ObjectiveTo systematically compare the differential regulation of the maternal-fetal interface cell lineages and communication networks in the CBA/J×DBA/2 mouse model of recurrent pregnancy loss （RPL） by the two classic therapeutic methods-tonifying the kidney to stabilize the fetus and invigorating the spleen to stabilize the fetus （Shoutai Wan， Juyuan Jian）-of traditional Chinese medicine （TCM） at the single-cell resolution and clarify their modern scientific connotations. MethodsFemale non-pregnant CBA/J mice were caged with male BALB/c （blank group） and DBA/2 （modeling group） mice separately. Pregnant mice in the modeling group were randomly grouped as follows： high/low-dose Shoutai Wan， high/low-dose Juyuan Jian， model （RPL）， and positive control （dydrogesterone）， with 10 mice in each group. Starting from the day after the detection of the vaginal plug， mice were administrated with drugs or an equal volume of normal saline by gavage for 10 consecutive days. After the intervention， the following indicators were measured. ① Macroscopic evaluation： general conditions， uterine wet weight， embryo loss rate， four coagulation parameters ［prothrombin time （PT）， activated partial thromboplastin time （APTT）， fibrinogen （FIB）， and thrombin time （TT）］， and peripheral blood estradiol （E₂） and progesterone （Pg） levels. The decidua with embryos was stained with hematoxylin-eosin （HE） and evaluated by transmission electron microscopy （TEM）. The expression of B-cell lymphoma-2 （Bcl-2）， vascular endothelial growth factor （VEGF）， angiotensin Ⅱ （AngⅡ）， matrix metalloproteinase-2 （MMP-2）， interleukin-6 （IL-6）， leukemia inhibitory factor （LIF）， CXC chemokine ligand 12 （CXCL12）， and microtubule-associated protein 1 light chain 3 homolog （LC3）Ⅰ/Ⅱ was quantified by Western blot. ② Mechanism analysis at the single-cell level： The decidua with embryos from the blank， model， high-dose Shoutai Wan， and high-dose Juyuan Jian groups （6 mice per group， with 3 single-cell samples per group， totaling 24 mice） were analyzed by the BD Rhapsody™ platform， and the whole-cell atlas was drawn by uniform manifold approximation and projection （UMAP） dimensionality reduction clustering combined with the single-cell mouse cell atlas （scMCA）. The differentially expressed genes （DEGs） and cell interaction networks were analyzed via Gene Ontology （GO）， Kyoto Encyclopedia of Genes and Genomes （KEGG）， and CellChat， and the protein-protein interaction （PPI） map of subtype cells was constructed. The CytoTRACE pseudo-temporal analysis was performed to explore the developmental trajectories of core immune cells （natural killer cells， NK cells） from maternal and fetal sources. Results① Pathological and Western blot results indicated that compared with the blank group， the RPL group showed an increase in the embryo loss rate （P<0.01）， down-regulated expression of Bcl-2， LIF， MMP-2， and Vegf in the decidua with embryos （P<0.05）， up-regulated protein levels of CXCL-12， AngⅡ， and IL-6 （P<0.05）， blocked angiogenesis， apoptosis-inflammation imbalance， and coagulation dysfunction. Both prescriptions dose-dependently reduced the abortion rate and restored the angiogenesis-inflammation balance， and Shoutai pill showed superior performance in restoring the E₂ level to the Pg level （P<0.05）. ② Single-cell transcriptome analysis indicated that compared with the blank group， the RPL group showed differences in multiple key cell populations such as decidual cells， trophoblast cells， endothelial cells， erythroblasts， NK cells， and macrophages at the maternal-fetal interface. Immunity and angiogenesis were the key links in RPL. Compared with the RPL group， high-dose Shoutai Wan reversed the changes of NK cells in the embryonic layer （upregulating the mRNA levels of 17 genes and downregulating the mRNA levels of 29 genes） and macrophages （upregulating the mRNA levels of 117 genes and downregulating the mRNA levels of 53 genes） through the regulation of gene expression. High-dose Shoutai pill regulated the immune cells to affect unfolded proteins， cell adhesion， and programmed cell death， thereby promoting decidualization and angiogenesis and modulating embryo-membrane development. High-dose Juyuan Jian regulated the key subgroups of NK cells （up-regulating the mRNA levels of 9 genes and down-regulating the mRNA levels of 17 genes） and macrophages （up-regulating the mRNA levels of 110 genes and down-regulating the mRNA levels of 81 genes）， which affected decidual inflammation and apoptosis and intervened in glycolysis. ③ The pseudo-temporal analysis and communication network indicated that the communication frequency of the RPL group decreased. High-dose Shoutai Wan restored maternal-fetal tolerance through pathways such as NKG2D， CDH5， GDF， and FASLG. High-dose Juyuan Jian enhanced the IL-6/LIFR/JAK/signal transducer and activator of transcription 3 （STAT3） and desmosome/SEMA6/tumor necrosis factor-like weak inducer of apoptosis （TWEAK） signaling to improve endometrial receptivity. The RPL group showed an increased proportion of toxic dNK7， a decreased proportion of reparative dNK4， and blocked embryo fNK1. High-dose Shoutai Wan down-regulated dNK7 and up-regulated dNK4. High-dose Juyuan Jian inhibited the terminal differentiation of dNK7 and up-regulated LILRB1， thus restoring the balance of cytotoxicity and repair. ConclusionBoth the kidney-tonifying and spleen-invigorating methods are effective in treating RPL. NK and macrophages are the key immune cells in the interaction between the embryo and the membrane. The kidney-tonifying method （Shoutai Wan） has an advantage in regulating the phenotypes of unfolded protein， cell adhesion， and programmed cell death， and shows expression characteristics closer to the physiological state in the regulation of NKG2D and CDH5 signals. The spleen-invigorating method （Juyuan Jian） has an advantage in regulating epithelial-mesenchymal transition （EMT）， angiogenesis， and glycolysis and shows higher communication intensity in the IL-6 and LIFR pathways.

ObjectiveTo explore the mechanism of Huanglian Wendantang on damp-heat type diabetes enteropathy rats based on the G protein coupled bile acid receptor 5/glucagon like peptide-1 （TGR5/GLP-1） signaling pathway and intestinal flora. MethodsA total of 72 male Sprague Dawley （SD） rats were adaptively fed for one week. Twelve SD rats were randomly selected as a blank group and fed with an ordinary diet. The rest of the SD rats were fasted for 12 hours without water. A rat model with damp-heat type diabetes enteropathy was made by left intraperitoneal injection of streptozotocin （55 mg·kg^-1） and high sugar and high fat diet （20% sucrose solution + high fat diet） in a humid and hot environment （artificial climate box： temperature 30-34 ℃， relative humidity： 85%-95%）. After successful modeling， the rats were randomly divided into a model group， a metformin group （200 mg·kg^-1）， low-dose， medium-dose， and high-dose Huanglian Wendantang groups （7.10， 14.20， 28.39 g·kg^-1）， with 12 rats in each group. The normal group and the model group were orally administered with physiological saline once a day for 6 consecutive weeks. During the observation period， the weight and blood glucose levels of rats were measured and recorded weekly. After the administration， fresh feces were collected from rats， and 16S rRNA sequencing technology was used to study the differences and changes in intestinal flora among different groups. The levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in the serum of rats were detected by enzyme-linked immunosorbent assay （ELISA）， and the pathological morphological changes of colon tissue were examined. The expression of TGR5 and GLP-1 in colon tissue was detected by immunohistochemistry， and the expression of TGR5 and GLP-1 proteins in colon tissue was measured by Western blot. ResultsCompared with the blank group， the model group showed a decrease in body weight， an increase in blood glucose， and significant damp-heat symptoms. The levels of IL-6 and TNF-α in serum were significantly increased （P<0.01）. The expression of TGR5 and GLP-1 was decreased （P<0.01）， and the pathogenic bacteria were increased. Compared with the model group， the treatment groups exhibited improvements in body weight， blood glucose levels， and damp-heat syndrome in rats. Among them， the high-dose group of Huanglian Wendantang displayed the most significant improvement effect， with significantly reduced inflammation levels （P<0.01） and elevated expression of TGR5 and GLP-1 （P<0.01）. Colonic pathological sections showed that Huanglian Wendantang could effectively ameliorate colonic pathological changes. The 16S rRNA sequencing result indicated a significant increase in beneficial bacteria in the treatment groups. ConclusionHuanglian Wendantang can effectively ameliorate the damp-heat symptoms and blood glucose levels in rats with damp-heat type diabetes enteropathy， and it may exert an effect by regulating the TGR5/GLP-1 signaling pathway and intestinal flora disorder.

Objective To evaluate the effect of irregular follow-up during normalized prevention and control of novel coronavirus pneumonia (COVID-19) epidemic on BK virus (BKV) reactivation and clinical prognosis of kidney transplant recipients. Methods Clinical data of 363 kidney transplant recipients were retrospectively analyzed, and they were divided into the pre-epidemic follow-up group and during-epidemic follow-up group according to the follow-up time. All patients were followed up for 1 year. The follow-up interval was compared between two groups. The infection of BKV and the correlation between the infection process of BKV and renal graft function were analyzed in two groups. Results A total of 1 790 preson-times were followed up before COVID-19 epidemic and 2 680 during COVID-19 epidemic. Compared with the during-epidemic follow-up group, the follow-up intervals within 3, 3-6 and 7-12 months after kidney transplantation were shorter in the pre-epidemic follow-up group, and the differences were statistically significant (all P<0.05). Within 1 year after kidney transplantation, 35 cases（32%） were diagnosed with BKV viruria, 3 cases（3%） of BKV viremia and 1 case（1%） of BKV-associated nephropathy (BKVAN) in the pre-epidemic follow-up group, and 53（25%）, 3（1%） and 1（1%） in the during-epidemic follow-up group, with no statistical significance (all P>0.05). In the pre-epidemic follow-up group, the time for the initial diagnosis of BKV viruria was longer and the viral load of the first urinary BKV reactivation was smaller than those in the during-epidemic follow-up group, with statistical significance (both P<0.05). The load of the first urinary BKV reactivation was positively correlated with the peak load of urinary BKV, and the differences between the baseline and serum creatinine levels at 1 and 3 months after BKV reactivation (all P<0.05). Conclusions Irregular follow-up after kidney transplantation may lead to early BKV reactivation and higher detection value of the first viral load of urinary BKV, delay diagnosis and interventions, and lead to poor prognosis. It is urgent to establish a remote follow-up system to meet the follow-up requirements of kidney transplant recipients when public health incidents occur.

Objective:To investigate the clinical characteristics, diagnosis and treatment of chronic natural killer cell lymphoproliferative disease (CLPD-NK) associated peripheral neuropathy.Methods:The clinical data of 1 case of CLPD-NK associated peripheral neuropathy who was hospitalized in Beijing Chaoyang Hospital on March 17, 2022 were reported. The clinical characteristics, laboratory examinations, nerve biopsy, treatment and prognosis of CLPD-NK associated peripheral neuropathy were summarized in combination with domestic and foreign literature reports.Results:This patient was a 62-year-old woman with progressive weakness and numbness of limbs. Nerve conduction test revealed peripheral nerves injures of limbs. No abnormality was found in a routine biochemistry test of cerebrospinal fluid. Lymphocyte infiltration was found in the nerve bundle of sural nerve with CD56(+), TIA-1(+). After prednisone combined with cyclophosphamide treatment, her weakness and numbness of limbs were relieved, and the white blood cells count decreased. A total of 10 cases of CLPD-NK associated peripheral neuropathy were summarized, including 5 males and 5 females. The median onset age was 64 years. The peripheral blood white cells count was 5.50×10 9/L-24.66×10 9/L, the lymphocytes count was 1.54×10 9/L-32.00×10 9/L, and cerebrospinal fluid protein increased in 3 cases. Biopsy of sural nerve showed NK cell infiltration in all patients. Immunosuppression was the main treatment, and most patients had a good prognosis. Conclusions:CLPD-NK associated peripheral neuropathy is rare. Peripheral nerve biopsy is the important diagnostic method. Corticosteroids and immunosuppressants are effective for this disease.

Acute Disease ; Allografts ; Humans ; Kidney ; Kidney Transplantation ; Nephritis ; Pyelonephritis ; Transplantation, Homologous

Objective To investigate the clinical characteristics and the experience of multi-disciplinary team (MDT) on recurrence of primary hyperoxaluria (PH) type I after renal transplantation. Methods One case presenting with unexplained rapid decline of renal allograft function after allogeneic renal transplantation was discussed by MDT. The role of MDT in diagnosing rare hereditary diseases and improving the long-term survival of renal transplant recipients was summarized. Results After MDT consultation, the patient was diagnosed with recurrence of PH type I. Routine immunosuppressive regimen was initiated after the exclusion of rejection. The patient was instructed to drink a large quantity of water, and given with high-quality protein and low-phosphorus diet, vitamin B6, calcium and other conservative therapies to actively prevent and treat postoperative complications. The deterioration of renal graft function was delayed. Nevertheless, regular hemodialysis was resumed at 5 months after renal transplantation until the submission date of this manuscript. Conclusions Recurrence of PH type I after renal transplantation is relatively rare. The main clinical manifestations are recurrent kidney stones and decreased renal function with multiple complications and poor prognosis. The condition of the patient is consulted by MDT for confirming the diagnosis, determining the optimal treatment scheme, delaying the progression and improving the clinical prognosis.

Objective:To summarize the clinical characteristics of central nerve system (CNS) infection and grasp the necessity and possibility of early diagnosis and precise intervention of CNS infection after renal transplantation.Methods:This retrospective study enrolled consecutive recipients of renal transplantation with CNS infection after transplant between January 2000 and December 2020. Correlative factors for CNS infection after renal transplant were determined by comparing the clinical data between recipients with and without CNS infection. After screening 3, 199 consecutive renal transplant recipients, 12 patients with CNS infection post-transplant were identified and recruited. The median age-of-onset was 48.5 (23-65) years. And the median time to disease onset after transplant was 50.5(1-204) months. The most common symptoms of CNS infection after renal transplant included fever (75.00%), consciousness disorder (58.33%), headache (58.33%) and neck rigidity (41.67%).Results:Hepatitis B virus carrier and pulmonary infection were correlated with CNS infection after transplantation ( P<0.05). Nine patients failed to identify the pathogen and only received empirical anti-infective regimen. The outcomes were curing ( n=3) and death ( n=6). Metagenomic sequencing was performed for identifying the pathogen in three recipients and actively adjusting the anti-infective regimen. As a result, 2 were cured and 1 died. The overall mortality was 58.33%. The median time to death or curing from disease onset were 20(2-19) and 25(16-35) days respectively in surviving and non-surviving recipients. Conclusions:The progress of CNS infection after transplantation is rapid with a high mortality. HBV carrier and pulmonary infection are possible risk factors of CNS infection after renal transplantation. Early pathogenic identification and precise etiological intervention are vital for better clinical outcomes.

Ischemic stroke is prone to recurrence, which is the leading cause of death and disability in stroke. Using predictive model to assess the recurrence risk in patients with ischemic stroke, stratifying risk, and formulating corresponding interventions to reduce the recurrence rate are the core contents of secondary prevention. In this paper, research progress on the prediction of recurrence risks of ischemic stroke recently is summarized from the predicting content or factors, including clinical factors, imaging factors, biological markers and traditional Chinese Medicine syndrome differentiation, and the methods of constructing prediction models about traditional statistical methods and machine learning, in order to provide a reference for clinical work.

The incidence of prostate cancer has shown an obvious upward trend in recent years.18F-fluorodeoxyglucose(FDG)is a broad-spectrum imaging agent for cancer,but there is a " blind zone" in the application of prostate cancer.Therefore,exploring prostate imaging agents with better performance can help to make up the deficiency.At present,there are a number of positron imaging agents for prostate cancer,but the overall advantage is not obvious.Recently,a new imaging agent,68Ga-prostate specific membrane antigen(PSMA),has been demonstrated its better value in clinical application of prostate cancer.This review summarizes the research progress of 68 Ga-PSMA,