Jaws and alveolar defects present significant challenges in reconstructive surgery and implant restoration.Calcium phos-phate(CaP)bioceramics are commonly used as bone substitute and play a crucial role in repairing bone defects.Recent studies have shown that T cells play an important regulatory role in bone regeneration.The studies on CaP bioceramics and T cells,including their subpopulations,in bone regeneration,and the mechanisms through which CaP bioceramics regulate the behavior of T cells has been re-viewed.

Jaws and alveolar defects present significant challenges in reconstructive surgery and implant restoration.Calcium phos-phate(CaP)bioceramics are commonly used as bone substitute and play a crucial role in repairing bone defects.Recent studies have shown that T cells play an important regulatory role in bone regeneration.The studies on CaP bioceramics and T cells,including their subpopulations,in bone regeneration,and the mechanisms through which CaP bioceramics regulate the behavior of T cells has been re-viewed.

Objective:To analyze the clinical characteristics and genetic basis of a male patient with primary infertility caused by Acephalic spermatozoa syndrome.Methods:A patient who had presented at the Henan Provincial People′s Hospital on October 1, 2022 was selected as the study subject. Clinical data and results of laboratory exams and sperm electron microscopy were collected. The patient was subjected to whole exome sequencing (WES), and candidate variants were verified by Sanger sequencing and pathogenicity analysis.Results:WES revealed that the patient has harbored compound heterozygous variants of the PMFBP1 gene, namely c. 853del (p.Ala285Leufs*24) and c. 1276A>T (p.Lys426X), which were both unreported previously. Sanger sequencing suggested that the c. 853del (p.Ala285Leufs*24) variant has derived from his deceased mother, whilst the c. 1276A>T (p.Lys426X) variant has derived from his father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were classified as pathogenic (PVS1+ PM2_Supporting+ PP4). Conclusion:The compound heterozygous variants of the PMFBP1 gene probably underlay the Acephalic spermatozoa syndrome in this patient. The discovery of the novel variants has also enriched the mutational spectrum of Acephalic spermatozoa syndrome.

Bone substitute material implantation has become an important treatment strategy for the repair of oral and maxillofacial bone defects. Recent studies have shown that appropriate inflammatory and immune cells are essential factors in the process of osteoinduction of bone substitute materials. Previous studies have mainly focused on innate immune cells such as macrophages. In our previous work, we found that T lymphocytes, as adaptive immune cells, are also essential in the osteoinduction procedure. As the most important antigen-presenting cell, whether dendritic cells (DCs) can recognize non-antigen biomaterials and participate in osteoinduction was still unclear. In this study, we found that surgical trauma associated with materials implantation induces necrocytosis, and this causes the release of high mobility group protein-1 (HMGB1), which is adsorbed on the surface of bone substitute materials. Subsequently, HMGB1-adsorbed materials were recognized by the TLR4-MYD88-NFκB signal axis of dendritic cells, and the inflammatory response was activated. Finally, activated DCs release regeneration-related chemokines, recruit mesenchymal stem cells, and initiate the osteoinduction process. This study sheds light on the immune-regeneration process after bone substitute materials implantation, points out a potential direction for the development of bone substitute materials, and provides guidance for the development of clinical surgical methods.
Biocompatible Materials/metabolism* ; HMGB1 Protein/metabolism* ; Myeloid Differentiation Factor 88/metabolism* ; Bone Substitutes/metabolism* ; Dendritic Cells/metabolism*

ObjectiveTo observe the effect of Feiyanning prescription （FYN） on cisplatin （DDP） resistance in non-small cell lung cancer （NSCLC） and explore the underlying mechanism. MethodCell counting kit-8 （CCK-8） assay was used to detect the proliferation of A549 and A549/DDP （DDP-resistant） cells treated by DDP （0， 2.0， 4.0， 6.0， 8.0， 10.0 mg⋅L^-1） and the proliferation of A549/DDP cells treated by FYN （0， 100， 200， 300， 400， 500， 600 mg⋅L^-1）. Based on immunofluorescence staining and Western blot （WB）， the expression of epithelial mesenchymal transition （EMT）-related proteins in A549 and A549/DDP groups was observed. A549/DDP cells were classified into control group， FYN group （200 mg⋅L^-1）， DDP group （6.0 mg⋅L^-1）， and combination group ［FYN （200 mg⋅L^-1） + DDP （6.0 mg⋅L^-1）］ and respectively treated with corresponding drugs. Then， invasion ability of each group was examined by transwell assay， and the expression of EMT-related proteins in each group by WB. Moreover， real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） and immunofluorescence staining were separately applied to detect the mRNA and protein expression of drug resistance-related factors in each group， respectively. ResultCompared with A549 group， A549/DDP group showed high resistance to DDP （P<0.01）， low expression of E-cadherin， and high protein expression of Vimentin， N-cadherin， and Snail （P<0.05， P<0.01）. As compared with the control group， FYN inhibited the proliferation of A549/DDP cells in a concentration-dependent manner （P<0.01）， and the FYN group， DDP group， and combination group demonstrated low invasion ability （P<0.01）. In addition， the invasion ability in the combination group was particularly lower than that in the DDP group （P<0.01）. The expression of E-cadherin protein was higher and the protein expression of N-cadherin， Vimentin， and Snail was lower in the in FYN group than in the control group （P<0.01）. The protein expression of E-cadherin， N-cadherin， and Vimentin was lower and the expression of Snail was higher in the DDP group than in the control group （P<0.05，P<0.01）. The protein expression of E-cadherin， N-cadherin， Vimentin， and Snail in the combination group decreased as compared with that in the control group （P<0.01）. Compared with the DDP alone， the combination raised the expression of E-cadherin and lowered the protein expression of N-cadherin， Vimentin， and Snail （P<0.01）. The protein and mRNA expression of lung resistance-related protein （LRP） and multidrug resistance 1 （MDR1） was lower and the protein and mRNA expression of topoisomerase Ⅱα （TOPO Ⅱα） was higher in the FYN group than in the control group （P<0.01）. The protein and mRNA expression of LRP， MDR1， and TOPO Ⅱα was higher in the DDP group than in the control group （P<0.01）. The expression of LRP protein and mRNA showed no significant variation， but the protein and mRNA expression of MDR1 and TOPO Ⅱα increased in the combination group compared with those in the control group （P<0.01）. Compared with the DDP group， FYN group and combination group showed low protein and mRNA expression of LRP and MDR1 and high protein and mRNA expression of TOPO Ⅱα （P<0.01）. Compared with FYN， the combination elevated the protein and mRNA expression of LRP， MDR1， and TOPO Ⅱα （P<0.01）. ConclusionFYN prescription can reverse the DDP resistance of NSCLC by modulating EMT.

Objective To study the value of postmortem imaging on the diagnosis of intestinal perforation.Method Postmortem imaging(PMCT and PMCTA)data of 2 intestinal perforation deaths(and 4 controlled cases)were reviewed retrospectively.Diagnosing capacities of intestinal perforation by postmortem imaging method were further investigated.Results PMCT is sensitive in detecting the free air and liquid induced by intestinal perforation.PMCT can sometimes detect the gravity-dependent purulent secretions in the abdominopelvic cavity.PMCTA can visualize the extravasation of contrast agent from the perforation,which can be used to locate the accurate perforation region.Conclusion Postmortem imaging method(PMCT and PMCTA)is an important tool for the diagnosis of intestinal perforation,which can not only be used as a forensic diagnosis method,but is also useful to locate the perforation site before an forensic autopsy.

Objective:To investigate the clinical outcomes of infertility patients with multiple morphological abnormalities of the sperm flagella (MMAF) caused by DNAH1 gene mutation after intracytoplasmic sperm injection (ICSI). Methods:A retrospective cohort study analyzed the clinical data and genetic test results of 39 MMAF infertility patients who were treated in the Center for Reproductive Medicine of Henan Provincial People's Hospital from February 2018 to January 2020. Twelve MMAF patients caused by DNAH1 mutations were acted as DNAH1 positive group and 27 MMAF patients with no DNAH1 mutations were acted as DNAH1 negative group. Totally 100 cases of infertility patients with normal sperm morphology and their spouses who were age-matched by both men and women for ICSI during the same period were selected as control group. The outcomes of assisted pregnancy treatment in the three groups were analyzed. Results:All 39 MMAF patients underwent whole-exome sequencing. Among them, 12 patients had DNAH1 gene mutations, 10 cases of compound heterozygous mutations and 2 cases of homozygous mutations, and the other 27 cases were not detected the currently known DNAH1 mutations. The patients of three groups were treated with ICSI, and the differences in the number of oocytes obtained and the number of M II oocytes in the DNAH1 gene positive group, DNAH1 gene negative group and control group were statistically significant (17.08±5.32, 9.59±3.98, 10.44±6.33, P=0.001; 14.58±5.18, 6.78±3.38, 8.32±5.31, P<0.001). There were no statistically significant differences in the embryo implantation rate, the clinical pregnancy rate, the embryo miscarriage rate and the live birth rate (all P>0.05). Among them, 12 couples of male infertility caused by DNAH1 mutation received a total of 12 cycles of oocyte extraction, forming 79 day 3 embryos, 12 times of the first fresh or frozen embryo transplantation, and 10 biological offspring were obtained. Conclusion:For patients with MMAF caused by DNAH1 gene mutation, ICSI can help them to give birth to their own offspring, and has a higher clinical pregnancy rate and live birth rate.

Objective:To investigate the clinical outcomes of infertility patients with multiple morphological abnormalities of the sperm flagella (MMAF) caused by DNAH1 gene mutation after intracytoplasmic sperm injection (ICSI). Methods:A retrospective cohort study analyzed the clinical data and genetic test results of 39 MMAF infertility patients who were treated in the Center for Reproductive Medicine of Henan Provincial People's Hospital from February 2018 to January 2020. Twelve MMAF patients caused by DNAH1 mutations were acted as DNAH1 positive group and 27 MMAF patients with no DNAH1 mutations were acted as DNAH1 negative group. Totally 100 cases of infertility patients with normal sperm morphology and their spouses who were age-matched by both men and women for ICSI during the same period were selected as control group. The outcomes of assisted pregnancy treatment in the three groups were analyzed. Results:All 39 MMAF patients underwent whole-exome sequencing. Among them, 12 patients had DNAH1 gene mutations, 10 cases of compound heterozygous mutations and 2 cases of homozygous mutations, and the other 27 cases were not detected the currently known DNAH1 mutations. The patients of three groups were treated with ICSI, and the differences in the number of oocytes obtained and the number of M II oocytes in the DNAH1 gene positive group, DNAH1 gene negative group and control group were statistically significant (17.08±5.32, 9.59±3.98, 10.44±6.33, P=0.001; 14.58±5.18, 6.78±3.38, 8.32±5.31, P<0.001). There were no statistically significant differences in the embryo implantation rate, the clinical pregnancy rate, the embryo miscarriage rate and the live birth rate (all P>0.05). Among them, 12 couples of male infertility caused by DNAH1 mutation received a total of 12 cycles of oocyte extraction, forming 79 day 3 embryos, 12 times of the first fresh or frozen embryo transplantation, and 10 biological offspring were obtained. Conclusion:For patients with MMAF caused by DNAH1 gene mutation, ICSI can help them to give birth to their own offspring, and has a higher clinical pregnancy rate and live birth rate.

Objective:To explore the effect of dibutyl phthalate (DBP) on the rat testis Leydig cell apoptosis by AMP activated protein kinase/mammalian rapamycin target protein (AMPK/mTOR) signaling pathway.Methods:Rats with reproductive function impairment were divided into model (DBP) group of 17 rats, model+AMPK inhibitor [DBP+compound C (CC)] group of 17 rats, model+AMPK agonist [DBP+metformin (MF)] group of 17 rats, DBP+AMPK inhibitor+agonist (DBP+CC+MF) group of 17 rats by body mass ranking grouping method. Another 11 rats were taken as the blank group. The blank group and DBP group were intraperitoneally injected with the same amount of normal saline, while DBP+CC group and DBP+MF group were intraperitoneally injected with 20 mg/kg CC and 200 mg/kg MF respectively, and DBP+CC+MF group was intraperitoneally injected with CC and MF once a day for 4 weeks. Luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone (T) were measured by radioimmunoassay. Sperm quality was analyzed by automatic sperm quality analysis system. Leydig cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) and flow cytometry. The expressions of AMPK, mTOR, Caspase 3 mRNA and protein, p-AMPK and p-mTOR protein were detected by RT-PCR and Western blotting. Results:The serum level of FSH in DBP+MF group [(9.88±0.67) U/L] increased, while that in DBP+CC group [(6.82±0.60) U/L] decreased compared with DBP group [(9.07±0.52) U/L] (all P<0.001). The serum LH, T levels and sperm concentration, percentage of (a+b) grade sperm in DBP+MF group [(3.97±0.70) U/L, (2.96±0.11) mg/L, (13.15±2.63)×10 6/mL, (22.20±4.13)%], DBP+CC group [(6.52±0.71) U/L, (4.48±0.15) mg/L, (25.47±2.18)×10 6/mL, (45.60±4.78)%] increased compared with DBP group [(4.51±0.75) U/L, (3.25±0.11) mg/L, (16.46±3.40)×10 6/mL, (25.43±4.36)%] (DBP group vs. DBP+MF group PLH=0.038, the other all P<0.001). HE staining showed that the structure of testis in blank group was normal. In DBP group and DBP+CC+MF group, the epithelial cells of seminiferous tubules atrophied and twisted in irregular shape, and the disease became serious in DBP+MF group, and there were a lot of vacuoles around the nucleus. The number of apoptosis, p-AMPK/AMPK protein relative expression and Caspase 3 mRNA and protein relative expression of Leydig cells in DBP+MF group (286.60±30.17, 0.95±0.08, 2.17±0.18, 1.23±0.10) increased, and DBP+CC group (88.00±21.34, 0.42±0.04, 1.35±0.15, 0.54±0.06) decreased compared with those in DBP group (142.40±26.78, 0.70±0.07, 1.85±0.14, 0.80±0.09, all P<0.001). Compared with DBP group (0.45±0.06), the p-mTOR/mTOR of DBP+MF group (0.23±0.04) decreased, and the p-mTOR/mTOR of DBP+CC group (0.84±0.07) increased (all P<0.001). Conclusion:DBP can damage the reproductive system of rats and increase the apoptosis rate of Leydig cells, which may be related to AMPK activation and mTOR inhibition.

Objective:To investigate the effects of different partial deletions in azoospermia factor (AZF) locus of Y-chromosome on the clinical outcome of severe oligoasthenozoospermia patients by intracytoplasmic sperm injection (ICSI).Methods:A retrospective cohort study was conducted on the patients undergoing high-throughput sequencing for Y chromosome microdeletion screening and ICSI treatment in Reproductive Medicine Center of Henan Provincial People's Hospital from December 2017 to July 2020. According to whether carrying AZFc microdeletions or not, the patients were divided into the AZFc-deletion group and control group. And AZFc-deletion group was divided into 3 subgroups, b2/b3 deletion, b2/b4 deletion and gr/gr deletions subgroup, by the types of partial deletion.Results:The day 3 (D3) available embryo rate, the high-quality embryo rate, and the blastocyst formation rate in patients with AZFc deletion were statistically lower than those in control group [70.4% (556/790) vs. 78.5% (2867/3651), P<0.001; 24.7% (199/807) vs. 34.3% (1284/3747), P<0.001; 51.7% (277/536) vs. 58.0% (1540/2592), P=0.007], and there were no statistical differences in implantation rate, clinical pregnancy rate, live birth rate during transplantation cycle between the two groups (all P>0.05). The AZFc b2/b3 deletion subgroup had no significant differences in D3 available embryo rate, high-quality embryo rate, blastocyst formation rate, implantation rate, clinical pregnancy rate and live birth rate, compared with control group (all P>0.05). The rate of high-quality embryos in patients with the b2/b4 deletion subgroup [23.2% (32/138)] was lower than that of control group ( P=0.004), but there were no statistical differences in D3 available embryo rate, blastocyst formation rate, implantation rate, clinical pregnancy rate and live birth rate (all P>0.05). The D3 available embryo rate [71.6% (280/391)], the high-quality embryo rate [20.8% (84/403)] and the blastocyst formation rate [48.7% (133/273)] in patients of gr/gr deletion subgroup were significantly lower than those in control group ( P=0.002, P<0.001, P<0.001), but there were no statistical differences in implantation rate, clinical pregnancy rate and live birth rate (all P>0.05). Conclusion:AZFc b2/b3 deletion and b2/b4 deletion in the AZFc locus of Y chromosome have no significant effect on embryonic development and pregnancy outcome in patients with severe oligoasthenozoospermia undergoing ICSI. Gr/gr deletion has most adverse effect on embryonic development but no effect on pregnancy outcome.