Whole-process individualized pharmaceutical care for a case of melioidosis sepsis / 中国药房

OBJECTIVE To provide reference for the adjustment of antibiotic treatment regimens， identification of adverse reactions， and individualized pharmaceutical care for melioidosis sepsis （MS）. METHODS Clinical pharmacists participated in the intensive and eradicating therapeutic processes for an MS patient by using blood concentration and gene detection. Based on the literature， antibiotic treatment regimens of MS were adjusted by determining the blood concentrations of β-lactam and trimethoprim/ sulfamethoxazole （TMP/SMZ） and calculating PK/PD parameters. The causes of adverse drug reactions were analyzed and addressed by detecting drug-related gene polymorphisms through high-throughput sequencing. RESULTS Clinical pharmacists used blood concentration and genetic testing methods to propose adjustments to imipenem-cilastatin sodium dosage and analyze the causes of various adverse drug reactions. PK/PD targets were calculated by measuring the blood concentrations of β-lactam and TMP/SMZ. Clinical pharmacists explained to clinical doctors the compliance status of patients with melioidosis in sepsis and non- sepsis stages through reviewing guidelines and literature； the results of blood concentration and genetic test were used to analyze the correlation of neurotoxicity of MS patients with B14） IMP cmin， and it was found that nephrotoxicity was not related to the cmax of TMP/SMZ， but to the patient’s water intake. After whole-process antibiotic treatment， the patient’s condition improved and was discharged， and the adverse reactions were effectively treated. CONCLUSIONS Clinical pharmacists use blood concentration and genetic tests to assist clinicians in formulating MS treatment regimens， and provide whole-course pharmaceutical care for a MS patient. This method has improved the safety and effectiveness of clinical drug therapy.

Changes of photopic negative response of multifocal electroretinogram after treatment with Aflibercept in patients with diabetic macular edema / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To observe the changes of photopic negative response(PhNR)of multifocal electroretinogram(mf-ERG)in patients with diabetic macular edema(DME)before and after treatment with Aflibercept.METHODS: A total of 37 patients(37 eyes)with DME who visited the Aier Eye Hospital of Wuhan University(Wuhan Aier Eye Hospital)from May 2019 to June 2022, and 0.05 mL of aflibercept was injected per month for consecutive 3mo were included in this retrospective cohort study. Another 20 cases(20 eyes)with normal physical examination to exclude related eye diseases were selected as the control group. The PhNR amplitude of mf-ERG, best-corrected visual acuity(BCVA; LogMAR), central retinal thickness(CRT), capillary plexus in macular area and vessel density(CPVD)of the participants between the two groups were compared before and after treatment.RESULTS: The PhNR amplitude of mf-ERG in DME patients before treatment(201.69±80.92nV)was significantly lower than that in the normal control group(398.87±77.92nV; P<0.01), and the average PhNR amplitude of mf-ERG in DME patients at 6mo after treatment was significantly higher than that before treatment(P=0.036), but it was still significantly lower than the normal control group at 6mo after treatment(P=0.031). In addition, the BCVA(LogMAR)of DME patients increased from 0.64±1.33 to 0.37±1.39(P=0.021)at 6mo after treatment, and CPVD significantly increased compared to that before treatment(P=0.029). Meanwhile, the PhNR amplitude of mf-ERG in DME patients at 6mo after treatment was positively correlated with CPVD at 6mo after treatment(r=0.448, P=0.043), and negatively correlated with BCVA(LogMAR)and CRT(r=-0.647, P=0.011; r=-0.337, P=0.032).CONCLUSION: The PhNR amplitude of mf-ERG in DME patients increased significantly after receiving aflibercept, and it can be used to observe and evaluate the functional changes of retinal ganglion cells in DME patients.

The effects of dynamic instability training on the postural control, balance and walking of stroke survivors / 中华物理医学与康复杂志

Objective:To observe any effect of dynamic motor instability training on the balance and postural control of stroke survivors.Methods:Forty stroke survivors with poor balance were randomly divided into a control group and an observation group, each of 20. In addition to routine rehabilitation, the observation group was given 20 minutes of dynamic motor instability training, 5 days a week for 8 weeks, while the control group underwent routine rehabilitation for the same length of time. Before and after the intervention, surface electromyogram of the rectus femoris, biceps femoris, and erector spinae were recorded during perturbation. Activation time and the intensity of the anticipatory and complementary postural adjustments (APAs and CPAs) were also observed. Balance and lower limb motor functioning were assessed using the Berg balance scale (BBS), the Fugl-Meyer lower extremity assessment (FMA-LE), and GaitWatch analysis.Results:After the treatment the average activation time of the rectus femoris, biceps femoris in the affected side and those of the biceps femoris [(-84.31±5.74)s] and erector spinae in the intact side in APAs were all significantly shorter in the observation group than in the control group, while the average activation intensity of the rectus femoris and erector spinae was significantly greater. There was no significant difference in the activation intensity of each muscle group in CPAs after the treatment. After the intervention the average BBS score, FMA-LE score, stride length and walking speed of the observation group all were significantly better than the control group′s averages.Conclusions:Supplementing traditional rehabilitation training with dynamic motor instability training can further improve the posture control of stroke survivors and promote recovery of their balance and walking ability.

Development of radiolabeled tetramer that targeting fibroblast activation protein and theranostic research in tumor xenografts / 中华核医学与分子影像杂志

Objective:To develop a tetramer probe targeting fibroblast activation protein (FAP), named 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-4P(FAP inhibitor (FAPI)) 4, evaluate its biodistribution and PET image in FAP-positive-tumor bearing nude mice, and explore its feasibility as a novel radio-regent for treatment of FAP-positive tumor. Methods:FAP tetramer probe was constructed on the FAPI-46 motif with four mini-polyethylene glycol (PEG)(PEG 3) spacers between the four FAPI motifs, denoted as 4P(FAPI) 4. DOTA was used as the chelator for radiolabeling with 68Ga and 177Lu. The FAP binding characteristics were test by in vitro cell competitive binding experiment. Small-animal PET, in vivo biodistribution, and radionuclide targeting therapy were performed in HT-1080-FAP tumor bearing nude mice ( n=39). Independent-sample t test was performed to analyze tumor uptake data, and two-factor repeated measures analysis of variance was utilized to compare tumor volume data in radioactive isotope therapy. Results:Cell experiment showed that FAPI-tetramer and FAPI-monomer had similar half maximal inhibitory concentration values (3.29 and 2.15 nmol/L). 68Ga/ 177Lu radiolabeled FAPI-tetramer had better tumor uptake and retention than FAPI-monomer in small-animal PET and in vivo biodistribution experiment, with the tumor uptake for 177Lu-DOTA-4P(FAPI) 4 and 177Lu-FAPI-46 at 48 h of (18.72±1.32) vs (2.72±1.20) percentage activity of injection dose per gram of tissue (%ID/g) ( t=15.55, P<0.001). 177Lu-DOTA-4P(FAPI) 4 group showed best anti-tumor efficacy compared with 177Lu-FAPI-46 and control group in radionuclide targeting therapy. On the 2nd day after the start of treatment, the tumor volume in the tetramer treatment group was significantly smaller than that in the control group (mean difference 67.19 mm 3, P=0.049); on the 14th day after the start of treatment, the tumor volume in the tetramer treatment group was significantly smaller than that in the monomer treatment group (mean difference 414.33 mm 3, P=0.005). Conclusion:FAPI-tetramer can improve tumor uptake and retention ability compared with FAPI-46, and 177Lu-DOTA-4P(FAPI) 4 can be a promising radio-agent for FAP-positive tumor therapy.

Comparison of 68Ga-FAPI and 18F-FDG PET/CT for the diagnosis of primary and metastatic gastric signet-ring cell carcinoma / 中华核医学与分子影像杂志

Objective:To investigate the clinical utility of 68Ga-labeled fibroblast activation protein inhibitor (FAPI) PET/CT in the detection of primary and metastatic gastric signet-ring cell carcinoma (GSRCC) and compared the results with those of 18F-FDG PET/CT. Methods:A total of 21 patients (10 males, 11 females, average age 52 years) with primary and metastatic GSRCC who underwent 68Ga-FAPI and 18F-FDG PET/CT at the First Affiliated Hospital of Xiamen University from June 2020 to May 2022 were retrospectively analyzed. Pathological results of surgery and (or) biopsy were used as the " gold standard" for final diagnosis. In cases whose surgery or tissue biopsies were not available, clinical and radiographic follow-up results were used as the reference standards. Wilcoxon signed-rank test was used to compare the SUV max of 18F-FDG and 68Ga-FAPI. McNemar χ2 test was used to compare the detection rate between 18F-FDG and 68Ga-FAPI PET/CT. Results:68Ga-FAPI PET/CT showed higher SUV max than 18F-FDG in primary tumors (5.3(2.4, 15.7) vs 2.4(1.8, 2.5); z=2.31, P=0.021), local recurrences (7.8(6.0, 8.9) vs 2.4(1.9, 3.4); z=2.20, P=0.028), lymph nodes metastases (7.7(4.5, 12.2) vs 2.4(1.9, 3.6); z=6.01, P<0.001) and bone/visceral metastases (6.7(5.3, 11.1) vs 2.4(2.0, 3.4); z=11.36, P<0.001). Regarding diagnostic accuracy, 68Ga-FAPI PET/CT showed higher sensitivities than 18F-FDG for primary tumors (7/9 vs 2/9; χ2=3.20, P=0.063) and local recurrences (7/7 vs 2/7; χ2=3.20, P=0.063). It also demonstrated higher lesion detection rates than 18F-FDG for suspicious lymph node metastases (86%(65/76) vs 32%(24/76); χ2=31.37, P<0.001) and bone/visceral metastases (99%(184/185) vs 39%(73/185); χ2=107.08, P<0.001). Conclusions:68Ga-FAPI PET/CT showed higher tumor uptake and lesion detection rate than 18F-FDG in the primary and metastatic GSRCC. 68Ga-FAPI PET/CT demonstrates good diagnostic performance for tumor detection, staging, and restaging of GSRCC, which is helpful to further guide clinical treatment strategy.

Effects of Zishen Huoxue Prescription on OGD/R-induced mitophagy in hippocampal neurons / 中国药理学通报

Aim To explore the protective effect of Zishen Huoxue Prescription on OGD/R-induced primary hippocampal neuron damage in rats and the possible mechanism. Methods After the isolated primary hippocampal neurons were identified by immunofluorescence, OGD/R induced neuronal damage, and the changes of autophagic flux at different re-oxygenation time were observed by confocal laser scanning microscopy. After OGD/R-induced primary hippocampal neurons were intervened with serum containing Zishen Huoxue Prescription, cell viability was detected by CCK-8, cell apoptosis was detected by flow cytometry, autophagosomes were detected by transmission electron microscopy, and autophagy-related protein expressions were detected by Western blot. Results 10% Zishen Huoxue Prescription-containing serum could significantly improve cell viability and reduce the proportion of cell apoptosis, increase the number of autophagosomes in neurons, and up-regulate the expression of autophagy-related protein PINK1, Parkin, and pATG16L1. Conclusions Zishen Huoxue Prescription can effectively resist OGD/R-induced apoptosis of primary hippocampal neurons in rats, and its effect may be related to the regulation of PINK1-Parkin pathway to promote mitophagy.

Exploring the common mechanism of Yindan Xinnaotong soft capsule in the treatment of stroke and coronary heart disease through HIF1α-MMP9-mediated HIF1α signaling pathway / 药学学报

Coronary heart disease (CHD) and stroke are the most well-known cardiovascular diseases, which share many common pathological basis. Yindan Xinnaotong soft capsule (YDXNT) is a commonly used Chinese patent medicine in the treatment of stroke and CHD. However, its action of mechanism of co-treatment for stroke and CHD is still unclear. The aim of this study was to explore the common mechanism of YDXNT in co-treatment of CHD and stroke using network pharmacology, experimental verification and molecular docking. An integrated literature mining and databases of IPA, ETCM, HERB, Swiss Target Prediction, OMIM and GeneCards were used to screen and predict active ingredients and potential targets of YDXNT in co-treatment of CHD and stroke. The protein-protein interaction network, GO analysis and pathway analysis were analyzed by IPA software. The effect of YDXNT on core targets was verified by immunofluorescence. UPLC-QTOF/MS and molecular docking were used to screen and predict the main active constituents of YDXNT and their interactions with core targets. A total of 151 potential targets are predicted for YDXNT in co-treatment of CHD and stroke. Hypoxia-inducible factor-1α (HIF1α)-matrix metalloproteinase-9 (MMP9)-mediated HIF1α signaling pathway serves as one of the common mechanisms. YDXNT could reduce the increase of mitochondrial fluorescence intensity and the protein expression of HIF1α and MMP9 in HL-1 and HA induced by oxygen and glucose deprivation/reperfusion (OGD/R) in a dose-dependent manner. Baicalin may be the material basis for treating stroke and CHD with YDXNT. In conclusion, the HIF1α signaling pathway is one of the common key mechanisms of YDXNT in the co-treatment of stroke and CHD. The study provides support and basis for the in-depth scientific connotation of the traditional Chinese medicine theory of "same treatment to different diseases".

Circular RNA circRSF1 binds to HuR to promote radiation-induced inflammatory phenotype in hepatic stellate cells / 南方医科大学学报

OBJECTIVE@#To investigate whether circular RNA circRSF1 regulates radiation-induced inflammatory phenotype of hepatic stellate cells (HSCs) by binding to HuR protein and repressing its function.@*METHODS@#Human HSC cell line LX2 with HuR overexpression or knockdown was exposed to 8 Gy X-ray irradiation, and the changes in the expression of inflammatory factors (IL-1β, IL-6 and TNF-α) were detected by qRT-PCR. The expressions of IκBα and phosphorylation of NF-κB were detected with Western blotting. The binding of circRSF1 to HuR was verified by RNA pull-down assay and RNA-binding protein immunoprecipitation (RIP). The expressions of inflammatory factors, IκBα and the phosphorylation of NF-κB were detected after modifying the interaction between circRSF1 and HuR.@*RESULTS@#Knockdown of HuR significantly up- regulated the expressions of IL-1β, IL-6 and TNF-α, decreased IκBα expression and promoted NF-κB phosphorylation in irradiated LX2 cells, whereas overexpression of HuR produced the opposite changes (P < 0.05). Overexpression or knockdown of circRSF1 did not significantly affect the expression of HuR. RNA pull-down and RIP experiments confirmed the binding between circRSF1 and HuR. Overexpression of circRSF1 significantly reduced the binding of HuR to IκBα and down-regulated the expression of IκBα (P < 0.05). Overexpression of circRSF1 combined with HuR overexpression partially reversed the up-regulation of the inflammatory factors, down-regulated IκBα expression and increased phosphorylation of NFκB in LX2 cells, while the opposite effects were observed in cells with knockdown of both circRSF1 and HuR (P < 0.05).@*CONCLUSION@#circRSF1 reduces IκBα expression by binding to HuR to promote the activation of NF-κB pathway, thereby enhancing radiation- induced inflammatory phenotype of HSCs.

Slicing specifications in general rule of processing in Chinese Pharmacopoeia from slicing development of Chinese materia medica processed product and thinking and suggestion on slicing techniques / 中国中药杂志

Slicing is critical in the processing of Chinese materia medica(CMM) processed product and the specification(thickness) is closely related to the quality of the decoction. On the basis of clarifying the concept and evolution of slicing of CMM processed product by reviewing the Chinese herbal classics of the past dynasties and general rules of local processing standards, this study discussed the development history of slicing specifications in general rules of Chinese Pharmacopoeia(2020 edition), analyzed the current situation and key problems, and proposed the thinking and suggestion on promoting the sound development of slicing of CMM processed product. Since 2000, the slicing thickness of CMM processed product in the general rules of local CMM processed product processing specifications newly revised and issued by 27 provinces, autonomous regions, and municipalities has been consistent with that in the general rules of the Chinese Pharmacopoeia(2020 edition). The standard that the thickness of extremely thin pieces is less than 0.5 mm is rarely retained, and the pieces in 0.5-1 mm thickness have not been found on the market, which is consistent with the provisions of the general rules of the Chinese Pharmacopoeia. This study can provide a historical and modern basis for the rationality of slicing of CMM processed product.

Comparison on volatile components between Artemisiae Verlotori Folium and Artemisiae Argyi Folium based on GC-MS and chemometrics / 中国中药杂志

Artemisiae Argyi Folium is commonly used in clinical practice. Artemisiae Verlotori Folium, the dried leaves of Artemisia verlotorum, is often used as a folk substitute for Artemisiae Argyi Folium in Lingnan area. In this study, gas chromatography-triple quadrupole mass spectrometry(GC-MS) was used to detect the volatile oil components of 27 samples of Artemisiae Verlotori Folium and 13 samples of Artemisiae Argyi Folium, and the volatile components were compared between the two species. The internal standard method was combined with multi-reaction monitoring mode(MRM) to determine the content of six major volatile components. Hierarchical clustering analysis(HCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were carried out for the content data. The results showed that the Artemisiae Argyi Folium samples had higher content and more abundant volatile oils than the Artemisiae Verlotori Folium samples. Artemisiae Argyi Folium mainly had the components with lower boiling points, while Artemisiae Verlotori Folium mainly had the components with higher boiling points. Terpenoids were the main volatile components in Artemisiae Verlotori Folium(mainly sesquiterpenoids) and Artemisiae Argyi Folium(monoterpenoids). In addition, Artemisiae Argyi Folium had higher content of oxygen-containing derivatives than Artemisiae Verlotori Folium. Furthermore, the stoichiometric analysis showed that the two species could be distinguished by both HCA and OPLS-DA, indicating that the volatile components of the two were significantly different. This study can provide a scientific basis for the quality evaluation and data support for the local rational application of Artemisiae Verlotori Folium in Lingnan.

Textual research on Bungarus Parvus / 中国中药杂志

Bungarus Parvus, a precious animal Chinese medicinal material used in clinical practice, is believed to be first recorded in Ying Pian Xin Can published in 1936. This study was carried out to analyze the names, geographical distribution, morphological characteristics, ecological habits, poisonousness, and medicinal parts by consulting ancient Chinese medical books and local chronicles, Chinese Pharmacopeia, different processing standards of trditional Chinese medicine(TCM) decoction pieces, and modern literatures. The results showed that the earliest medicinal record of Bungarus Parvus was traced to 1894. In 1930, this medicinal material was used in the formulation of Annao Pills. The original animal, Bungarus multicinctus, was recorded by the name of "Bojijia" in 1521. The morphological characteristics, ecological habits, and poisonousness of the original animal are the same in ancient and modern records. The geographical distribution is similar between the ancient records and modern documents such as China Medicinal Animal Fauna. The dried body of young B. multicinctus is used as Bungarus Parvus, which lack detailed references. As a matter of fact, it is still inconclusive whether there are differences between young snakes and adult snakes in terms of active ingredients, pharmacological effects, and clinical applications. This study clarified the medicinal history and present situation of Bungarus Parvus. On the basis of the results, it is suggested that systematic comparison on young and adult B. multicinctus should be carried out to provide references for revising the medicinal parts of B. multicinctus.

Huangdi Anxiao Capsules-containing serum protects cell model from cognitive dysfunction in diabetes via inhibiting NLRP3-mediated pyroptosis / 中国中药杂志

This study aims to investigate the effects and the molecular mechanism of Huangdi Anxiao Capsules(HDAX)-containing serum in protecting the rat adrenal pheochromocytoma(PC12) cells from diabetes-associated cognitive dysfunction induced by high glucose and whether the mechanism is related to the regulation of NOD-like receptor thermal protein domain associated protein 3(NLRP3)-mediated pyroptosis. The PC12 cell model of diabetes-associated cognitive dysfunction induced by high glucose was established and mcc950 was used to inhibit NLRP3. PC12 cells were randomized into control, model, HDAX-containing serum, mcc950, and HDAX-containing serum+mcc950 groups. Methyl thiazolyl tetrazolium(MTT) assay was employed to determine the viability, and Hoechst 33258/PI staining to detect pyroptosis of PC12 cells. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of interleukin-1 beta(IL-1β) and IL-18. Western blot was employed to determine the protein levels of postsynaptic density protein 95(PSD-95), NLRP3, apoptosis-associated speck-like protein containing a CARD(ASC), gasdermin D(GSDMD), GSDMD-N, and cleaved cysteinyl aspartate specific proteinase-1(caspase-1), and RT-PCR to determine the mRNA levels of NLRP3, ASC, GSDMD, and caspase-1. The immunofluorescence assay was adopted to measure the levels and distribution of NLRP3 and GSDMD-N in PC12 cells. Compared with the control group, the model group showed decreased cell proliferation, increased PI positive rate, down-regulated protein level of PSD-95, up-regulated protein levels of NLRP3, ASC, GSDMD-N, GSDMD, and cleaved caspase-1, up-regulated mRNA levels of NLRP3, ASC, GSDMD, and caspase-1, and elevated levels of IL-1β and IL-18. Compared with the model group, HDAX-containing serum, mcc950, and the combination of them improved cell survival rate and morphology, decreased the PI positive rate, down-regulated the protein levels of NLRP3, ASC, GSDMD-N, GSDMD, and cleaved caspase-1 and the mRNA levels of NLRP3, ASC, GSDMD, and caspase-1, and promoted the secretion of IL-1β and IL-18. The findings demonstrated that HDAX-containing serum can inhibit the pyroptosis-mediated by NLRP3 and protect PC12 cells from the cognitive dysfunction induced by high glucose.

Effect and mechanism of Zuogui Pills on neural function recovery in ischemic stroke mice based on OPN/IGF-1/mTOR / 中国中药杂志

To explore the effect and mechanism of Zuogui Pills in promoting neural tissue recovery and functional recovery in mice with ischemic stroke. Male C57BL/6J mice were randomly divided into a sham group, a model group, and low-, medium, and high-dose Zuogui Pills groups(3.5, 7, and 14 g·kg~(-1)), with 15 mice in each group. The ischemic stroke model was established using photochemical embolization. Stiker remove and irregular ladder walking behavioral tests were conducted before modeling and on days 7, 14, 21, and 28 after medication. Triphenyl tetrazolium chloride(TTC) staining was performed on day 3 after modeling, and T2-weighted imaging(T2WI) and diffusion-weighted imaging(DWI) were performed on day 28 after medication to evaluate the extent of brain injury. Hematoxylin-eosin(HE) staining was performed to observe the histology of the cerebral cortex. Axonal marker proteins myelin basic protein(MBP), growth-associated protein 43(GAP43), mammalian target of rapamycin(mTOR), and its downstream phosphorylated s6 ribosomal protein(p-S6), as well as mechanism-related proteins osteopontin(OPN) and insulin-like growth factor 1(IGF-1), were detected using immunofluorescence and Western blot. Zuogui Pills had a certain restorative effect on the neural function impairment caused by ischemic stroke in mice. TTC staining showed white infarct foci in the sensory-motor cortex area, and T2WI imaging revealed cystic necrosis in the sensory-motor cortex area. The Zuogui Pills groups showed less brain tissue damage, fewer scars, and more capillaries. The number of neuronal axons in those groups was higher than that in the model group, and neuronal activity was stronger. The expression of GAP43, OPN, IGF-1, and mTOR proteins in the Zuogui Pills groups was higher than that in the model group. In summary, Zuogui Pills can promote the recovery of neural function and axonal growth in mice with ischemic stroke, and its mechanism may be related to the activation of the OPN/IGF-1/mTOR signaling pathway.

Correlation between body composition and cardiorespiratory fitness decline in physical examination population of different genders / 中华健康管理学杂志

Objective:To analyze the correlation between the body composition and cardiorespiratory fitness (CRF) decline in physical examination population of different genders.Methods:Clinical data of the cardiopulmonary exercise testing (CPET) and body composition analysis of 439 people who received physical examination in the Medical Examination Center of Peking University Third Hospital from May 2021 to September 2021 were retrospectively analyzed. The general data, physical examination, biochemical parameters, body composition and CPET results were collected. The subjects were divided into normal group and decline group according to the percentage of peak oxygen uptake (VO 2peak) levels ≥ 85% or<85%. Multivariate logistic regression was applied to investigate the influencing factors of CRF decline in subjects of different genders. Results:Among men, total cholesterol and triglyceride in the decline group were significantly higher than those in the normal group [(5.097±0.890) vs (4.865±0.856) mmol/L, (1.778±1.200) vs (1.485±0.709) mmol/L], and the blood homocysteine (Hcy) and skeletal muscle index were significantly lower than those in the normal group [13.00 (11.30, 15.90) vs 13.80 (12.05, 17.10) μmol/L, (7.89±0.65) vs (8.08±0.64) kg/m 2] (all P<0.05). Among women, skeletal muscle index in the decline group was significantly lower than that in the normal group [(6.21±0.52) vs (6.53±0.56)kg/m 2], and percent body fat was significantly higher than that in the normal group [(32.83±4.92)% vs (31.21±4.55)%] (all P<0.05). The elevation of triglyceride level ( OR=1.487, 95% CI: 1.042-2.121) and visceral fat area ( OR=1.032, 95% CI: 1.014-1.051) were positively correlated with the decline of CRF in man, the decrease of skeletal muscle index ( OR=0.215, 95% CI: 0.106-0.435) and the increase of percent body fat ( OR=1.149, 95% CI: 1.060-1.245) were positively correlated with the decrease of CRF in women (all P<0.05). Conclusions:There is a correlation between body composition and CRF decline in physical examination population of different genders. Men should control visceral fat more effectively, and women should pay attention to increase muscle mass while reducing body fat, in order to improve CRF.

Analysis of clinical phenotype and genotype of Chinese children with disorders of sex development / 中华儿科杂志

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.

Application of ureteral access sheath in the operation of middle and lower ureteral calculi in patients with massive benign prostatic hyperplasia / 中华外科杂志

Objective: To examine the effectiveness and safety of application of the ureteral access sheath in the treatment of middle or lower ureteral calculi in patients with large-volume benign prostatic hyperplasia above grade Ⅲ, which is expected to avoid the simultaneous or staged treatment of benign prostatic hyperplasia via eliminate the difficult angle and resistance of ureteroscopy caused by severe prostatic hyperplasia. Methods: From April 2018 to December 2020, the clinical data of 27 patients with massive benign prostatic hyperplasia above grade Ⅲ and middle and lower ureteral calculi treated with indwelling ureteral access sheath plus ureteroscopy holmium laser lithotripsy at Department of Urology, Zhejiang Quhua Hospital were retrospectively analyzed and followed up. All the patients were male, aged (69.7±12.8) years (range: 55 to 87 years). Prostate volume measured by transrectal ultrasound was (94.8±16.2) cm3 (range: 85 to 186 cm3). The ureteral access sheath was indwelled in advance, and then the semirigid ureteroscopy was introduced through the working channel of the sheath. Holmium laser lithotripsy was performed, and intraoperative and postoperative complications were recorded. Urinary abdominal plain X-ray or CT urography were performed at 1-and 2-month postopaerative to evaluate the residual stones and clinical efficacy. Results: The ureteral access sheath was placed and holmium laser lithotripsy under a semirigid ureteroscopy was performed successfully in all the 27 patients. In 2 patients, a second session of auxiliary procedure was required due to the large load of preoperative stones and residual stones after surgery, among whom 1 patient received extracorporeal shock wave lithotripsy and 1 patient underwent extracorporeal shock wave lithotripsy plus ureteroscopic lithotripsy. The stone free rate at 1-and 2-month postoperative were 92.6% (25/27) and 100% (27/27), respectively. There were no severe complications such as ureteral avulsion and perforation, perirenal hematoma, septic shock, severe hematuria, urinary retention, iatrogenic ureteral stricture occurred during and after the surgery. The ureteral calculus was wrapped by polyps heavily in 1 patient, he was diagnosed as ureteral stenosis 1 month postoperative, receiving laparoscopic resection of ureteral stricture plus anastomosis 3 months postoperative. Conclusions: In the operations of middle and lower ureteral calculi in patients with large-volume prostatic hyperplasia above grade Ⅲ, the ureteral access sheath can be placed first to effectively eliminate the difficult angle and resistance of ureteroscopy caused by severe prostatic hyperplasia, and then semirigid ureteroscopic lithotripsy can be safely performed. It could avoid the treatment of benign prostatic hyperplasia at the same time or by stages.

Index design of core elements of health examination report and pilot data analysis / 中华健康管理学杂志

Objective:To analyze the core elements′ index design of physical examination reports and pilot data.Methods:We searched and analyzed the core element indexes of the physical examination report in databases such as CNKI and Wanfang through the literature analysis method, forming the initial core element indicator set. Special working meetings were organized to discuss revisions and improvements. The core elements′ index set was formed using a mixed research method combined with the quantitative analysis results of pilot data and expert opinions. Six hundred and thirteen cases from five hospitals were included in this study, including Anzhen Hospital, Peking University Third Hospital, Beijing Physical Examination Center, Beijing Tongren Hospital, China-Japan friendship hospital.Results:The subjects were (49.5±17.6) years old, including 302 males (49.3%) and 311 females (50.7%). The physical examination conclusion indicates that the number of health problems is between five and eight, with no significant difference between men and women. The health history data analysis of different sexes showed that hypertension in men was significantly higher than in women (17.9% vs. 10.6%, P=0.010). The lifestyle and eating habits survey showed that men had significantly higher incidences of smoking and drinking than women (24.8% vs. 2.2%, P?0.001; 9.9% vs. 1.3%, P?0.001). The exercise habits and sleep survey showed that the proportion of men who did not exercise was lower than that of women (13.2% vs. 22.8%, P=0.022). There was no statistically significant difference in sleep duration between the sexes. Conclusions:The core elements of health examination reports can standardize the collection of physical examination data and improve its sharing and application. This can allow the reports to better assist the decisions based upon physical examination report data.

Epidemiological and clinical characteristics of melioidosis in Haikou City in 2000 - 2020 / 中华地方病学杂志

Objective:To understand the epidemiological and clinical characteristics of melioidosis in Haikou City, to rise the people's awareness of melioidosis and to provide basis for prevention and control of the disease.Methods:The clinical data of 254 patients with melioidosis treated in 4 Class A tertiary hospitals in Haikou City from January 2000 to September 2020 were collected, and the epidemiological characteristics, clinical manifestations, infection site, prognosis and drug sensitivity were retrospectively analyzed.Results:Among 254 patients with melioidosis, 226 males (88.98%) and 28 females (11.02%), and the gender ratio was 8.07 ∶ 1.00. Farmers were the main occupation, accounting for 37.80% (96/254). The median age was 53 years old, mainly in 41 - 80 years old, accounting for 83.46% (212/254). Han nationality was the most, accounting for 89.76% (228/254). The onset season was mainly in summer and autumn, and the peak was from August to October (117 cases). Patients were mainly distributed in coastal areas, among which Haikou City (49 cases) was the most, followed by Dongfang City (46 cases), Danzhou City (23 cases) and Wenchang City (21 cases). Totally 196 cases (77.17%) had basic diseases, diabetes was the most common (162 cases). The main symptoms of admission were fever (211 cases), followed by cough (108 cases) and expectoration (88 cases). The infection sites were mainly blood (104 cases, 40.94%), lung (60 cases, 23.62%), liver and spleen (32 cases, 12.60%). Totally 195 patients were treated with sensitive antibiotics, at discharge, 37 cases (18.97%) were cured, 129 cases (66.15%) improved, 18 cases (9.23%) did not heal, 7 cases (3.59%) died and 4 cases (2.05%) were discharged voluntarily. Results of drug sensitivity tests from 2010 to 2020 showed that the sensitivity rates of Burkholderia pseudomallei to imipenem (142 cases), meropenem (16 cases) and ceftazidime (141 cases) were all 100.00%, and the sensitivity rates of doxycycline (25 cases) and compound sulfamethoxazole (142 cases) were 92.00% (23/25) and 99.30% (141/142), respectively. Conclusions:Males, farmers, middle-aged and elderly people and people with diabetes and other basic diseases are the high incidence population of melioidosis in Haikou City. The incidence peak is in summer and autumn. The common clinical manifestations are fever, pulmonary infection, abscess of liver and spleen, etc. In the treatment, Burkholderia pseudomallei is more sensitive to imipenem, meropenem and ceftazidime.

Effect of ligustrazine on Gas/cAMP/PKA signal activity and airway inflammation in asthmatic rats / 中国药理学通报

Aim To investigate the effect of ligus- trazine on G-protein coupled receptor signal activity in ovalbumin ( OVA)-sensitized and challenged asthmatic rats.Methods This study replicated an OVA-in¬duced juvenile asthmatic rat model, and investigated the effect of ligustrazine on airway hyperresponsive- ness, airway inflammation, lung histopathology, IL-4, IL-5 , 1L-13 , TNF-cx levels in serum, cAMP concentra¬tion in plasma, CREB, PKA, Gas and GRK2 expres¬sion in lung tissues.Results It was showed that the resistance of lung (RL) in asthmatic rats increased, while the pulmonary dynamic compliance ( Cdvn) sig¬nificantly decreased ( P < 0.05 ) compared with the control rats, and the lung tissue injury was serious; the levels of IL-4, IL-5, IL-13, and TNF-cx in serum were significantly increased ( P <0.01 ).The cAMP level in plasma was reduced and the CREB and PKA expres¬ sions were down-regulated significantly ( P < 0.05 ).The Gas expression in lung in asthmatic rats was down- regulated while the GRK2 expression was up-regulated ( P <0.01 ).Ligustrazine coulrl improve the lung inju¬ry and lung function of asthmatic rats, decrease RL and increase Cdvn ( P < 0.05 ) , decrease the levels of 1L-4, 1L-5, 1L-13, and TNF-a in serum (P <0.01) , increase cAMP in plasma and up-regulate the PKA and CREB expression, down-regulate the GRK2 expression and up-regulate the Gas expression significantly ( P < 0.01).Conclusions The above study shows that li¬gustrazine can reduce the AHR, inhibit the inflamma¬tion in asthma, and the up-regulating of Gas/cAMP/ PKA signal activity may be its mechanism.

Gene expression signature analysis of peripheral blood mononuclear cells from patients with for high altitude pulmonary hypertension and value for potential drug selection / 中华心血管病杂志

Objective: To investigate the gene expression characteristics of peripheral blood mononuclear cells from patients with high altitude pulmonary hypertension (HAPH) in Naxi residents living in Lijiang, Yunnan, and to explore the underlying pathogenesis and value for potential drug selection. Methods: This is a case-control study. Six patients with HPAH (HPAH group) and 4 normal subjects (control group) were selected from the Naxi residents who originally lived in Lijiang, Yunnan Province. The general clinical data of the two groups were collected, and the related indexes of pulmonary artery pressure were collected. Peripheral blood mononuclear cells of the subjects were collected for RNA sequencing. The differences on gene expression, regulatory network of transcription factors and drug similarity between the two groups were compared. The results were compared with the public data of idiopathic pulmonary arterial hypertension (IPAH). Biological processes and signal pathways were analyzed and compared between HPAH and IPAH patients. Results: The age of 6 patients with HAPH was (68.1±8.3) years old, and there were 2 males (2/6). The age of 4 subjects in the control group was (62.3±10.9) years old, and there were 2 males (2/4). Tricuspid regurgitation velocity, tricuspid pressure gradient and pulmonary systolic pressure in HAPH group were significantly higher than those in control group (all P<0.05). The results of RNA sequencing showed that compared with the control group, 174 genes were significantly upregulated and 169 genes were downregulated in peripheral blood mononuclear cells of HAPH group. These differentially expressed genes were associated with 220 biological processes, 52 molecular functions and 23 cell components. A total of 21 biological processes and 2 signal pathways differed between HPAH and IPAH groups, most of which were related to inflammation and immune response. ZNF384, SP1 and STAT3 were selected as highly correlated transcription factors by transcription factor prediction analysis. Trichostatin A and vorinostat were screened out as potential drugs for the treatment of HAPH by drug similarity analysis. Conclusions: There are significant differences in gene expression in peripheral blood monocytes between HAPH patients and normal population, and inflammation and immune dysfunction are the main pathogenic factors. Trichostatin A and Vorinostat are potential drugs for the treatment of HAPH.