Research progress in optimization of therapeutic effect of antibodies against flavivirus / 中华微生物学和免疫学杂志

Flaviviruses are a class of positive-strand RNA viruses mainly transmitted by arthropods, which can cause high mortality and morbidity worldwide. At present, there is no specific therapy. Therapeutic antibodies bring hope for the treatment of flavivirus infection, but the antibody-dependent enhancement (ADE) effect induced by flavivirus infection can lead to disease progression. The ideal therapeutic antibodies against flaviviruses should not only treat flavivirus infection, but also avoid the harm caused by ADE. Therefore, researchers have optimized some of the antibodies to seek the best therapeutic antibodies. This review briefly described the research progress and mechanism of therapeutic antibodies against flaviviruses as well as some strategies to reduce the ADE effect induced by the therapeutic antibodies.

Establishment of an in vivo neutralization model based on H5N1 pseudovirus / 中华微生物学和免疫学杂志

Objective:To establish an in vivo infection model of H5N1 pseudovirus and to detect the neutralizing activity of FHA3 antibody using this model. Methods:Based on the sequence information of hemagglutinin (HA) and neuraminidase (NA) of A/Anhui/1/2005/H5N1 strain, two recombinant plasmids of pcDNA3.1-HA5 and pcDNA3.1-NA1 were constructed. The two plasmids and plasmid pNL4-3.Luc.R-E- were co-transfected into 293T cells to prepare H5N1 pseudovirus supernatant. The morphology of pseudovirus particles in the supernatant was observed by electron microscopy. MDCK cells were infected with the pseudovirus supernatant and the virus titer was detected. BALB/c mice were injected with the pseudovirus supernatant by intraperitoneal injection and subjected to bioluminescence imaging at 2, 5, 8, and 12 d after infection to detect the pseudovirus infection in vivo. The functional activity of FHA3 antibody in vivo was evaluated using the established mouse infection model. Results:The recombinant plasmids pcDNA3.1-HA5 and pcDNA3.1-NA1 were correctly constructed and could be used to prepare pseudovirus supernatants of high titer by co-transfecting 293T cells with the plasmid pNL4-3.Luc.R-E-. The virus particles were round under electron microscope. H5N1 pseudovirus-infected mice exhibits strong fluorescence signals, which were attenuated by FHA3 treatment before challenge.Conclusions:The in vivo infection model of H5N1 pseudovirus was successfully constructed and FHA3 antibody was proved to be protective against the pseudovirus infection.

Study on the objectivity and biological mechanism of Psoralea corylifolia Linn.'s 'Great dryness damages the liver' / 药学学报

According to the theory of 'Xingben Dazao' of Psoralea corylifolia Linn. (BL), the susceptible syndromes and biomarkers of liver injury caused by BL were searched. Rat models of kidney-yin deficiency syndrome (M_yin) and kidney-yang deficiency syndrome (M_yang) were established, and all animal experimental operations and welfare following the provisions of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Traditional Chinese Medicine (No. YFYDW2020017). The results showed that BL significantly decreased the body weight, water intake, and urine weight of M_yin rats and increase the organ indexes of the liver, testis, adrenal gland, and spleen and the expression of alanine aminotransferase (ALT). Meantime, BL significantly increased the urine weight of M_yang rats and decreased the expression of ALT and aspartate aminotransferase (AST). Hematoxylin and eosin (HE) staining showed that BL could aggravate inflammatory infiltration of hepatocytes in rats with M_yin and alleviate liver injury in rats with M_yang. Metabolomics identified 17 BL co-regulated significant differential metabolic markers in M_yin and M_yang rats. Among them, 8 metabolites such as glutamine, quinolinate, biliverdin, and lactosylceramide showed opposite trends, mainly involving cysteine and methionine metabolism, tyrosine metabolism, tryptophan metabolism, purine metabolism, sphingolipid metabolism, glycerol phospholipid metabolism, glutamine metabolism, and other pathways. M_yin/M_yang may be the susceptible constitution of BL for liver damage or protection, which may be related to the regulation of amino acid metabolism and sphingolipid metabolism. The study can provide some experimental data support for the safe and accurate use of BL in the clinical practice of traditional Chinese medicine.

Exploring the safe and rational use of Epimedii Folium based on the evolution of efficacy/toxicity records in ancient and modern literature / 药学学报

Epimedii Folium is a traditional non-toxic Chinese herbal medicine. However, liver injury caused by Chinese herb preparations, including Epimedii Folium, is frequently reported over the years. Based on ancient and modern literature, this paper systematically summarized and analyzed the safe application of Epimedii Folium from the perspectives of varieties, processing methods, clinical adverse reactions, pharmacological effects and toxic mechanism. Combined with our team work, we build the comprehensive prevention and control system "human-drug-application", for the safe and rational application of Epimedii Folium. This study is expected to provide support for scientific evaluation and precise prevention and control of the safety risk of Epimedii Folium.

New outlook on safety of traditional Chinese medicine: concept and practice / 中国中药杂志

Profound changes have taken place in human disease spectrum, constitution spectrum, and drug use behavior, and the safety of traditional Chinese medicine(TCM) faces new trends and problems. In particular, serious adverse reactions/events such as liver injury and kidney injury caused by non-toxic TCM have been frequently reported, overturning people's understanding of TCM safety, and even shaking the public's confidence in the development of TCM. In the new era of globalization, correctly understanding the situation and problems of TCM safety and addressing the dilemmas in safety evaluation and risk prevention of TCM are the key missions to be undertaken by TCM practitioners. This paper suggests that the situation and problems of TCM safety should be viewed objectively and dialectically, and the use standard of TCM should be advanced with the times. Furthermore, this paper puts forward the new conception and methodology of TCM safety(including one innovative understanding, two types of evaluation modes, tri-elements injury hypothesis; four-quadrant risk decision processes, and five-grade safety evidence body) for the first time, hoping to provide new theories, new strategies, new methods and successful examples for solving the safety problems of TCM.

Interpretation on Consensus on drug-induced liver injury by CIOMS Working Group:liver injury attributed to herbal and dietary supplements / 中国中药杂志

With the increase in the medical level, the improvement of adverse drug reaction(ADR) monitoring systems, and the enhancement of public awareness of safe medication, drug safety incidents have been frequently reported. Drug-induced liver injury(DILI), especially liver injury attributed to herbal and dietary supplements(HDS), has globally attracted high attention, bringing great threats and severe challenges to the people for drug safety management such as clinical medication and medical supervision. Consensus on drug-induced liver injury had been published by the Council for International Organizations of Medical Sciences(CIOMS) in 2020. In this consensus, liver injury attributed to HDS was included in a special chapter for the first time. The hot topics, including the definition of HDS-induced liver injury, epidemiological history, potential risk factors, collection of related risk signals, causality assessment, risk prevention, control and management were discussed from a global perspective. Based on the previous works, some experts from China were invited by CIOMS to undertake the compilation of this chapter. Meanwhile, a new causality assessment in DILI based on the integrated evidence chain(iEC) method was widely recognized by experts in China and abroad, and was recommended by this consensus. This paper briefly introduced the main contents, background, and characteristics of the Consensus on drug-induced liver injury. Significantly, a brief interpretation was illustrated to analyze the special highlights of Chapter 8, "Liver injury attributed to HDS", so as to provide practical references for the medical staff and the researchers who worked on either Chinese or Western medicine in China.

Thoughts on path of R&D and registration of innovative traditional Chinese medicine with synchronous transformation of "series prescriptions" / 中国中药杂志

Since the implementation of drug registration in China, the classification of Chinese medicine has greatly met the needs of public health and effectively guided the transformation, inheritance, and innovation of research achievements on traditional Chinese medicine(TCM). In the past 30 years, the development of new Chinese medicine has followed the registration transformation model of " one prescription for single drug". This model refers to the R&D and registration system of modern drugs, and approximates to the " law-abiding" medication method in TCM clinic, while it rarely reflects the sequential therapy of syndrome differentiation and comprehensive treatment with multiple measures. In 2017, Opinions on Deepening the Reform of Review and Approval System and Encouraging the Innovation of Drugs and Medical Devices released by the General Office of the CPC Central Committee and the General Office of the State Council pointed out that it is necessary to " establish and improve the registration and technical evaluation system in line with the characteristics of Chinese medicine, and handle the relationship between the traditional advantages of Chinese medicine and the requirements of modern drug research". Therefore, based on the development law and characteristics of TCM, clinical thinking should be highlighted in the current technical requirements and registration system of research and development of Chinese medicine. Based on the current situation of registration supervision of Chinese medicine and the modern drug research in China, the present study analyzed limitations and deficiency of " one prescription for single drug" in the research and development of Chinese medicine. Additionally, a new type of " series prescriptions" was proposed, which was consistent with clinical thinking and clinical reality. This study is expected to contribute to the independent innovation and high-quality development of the TCM industry.

Meta-analysis of efficacy and safety of Liuwei Wuling Tablets combined with conventional drugs in treatment of liver fibrosis and cirrhosis in chronic hepatitis B / 中国中药杂志

The present study evaluated the clinical efficacy and safety of Liuwei Wuling Tablets combined with conventional drugs for the treatment of liver fibrosis and cirrhosis in chronic hepatitis B. CNKI, Wanfang, VIP, CBM, PubMed, EMbase and Cochrane Library were searched for the relevant randomized controlled trials(RCTs) published from database inception to February 2021. All the retrieved papers were independently screened, extracted and evaluated by two researchers, followed by Meta-analysis by Review Manager 5.4. Finally, 18 RCTs were included, involving 2 168 patients(1 106 in the treatment group and 1 062 in the control group). The Meta-analysis results showed that compared with conventional drugs alone, Liuwei Wuling Tablets combined with conventional drugs could increase the effective rate of clinical treatment by reducing serum hyaluronic acid(HA), laminin(LN), procollagen type Ⅲ(PCⅢ), and type Ⅳ collagen(Ⅳ-C) to improve liver function, decreasing the levels of total bilirubin(TBiL), alanine amino-transferase(ALT), and aspartate aminotransferase(AST), and improving the negative conversion ratio of hepatitis B virus(HBV) DNA. In terms of safety, there were no serious adverse reactions in the treatment group and the control group. The results showed that Liuwei Wuling Tablets combined with antiviral or other conventional liver-protecting drugs could improve liver function, treat liver cirrhosis, and reduce liver fibrosis with high safety. However, due to the influence of literature quality and quantity, multi-center and high-quality RCTs with large sample size are needed for verification.

Jujuboside A inhibits oxidative stress damage and enhances immunomodulatory capacity of human umbilical cord mesenchymal stem cells through up-regulating IDO expression / 中国天然药物

Impaired immunomodulatory capacity and oxidative stress are the key factors limiting the effectiveness of mesenchymal stem cell transplantation therapy. The present study was aimed to investigate the effects of jujuboside A (JuA) on the protective effect and immunomodulatory capacity of human umbilical cord mesenchymal stem cells (hUC-MSCs). Hydrogen peroxide was used to establish an oxidative damage model of hUC-MSCs, while PBMCs isolated from rats were used to evaluate the effect of JuA pre-treatment on the immunomodulatory capacity of hUC-MSCs. Furthermore, Hoechst 33258 staining, lactate dehydrogenase test, measurement of malondialdehyde, Western blot, high-performance liquid chromatography; and flow cytometry were performed. Our results indicated that JuA (25 μmol·L-1) promoted the proliferation of hUC-MSCs, but did not affect the differentiating capability of these cells. JuA pre-treatment inhibited apoptosis, prevented oxidative damage, and up-regulated the protein expression of nuclear factor-erythroid factor 2-related factor 2 and heme oxygenase 1 in hUC-MSCs in which oxidative stress was induced with H2O2. In addition, JuA pre-treatment enhanced the inhibitory effect of hUC-MSCs against abnormally activated PBMCs, which was related to stimulation of the expression and activity of indoleamine 2,3-dioxygenase. In conclusion, our results demonstrate that JuA pre-treatment can enhance the survival and immunomodulatory ability through pathways related to oxidative stress, providing a new option for the improvement of hUC-MSCs in the clinical setting.

Schisandra chinensis Oil Attenuates Aristolochic Acid I-Induced Nephrotoxicity in vivo and in vitro / 中国结合医学杂志

OBJECTIVE@#To investigate the protective effects of Schisandra chinensis oil (SCEO) against aristolochic acid I (AA I)-induced nephrotoxicity in vivo and in vitro and elucidate the underlying mechanism.@*METHODS@#C57BL/6 mice were randomly divided into 5 groups according to a random number table, including control group, AA I group, and AA I +SCEO (0.25, 0.5 and 1 g/kg) groups (n=5 per group). Pretreatment with SCEO was done for 2 days by oral administration, while the control and AA I groups were treated with sodium carboxymethyl cellulose. Mice of all groups except for the control group were injected intraperitoneally with AA I (5 mg/kg) from day 3 until day 7. Histopathological examination and apoptosis of kidney tissue were observed by hematoxylin and eosin and TdT-mediated dUTP nick-end labeling (TUNEL) staining, respectively. The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and serum creatinine (SCr), as well as renal malondialdehyde (MDA), glutathione, r-glutamyl cysteingl+glycine (GSH), and superoxide dismutase (SOD) were analyzed using enzyme-linked immunosorbent assay (ELISA). Expressions of hepatic cytochrome P450 1A1 (CYP1A1), CYP1A2, and nad(p)hquinonedehydrogenase1 (NQO1) were analyzed using ELISA, quantitative real-time polymerase chain reaction (qPCR) and Western blot, respectively. In vitro, SCEO (40 µ g/mL) was added 12 h before treatment with AA I (40 µ mol/mL for 48 h) in human renal proximal tubule cell line (HK-2), then apoptosis and reactive oxygen species (ROS) were analyzed by flow cytometry.@*RESULTS@#SCEO 0.5 and 1 g/kg ameliorated histopathological changes and TUNEL+ staining in the kidney tissues of mice with AA I-induced nephrotoxicity, and reduced serum levels of ALT, AST, BUN and SCr (P<0.01 or P<0.05). SCEO 0.5 and 1 g/kg alleviated the ROS generation in kidney, containing MDA, GSH and SOD (P<0.01 or P<0.05). SCEO 1 g/kg increased the expressions of CYP1A1 and CYP1A2 and decreased NQO1 level in the liver tissues (P<0.01 or P<0.05). Besides, in vitro studies also demonstrated that SCEO 40 µ g/mL inhibited apoptosis and ROS generation (P<0.05 or P<0.01).@*CONCLUSIONS@#SCEO can alleviate AA I-induced kidney damage both in vivo and in vitro. The protective mechanism may be closely related to the regulation of metabolic enzymes, thereby inhibiting apoptosis and ROS production.

Preparation and identification of antibodies targeting influenza A virus N1 subtype neuraminidase / 中华微生物学和免疫学杂志

Objective:To prepare and identify a functional antibody FNA1 targeting the neuraminidase (NA) of influenza A virus N1 subtype.Methods:According to single-chain antibody fragment (scFv) sequence, the heavy chain and light chain variable region sequences of FNA1 were synthesized, and the recombinant expression plasmid pFRT-IgG1κ-FNA1 was constructed by linking the expression vector pFRT-IgG1κ. The FNA1 antibody was expressed in ExpiCHO cells and purified using affinity purification technique. The binding ability of FNA1 to the target proteins, influenza A virus N1 subtype NA antigens, was detected by ELISA. Flow cytometry was performed to analyze the binding ability of FNA1 to the NA antigens expressed on the surface of cell membrane. The in vitro activity of FNA1 against NA was evaluated by infecting 293T cells with pseudovirus. Results:Protein electrophoresis showed that FNA1 with high purity was obtained. FNA1 specifically recognized and bound to N1 subtype NA antigens in a concentration-dependent manner. FNA1 could effectively block NA activity by binding to N1 subtype NA protein expressed on the surface of cell membrane, thus inhibiting the release of packaged pseudovirus from cell surface and further inhibiting target cell infection.Conclusions:An antibody FNA1 targeting influenza A virus N1 subtype NA with in vitro functional activity was obtained.

Preparation and identification of a broad-spectrum antibody targeting hemagglutinin protein of influenza A virus / 中华微生物学和免疫学杂志

Objective:To prepare and identify a broad-spectrum antibody FHA3 targeting influenza A virus hemagglutinin (HA).Methods:According to the single-chain antibody fragment (scFv) sequence, the heavy chain (VH) and light chain (VL) variable regions of FHA3 were amplified by PCR and a recombinant plasmid pFRT-IgG1κ-FHA3 was constructed by linking the expression vector pFRT-IgG1κ. FHA3 was expressed in the ExpiCHO system and purified by affinity purification. The binding activity of FHA3 to influenza A virus HA was detected by ELISA. The neutralizing activity of FHA3 was detected in vitro by infecting host cells with pseudovirus. Results:SDS-PAGE showed that high-purity FHA3 was obtained. FHA3 could bind to H1N1 HA, H2N2 HA, H3N2 HA, H5N1 HA, H7N9 HA and H9N2 HA in a concentration-dependent manner. FHA3 had good neutralizing activity in vitro that was it could effectively block the invasion of H5N1 and H7N9 pseudoviruses into target cells at a low concentration of 5 μg/ml and H1N1 pseudovirus at 0.012 5 μg/ml. Conclusions:A broad spectrum antibody targeting HA protein of influenza A virus with neutralizing activity in vitro was obtained.

Progress in cross reactivity of neutralizing monoclonal antibodies against dengue virus / 中华微生物学和免疫学杂志

Neutralizing monoclonal antibodies against dengue virus cross-react with other flaviviruses due to the sequence homology between them, such as the antibodies targeting envelope protein and non-structural protein 1. Apart from exerting protective effects in infected animals, cross-neutralizing antibodies could also cause antibody-dependent enhancement (ADE) in vivo. This review summarized the progress in cross-reactivity of neutralizing antibodies against dengue virus.

Dengzhan shengmai capsule combined with donepezil hydrochloride in the treatment of Alzheimer's disease: preliminary findings, randomized and controlled clinical trial

SUMMARY OBJECTIVE: To observe the effects of Dengzhan Shengmai capsule combined with donepezil hydrochloride on cognitive function, daily living ability, and safety in patients with Alzheimer's disease. METHODS: A total of 294 patients with Alzheimer's disease were randomly divided into a treatment group and a control group, 147 cases each group. The control group was given oral donepezil hydrochloride 5 mg once a day, and the treatment group was given oral Dengzhan Shengmai capsule 0.36 g three times a day, based on the control group. RESULTS: At 3 and 6 months of treatment, the ADAS-cog score of the treatment group was 48.69±6.23 and 44.24±5.53; for the control group, 45.48±5.94 and 41.57±5.10. The difference between the two groups is statistically significant (p<0.05). At 3 and 6 months of treatment, the NO level in the treatment group was (46.28±6.68) umol/l, (43.55±7.92) umol/l, and the control group was (42.95±7.92) umol/l, (38.89±5.93) umol/l. The differences between both groups were statistically significant (p<0.05). At 3 and 6 months of treatment, ET levels in the treatment group were (156.08±17.39) ng/l, (144.91±17.60) ng/l, and the control group was (150.48±22.94) ng/l, (135.04±10.08) ng/l. Correlation analysis showed that ADAS-cog score was negatively correlated with NO and ET (p<0.001). CONCLUSIONS: Dengzhan Shengmai capsule combined with donepezil hydrochloride can improve cognitive function and the living capacity of patients with Alzheimer's disease, reduce the production of neurotoxic substances NO and ET, and provide higher safety.

Integrative medicine in the era of cancer immunotherapy: Challenges and opportunities / 中西医结合学报

Cancer immunotherapy has led to a new era of cancer treatment strategies, and transforming healthcare for cancer patients. Meanwhile, reports of immune-related adverse events have been increasing, greatly hindering the use of cancer immunotherapy. Traditional Chinese medicine (TCM), which has been widely used in Asian countries for thousands of years, is known to play a complementary role in the treatment of cancer. Taken in combined with conventional modern therapies, such as resection, ablation and radiotherapy, TCM exerts its main anti-cancer effects in two ways: health-strengthening (Fu-Zheng) and pathogen-eliminating (Qu-Xie). Theoretically, pathogen-eliminating TCM can promote the release of tumor-related antigens and should be able to increase the effect of immunotherapy, while health-strengthening TCM may have immune-enhancing mechanisms that overlap with immunotherapy. In the era of cancer immunotherapy, it is important to balance the use of TCM and immunotherapy, with the goal of enhancing immune efficacy and antagonizing immune toxicity. In this article, we discuss this issue by considering the mechanism of tumor immunotherapy, alongside the theoretical basis of TCM treatment of tumors, with the aim of bringing new insights to future research in this field.

Anti-inflammatory target prediction of Gentianae Radix et Rhizoma based on network pharmacology and construction of a bioassay method for its quality control / 中国中药杂志

Based on the heat-clearing and detoxifying effects of Gentianae Radix et Rhizoma, the network pharmacology is mainly used to predict the potential targets of Gentianae Radix et Rhizoma for anti-inflammatory activity and to perform the experimental verification. A method for detecting the biological potency of Gentianae Radix et Rhizoma based on verifiable targets has been established to provide a reference for improving the quality evaluation and control standards of Gentianae Radix et Rhizoma. High performance liquid chromatography can be used to construct chemical fingerprints of different batches of Gentianae Radix et Rhizoma. Constructing a component-target-disease network of Gentianae Radix et Rhizoma for its anti-inflammatory activity was applied to screen potential anti-inflammatory components and related targets of Gentianae Radix et Rhizoma, and to verify the target of Gentianae Radix et Rhizoma by using biological evaluation methods. Detecting the biological potency of different batches of Gentianae Radix et Rhizoma extracts was used to inhibit COX-2 enzyme activity based the verifiable target cyclooxygenase-2(COX-2). The results showed that different batches of Gentianae Radix et Rhizoma accorded with the pharmacopoeia testing regulations, and the chemical fingerprints have a high similarity(similarity>0.93), suggesting that there is no significant difference in the characteristics of the chemical components. Based on network pharmacology predictions, 18 candidate targets were found to have potential direct interactions with the ingredients in Gentianae Radix et Rhizoma. Among them, the most important target is COX-2. Based on the experimental verification of recombinant human COX-2 protease activity inhibition, Gentianae Radix et Rhizoma can inhibit the COX-2 enzyme activity in a dose-dependent manner. It can function with a low concentration(0.75 mg·mL~(-1)), which preliminarily confirmed the accuracy of network pharmacology prediction. The biological potency detection method of Gentianae Radix et Rhizoma based on COX-2 inhibitory activity was optimized and established. The qualitative response parallel line method was used to calculate the biological potency of anti-inflammatory activity, which ranged from 23.04 to 46.60 U·mg~(-1). For network pharmacology prediction, it can screen and clarify the possible targets of traditional Chinese medicine rapidly, which can guide the establishment of a biological evaluation method for the quality of medicinal materials with related activities. Compared with chemical fingerprints, the biological potency testing can better detect quality fluctuations of traditional Chinese medicine.

Research progress of correlation between multidrug resistance and transporters and traditional Chinese medicine intervention / 中国中药杂志

With the emergence of drug resistance in Western medicine, the repeated administration of clinical first-line drugs becomes more severe. There are many factors leading to multidrug resistance(MDR), so it is very difficult to solve the problem. Since traditional Chinese medicine(TCM) has been used in the field of MDR in recent years, the research on the transporter-associated drug resistance and intervention of TCM has gradually become a hot spot. Therefore, in order to further explore the relationships among drug resistance, transporters, and TCM intervention, we review the relevant research progress in recent years and comb the achievements and limitations of this research at present. In the end, we put forward the research direction of changing body's ADME through the host's transporters and gastrointestinal flora, which provides new ideas for future research.

Metabonomics study of Shouhui Tongbian Capsules in slow transit constipation based on UPLC-ESI-QE-Orbitrap-MS / 中国中药杂志

The effect of Shouhui Tongbian Capsules(SHTB) on the endogenous metabolites of colon tissue in mice with slow transit constipation was analyzed by metabolomics methods to explore its mechanism in the treatment of constipation. ICR mice were randomly divided into normal group, model group and SHTB group according to the body weight. The mice were given diphenoxylate to establish the slow transit constipation model. Mouse carbon ink pushing rate, first defecation time and the number of defecation particles in 12 h were observed. The mouse colon tissue was separated and the mucous cells were detected by Periodic acid Schiff and Alcian blue(AB-PAS) staining. Ultra-high-performance liquid chromatography electrospray ionization orbitrap tandem mass spectrometry(UPLC-ESI-Orbitrap-MS/MS) technology was used to characterize the differences in tissue metabolism to screen out the potential different metabolites and possible metabolic pathways in colon tissue. The results indicated that SHTB could significantly shorten the first defecation time and the number of defecations, and increase the number of intestinal peristalsis and mucous cells in the colonic mucosa compared to the model mice. Metabolomics results showed that, compared with the normal group, a total of 17 potential biomarkers, including L-kynurenine, N6,N6,N6-trimethyl-L-lysine, L-formylkynurenine, N6-acetyl-L-lysine, L-phenylalanine, phenylacetaldehyde, xanthoxin, thymidine, glycyl-L-leucine, cystathionine,(R)-1-aminopropan-2-ol, deoxycytidine, gamma-glutamyl-gamma-aminobutyraldehyde, D-galactose, L-arginine, L-proline and pyruvate, were found and identified in colon tissue. Treated with SHTB, these metabolic differences tended to return to normal levels. Therefore, it could be made a conclusion that the therapeutic effect of SHTB on chronic transit constipation may be related to regulating phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, arginine and proline metabolism, cysteine and methionine metabolism, tyrosine metabolism, arginine biosynthesis, pyruvate metabolism, glycolysis, pyrimidine metabolism, tricarboxylic acid cycle and galactose metabolism.

Comparative observation of laparoscopic robot-assisted pyeloplasty through transmesenteric approach and retrocolic approach in the treatment of children with hydronephrosis / 中华泌尿外科杂志

Objective:To compare the advantages and disadvantages of laparoscopic robot-assisted transmesenteric approach and retrocolic approach disconnected pyeloplasty in the treatment of children with hydronephrosis.Methods:From October 2020 to March 2021, 19 children with hydronephrosis were divided into two groups: intra-renal type and extra-renal type. Among them, 15 were males and 4 were females. The average age of the patients was 3.5 years old (0.2 years old to 16.8 years old), and the average weight was 18.4 kg (5.5 kg to 67.0 kg). The average ERPF of affected kidney before surgery was 35.4%(23.0%-49.8%). All of them were treated with laparoscopic robot-assisted transmesenteric approach and retrocolic approach disconnected pyeloplasty. The operation was performed in accordance with the standard surgical procedures of the guidelines. After the insertion of the trocar, the children in the transmesenteric group were exposed to the renal pelvis by incising the colonic mesangium into the retroperitoneal space, while in the retrocolic group, the peritoneum was cut into the retroperitoneal space to expose the renal pelvis. After that, the steps of incision, cutting, tube placement, and suture of the renal pelvis and ureter were the same in the two groups. Among the 10 cases of the extrarenal type, 6 cases were in the transmesenteric group and 4 cases were in the retrocolic group; among the 9 cases of the intrarenal type, 5 cases were in the transmesenteric group and 4 were in the retrocolic group. There was no statistically significant difference in age, weight, and renal function of the affected side before operation in different surgical approach groups ( P>0.05). The operation time, intraoperative anastomosis time, intraoperative blood loss and postoperative hospital stay were recorded and compared. There was no statistical difference in the age, weight, and renal function of the affected side before the operation. Results:19 cases were followed up for 6 months, no complications such as fever or wound infection occurred. The operation was successfully completed in all patients, no patients were transferred to open surgery, and the hydronephrosis was significantly reduced. Symptoms disappeared in both groups. Of the 19 children. In children with extrarenal type, the operation time of the transmesenteric group and the retrocolic group were (108.8±15.5) min and (132.8±7.6) min, and the intraoperative anastomosis time was (40.7±6.1) min and (51.5±5.5)min, the estimated intraoperative blood loss was (9.5±2.1) ml and (9.3±0.8) ml, respectively, and the postoperative hospital stay was (9.0±1.6) d and (9.3±2.9) d. The operation time and the difference of intraoperative anastomosis time was statistically significant ( P<0.05). In children with intrarenal type, the operation time of the transmesenteric group and the retrocolic group were (136.6±7.9) min and (116.5±13.5) min, and the intraoperative anastomosis time was (52.8±6.9) min and (40.8±6.2), min, the estimated blood loss during the operation was (11.4±2.3) ml and (10.5±0.9) ml, and the postoperative hospital stay was (8.8±1.7) d and (8.0±1.6) d. The operation time and The difference of intraoperative anastomosis time was statistically significant ( P<0.05). The 19 cases were followed up for 6 months, and there was no complications such as fever or wound infection. The volume of hydronephrosis was significantly reduced compared with that before operation, and the renal blood perfusion increased compared with that before operation. The difference was statistically significant ( P<0.05). Conclusion:In terms of shortening the operation time and suture time, for laparoscopic robot-assisted transmesenteric approach and retrocolic approach disconnected pyeloplasty in the treatment of children with hydronephrosis, the transtransmesenteric approach is more advantageous in the treatment of extrarenal hydronephrosis, while the retrocolic approach is more advantageous in the treatment of intrarenal hydronephrosis.

Fibrous hamartoma of infancy in the scrotum: a case report / 中华泌尿外科杂志

Fibrous hamartoma of infancy (FHI) in the scrotum of children is a rare benign soft tissue tumor, which mostly occurs in children under 2 years old. It grows rapidly in the early stage and is easily misdiagnosed as a malignant tumor adjacent to the testis. A case of FHI in the scrotum was admitted in our hospital in recent years, a tumor resection with preservation of testicle was performed, the lesion was completely removed. Postoperative follow-up was 20 months, and there was no evidence revealing recurrence of the tumor after excision.