Riesgos y beneficios de la profilaxis con sulfato ferroso en lactantes nacidos a término con niveles de hemoglobina y ferremia desconocidos / Risks and benefits of iron supplementation in full-term infants with unknown hemoglobin and ferritin levels

La seguridad y eficacia de los programas de suplementación con hierro a lactantes, está actualmente en discusión. El objetivo de esta revisión fue identificar estudios sobre riesgos y beneficios de la suplementación con hierro profiláctico en lactantes menores de un año, nacidos a término, con niveles de hemoglobina (Hb) y ferremia desconocidos. Se realizó una búsqueda en Pubmed y Cochrane, identificando 3 revisiones sistemáticas y metaanálisis. Estos estudios arrojaron resultados que indican mejoras en los niveles séricos de hierro y hemoglobina como resultado de la suplementación con hierro. Sin embargo, no se observó un beneficio significativo en el desarrollo cognitivo de los lactantes. Los efectos adversos más reportados son los gastrointestinales, efectos en el crecimiento (menor ganancia de talla y peso) y menor absorción de zinc. En resumen, la evidencia en cuanto a la profilaxis con hierro en lactantes es limitada, lo que nos lleva a recomendar un seguimiento cercano de los lactantes que reciben suplementos de hierro, con el objetivo de detectar posibles eventos adversos. Es fundamental evaluar cuidadosamente los riesgos y beneficios de esta intervención antes de su implementación (AU)

The safety and efficacy of iron supplementation programs for infants are currently under discussion. The objective of this review was to identify studies on the risks and benefits of prophylactic iron supplementation in infants under one year of age, born at term, with unknown hemoglobin (Hb) and serum iron levels. The search was conducted on Pubmed and Cochrane, identifying three systematic reviews and meta-analyses. The results indicate improvements in serum iron and hemoglobin levels as a result of iron supplementation. However, a significant benefit in infant cognitive development was not observed. The most reported adverse effects were gastrointestinal, effects on growth (reduced height and weight gain), and reduced zinc absorption. In summary, the evidence regarding iron prophylaxis in infants is limited, leading us to recommend close monitoring of infants receiving iron supplements to detect potential adverse events. It is crucial to carefully assess the risks and benefits of this intervention before implementation (AU)

Formation of Hyperprogression of Immunotherapy from Perspective of "Yang Deficiency and Toxin Knot" and Role of "Five Views on Differentiation and Treatment" Intervention / 中国实验方剂学杂志

Immune checkpoint inhibitors （ICIs） have shown good efficacy in tumor treatment and have changed the landscape of tumor treatment. However， some patients treated with ICIs have not only failed to achieve the desired therapeutic effect， but also developed an atypical response pattern of abnormally accelerated tumor growth， namely hyperprogressive disease （HPD）. The pathogenesis of HPD is still unclear and it is difficult to diagnose， which poses a challenge for clinical identification and treatment decisions. Exploring the underlying mechanism of HPD is important to improve the effect of immunotherapy. Based on the theory of "Yang deficiency and toxic knot"， this paper discussed the mechanism of HPD in immunotherapy from the perspective of "spleen and kidney Yang deficiency and hefty toxic pathogens". It was concluded that the inactivation of p53 oncogene and immunosuppressive microenvironment were the manifestations of the deficiency of healthy qi in the body and declined yang in the spleen and kidney， serving as an important basis for the occurrence of HPD. Adverse reactions caused by ICIs belong to the category of "drug toxicity". The occurrence and development of murine double minute 2 （MDM2）/murine double minute 4 （MDM4） activation， epidermal growth factor receptor （EGFR） mutation， and tumor inflammatory microenvironment are the manifestations of the hyperactivity of pathogenic Qi， conflict of cancer toxicity and drug toxicity， and being hefty by virtue of deficiency， which can promote the abnormal proliferation of tumor cells， and they are the core pathogenic elements of HPD and are closely related to disease prognosis. In terms of treatment， under the guidance of the theory of "five views on differentiation and treatment" （time-space view， core view， symptom view， precision view， and disease-before-onset view）， which was summarized according to the clinical practice of this research team， this paper， taking the prevention and treatment of HPD as the entry point， formulated traditional Chinese medicine （TCM） compounds to reinforce healthy Qi and warm Yang and realize the dynamic management of the whole spatiotemporal cycle， and removed toxins and resisted cancer to realize the all-round systemic intervention of the specimen. Additionally， targets were enriched in the macro-clinical manifestations and microscopic pathological changes of HPD to improve the targeting of drug selection and the precision of prevention and treatment， giving full play to the unique therapeutic advantages of TCM， and providing new ideas for the clinical application of TCM in the prevention and treatment of HPD.

Combined Therapies of Traditional Chinese Medicine Treat Low-prognosis Patients Undergoing IVF-ET Again / 中国实验方剂学杂志

ObjectiveTo objectively evaluate the clinical efficacy of multiple therapies of traditional Chinese medicine （TCM） in low-prognosis patients who received antagonist protocol for in vitro fertilization and embryo transfer （IVF-ET） again. MethodA total of 128 patients with kidney Yin deficiency， liver depression， and blood stasis who planned to receive antagonist protocol for IVF-ET in the West China Second Hospital of Sichuan University were enrolled and assigned into two groups by random number table method. The observation group （64 casces） was treated by oral administration of Chinese medicine decoction + enema of kidney-tonifying and blood-activating method + auricular point sticking + oral administration of dehydroepiandrosterone （DHEA）， while the control group （64 casces） was treated by only oral administration of DHEA. After treatment for three menstrual cycles， both groups received the antagonist protocol for IVF-ET. The TCM syndrome scores， basic sex hormone levels， antral follicle count （AFC）， the usage of gonadotropin （Gn）， endometrial receptivity indicators， embryo quality indicators， and pregnancy outcomes were compared between the two groups. ResultAfter treatment， the observation group showed decreased follicle-stimulating hormone （FSH）/luteinizing hormone （LH） ratio， lowered level of estradiol （E2）， increased AFC， decreased amount and days of Gn usage， improved endometrial receptivity indicators （endometrial thickness on trigger and ET days， proportion of endometrial type A in endometrial types and the level of E2 on trigger day） and embryo quality indicators （the rates of mature follicles， fertilization， normal fertilization， and premium embryos）， and decreased TCM syndrome scores （P<0.05， P<0.01）. Moreover， the observation group had lower FSH/LH ratio， E2 level， and amount of Gn usage， higher AFC， poorer endometrial receptivity and embryo quality indicators， and lower TCM syndrome scores than the control group after treatment （P<0.05， P<0.01）. In addition， except for 3 cases of natural pregnancy， the observation group outperformed the control group in terms of improving the clinical pregnancy rates during initiation cycle and transplantation cycle and clinical pregnancy rate and decreasing biochemical pregnancy rate and early abortion rate （P<0.05）. ConclusionCombined therapies of TCM can alleviate the clinical symptoms， reduce TCM syndrome scores， reduce the Gn usage amount， improve the number and quality of embryos and endometrial receptivity， and coordinate the synchronous development of endometrium and embryo. In this way， they can increase the clinical pregnancy rate and reduce biochemical pregnancy rate and early abortion rate in the low prognosis patients with kidney yin deficiency， liver depression， and blood stasis who are undergoing IVF-ET again.

Clinical, biochemical, and radiologic profiles of Filipino patients with 6-Pyruvoyl-Tetrahydrobiopterin Synthase (6-PTPS) deficiency and their neurodevelopmental outcomes

Background@#Six-pyruvoyl-tetrahydrobiopterin synthase (6-PTPS) deficiency is an inherited metabolic disorder which results in tetrahydrobiopterin (BH4) deficiency causing hyperphenylalaninemia.@*Objective@#This study aimed to describe the clinical, biochemical, and radiologic profiles, and neurologic and developmental outcomes of patients diagnosed with 6-pyruvoyl tetrahydrobiopterin (PTPS) deficiency through newborn screening and confirmed by BH4 loading test, pterin analysis, and gene sequencing who were following-up with the metabolic team.@*Methods@#The research was a single-center descriptive case series study design that was done at the Philippine General Hospital, a tertiary government hospital. The clinical, biochemical, radiologic profiles and neurodevelopmental evaluation of each patient were described.@*Results@#Nine patients from 1 year 2 months to 14 years 5 months of age were enrolled in the study. Clinical manifestations before treatment were hypotonia, poor suck, and seizure. The most common clinical manifestation even after treatment initiation was seizure. The mean phenylalanine level on newborn screening was 990.68 umol/L, but after treatment was started, mean levels ranged from 75.69 to 385.09 umol/L. Two of the patients had focal atrophy of the posterior lobe on brain imaging. Pathogenic variants on molecular analysis were all missense, with two predominant variants, c.155A>G and c.58T>C. Eight of the nine patients had varying degrees of developmental delay or intellectual disability, while the remaining patient had signs of a learning disorder. @*Conclusion@#Newborn screening has played a crucial role in the early identification and management of patients with hyperphenylalaninemia due to 6-PTPS deficiency. Confirmation of diagnosis through determination of DHPR activity, urine pterins and/or molecular analysis is necessary for appropriate management. However, despite early initiation of treatment, neurodevelopmental findings of patients with 6-PTPS deficiency were still unsatisfactory.

Clinical Efficacy of Fuzheng Huaji Longbi Decoction in Treating Benign Prostatic Hyperplasia with Syndrome of Healthy Qi Deficiency and Blood Stasis / 中国实验方剂学杂志

ObjectiveTo explore the clinical efficacy and safety of Fuzheng Huaji Longbi decoction in treating benign prostatic hyperplasia （BPH） in the patients with the syndrome of healthy Qi deficiency and blood stasis. MethodA total of 94 BPH patients were randomized into control and observation groups， with 47 patients in each group. The control group was treated with doxazosin mesylate sustained-release tablets， and the observation group with Fuzheng Huaji Longbi decoction on the basis of the therapy in the control group. After eight weeks， the international prostate symptom score （IPSS）， quality of life （QOL） score， residual urine volume （RUV）， maximum urinary flow rate （Qmax）， TCM syndrome score， TCM symptom score， electrocardiogram， and liver and kidney function were determined to evaluate the clinical efficacy and safety of the two groups. ResultAfter 8 weeks of treatment， the total response rate in the control group was 63.64% （28/44）， which was lower than that （84.44%， 38/45） in the observation group （χ2=5.026， P<0.05）. The clinical efficacy in the observation group was higher than that in the control group （Z=-2.17， P=0.030）. The treatment in both groups decreased the IPSS， QOL score， RUV， and TCM syndrome scores and increased the Qmax （P<0.05）. Moreover， the observation group had lower IPSS， QOL score， RUV， and TCM syndrome score （P<0.05） and higher Qmax than the control group after treatment （P<0.05）. The treatment in the observation group decreased all the TCM symptom scores （P<0.05）， while that in the control group only decreased the frequency of urination at night and the scores of dysuria， weak urine stream， and post-urinary drainage （P<0.05）. After treatment， the observation group had lower frequency of urination at night and lower scores of mental fatigue， cold limbs， lower abdominal discomfort， and loose stool than the control group （P<0.05）. No adverse events associated with the administration of Fuzheng Huaji Longbi decoction were observed during the treatment period. ConclusionFuzheng Huaji Longbi decoction is effective in treating BPH in the patients with the syndrome of healthy qi deficiency and blood stasis. It can relieve the clinical symptoms and improve the quality of life， being a safe and reliable choice for clinical application.

Staging Sequential Treatment of Ischemic Stroke Based on Syndrome Differentiation of Deficiency and Excess in Eight Principles / 中国实验方剂学杂志

The core of diagnosing and treating diseases in traditional Chinese medicine lies in syndrome differentiation. The eight principles of syndrome differentiation serve as guidance for syndrome differentiation. As one of the eight principles of syndrome differentiation， the differentiation of deficiency and excess is the basic and critical method. Ischemic stroke is currently the leading cause harming the health of Chinese residents. Although the hypotheses about the cause of ischemic stroke have evolved from external wind to the later internal wind and to the modern theory of toxin damaging the brain collaterals， they all believe that this disease is rooted in internal deficiency and external excess. According to available studies， although stroke is characterized by complex pathogenesis and rapid progression of syndromes， the key cause evolution has a regularity， that is， from excess to deficiency. This article analyzes the historical evolution of the etiology， pathogenesis， and syndrome differentiation schemes of stroke. There are diverse schemes for the syndrome differentiation of stroke， which make it difficult to choose in clinical practice. In view of this problem， this paper puts forward a new approach of staging sequential treatment of ischemic stroke based on the differentiation of deficiency and excess according to the evolution law of the key cause of stroke. Furthermore， we conducted a randomized controlled study on 100 patients with ischemic stroke to evaluate this new approach. The results showed that the staging sequential treatment of ischemic stroke based on the differentiation of deficiency and excess demonstrated definite clinical efficacy. In addition， this article reviews the previous research results of our team and the research achievements of other teams to preliminarily explore the relationship between stroke syndromes and biomarkers， aiming to provide an objective basis for unveiling the pathogenesis of stroke. In summary， according to the key cause evolution （from excess to deficiency）， the treatment of ischemic stroke by stages based on differentiation of deficiency and excess can facilitate the rapid intervention and improve the clinical efficacy on ischemic stroke.

Mitochondrial Quality Control Affects Diabetic Cardiomyopathy：Based on Theory of Qi Deficiency and Stagnation / 中国实验方剂学杂志

With the increasing incidence of diabetes mellitus in recent years， cardiomyopathy caused by diabetes mellitus has aroused wide concern and this disease is characterized by high insidiousness and high mortality. The early pathological changes of diabetic cardiomyopathy （DCM） are mitochondrial structural disorders and loss of myocardial metabolic flexibility. The turbulence of mitochondrial quality control （MQC） is a key mechanism leading to the accumulation of damaged mitochondria and loss of myocardial metabolic flexibility， which， together with elevated levels of oxidative stress and inflammation， trigger changes in myocardial structure and function. Qi deficiency and stagnation is caused by the loss of healthy Qi， and the dysfunction of Qi transformation results in the accumulation of pathogenic Qi， which further triggers injuries. According to the theory of traditional Chinese medicine （TCM）， DCM is rooted in Qi deficiency of the heart， spleen， and kidney. The dysfunction of Qi transformation leads to the generation and lingering of turbidity， stasis， and toxin in the nutrient-blood and vessels， ultimately damaging the heart. Therefore， Qi deficiency and stagnation is the basic pathologic mechanism of DCM. Mitochondria， similar to Qi in substance and function， are one of the microscopic manifestations of Qi. The role of MQC is consistent with the defense function of Qi. In the case of MQC turbulence， mitochondrial structure and function are impaired. As a result， Qi deficiency gradually emerges and triggers pathological changes， which make it difficult to remove the stagnant pathogenic factor and aggravates the MQC turbulence. Ultimately， DCM occurs. Targeting MQC to treat DCM has become the focus of current research， and TCM has the advantages of acting on multiple targets and pathways. According to the pathogenesis of Qi deficiency and stagnation in DCM and the modern medical understanding of MQC， the treatment should follow the principles of invigorating healthy Qi， tonifying deficiency， and regulating Qi movement. This paper aims to provide ideas for formulating prescriptions and clinical references for the TCM treatment of DCM by targeting MQC.

Clinical Observation on Rongjin Tongbi Decoction in Treating Sciatica Caused by Lumbar Intervertebral Disc Herniation with Liver and Kidney Deficiency Type / 中国实验方剂学杂志

ObjectiveTo evaluate the efficacy and safety of Rongjin Tongbi decoction on sciatica caused by lumbar intervertebral disc herniation with liver and kidney deficiency type based on a randomized controlled study. MethodFrom January 2019 to July 2022， 90 patients in the department of Traditional Chinese medicine（TCM） of Beijing Jishuitan Hospital who met the inclusion criteria were selected and divided into two groups according to the random number table， with 45 patients in each group. During the study， 19 cases dropped out， with 41 cases included in the final observation group and 30 cases in the control group. The observation group was given Rongjin Tongbi decoction orally， and the control group was given Loxoprofen Sodium Tablets orally for 28 days. The differences in the visual analog scale （VAS） scores， the Japanese Orthopaedic Association （JOA） scores， activities of daily living （ADL） assessments， TCM clinical symptoms， subjective symptoms， and clinical signs scores between two groups before and after treatment were observed. Liver and kidney functions and gastrointestinal adverse reactions were detected for safety evaluation. ResultBefore treatment， there was no statistically significant difference in scores between the observation group and the control group. After treatment， the absolute values of the differences in VAS and ADL scores in the observation group were higher than those in the control group （P<0.05）. There was no statistically significant difference in the absolute value of the difference in JOA scores between two groups. The absolute value of the difference in TCM clinical symptom scores in the observation group was higher than that in the control group （P<0.01）. There was no statistically significant difference in the absolute values of the differences in subjective symptom and clinical sign scores between two groups. The levels of liver and kidney function indicators in both groups before and after the experiment were normal， and there was no significant difference in gastrointestinal reactions. ConclusionRongjin Tongbi decoction can significantly improve the symptoms of sciatica patients caused by lumbar intervertebral disc herniation with liver and kidney deficiency type. After treatment， the patients exhibited significant improvements in pain， activity and other aspects， and it is proven to be safe and reliable， which is conducive to the recovery of physical function.

Adenine phosphoribosyltransferase deficiency after kidney transplantation: a case report and literature review / 器官移植

Objective To summarize the diagnosis and treatment experience of adenine phosphoribosyltransferase deficiency after kidney transplantation. Methods Clinical data of 1 patient with adenine phosphoribosyltransferase deficiency after kidney transplantation were retrospectively analyzed. Clinical characteristics, diagnosis, treatment and prognosis of adenine phosphoribosyltransferase deficiency were summarized by literature review. Results Renal biopsy showed that salt crystallization was found in most renal tubule lumen and positive results were observed under polarized light microscopy. After allopurinol, hemodialysis and anti-crystallization treatment, the graft function was gradually recovered. After postoperative 1-year follow-up, the patient's renal function was properly recovered. Conclusions Adenine phosphoribosyltransferase deficiency after kidney transplantation may lead to delayed graft function or graft dysfunction. Early detection, diagnosis and treatment may delay disease progression and improve renal function.

Sishenwan Combined with Tongxie Yaofang Treats Ulcerative Colitis with Spleen-kidney Yang Deficiency and Liver Depression / 中国实验方剂学杂志

ObjectiveTo induce the rat model of ulcerative colitis （UC） with spleen-kidney Yang deficiency and liver depression， and explore the efficacy and mechanism of Sishenwan combined with Tongxie Yaofang （SSW&TXYF） based on the therapeutic principles of tonifying spleen， soothing liver， warming kidney， and astringing intestine. MethodSixty male SD rats were randomized into normal， model， mesalazine， and high-， medium-， and low-dose SSW&TXYF groups. The rats in other groups except the normal group were administrated with Sennae Folium decoction and hydrocortisone and received tail clamping for 14 days. On day 14， rats received enema with TNBS-ethanol solution to induce UC. The rats were administrated with corresponding drugs from day 15 of modeling， and the body weight and mental state were observed and recorded. The sucrose preference test was performed from day 25. On day 28， the rectal temperature was measured， and the rats were administrated with 3% D-xylose solution at a dose of 10 mL·kg-1 by gavage. Blood was sampled 1 h later， from which the serum was collected for measurement of the D-xylose content. The serum， hippocampus， and colorectum samples of rats were collected on day 29. The levels of gastrin （GAS）， adrenocorticotropic hormone （ACTH）， corticosterone （CORT）， cyclic adenosine monophosphate （cAMP）， cyclic guanosine monophosphate （cGMP）， interleukin （IL）-4， tumor necrosis factor （TNF）-α， and interferon （IFN）-γ in the serum and 5-hydroxytryptamine （5-HT） in the hippocampus were determined by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was employed to reveal the colonic lesions. The mRNA and protein levels of p38 mitogen-activated protein kinase （MAPK）， extracellular signal-regulated kinase （ERK）， and c-Jun N-terminal kinase （JNK） in the colon tissue were determined by Real-time PCR and Western blot， respectively. ResultCompared with the normal group， the model group showed decreased body weight， anal temperature， and D-xylose content in the serum and increased GAS content （P<0.01）. The modeling led to cAMP/cGMP unbalance and decreased the ACTH and CORT content in the serum （P<0.01）， the preference for sucrose water， and the 5-HT content in the hippocampus （P<0.01）. Moreover， it shortened the colorectal length and caused massive infiltration of inflammatory cells and severe structural damage in the colon tissue. High， medium， and low doses of SSW&TXYF improved above indicators （P<0.05， P<0.01）， reduced inflammatory infiltration， and repaired the pathological damage of the tissue. Compared with the normal group， the model group showed lowered IL-4 level （P<0.01） and elevated TNF-α and IFN-γ levels （P<0.05， P<0.01） in the serum， as well as up-regulated expression of p38 MAPK， ERK， and JNK （P<0.05， P<0.01）. Compared with the model group， SSW&TXYF elevated the IL-4 level （P<0.01）， lowered the TNF-α and IFN-γ levels （P<0.05， P<0.01）， and down-regulated the mRNA and protein levels of p38 MAPK， ERK， and JNK （P<0.05， P<0.01）. ConclusionA rat model of UC with spleen-kidney Yang deficiency and liver depression was successfully established. SSW&TXYF can significantly mitigate this syndrome by reducing the inflammatory response in the colon and inhibiting the MAPK pathway.

Identification of banana ADA1 gene family members and their expression profiles under biotic and abiotic stresses / 生物工程学报

The Spt-Ada-Gcn5-acetyltransferase (SAGA) is an ancillary transcription initiation complex which is highly conserved. The ADA1 (alteration/deficiency in activation 1, also called histone H2A functional interactor 1, HFI1) is a subunit in the core module of the SAGA protein complex. ADA1 plays an important role in plant growth and development as well as stress resistance. In this paper, we performed genome-wide identification of banana ADA1 gene family members based on banana genomic data, and analyzed the basic physicochemical properties, evolutionary relationships, selection pressure, promoter cis-acting elements, and its expression profiles under biotic and abiotic stresses. The results showed that there were 10, 6, and 7 family members in Musa acuminata, Musa balbisiana and Musa itinerans. The members were all unstable and hydrophilic proteins, and only contained the conservative SAGA-Tad1 domain. Both MaADA1 and MbADA1 have interactive relationship with Sgf11 (SAGA-associated factor 11) of core module in SAGA. Phylogenetic analysis revealed that banana ADA1 gene family members could be divided into 3 classes. The evolution of ADA1 gene family members was mostly influenced by purifying selection. There were large differences among the gene structure of banana ADA1 gene family members. ADA1 gene family members contained plenty of hormonal elements. MaADA1-1 may play a prominent role in the resistance of banana to cold stress, while MaADA1 may respond to the Panama disease of banana. In conclusion, this study suggested ADA1 gene family members are highly conserved in banana, and may respond to biotic and abiotic stress.

Functions of HIV-1 Tat and its association with diseases / 中国生物制品学杂志

@#Acquired immune deficiency syndrome,or AIDS,has been a major infectious disease that troubles the public health in a global scale. Human immunodeficiency virus type 1(HIV-1)is the causative reagent responsible for AIDS development. Even though the highly active anti-retroviral therapy(HAART,or the cocktail therapy)that has been widely applied could effectively suppress the infection and replication of HIV-1,the infected people suffer from other related diseases,such as the HIV-associated neurocognitive disorder(HAND). This paper mainly focused on the function of an important regulatory protein of HIV-1,trans-activator of transcription(Tat),and its correlation with HIV-1 replication and HAND development,so as to clarify the importance of developing anti-AIDS drugs targeting Tat protein

Yunkang Oral Liquid Promotes Restoration of Mice from Postpartum Kidney Deficiency via TGF-β/Smads Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Yunkang oral liquid on postpartum kidney deficiency in mice. MethodPostpartum mice were randomized into model and low-dose （6 mL·kg-1）， medium-dose （9 mL·kg-1）， and high-dose （12 mL·kg-1） Yunkang oral liquid groups. The mouse model of postpartum kidney deficiency was established by sleep deprivation combined with forced swimming. Another 9 female ICR mice were selected as the normal control group. The mice were administrated with Yunkang oral liquid during the period of modeling. The levels of estradiol （E2）， progesterone （P）， follicle-stimulating hormone （FSH）， and luteinizing hormone （LH） in the serum were measured by the enzyme-linked immunosorbent assay. The morphological changes of ovaries and uterus were observed by hematoxylin-eosin （HE） staining， and the expression of transforming growth factor （TGF）-β and Smad2/3 was determined by immunohistochemistry and Western blotting. ResultThe mice in the model group showed prolonged estrous cycle， reduced voluntary activity， dorsal temperature， grip strength， and bone strength， and whitening tongue coating. Compared with the model group， Yunkang oral liquid shortened the estrous cycle， increased the voluntary activity， dorsal temperature， grip strength， and bone strength， and alleviated the whitening of tongue coating. Moreover， it elevated the E2 and P levels and lowered the FSH and LH levels in the serum， decreased ovarian follicular atresia rate， promoted uterine repair， and down-regulated the expression of TGF-β and Smad2/3 in the ovarian and uterine tissues. ConclusionYunkang oral liquid can ameliorate postpartum kidney deficiency in mice by regulating the TGF-β/Smads signaling pathway.

Syndromes and Mechanisms of Depression Induced by Second Hit in Mice / 中国实验方剂学杂志

ObjectiveTo explore the syndromes and mechanisms of depression induced by maternal separation （MS） combined with chronic restraint stress （RS） in mice. MethodOn postnatal day 0 （PD0）， the offspring mice were randomized into a blank group （NC） and a modeling group. The mouse model of depression was established by MS+RS for 21 days. After removal of female mice on PD21， the modeled mice were randomized into model， Wenyang， Jieyu， Wenyang Jieyu， and fluoxetine groups， with 15 mice in each group. The sucrose preference， tail suspension， and open field tests were carried out to evaluate the anxiety and depression-like behavior in mice. Enzyme-linked immunosorbent assay was used to measure the adrenocorticotrophic hormone （ACTH） and corticosterone （CORT） levels in mouse plasma. High performance liquid chromatography-electrochemical detector was used to determine the content of monoamine neurotransmitters in the hippocampus. Real-time fluorescence quantitative polymerase chain reaction was employed to determine the mRNA levels of genes in the 5-hydroxytryptamine （5-HT） system， hypothalamic-pituitary-adrenal （HPA） axis， and brain-derived neurotrophic factor （BDNF） signaling pathway in the hippocampus. Immunohistochemistry was employed to determine the expression levels of proteins in the 5-HT system and HPA axis in the hippocampus. The Simple Western system was used to determine the protein levels of BDNF and tyrosine kinase receptor B （TrkB） in the hippocampus. ResultCompared with the NC group， the model group exhibited depression-like behavior， which was significantly relieved by Wenyang Jieyu prescription and fluoxetine. Compared with the NC group， the model group showed elevated levels of CORT and ACTH in the plasma （P<0.01）， which， however， were lowered by Wenyang Jieyu prescription and fluoxetine （P<0.05， P<0.01）. Compared with the NC group， the model group showed inhibited expression of neurotransmitters in the hippocampus （P<0.05， P<0.01）， while Wenyang Jieyu prescription and fluoxetine restored the expression of neurotransmitters （P<0.05， P<0.01）. Compared with NC group， the model group showed inhibition of the 5-HTergic nerve and abnormal activation of the HPA axis， and Wenyang Jieyu prescription and fluoxetine regulated the abnormal state of the 5-HTergic nerve and HPA axis. Compared with NC group， the modeling down-regulated the mRNA and protein levels of BDNF and TrkB in the hippocampus （P<0.05， P<0.01）， which， however， were recovered in Wenyang， Jieyu， Wenyang Jieyu， and fluoxetine groups （P<0.05， P<0.01）. ConclusionThe mouse model of depression induced by MS+RS may present the syndrome of Yang deficiency and liver depression. Wenyang Jieyu prescription may increase the content of hippocampal neurotransmitters by regulating the 5-HT system and the BDNF signaling pathway mediated by the HPA axis， thereby alleviating depression-like behavior in mice.

Mechanism of Bushen Yijing Method in Treatment of Oligoasthenozoospermia Based on Intestinal Microbiota / 中国实验方剂学杂志

Oligoasthenozoospermia is the main cause of male infertility， with complex and diverse causes. Currently， there are still some unclear causes of oligoasthenozoospermia in clinical practice， known as idiopathic oligoasthenozoospermia. With the development of high-throughput sequencing technology， it has been found that intestinal microbiota disorder may be an important promoting factor for the onset of oligoasthenozoospermia. Traditional Chinese medicine believes that "deficiency of kidney essence" is the core pathogenesis of oligoasthenozoospermia. In clinical practice， the method of tonifying the kidney and strengthening the essence has a significant therapeutic effect on oligoasthenozoospermia， but its mechanism of action has not been fully elucidated. Based on the basic theories of traditional Chinese medicine and molecular biology research， it has been found that there is a similarity between "kidney essence" and intestinal microbiota. During the onset of oligoasthenozoospermia， the disorder of intestinal microbiota has similarities with the pathogenesis of "deficiency of kidney essence" in traditional Chinese medicine. Moreover， traditional Chinese medicine for tonifying the kidney and strengthening the essence can regulate the disorder of intestinal microbiota， which may be one of the effective mechanisms for the treatment of oligoasthenozoospermia with the Bushen Yijing method. Based on this， this article explored the mechanism of Bushen Yijing method of traditional Chinese medicine in treating oligoasthenozoospermia from the perspective of intestinal microbiota， so as to provide new ideas for the treatment of oligoasthenozoospermia with traditional Chinese medicine.

Evaluation of A Liver Yin Deficiency Mouse Model Based on Untargeted Metabolomics / 中国实验方剂学杂志

ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry（UPLC-Q-TOF-MS）， to evaluate the establishment of a mouse model of liver Yin deficiency by thyroid tablet suspension combined with 10% carbon tetrachloride（CCl4） from the perspective of non-targeted metabolomics， in order to lay the foundation for the establishment of a traditional Chinese medicine（TCM） syndrome model. MethodA total of 24 mice were randomly divided into blank group and model group. The model group was given thyroid tablet suspension（0.003 2 g·kg-1） by gavage for 14 consecutive days， and 10% CCl4（5 mL·kg-1） was intraperitoneally injected once a week to establish a liver Yin deficiency model， while the blank group was injected with an equal amount of olive oil intraperitoneally and gavaged with an equal amount of distilled water， and was fed with normal feed. After the modeling was completed， 6 mice in each group were randomly selected， the levels of alanine aminotransferase（ALT）， aspartate aminotransferase（AST）， cyclic adenosine monophosphate（cAMP）， cyclic guanosine monophosphate（cGMP）， interleukin（IL）-6， IL-10， tumor necrosis factor-α（TNF-α）were measured in the mice serum， and malondialdehyde（MDA）， superoxide dismutase（SOD）， total protein（TP）， hydroxyproline（HYP） and other indicators were measured in the mice liver. Liver tissue sections were taken for hematoxylin-eosin（HE） staining and observing pathological changes. The remaining 6 mice in each group were subjected to UPLC-Q-TOF-MS combined with principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were used to screen differential metabolites in the liver Yin deficiency mouse model， Kyoto Encyclopedia of Genes and Genomes（KEGG） database was used to analyze the corresponding metabolic pathways of differential metabolites. ResultCompared with the blank group， mice in the model group showed liver Yin deficiency manifestations such as reduced body weight， fatigue and sleepiness， disheveled and lusterless hair， irritability. The levels of ALT， cAMP/cGMP， IL-6， AST， MDA， cAMP， TNF-α significantly increased（P<0.05， P<0.01）， while the levels of SOD， IL-10 and cGMP significantly decreased（P<0.05， P<0.01）， and the changes of HYP and TP were not statistically significant. Hepatic steatosis and distortion of the radial arrangement of the liver plate cells were seen in the section images of the model group， endogenous substances were clearly separated， and 252 differential metabolites were identified in the serum samples， which were mainly involved in the metabolic pathways of purine metabolism， steroid hormone biosynthesis and pyrimidine metabolism. A total of 229 differential metabolites were identified in the liver samples， mainly involving nucleotide metabolism， purine metabolism， steroid hormone biosynthesis， pyrimidine metabolism， antifolate resistance， insulin resistance， primary bile acid biosynthesis， prostate cancer， sulfur relay system， arachidonic acid metabolism and other metabolic pathways. ConclusionThe successful establishment of liver Yin deficiency model in mice by CCl4 combined with thyroid hormone is evaluated through the investigation of serum and liver metabolomics， combined with biochemical indicators， which provides a biological basis and experimental foundation for the Yin deficiency syndrome model of TCM.

She Medicine （畲药） Diren Zishen Formula （地稔滋肾方） Combined with Acupuncture as Adjunctive Treatment for 32 Cases of Primary Biliary Cholangitis with Liver and Kidney Yin Deficiency Syndrome / 中医杂志

ObjectiveTo observe the clinical effectiveness and safety of She medicine （畲药） Diren Zishen Formula（地稔滋肾方） combined with acupuncture as adjunctive treatment for primary biliary cholangitis with liver and kidney yin deficiency syndrome. MethodsSeventy patients of primary biliary cholangitis with liver and kidney yin deficiency syndrome were randomly divided into a control group and a treatment group， with 35 patients in each group. The control group received oral ursodeoxycholic acid capsules （250 mg per dose， three times daily）. The treatment group received She medicine Diren Zishen Formula oral decoction （one dose daily， 200 ml per dose in the morning and evening， served warm） and acupuncture ［bilateral Sanyingjiao （SP6）， Taichong （LR3）， Ganshu （BL18）， Zusanli （ST36）， Fenglong （ST17）， once daily， 5 consecutive days per week］ in addition to the same treatment as the control group. The treatment duration was three months for both groups. Comparisons were made between the two groups before and after treatment for the following parameters， which were four traditional Chinese medicine （TCM） symptoms scores （skin itching， fatigue， jaundice， and flank pain）， TCM syndrome scores， liver function indicators including aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， alkaline phosphatase （ALP）， gamma-glutamyl transferase （GGT） and total bilirubin （TBiL）， liver fibrosis markers including serum laminin （LN）， serum hyaluronic acid （HA）， serum type Ⅳ collagen （Ⅳ-C） and serum type Ⅲ procollagen （PC-Ⅲ）， and inflammatory factor indicators including serum interleukin-6 （IL-6） and tumor necrosis factor-alpha （TNF-α）. The effectiveness of TCM syndrome between the two groups was compared and safety evaluations were also conducted after treatment. ResultsA total of 32 cases were finally analyzed in the treatment group， while the control group had 31 cases. The total effective rate of TCM syndrome in the treatment group （87.50%， 28/32） was higher than that in the control group （67.74%， 20/31） （P＜0.05）. After treatment， the TCM symptom scores， syndrome scores， liver function， and liver fibrosis markers in both groups signi-ficantly decreased， while in the treatment group， the inflammatory factor indicators decreased after treatment， and more decreases were found than those in the control group （P＜0.05 or P＜0.01）. Both groups had good safety， and no adverse reactions were observed. ConclusionThe combination of She medicine Diren Zishen Formula and acupuncture as an adjunctive treatment for primary biliary cholangitis can significantly improve the clinical effectiveness， improve liver function， reduce inflammatory response， and alleviate liver fibrosis， with good safety.

Clinical Study of Modified Shenqi Pill （肾气丸） Plus Tongdu Tiaoshen Acupuncture （通督调神针刺） for Neurogenic Bladder After Spinal Cord Injury of Kidney-Yang Deficiency Syndrome / 中医杂志

ObjectiveTo observe the clinical efficacy of modified Shenqi Pill （肾气丸） plus Tongdu Tiaoshen Acupuncture （通督调神针刺） in the treatment of neurogenic bladder after spinal cord injury of kidney-yang deficiency syndrome. MethodsForty-six patients were randomly divided into 23 cases each in the control group and the treatment group. Both groups were given conventional treatment， i.e. oral methylcobalamin tablets （0.5 mg each time， 3 times a day） and paraplegic conventional acupuncture （once a day， 6 consecutive days a week）. The control group was given simple bladder function rehabilitation training on the basis of the conventional treatment； and the treatment group was given modified Shenqi Pill orally （1 dose a day， 150 ml each time， taken warmly in morning and evening） and Tongdu Tiaoshen Acupuncture （once a day， 6 consecutive days per week） in addition to what were given to the control group. The treatment course lasted for 4 weeks. The 24 h urination frequency， 24 h urine leakage frequency， 24 h single urine volume， bladder residual urine volume， international lower urinary tract symptom （LUTS） score， traditional Chinese medicine （TCM） syndrome score were compared between the two groups， and clinical effectiveness and TCM syndrome effectiveness were compared between the two groups after treatment. ResultsTwenty patients in each group were finally analyzed in this study. The number of 24 h urination， the number of 24 h urine leakage， bladder residual urine volume， LUTS score， and the TCM syndrome scores decreased after treatment in both groups， and the 24 h single urine volume increased （P＜0.01）； and much more improvement was found of each index in the treatment group than in the control group （P＜0.05 or P＜0.01）. The total clinical effectiveness and TCM syndrome effectiveness in the treatment group was 85.00% （17/20） respectively， which were statistically significantly higher than 45.00% （the total clinical effectiveness， 9/20） and 60.00% （TCM syndrome effectiveness， 12/20） in the control group （P＜0.01）. ConclusionModified Shenqi Pill plus Tongdu Tiaoshen Acupuncture can signi-ficantly improve the clinical symptoms of neurogenic bladder patients after spinal cord injury of kidney-yang deficiency syndrome， having better effectiveness than simple bladder function rehabilitation training， and its mechanism may be related to the improvement of the injured nerve function innervating the bladder.

Discussion on the Scientific Connotation of Fortifying Spleen， Resolving Phlegm and Dispelling Stasis in the Treatment of Coronary Heart Disease under the Guidance of Dysfunctional High-Density Lipoprotein / 中医杂志

The key pathogenesis of coronary heart disease （CHD） is spleen deficiency and phlegm stasis， and dysfunctional high-density lipoprotein （dys-HDL） may be the biological basis for the occurrence of CHD due to spleen deficiency and phlegm stasis. Considering the biological properties and effects of high-density lipoprotein （HDL）， it is believed that the structure and components of HDL are abnormal in the state of spleen deficiency which led to dys-HDL； and dys-HDL contributes to the formation of atherosclerotic plaques through two major pathways， namely， mediating the dysfunction of endothelial cells and mediating the foaminess of macrophages and smooth muscle cells， thus triggering the development of CHD. It is also believed that dys-HDL is a microcosmic manifestation and a pathological product of spleen deficiency， and spleen deficiency makes foundation for the production of dys-HDL； dys-HDL is also an important biological basis for the phlegm-stasis interactions in CHD. The method of fortifying spleen， resolving phlegm， and dispelling stasis， is proposed as an important principle in the treatment of CHD by traditional Chinese medicine， which can achieve the therapeutic purpose by affecting the changes in the structure and components of dys-HDL， thus revealing the scientific connotation of this method， and providing ideas for the diagnosis and treatment of CHD by traditional Chinese medicine.

Mechanism of Shengmaisan Regulating Cardiac Remodeling of Arrhythmias with Deficiency of Qi and Yin / 中国实验方剂学杂志

Arrhythmia is an important disease among cardiovascular diseases. Malignant arrhythmias often occur clinically and are induced by abnormal ion channels， electrical activity disorders， myocardial fibrosis， inflammation， dysfunctional mitochondrial biogenesis， mitochondrial calcium overload， out-of-balance energy metabolism， oxidative stress， sympathetic hyperactivity， and other pathological cardiac remodeling， and they are the main causes of sudden cardiac death. In traditional Chinese medicine， arrhythmias are considered to be palpitations， which are commonly caused by deficiency of Qi and Yin. It is often manifested as a deficiency of the spleen and stomach， resulting in malfunction of the Qi mechanism， followed by a particularly severe decline in cardiac function. Shengmaisan is a representative formula for nourishing Qi and Yin， consisting of Ginseng Radix et Rhizoma， Ophiopogonis Radix， and Schisandrae Chinensis Fructus. In recent years， clinical studies have shown that Shengmaisan and its additions and subtractions are commonly used in the treatment of arrhythmias. In this article， the mechanisms of the active ingredients of Shengmaisan in the electrophysiology， biochemistry， structure， autonomic nervous system， and subcellular fraction of the heart are reviewed， and the multi-target， multi-system， and integrality of Shengmaisan in the treatment of arrhythmias of Qi and Yin deficiency are described. In addition， energy metabolism disorder is tightly juxtaposed with Qi and Yin deficiency syndrome. Mitochondria， as the center of myocardial energy metabolism， play a paramount role in cardiac remodeling， indicating that Shengmaisan will be a salient part of future research to ameliorate cardiac pathologic remodeling through energy metabolism of mitochondria， so as to provide a theoretical basis for the clinical treatment of these arrhythmias.