Houpo Qiwutang originated from the Synopsis of the Golden Chamber， and it consists of seven medicines： Magnoliae Officinalis Cortex， Rhei Radix et Rhizoma， Aurantii Fructus Immaturus， Cinnamomi Ramulus， Zingiberis Rhizoma Recens， Glycyrrhizae Radix et Rhizoma， and Jujubae Fructus. It is a basic formula for the treatment of abdominal fullness. Through the bibliometric method， the historical history， drug base， preparation and dosage， decoction method， and ancient and modern applications of Houpu Qiwu Tang were analyzed by means of textual research. The research finds that Houpu Qiwu Tang has been passed down through the generations in an orderly manner with fewer changes. The drug base of this formula is basically clear， and the base of Magnoliae Officinalis Cortex， Rhei Radix et Rhizoma， Cinnamomi Ramulus， Zingiberis Rhizoma Recens， and Jujubae Fructus is consistent with the 2020 edition of Chinese Pharmacopoeia. The mainstream base of Aurantii Fructus Immaturus is the dried young fruit of Citrus aurantium of Rutaceae family， and the historical mainstream base of Glycyrrhizae Radix et Rhizoma is the dried root of Glycyrrhiza uralensis of Leguminosae family. The modern dosage of this formula is 110.40 g of Magnoliae Officinalis Cortex， 41.40 g of Rhei Radix et Rhizoma， 69 g of Aurantii Fructus Immaturus， 27.60 g of Cinnamomi Ramulus， 69 g of Zingiberis Rhizoma Recens， 41.40 g of Glycyrrhizae Radix et Rhizoma， and 30 g of Jujubae Fructus. In addition， the decoction method is to add 2 000 mL of water with the above seven flavors of the medicine， boil it to 800 mL， and then take 160 mL in a warm state each time. The amount of the medicine taken for each time is 22.08 g of Magnoliae Officinalis Cortex， 8.28 g of Rhei Radix et Rhizoma， 13.80 g of Aurantii Fructus Immaturus， 5.52 g of Cinnamomi Ramulus， 13.80 g of Zingiberis Rhizoma Recens， 8.28 g of Glycyrrhizae Radix et Rhizoma， and 6 g of Jujubae Fructus. The modern application of this formula involves the digestive system， respiratory system， and urinary system. It is more advantageous in digestive system diseases such as early postoperative inflammatory bowel obstruction， functional dyspepsia， gastric pain， functional abdominal distension， and gastric reflux esophagitis. By comprehensively examining the key information of Houpu Qiwu Tang， this paper aims to provide literature support for the development and clinical application of this formula.

BACKGROUND:A large number of studies have confirmed that the therapeutic effectiveness of mesenchymal stem cell secretome is comparable to that of mesenchymal stem cells,but the mechanism of its action is still unclear. OBJECTIVE:To summarize the research progress of mesenchymal stem cell secretome in recent years,to investigate the molecular mechanism of its therapeutic effect,to analyze the current problems and to look forward to the future development. METHODS:The terms"exosomes,mesenchymal stem cells secrete,extracellular vesicles,mesenchymal stem cells,mechanism"were used as English search terms in the PubMed database.Articles that were not related to the research purpose of the article and duplicated articles were excluded.At the same time,we combined the method of literature tracking.Finally,109 articles that met the criteria were incuded for the review. RESULTS AND CONCLUSION:(1)The mesenchymal stem cell secretome promotes tissue repair and regeneration through delivering genetic material,immunomodulatory factors,growth factors,etc.to target cells,by activating anti-apoptotic,regulating angiogenesis,modulating fibrosis and pro-survival pathways in target cells.(2)The potential of mesenchymal stem cell secretome in disease therapy has also been confirmed.Numerous research results have shown that mesenchymal stem cell secretome can be used as a new cell-free treatment for inflammatory and degenerative diseases.(3)Mesenchymal stem cell secretome has been engineered to have more efficient therapeutic effects in recent years.However,due to the heterogeneity of the mesenchymal stem cell secretome and the complexity of its components,the exact mechanism of its therapeutic effect is still unclear.(4)At present,further research is needed to identify the key targets of mesenchymal stem cell secretome,and innovative specific and enhanced mesenchymal stem cell secretome should be developed by combining with engineering and genetic engineering technologies in the future.

Objective To investigate the impact of SARS-CoV-2 infection on male semen quality through meta-analysis and retrospec-tive study.Methods Literature retrieval was conducted in PubMed,CNKI,Wanfang Database and CBM database.Meta-analysis was performed using Stata 15.0.The male patients meeting the inclusion criteria from our hospital were enrolled as study subjects.General demographic data and semen parameters were collected.Single factor analysis of variance and graphing of semen parameters were con-ducted using GraphPad Prism 9.5.1.The test level was set at 0.05.Results A total of 9 studies involving 267 patients were included in the meta-analysis.There were no significant differences in sperm concentration and survival rate before and after SARS-CoV-2 infec-tion(P＞0.05).Semen volume and percentage of normal morphology significantly increased during 1-3 months after infection(P=0.005,P=0.010),with semen volume recovering to pre-infection level＞3 months later(P＞0.05).Sperm motility and progressive mo-tility increased＞3 months after infection(P=0.046,P=0.045),recovering to pre-infection levels(P=0.099,P=0.098).Sperm DNA fragmentation index may be temporarily elevated within 3 months after infection but gradually decreased＞3 months later.In the retrospective study of 8 cases,there were no statistical differences in semen parameters at different stages compared with pre-infection(P＞0.05),but semen parameters showed a negative trend during＜1 month after infection and recovered to pre-infection levels＞3 months later.Conclusion The results of this laboratory study are basically consistent with the meta-analysis.SARS-CoV-2 infection in males only caused short-term negative effects on sperm morphology,vitality and DNA integrity,but generally recovered to pre-infection levels＞3 months after infection.Due to the limitations of study subjects and sample size,the impact of SARS-CoV-2 infection on male semen quality needs to be further confirmed by long-term large-scale prospective studies.

Objective:To investigate the impact of BMI1 expression in OSCC on the recruitment and differentiation of tumor-associat-ed macrophages(TAMs).Methods:BMI1 expression in 519 cases of OSCC tissues and 44 normal controls was analyzed using online datasets of GEPIA 2.0,and validated in 3 cases of OSCC samples and controls by qRT-PCR and western blotting.The function of BMI1/NF-κB axis during OSCC carcinogenesis was investigated by CCK8 assays,wound healing test and transwell assays.Macrophage phenotypes and recruitment were determined using qRT-PCR and western blotting following coculture of the cells with human monocyte cells(THP-1)by OSCC conditioned medium.Moreover,a cell line-derived xenograft(CDX)model was used to detect the effect of BMI1 on tumor growth in vivo.Results:Compared with the normal tissues and cells,the expression level of BMI1 in OSCC tissues and cells was significantly upregulated.BMI1 knockdown impaired the proliferation,migration,and invasion abilities of OSCC cell lines in NF-κB-dependent manner.Furthermore,OSCC cells with high BMI1 expression inhibited the migration of THP-1 cells,promoted M2-like macrophage polarization through NF-κB pathway in vitro.Xenograft experiments further confirmed the inhibitory effect of BMI1 knockdown on the tumorigenesis ability of OSCC cells in vivo.Conclusion:BMI1 promotes M2-like polarization by regulating NF-κB and may be used as a potential therapeutic target for antitumor immunity.

Objective To explore the clinical features,diagnosis and treatment of liposarcoma of spermatic cord.Methods The clinical data of 1 case with multiple recurrence of liposarcoma of spermatic cord were retrospectively analyzed,and the clinical diagnosis and treatment were discussed in combination with relevant literature.Results The patient underwent the first operation to examine the adipocytes in the right spermatic cord area.Postoperative examination revealed highly differentiated liposarcoma.Within 1 year of follow-up,radical resection of both testis and retroperitoneal tumor were performed respectively due to recurrence.Conclusion liposarcoma of spermatic cord is an extremely rare disease,and currently there is no standard treatment protocol.Radical surgical resection of localized lesions is the key,and surgical treatment is still the first choice for local recurrence.As it is unable to achieve R0 resection,the recurrence rate is very high.Since liposarcoma is not sensitive to radiotherapy and chemotherapy,more precise adjuvant therapy is highly expected.

Objective:To investigate the value of fibrinogen to albumin ratio (FAR), creatinine to albumin ratio (CAR) and platelet to lymphocyte ratio (PLR) in predicting the poor prognosis of hyperlipidemic acute pancreatitis (HLAP).Methods:Clinical data of HLAP patients admitted to the hospital from January 2021 to January and December 2023 were retrospectively collected. According to the prognosis, the patients were divided into two groups: good prognosis group and poor prognosis group.The independent risk factors of HLAP in different prognostic groups were obtained by multivariate Logistic regression analysis. Receiver operating characteristic (ROC) curves were plotted to evaluate the prognostic value of FAR, CAR and PLR alone and in combination.Results:A total of 118 patients with HLAP were included, including 69 patients with good prognosis and 49 patients with poor prognosis.The difference of heart rate, lymphocyte, triglyceride, albumin, creatinine, urea nitrogen, blood calcium, blood glucose, C-reactive protein, procalcitonin, fibrinogen, FAR, CAR, PLR, Bedside indicator of acute pancreatitis Severity score, Acute Physiology and Chronic Health status score, hospitalization time assessment between the two groups was statistically significant ( P<0.05). Multivariate Logistic regression analysis showed that FAR (odds ratio ( OR) = 25.949, 95% confidence interval (95% CI):3.190 ~ 211.080, P = 0.002), CAR ( OR = 1.453, 95% CI:1.095 ~ 1.928, P = 0.010) and PLR ( OR = 1.005, 95% CI: 1.001 ~ 1.009, P = 0.020) were independent risk factors for poor prognosis in HLAP patients. ROC curve analysis showed that the area under the ROC curve (AUC) of FAR, CAR and PLR to predict poor prognosis of HLAP patients were 0.823, 0.781 and 0.652, respectively.The AUC of FAR combined with CAR, FAR combined with PLR and CAR combined with PLR were 0.840, 0.845 and 0.849, respectively.The combined ability of FAR, CAR and PLR to predict poor prognosis in HLAP patients was (AUC=0.875,95% CI:0.814 ~ 0.937). When the cut-off value was 0.387, the sensitivity was 83.7%, and the specificity was 79.7%. Conclusions:The prognostic value of FAR, CAR and PLR in HLAP patients is better than that of single or pairwise combination.

Objective:To explore the clinical characteristics and genetic variants in three children with late-onset Multiple acyl-Coenzyme A dehydrogenase deficiency (MADD type Ⅲ).Methods:Clinical data of three children diagnosed with late-onset MADD at the Children′s Hospital Affiliated to Zhengzhou University between March 2020 and March 2022 were retrospectively analyzed. All children were subjected to whole exome sequencing (WES), and candidate variants were verified by Sanger sequencing. All children had received improved metabolic therapy and followed up for 1 ~ 3 years.Results:The children had included 2 males and 1 female, and aged from 2 months to 11 years and 7 months. Child 1 had intermittent vomiting, child 2 had weakness in lower limbs, while child 3 had no symptom except abnormal neonatal screening. Tandem mass spectrometry of the three children showed elevation of multiple acylcarnitines with short, medium and long chains. Children 1 and 2 showed increased glutaric acid and multiple dicarboxylic acids by urine Gas chromatography-mass spectrometry (GC-MS) analysis. All children were found to harbor compound heterozygous variants of the ETFDH gene, including a paternal c. 1211T>C (p.M404T) and a maternal c. 488-22T>G variant in child 1, a paternal c. 1717C>T (p.Q573X) and a maternal c. 250G>A (p.A84T) variant in child 2, and a paternal c. 1285+ 1G>A and maternal c. 629A>G (p.S210N) variant in child 3. As for the treatment, high-dose vitamin B2, levocarnitine and coenzyme Q 10 were given to improve the metabolism, in addition with a low fat, hypoproteinic and high carbohydrate diet. All children showed a stable condition with normal growth and development during the follow-up. Conclusion:The compound heterozygous variants of the ETFDH gene probably underlay the muscle weakness, remittent vomiting, elevated short, medium, and long chain acylcarnitine, as well as elevated glutaric acid and various dicarboxylic acids in the three children with type Ⅲ MADD.

Objective:To analyze the clinical and genetic characteristics of a child featuring Dias-Logan syndrome.Methods:A child with speech disorders and delayed psychomotor development from childhood who was admitted to the Rehabilitation Medicine Department of Children′s Hospital Affiliated to Zhengzhou University in July 2022 was selected as the research subject. Clinical data of the child was collected. Genomic DNA was extracted from peripheral blood samples of the child and his parents. Potential variant was screened by whole exome sequencing, and candidate variant was verified by Sanger sequencing. This study was approved by the Children′s Hospital Affiliated to Zhengzhou University (Ethics No. 2023-K-011).Results:The child has presented with global developmental delay, microcephaly, special facial features and behavioral problems. Genetic testing revealed a de novo variant of the BCL11A gene, namely c. 561_567delACACGCA(p.Q187fs*7), which was classified as pathogenic (PVS1+ PS2+ PM2_Supporting). Conclusion:The heterozygous variant of BCL11A gene probably underlay the Dias-Logan syndrome in this child. Above finding has enriched the phenotypic and mutational spectrum of the BCL11A gene and provides a basis for genetic counseling and clinical decision-making.

Objective:To investigate the clinical and genetic features of patients with spastic paraplegia and psychomotor retardation with or without seizures (SPPRS) caused by HACE1 gene mutation. Methods:Clinical data, auxiliary examination and genetic test results of a child with SPPRS caused by HACE1 gene mutation who was admitted to Henan Children′s Hospital in April 2019 were collected. The clinical and genotypic characteristics of children with SPPRS were summarized by searching the relevant literature up to June 2024, retrieved from CNKI, Wanfang and PubMed databases with the terms of " HACE1" "SPPRS" "seizures" "spastic paraplegia". Results:The patient was a 11 months and 20 days old male, with a clinical phenotype including global developmental delay, leg spastic tremor, frequent epileptic seizures, obesity, and concurrent urethral malformation. Brain magnetic resonance imaging (MRI) showed enlarged bilateral ventricles, hypoplastic corpus callosum, delayed myelination. Genetic test results revealed compound heterozygous variants c.994C>T (p.R332 *) and c.1679-2A>G in the HACE1 gene (according to the transcript NM_020771), respectively inherited from his mother and father, with c.1679-2A>G being a newly reported variant. A total of 6 English literatures reported 21 SPPRS patients in 11 families, and HACE1 gene mutations were mainly characterized by nonsense mutations. The main clinical manifestations included global developmental delay (21 cases), movement disorders (21 cases), intellectual disabilities (18 cases), seizures (13 cases), obesity (13 cases), skeletal abnormalities (11 cases), microcephaly (9 cases), ocular abnormalities (9 cases), distinctive facial features (5 cases), sensorineural hearing loss (5 cases), and short stature (3 cases). MRI predominantly showed hypoplasia of the corpus callosum, ventricular dilation, paucity of white matter and cerebral atrophy. There were no clear genotype-phenotype correlations. A total of 13 HACE1 gene mutations were reported, including 9 nonsense mutations, 2 frameshift mutations, 1 in-frame mutation, and 1 missense mutation. Among the 11 families, only 2 families with 5 patients were caused by compound heterozygous mutations, c.1852_1853del (p.L832del) and c.454C>T (p.Q152 *), c.2242C>T (p.R748 *) and c.2019_2020insTTTAGGTATTTTTAGGTATT (p.P674fs). The other 16 patients in 9 families were caused by homozygous mutations of the remaining 9 mutations. Conclusions:SPPRS is rare and usually occurs in infancy. The main clinical manifestations include comprehensive developmental delay, movement disorders, epilepsy, etc. Currently, no clear genotype-phenotype correlation has been found. The c.1679-2A>G variant of the HACE1 gene is an unreported variant and enriches the mutation spectrum of the HACE1 gene.

AIM:To explore the expression of calcium binding and coiled-coil domain 2(CALCOCO2)in ani-mal models of atrial fibrillation(AF)and its role and mechanism in reversing atrial remodeling in AF mice.METHODS:Twelve rats and 12 mice were randomly divided into the following 2 groups(n=6 each):saline control group(saline group)and angiotensin Ⅱ(Ang Ⅱ)-induced AF group(Ang Ⅱ group).Western blot and immunohistochemistry(IHC)were used to detect CALCOCO2 expression in rat and mouse atrial muscle tissues.Another 24 mice were randomly divided into 4 groups(n=6 each):saline-oeNC,Ang Ⅱ-oeNC,saline-oeCALCOCO2,and Ang Ⅱ-oeCALCOCO2.An adeno-asso-ciated virus was used to induce CALCOCO2 overexpression in mouse atrial myocardium.Subsequently,transthoracic echocardiography and intracardiac electrophysiological testing were used to compare mouse cardiac function among the 4 groups.Western blot and TUNEL staining were also used to evaluate the effect of CALCOCO2 on apoptosis of cardiomyo-cytes in AF models.Additionally,IHC was used to assess the effect of CALCOCO2 on the levels of oxidative stress-related proteins[NADPH oxidase 2(NOX2)and NOX4]and fibrosis-related proteins[collagen type Ⅰ(Col Ⅰ),connexin 40(Cx40)and α-smooth muscle actin(α-SMA)]in AF atrial myocardium.RESULTS:The CALCOCO2 protein level in the atrial myocardium of rats and mice was significantly decreased in Ang Ⅱ group compared with saline group,as detected by Western blot and IHC(0.19±0.01 vs 0.32±0.03 for rats,0.37±0.10 vs 1.00±0.10 for mice,P<0.01).Compared with Ang Ⅱ-oeNC group,the mice in Ang Ⅱ-oeCALCOCO2 group exhibited decreased left atrial inner diameter,shorter AF duration,and increased ejection fraction(P<0.05).Semi-quantitative analysis of TUNEL staining revealed a signifi-cantly decreased apoptosis rate of mouse atrial myocytes in Ang Ⅱ-oeCALCOCO2 group compared with Ang Ⅱ-oeNC group(0.30±0.06 vs 0.61±0.03,P<0.01),which was consistent with the Western blot trend of apoptosis-related proteins such as BAX(1.94±0.34 vs 3.14±0.34,P<0.05)and cleaved caspase-3(2.19±0.41 vs 3.52±0.55,P<0.05).The semi-quantitative results of IHC and immunofluorescence revealed significantly increased levels of oxidative stress-related pro-teins(NOX2 and NOX4)and fibrosis-related proteins(Col Ⅰ and α-SMA),as well as decreased Cx40 levels,in Ang Ⅱ-oeNC group compared with saline-oeNC group.However,the expression levels of these proteins were significantly re-versed after CALCOCO2 overexpression(all P<0.05).CONCLUSION:Overexpression of CALCOCO2 reverses AF-in-duced electrical and structural remodeling by inhibiting the oxidative stress,apoptosis and fibrosis in mouse atrial tissues.