DCFH-DA fluorescent probe was used to measure the reactive oxygen species （ROS） content in granulosa cells. The content of cellular Ferrous ion （Fe2+）， lipid peroxide （LPO）， malondialdehyde （MDA）， glutathione （GSH）， and superoxide dismutase （SOD） was detected by colorimetry. The expression of the tumor suppressor protein p53，Nrf2， solute carrier family 7 member 11 （SLC7A11）， and glutathione peroxidase 4 （GPX4） was determined by immunohistochemistry and Western blot. ResultCompared with the control group， the model group showed decreased ovarian weight， body weight， and ovarian index （P<0.01）， reduced ovarian tissue volume and proportion of growing follicles （P<0.01）， increased proportion of atretic follicles （P<0.01）， lowered AMH and E2 levels and elevated FSH level in the serum （P<0.01）， and elevated levels of Fe2+， ROS， LPO， and MDA （P<0.01） and lowered levels of GSH and SOD in granulosa cells （P<0.01）. Moreover， the modeling up-regulated the expression of p53 （P<0.01） and down-regulated the expression of Nrf2， SLC7A11， and GPX4 （P<0.05， P<0.01） in the ovarian tissue. Compared with the model group， XJCTD increased the body weight， ovarian weight， and ovarian index （P<0.01）， alleviated the pathological changes in the ovarian tissue， increased the proportion of growing follicles （P<0.01）， decreased the proportion of atretic follicles （P<0.01）， and reduced the content of ROS in granulosa cells （P<0.05， P<0.01）. In addition， medium- and high-dose XJCTD lowered the FSH level （P<0.01） and raised E2 and AMH levels （P<0.01） in the serum， reduced the Fe2+ content （P<0.05， P<0.01）， and increased the SOD content （P<0.01） in granulosa cells. High-dose XJCTD reduced the LPO and MDA content （P<0.01） and increased the SOD content （P<0.01） in the granulosa cells， down-regulated the expression of p53 （P<0.05）， and up-regulated the expression of Nrf2， SLC7A11， and GPX4 in the ovarian tissue （P<0.05， P<0.01）. ConclusionXJCTD may protect the ovarian function in the rat model of POI by regulating the p53/Nrf2 signaling pathway to attenuate the ferroptosis of ovarian granulosa cells.

A novel predictor of unsustained return of spontaneous circulation in cardiac arrest patients through a combination of capnography and pulse oximetry: a multicenter observational study / 世界急诊医学杂志（英文）

@#BACKGROUND: Unsustained return of spontaneous circulation (ROSC) is a critical barrier to survival in cardiac arrest patients. This study examined whether end-tidal carbon dioxide (ETCO2) and pulse oximetry photoplethysmogram (POP) parameters can be used to identify unsustained ROSC. METHODS: We conducted a multicenter observational prospective cohort study of consecutive patients with cardiac arrest from 2013 to 2014. Patients’ general information, ETCO2, and POP parameters were collected and statistically analyzed. RESULTS: The included 105 ROSC episodes (from 80 cardiac arrest patients) comprised 51 sustained ROSC episodes and 54 unsustained ROSC episodes. The 24-hour survival rate was significantly higher in the sustained ROSC group than in the unsustained ROSC group (29.2% vs. 9.4%, P<0.05). The logistic regression analysis showed that the difference between after and before ROSC in ETCO2 (ΔETCO2) and the difference between after and before ROCS in area under the curve of POP (ΔAUCp) were independently associated with sustained ROSC (odds ratio [OR]=0.931, 95% confidence interval [95% CI] 0.881-0.984, P=0.011 and OR=0.998, 95% CI 0.997-0.999, P<0.001). The area under the receiver operating characteristic curve of ΔETCO2, ΔAUCp, and the combination of both to predict unsustained ROSC were 0.752 (95% CI 0.660-0.844), 0.883 (95% CI 0.818-0.948), and 0.902 (95% CI 0.842-0.962), respectively. CONCLUSION: Patients with unsustained ROSC have a poor prognosis. The combination of ΔETCO2 and ΔAUCp showed significant predictive value for unsustained ROSC.

Cinobufagin Combined with Thalidomide/Dexamethasone Regimen in the Treatment of Patients with Newly Diagnosed Multiple Myeloma of Phlegm and Stasis Obstruction： A Retrospective Study / 中医杂志

ObjectiveTo investigate the efficacy and safety of cinobufagin tablets combined with thalidomide/dexamethasone （TD） regimen in the treatment of newly diagnosed multiple myeloma （NDMM） with phlegm and stasis obstruction. MethodsThe clinical data of 50 patients with NDMM of phlegm and stasis obstruction who were hospitalized at the Jiangsu Province Hospital of Chinese Medicine from June 1st， 2015 to July 31th， 2019 were retrospectively analyzed， and they were divided into a control group （bortezomib/dexamethasone-containing regimen， 27 cases） and an observation group （cinobufagin tablets combined with TD regimen， 23 cases）. The clinical efficacy and safety were compared between the two groups after two or three courses of treatment. The primary outcomes were clinical remission rate including overall response rate and deep remission rate， one-year and two-year overall survival rate， and adverse effects. The secondary outcomes were the proportion of plasma cells in bone marrow， hemoglobin， β2-microglobulin， lactate dehydrogenase， serum creatinine， blood urea nitrogen， bone pain score， and KPS functional status score （KPS score） before and after treatment. ResultsIn terms of clinical efficacy， there was no statistically significant difference （P＞0.05） in the overall response rate ［the observation group 69.57%（16/23） vs the control group 70.37% （19/27）］ and deep remission rate ［the observation group 56.52% （13/23） vs the control group 55.56% （15/27）］ between groups after the treatment. The one-year overall survival rates of the observation group and the control group were 90.9% and 92.4%， and the two-year overall survival rates were 81.8% and 80.9% respectively， with no statistically significant differences between groups （P＞0.05）. During the treatment， no renal function injury occurred in both groups. The incidence of peripheral nerve injury in the observation group was 8.70%， which was lower than 48.15% in the control group （P＜0.01）. After the treatment， the proportion of myeloma plasma cells， β2-microglobulin， serum creatinine level， and bone pain score decreased， while the hemoglobin level and KPS score increased in both groups （P＜0.05 or P＜0.01）. Compared between groups after treatment， the bone pain score of the observation group was lower than that of the control group， while the KPS score was higher than that of the control group （P＜0.05）. ConclusionThe clinical efficacy of cinobufagin tablets combined with TD in the treatment of NDMM is equivalent to bortezomib/dexamethasone-containing regimen， but the former is more helpful in relieving the pain and improving the quality of life， and has better safety.

Traditional Chinese Medicine Against Fibrotic Diseases： A Review / 中国实验方剂学杂志

Fibrosis can occur in diverse tissue and organs and is the common outcome as multiple chronic diseases progress. It is characterized by over-activation of fibroblasts and excessive deposition of extracellular matrix. Targeting transforming growth factor-β （TGF-β）， a classical signaling molecule in fibrosis， is currently a routine strategy for drug therapy of this disease. The use of traditional Chinese medicine （TCM） in the treatment of fibrotic diseases has been supported by mature theories. The theories emphasize that the internally-accumulated pathogens and mixed deficiency-excess underlie the shared pathology of fibrotic diseases. Qi stagnation， blood stasis， phlegm turbidity， and mass accumulation are key pathological factors. "Yin suppression by Yang" is the core thought for treatment with TCM of the disease. Pharmacological investigations reveal the scientific nature of TCM in treating fibrotic diseases， namely multilevelled and multitargeted. In other words， it refers to networked regulation of signaling activities of fibrosis-related molecules such as TGF-β/Drosophila protein homolog （Smad）， phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）， Hedgehog， Wnt/β-catenin， and inflammatory cytokines， so as to inhibit fibroblast function and provide a promising insight into novel anti-fibrotic drug. This paper summarized the conventional understanding of fibrotic disease treatment with TCM and its mechanism of action by reviewing ancient literature and modern research reports， which offers an idea for follow-up research in this field.

Relationship between trace elements in synovial fluid and cartilage and severity of knee osteoarthritis / 中国修复重建外科杂志

OBJECTIVE@#To investigate the relationship between trace elements in synovial fluid and cartilage and severity of knee osteoarthritis (KOA).@*METHODS@#Patients with KOA who underwent knee arthrocentesis or total knee arthroplasty (TKA) were recruited based on inclusion criteria between June 2021 and December 2021. Synovial fluid samples were obtained during knee arthrocentesis and TKA, and participants were divided into the mild group (grading Ⅰ/Ⅱ) and the severe group (grading Ⅲ/Ⅳ) according to the Kellgren-Lawrence grading (K-L grading). Cartilage samples with different degrees of wear were collected during the TKA from the same patient and were divided into mild wear (0-1 point) and severe wear (2-4 points) groups based on the Pelletier score. The contents of copper (Cu), zinc (Zn), and manganese (Mn) in synovial fluid and cartilage were evaluated by inductively coupled plasma mass spectrometry, and the differences between groups were compared.@*RESULTS@#A total of 33 synovial fluid samples were collected, including 19 specimens from 14 patients who underwent knee arthrocentesis of mild group, with 5 bilateral sides knee arthrocentesis in them, and 14 specimens from 14 TKA patients of severe group. The patients were significantly younger in the mild group than in the severe group ( P<0.05), but there was no significant difference in gender or body mass index between the two groups ( P>0.05). Nineteen pairs of cartilage samples with mild and severe wear were collected from severe KOA patients (K-L grading Ⅲ and Ⅳ), including 9 males and 10 females, with an average age of 70.4 years (range, 58-80 years). The body mass index ranged from 21.2 to 30.7 kg/m 2, with an average of 25.6 kg/m 2. The content of Zn in synovial fluid and cartilage from KOA patients was the highest, followed by Cu, and Mn was the lowest. The Cu content in synovial fluid was significantly higher in the severe group than in the mild group ( P<0.05), and in the severe wear group than in the mild wear group ( P<0.05). There was no significant difference in Zn and Mn content between the two groups ( P>0.05).@*CONCLUSION@#The Cu content increases with the severity of cartilage wear in patients with KOA.

Network Meta-analysis of oral Chinese patent medicine in adjuvant treatment of rotavirus gastroenteritis in children / 中国中药杂志

This study aimed to evaluate the efficacy and safety of various oral Chinese patent medicines in the adjuvant treatment of rotavirus gastroenteritis(RVGE) in children based on network Meta-analysis. Randomized controlled trial(RCT) of oral Chinese patent medicine in the adjuvant treatment of RVGE in children was retrieved from the databases such as CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, EMbase, and Web of Science from database inception to October 22, 2022. The quality of the included RCT was evaluated according to the Cochrane risk-of-bias tool, and the data were analyzed by RevMan 5.4 and Stata 16 software. Sixty-three RCTs were included, with 11 oral Chinese patent medicines involved, including Xingpi Yanger Granules, Weichang'an Pills, Qiuxieling Mixture, Erxieting Granules, and Changyanning Granules/Syrup. The results of the network Meta-analysis showed that in terms of clinical total effective rate, the top 3 optimal interventions were Changyanning Granules/Syrup, Xiaoer Guangpo Zhixie Oral Liquid, and Xiaoer Shuangjie Zhixie Granules combined with conventional western medicine. In terms of the anti-diarrheal time, the top 3 optimal interventions were Shenling Baizhu Granules, Qiuxieling Mixture, and Shuangling Zhixie Oral Liquid combined with conventional western medicine. In terms of the antiemetic time, the top 3 optimal interventions were Changyanning Granules/Syrup, Xingpi Yanger Granules, and Xiaoer Shuangjie Zhixie Granules combined with conventional western medicine. In terms of the antipyretic time, the top 3 optimal interventions were Shenling Baizhu Granules, Xiaoer Shuangjie Zhixie Granules, and Qiuxieling Mixture combined with conventional western medicine. In terms of the negative conversion rate of rotavirus, the top 3 optimal interventions were Xingpi Yanger Granules, Erxieting Granules, and Cangling Zhixie Oral Liquid combined with conventional western medicine. In terms of reducing creatine kinase isoenzyme MB(CK-MB) level, the top 3 optimal interventions were Weichang'an Pills, Xingpi Yanger Granules, and Xiaoer Shuangjie Zhixie Granules combined with conventional western medicine. In terms of adverse reactions, no se-rious adverse reactions were reported in all studies. Oral Chinese patent medicines in the adjuvant treatment of children with RVGE have their own advantages, Specifically, Changyanning Granules/Syrup + conventional western medicine focuses on improving the clinical total effective rate and shortening the antiemetic time, Shenling Baizhu Granules + conventional western medicine on shortening the anti-diarrheal time and antipyretic time, Xingpi Yanger Granules + conventional western medicine on improving the negative conversion rate of rotavirus, and Weichang'an Pills + conventional western medicine on reducing the CK-MB level. Limited by the quantity and quality of literature included in this study, the results need to be verified by high-quality RCT with a larger sample size.

Treatment of rheumatoid arthritis by injection of sinomenine solid lipid nanoparticles under a fluorescence endoscopic laser confocal microscope / 中国中药杂志

A fluorescence endoscopic laser confocal microscope(FELCM) was used to direct the injection of sinomenine solid lipid nanoparticles(Sin-SLN) into the joint, and the in vitro effectiveness of Sin-SLN in the treatment of rheumatoid arthritis(RA) was evaluated. Sin-SLN was prepared with the emulsion evaporation-low temperature curing method. The Sin-SLN prepared under the optimal conditions showed the encapsulation efficiency of 64.79%±3.12%, the drug loading of 3.84%±0.28%, the average particle size of(215.27±4.21) nm, and the Zeta potential of(-32.67±0.84) mV. Moreover, the Sin-SLN demonstrated good stability after sto-rage for 30 days. The rabbit model of RA was established by the subcutaneous injection of ovalbumin and complete Freund's adjuvant. Five groups were designed, including a control group, a model group, a Sin(1.5 mg·kg~(-1)) group, a Sin-SLN(1.5 mg·kg~(-1)) group, and a dexamethasone(positive drug, 1.0 mg·kg~(-1), ig) group. The control group and the model group only received puncture treatment without drug injection. After drug administration, the local skin temperature and knee joint diameter were monitored every day. The knee joint diameter and the local skin temperature were lower in the drug administration groups than in the model group(P<0.05, P<0.01). FELCM recorded the morphological alterations of the cartilage of knee joint. The Sin-SLN group showed compact tissue structure and smooth surface of the cartilage. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the serum le-vels of interleukin-1(IL-1) and tumor necrosis factor-α(TNF-α). The findings revealed that the Sin-SLN group had lower IL-1 and TNF-α levels than the model group(P<0.05, P<0.01). Hematoxylin-eosin(HE) staining was employed to reveal the pathological changes of the synovial tissue, which were significantly mitigated in the Sin-SLN group. The prepared Sin-SLN had uniform particle size and high stability. Through joint injection administration, a drug reservoir was formed. Sin-SLN effectively alleviate joint swelling and cartilage damage of rabbit, down-regulated the expression of inflammatory cytokines, and inhibited the epithelial proliferation and inflammatory cell infiltration of the synovial tissue, demonstrating the efficacy in treating RA.

Advances in the pathogenesis, diagnosis, and treatment of renal injury in liver cirrhosis / 临床肝胆病杂志

Patients with decompensated cirrhosis often have a reduction in renal function due to severe hepatic insufficiency which results in reduced inactivation of vasodilators, hemodynamic disorders, immune disorders, and infections, and without timely intervention, patients may gradually develop from early prerenal injury to late renal failure. Patients tend to have a low survival rate and great difficulties in treatment. With the gradual clarification of the classification and diagnostic criteria for kidney injury and the discovery of an increasing number of markers for kidney injury, early diagnosis and localization of kidney injury are of great importance for improving the prognosis of patients. This article analyzes the new advances in the pathogenesis, diagnostic criteria, and treatment of renal injury in cirrhotic patients in recent years, so as to provide help for the clinical diagnosis and treatment of cirrhotic patients with renal injury.

Research progress of exosome drug loading system / 中国药房

Exosome is a kind of vesicle secreted by a variety of cells with lipid bilayer membrane structure， which has good biocompatibility， high targeting and high stability， and is a natural nanoscale drug carrier with great development potential in drug delivery system. In this paper， exosomes and their properties， exosome drug delivery pathways and methods， the design strategy of engineered exosome drug delivery systems for targeted disease therapy， and the application of exosome drug delivery systems in the treatment of a variety of diseases were reviewed. Exosome drug delivery pathways could be divided into two categories： exogenous and endogenous. Common exosome drug delivery methods included electroporation， co-incubation， and ultrasound. Engineered exosome drug delivery system can further improve drug loading and enhance drug targeting. The main way of engineering is to modify exosome surface through genetic engineering technology， physical modification， chemical modification， etc. Exosome drug delivery system provides a new idea for targeted therapy of arthritis， tumor， brain and other diseases.

Study on the correlation between opioid-induced constipation and gene polymorphism / 中国药房

OBJECTIVE To investigate the effect of gene polymorphism on opioid-induced constipation. METHODS The target genes related to opioid-induced constipation were screened out through searching guidelines， databases and evidence-based medical data， and then 100 cancer pain patients who received opioid drugs for analgesia were included as the study subjects. According to whether there were adverse effects of constipation after medication or not， they were divided into test group and control group， with 50 cases in each group. The target gene was detected by PCR or fluorescence in situ hybridization. The SNPStats program was used to carry out Hardy-Weinberg balance test and correlation analysis between gene polymorphism and opioid-induced constipation. The multivariate Logistic regression analysis was used to explore the relevant predictive factors of opioid-induced constipation， and receiver operating characteristic （ROC） curve of subjects was drawn to analyze the effectiveness of each predictive factor in predicting opioid-induced constipation. RESULTS CYP2D6， CYP3A5*3， ABCB1 and OPRM1 were selected as target genes for detection. The results of genotype detection showed that the frequency distribution of CYP2D6 （rs1065852， rs1135822， rs16947， rs28371725， rs28371735）， CYP3A5*3 （058rs776746）， ABCB1 （062rs1045642）， OPRM1 （047rs1799971） alleles were consistent with Hardy-Weinbergbalance test. The correlation analysis results showed that the proportion of genotype GG and AG in CYP3A5*3 （058rs776746， 163.com A＞G） and genotype AA and AG in OPRM1 （047rs1799971， A＞G） of patients was significantly higher in test group than that in the control group （P＜0.05）. Multivariate Logistic regression analysis showed that medication duration， CYP3A5*3 and OPRM1 gene polymorphism could be used as predictors of opioid- induced constipation in patients （P＜0.05）. The ROC curve analysis results showed that the areas under the ROC curves for medication duration and CYP3A5*3， OPRM1 gene polymorphism were 0.648， 0.640 and 0.670， respectively， with the optimal cutoff values of 124.0， 0.5 and 0.5， respectively. CONCLUSIONS Genotype GG and AG in CYP3A5*3 （058rs776746，A＞G） and genotype AA and AG in OPRM1 （047rs1799971，A＞G） are associated with opioid-induced constipation， which are expected to become clinical predictors of opioid-induced constipation， and more attention should be paid to the occurrence of constipation in patients who have been taking opioids for a long time.

Effects of Ranibizumab on ocular biological parameters in the treatment of retinopathy of prematurity / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effect of intravitreal ranibizumab injection on ocular parameters in the treatment of retinopathy of prematurity(ROP), and analyze its relationship with birth weight(BW)and postmenstrual age(PMA).METHODS: A total of 98 premature infants who received routine ROP screening at Northwest Women's and Children's Hospital from January 1, 2016 to January 31, 2022 were selected, and they were divided into ROP group(49 cases)and non-ROP group(49 cases)according to the results of Retcam3 fundus screening. All children in ROP group were treated with intravitreal ranibizumab injection, with an average PMA of 38.02±3.03 weeks. The ocular parameters were measured at the PMA of 0 month(40 weeks±14d), 3 months(52 weeks±28d)and 6 months(64 weeks±28d), respectively.RESULTS: There was no difference in axial length(AL), anterior chamber depth(ACD), lens thickness(LT), vitreous length(VL)and central corneal thickness(CCT)between ROP group and non-ROP group at the PMA of 0 month(P&#x003E;0.05); At the PMA of 3 and 6 months, ACD in ROP group was higher than that in non-ROP group, and LT was lower than that in non-ROP group(P&#x003C;0.05); at the PMA of 6 months, AL and VL in ROP group were lower than those in non-ROP group(P&#x003C;0.05). AL, ACD and VL were positively correlated with PMA in ROP group and non-ROP group, while CCT was negatively correlated with PMA; there was a positive correlation between LT and PMA in children without ROP. There was no correlation among LT, BW and PMA in ROP group.CONCLUSION: The ocular development of children with early ROP(PMA 0～6 months)treated by intravitreal ranibizumab injection is slower than that of premature infants without ROP, and BW and PMA are the main influencing factors of ocular parameters of premature infants.

Anti-inflammatory Effect and Mechanism of Duhuo Jishengtang on Rheumatoid Arthritis Rats Based on TLR2/p38 MAPK/NF-κB Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the anti-inflammatory effect of Duhuo Jishengtang （DHJST） on collagen-induced arthritis （CIA） model rats and its effect on the Toll-like receptor 2 （TLR2）/p38 mitogen-activated protein kinase （MAPK）/nuclear factor-κB （NF-κB） signaling pathway. MethodForty-eight male SD rats were randomly divided into the following six groups （n=8）： normal group， model group， methotrexate （MTX） group， low-dose DHJST （DHJST-L） group， medium-dose DHJST （DHJST-M） group， and high-dose DHJST （DHJST-H） group. The CIA model was established by injecting bovine type Ⅱ collagen into the rat tail root with the collagen antibody induction method. After model induction， rats were treated with drugs by gavage. The rats in the MTX group received MTX at 2.0 mg·kg-1， three times a week， and those in the DHJST groups received DHJST at 3.8， 7.6， 15.2 g·kg-1·d-1 for 28 days. The rats in the normal group and the model group were given the same dose of normal saline. The weight of the rats was recorded， and the paw swelling degree was observed. The arthritis index and immune organ index were measured， and the changes in the microcirculation indexes of the rats were detected with a microcirculation detector. Hematoxylin-eosin （HE） staining was used to detect the pathological morphologic changes in rat synovial tissues and the apoptosis rate of synovial cells was detected by flow cytometry to determine the therapeutic effect of DHJST on rheumatoid arthritis. Enzyme-linked immunosorbent assay （ELISA） was used to detect the changes in serum levels of tumor necrosis factor-α （TNF-α）， interleukin （IL）-1β， IL-17A， and interferon-γ （IFN-γ）. The protein expression of TLR2， NF-κB p65， phosphorylated NF-κB p65 （p-NF-κB p65）， p38 MAPK， and p-p38 MAPK was detected by Western blot. ResultCompared with the normal group， the model group showed reduced body weight （P<0.01）， increased paw swelling degree， arthritis index， and immune organ index （P<0.01）， increased comprehensive microvascular score and vascular resistance （P<0.01）， significant hyperplasia of synovial tissues and massive infiltration of inflammatory cells as revealed by pathological sections， and up-regulated expression levels of TNF-α， IL-1β， IL-17A， and IFN-γ in serum， and TLR2， p-NF-κB p65/NF-κB p65 and p-p38 MAPK/p38 MAPK in synovial tissues （P<0.01）. Compared with the model group， the DHJST groups showed increased body weight of rats （P<0.01）， decreased paw swelling degree， arthritis index， and immune organ index （P<0.05， P<0.01）， reduced comprehensive microvascular score and vascular resistance （P<0.05， P<0.01）， improved synovial histopathological injury， increased apoptosis rate of synovial cells （P<0.01）， and down-regulated levels of TNF-α， IL-1β， IL-17A， and IFN-γ in serum （P<0.05， P<0.01） and TLR2， p-NF-κB p65/NF-κB p65 and p-p38 MAPK/p38 MAPK in synovial tissues （P<0.05， P<0.01）. ConclusionDHJST may alleviate the inflammatory reaction in CIA rats by regulating the TLR2/p38 MAPK/NF-κB signaling pathway， thus exerting its anti-rheumatoid arthritis effect.

Advances in the risk factors, pathogenesis, and treatment of liver cirrhosis with osteoporosis / 临床肝胆病杂志

Osteoporosis is a common extrahepatic complication of liver cirrhosis, and it not only increases the economic burden of patients, but also brings adverse effects on their quality of life and prognosis. Recent studies have shown that sarcopenia, adiponectin, leptin, irisin, and inflammatory factors are involved in the development of osteoporosis in patients with liver cirrhosis, and commonly used anti-osteoporosis drugs include calcium supplement, vitamin D, and bisphosphonates. This article reviews the advances in the risk factors, pathogenesis, and treatment of liver cirrhosis with osteoporosis and points out that there are still controversies over the influence of some factors on osteoporosis, and further studies are needed to explore related pathogeneses and safe and effective treatment regimens.

Highly sensitive H2O2-scavenging nano-bionic system for precise treatment of atherosclerosis

In atherosclerosis, chronic inflammatory processes in local diseased areas may lead to the accumulation of reactive oxygen species (ROS). In this study, we devised a highly sensitive H2O2-scavenging nano-bionic system loaded with probucol (RPP-PU), to treat atherosclerosis more effectively. The RPP material had high sensitivity to H2O2, and the response sensitivity could be reduced from 40 to 10 μmol/L which was close to the lowest concentration of H2O2 levels of the pathological environment. RPP-PU delayed the release and prolonged the duration of PU in vivo. In Apolipoprotein E deficient (ApoE‒/‒) mice, RPP-PU effectively eliminated pathological ROS, reduced the level of lipids and related metabolic enzymes, and significantly decreased the area of vascular plaques and fibers. Our study demonstrated that the H2O2-scavenging nano-bionic system could scavenge the abundant ROS in the atherosclerosis lesion, thereby reducing the oxidative stress for treating atherosclerosis and thus achieve the therapeutic goals with atherosclerosis more desirably.

Chinese consensus guidelines for therapeutic drug monitoring of polymyxin B, endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Polymyxin B, which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections, became available in China in Dec. 2017. As dose adjustments are based solely on clinical experience of risk toxicity, treatment failure, and emergence of resistance, there is an urgent clinical need to perform therapeutic drug monitoring (TDM) to optimize the use of polymyxin B. It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use. We report a consensus on TDM guidelines for polymyxin B, as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society. The consensus panel was composed of clinicians, pharmacists, and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations, sample collection, reporting, and explanation of TDM results. The guidelines provide the first-ever consensus on conducting TDM of polymyxin B, and are intended to guide optimal clinical use.

Activation of JAK/STAT in ovarian high-grade serous cancers and its prognostic significance / 北京大学学报(医学版)

OBJECTIVE@#The activation of Janus kinase (JAK) and signal transducers and activators of transcription (STAT) plays an important role in the prognosis and targeted therapy of ovarian high-grade serous carcinoma (HGSC). Utilizing simple and practicable technique, this study aimed to evaluate the activation of JAK/STAT signaling pathway in ovarian HGSC patients, and investigated the correlation between the activation of JAK/STAT signaling pathway and the prognosis of the HGSC patients.@*METHODS@#We performed immunohistochemistry of phosphorylated STAT3 (pSTAT3) and phosphorylated STAT5 (pSTAT5) on paraffin imbedded slides of 73 ovarian HGSC patients, and evaluated the expression level and range of both markers. According to the grading score of the immunostaining of pSTAT3 and pSTAT5, we divided the 73 ovarian HGSC cases into STAT3 low/high expression and STAT5 low/high expression groups, and analyzed the prognosis of the patients in different groups, in order to explore the relationship between the expression of pSTAT3 and pSTAT5 proteins and the prognosis of the HGSC patients.@*RESULTS@#Some of the ovarian HGSC cases showed high expression of pSTAT3 and pSTAT5 protein level, which was related to the poorer prognosis of the HGSC patients. There was a significant difference in the expression level of pSTAT3 and pSTAT5 between the patients with better prognosis (survival time ≥3 years) and poorer prognosis (survival time < 3 years). The patients with higher protein expression of pSTAT3, pSTAT5 or both markers might have poorer prognosis, with significant shorter progression-free survival time and overall survival time (P < 0.001).@*CONCLUSION@#Immunostaining of pSTAT3 and pSTAT5 proteins might be helpful to evaluate and predict the prognosis of the ovarian HGSC patients, and to identify the patients who might have higher chances to respond to the STAT inhibitors and anti-angiogenesis therapy.