Human cytomegalovirus(HCMV)infection can manifest as asymptomatic,systemic symptoms or tissue invasive disease,etc.After infection,it can establish a persistent or latent infection in the host,and viral reactivation occurs in the case of immunocompromised organisms and leads to serious diseases.With the widespread use of antiviral drugs,the prognosis of HCMV infection has been improved,but long-term antiviral therapy is accompanied by the emergence of adverse drug reactions or drug resistance,and refractory or drug-resistant HCMV infections have become a clinical problem which should not be ignored and solved urgently.Therefore,this article reviews the latest advances of treatment strategies for HCMV infection for clinical reference.

BACKGROUND:Delayed healing and nonunion of fractures are common clinical issues.Clinical observations have shown that patients with limb fractures combined with traumatic brain injury experience significantly faster fracture healing compared with those without brain injury.The potential mechanisms behind this phenomenon have become a crucial focus of current research.Recent studies indicate that traumatic brain injury significantly accelerates callus formation and fracture healing processes by regulating cytokines,hormones,neural signals,and stem cell mechanisms.OBJECTIVE:To summarize the latest research progress in the mechanisms by which traumatic brain injury promotes callus formation and fracture healing,thereby providing a theoretical basis for clinical applications.METHODS:The first author conducted a search of CNKI,WanFang,VIP,PubMed,Embase,Web of Science,and Cochrane Library databases for literature published from January 2013 to October 2024,with some references traced back up to 20 years.The search terms used were"traumatic brain injury,callus,fracture healing,inflammatory response,cytokines,hormones,neuropeptides,genes,stem cells"in Chinese and English.A total of 83 articles meeting the inclusion criteria were ultimately selected.RESULTS AND CONCLUSION:The mechanism by which traumatic brain injury promotes callus formation and fracture healing is highly complex,involving multiple regulatory pathways such as cytokines,hormones,the nervous system,and stem cells.However,the precise mechanisms are still not fully understood and require further investigation.Current research suggests that traumatic brain injury accelerates bone callus formation and bone tissue regeneration by promoting the release of cytokines(e.g.,insulin-like growth factor-1)and hormones(e.g.,growth hormone and leptin),regulating the nervous system,and promoting stem cell proliferation and differentiation.Additionally,traumatic brain injury triggers a series of immune responses,including the release of inflammatory factors and activation of immune cells,which modulate fracture healing.These responses improve local blood flow,cell migration,and fibroblast activation,supporting various stages of bone healing.Stem cell activation induced by traumatic brain injury is also crucial,as activated stem cells differentiate into osteoblasts,chondrocytes,and adipocytes,facilitating bone tissue regeneration and repair.Therefore,traumatic brain injury-induced immune responses and stem cell activation work together to accelerate fracture healing,providing essential support for the process.These mechanisms significantly shorten the healing time and improve patient outcomes.In conclusion,traumatic brain injury promotes callus formation and fracture healing through multiple mechanisms,highlighting its importance in bone repair.Future research should focus on the signaling pathways and regulatory factors influenced by traumatic brain injury to further understand its mechanisms.These findings will provide a foundation for developing targeted therapies,stem cell treatments,and neural regulation therapies,with potential clinical value in shortening healing time,optimizing recovery protocols,and improving prognosis.Exploring traumatic brain injury-induced biological effects will open new avenues for fracture treatment.

This study explored the effect of the Mycobacterium tuberculosis(Mtb)PE/PPE family protein PE_PGRS37 on the growth of Mycobacterium smegmatis(Ms)and macrophage autophagy during Mtb infection.The pe_pgrs37 gene was amplified from Mtb genome through PCR,and the recombinant vector pAIN-PE_PGRS37 was successfully constructed through homologous recombi-nation.pAIN-PE_PGRS37 and pAIN were integrated into Ms through electroshock to construct pAIN-PGRS37/Ms and pAIN/Ms re-combinant bacteria.Western blotting indicated that the PE_PGRS37 protein was correctly expressed in pAIN-PE_PGRS37/Ms.The re-combinant bacteria were inoculated in 7H9/7H10 medium,and their colony morphology and growth curves were observed.No signifi-cant difference in colony morphology was observed between pAIN-PE_PGRS37/Ms and pAIN/Ms.The growth rate significantly in-creased between 10 and 16 h,and a plateau was reached at 26 h.After infection of U937 cells with pAIN-PE_PGRS37/Ms and pAIN/Ms,macrophage autophagy flow was detected with western blotting and immunofluorescence.In the pAIN-PE_PGRS37/Ms-infected group,compared with the pAIN/Ms-infected group,macrophage LC3-II and p62 protein expression was significantly up-regulated(P<0.001)and inhibited autophagosome and lysosome fusion.The intracellular survival of the recombinant bacteria was detected through colony counting,and pAIN-PE_PGRS37/Ms showed significantly greater survival in macrophages at 12 h,24 h,and 48 h than pAIN/Ms(P<0.05).Our results suggested that PE_PGRS37 protein promotes Mycobacterium survival in macrophages by blocking macro-phage autophagy flow,thus inhibiting macrophage autophagy.

To establish a rapid visual detection method for Akabane virus(AKAV)on site,specific primers and probes based on the S fragment of AKAV were designed in this experiment.Corre-sponding groups were added to the primers or probes to fulfil the requirement of the combination of recombinase polymerase amplification(RPA)with lateral flow dipstick(LFD).The reaction temperature and time,concentrations of the primer and probe were optimized to establish the RPA-LFD method for detecting AKAV.After that,the specificity,sensitivity and clinical reliability of the method were evaluated.The results showed that after 20 minutes of reaction at 37 ℃,the test results could be read on LFD paper.There was no cross reaction against blue tongue virus,Pasteurella multocida,bovine infectious rhinotracheitis virus and bovine Mycoplasma bovis,and the detection limit was 2.5 × 100 copies/μL of standard plasmid.Detection of clinical samples showed a consistent results with that by RT-PCR method.These findings indicated that the RPA-LFD method established had the advantages of good specificity,high sensitivity,simple operation and visualization,and could be applied to clinical detection,which provides new technical support for the rapid diagnosis and prevention and control of AKAV.

To establish a rapid visual detection method for Akabane virus(AKAV)on site,specific primers and probes based on the S fragment of AKAV were designed in this experiment.Corre-sponding groups were added to the primers or probes to fulfil the requirement of the combination of recombinase polymerase amplification(RPA)with lateral flow dipstick(LFD).The reaction temperature and time,concentrations of the primer and probe were optimized to establish the RPA-LFD method for detecting AKAV.After that,the specificity,sensitivity and clinical reliability of the method were evaluated.The results showed that after 20 minutes of reaction at 37 ℃,the test results could be read on LFD paper.There was no cross reaction against blue tongue virus,Pasteurella multocida,bovine infectious rhinotracheitis virus and bovine Mycoplasma bovis,and the detection limit was 2.5 × 100 copies/μL of standard plasmid.Detection of clinical samples showed a consistent results with that by RT-PCR method.These findings indicated that the RPA-LFD method established had the advantages of good specificity,high sensitivity,simple operation and visualization,and could be applied to clinical detection,which provides new technical support for the rapid diagnosis and prevention and control of AKAV.

Human cytomegalovirus(HCMV)infection can manifest as asymptomatic,systemic symptoms or tissue invasive disease,etc.After infection,it can establish a persistent or latent infection in the host,and viral reactivation occurs in the case of immunocompromised organisms and leads to serious diseases.With the widespread use of antiviral drugs,the prognosis of HCMV infection has been improved,but long-term antiviral therapy is accompanied by the emergence of adverse drug reactions or drug resistance,and refractory or drug-resistant HCMV infections have become a clinical problem which should not be ignored and solved urgently.Therefore,this article reviews the latest advances of treatment strategies for HCMV infection for clinical reference.

BACKGROUND:Delayed healing and nonunion of fractures are common clinical issues.Clinical observations have shown that patients with limb fractures combined with traumatic brain injury experience significantly faster fracture healing compared with those without brain injury.The potential mechanisms behind this phenomenon have become a crucial focus of current research.Recent studies indicate that traumatic brain injury significantly accelerates callus formation and fracture healing processes by regulating cytokines,hormones,neural signals,and stem cell mechanisms.OBJECTIVE:To summarize the latest research progress in the mechanisms by which traumatic brain injury promotes callus formation and fracture healing,thereby providing a theoretical basis for clinical applications.METHODS:The first author conducted a search of CNKI,WanFang,VIP,PubMed,Embase,Web of Science,and Cochrane Library databases for literature published from January 2013 to October 2024,with some references traced back up to 20 years.The search terms used were"traumatic brain injury,callus,fracture healing,inflammatory response,cytokines,hormones,neuropeptides,genes,stem cells"in Chinese and English.A total of 83 articles meeting the inclusion criteria were ultimately selected.RESULTS AND CONCLUSION:The mechanism by which traumatic brain injury promotes callus formation and fracture healing is highly complex,involving multiple regulatory pathways such as cytokines,hormones,the nervous system,and stem cells.However,the precise mechanisms are still not fully understood and require further investigation.Current research suggests that traumatic brain injury accelerates bone callus formation and bone tissue regeneration by promoting the release of cytokines(e.g.,insulin-like growth factor-1)and hormones(e.g.,growth hormone and leptin),regulating the nervous system,and promoting stem cell proliferation and differentiation.Additionally,traumatic brain injury triggers a series of immune responses,including the release of inflammatory factors and activation of immune cells,which modulate fracture healing.These responses improve local blood flow,cell migration,and fibroblast activation,supporting various stages of bone healing.Stem cell activation induced by traumatic brain injury is also crucial,as activated stem cells differentiate into osteoblasts,chondrocytes,and adipocytes,facilitating bone tissue regeneration and repair.Therefore,traumatic brain injury-induced immune responses and stem cell activation work together to accelerate fracture healing,providing essential support for the process.These mechanisms significantly shorten the healing time and improve patient outcomes.In conclusion,traumatic brain injury promotes callus formation and fracture healing through multiple mechanisms,highlighting its importance in bone repair.Future research should focus on the signaling pathways and regulatory factors influenced by traumatic brain injury to further understand its mechanisms.These findings will provide a foundation for developing targeted therapies,stem cell treatments,and neural regulation therapies,with potential clinical value in shortening healing time,optimizing recovery protocols,and improving prognosis.Exploring traumatic brain injury-induced biological effects will open new avenues for fracture treatment.

OBJECTIVE: To explore the corrective strategies and effectiveness of osteotomy surgery for severe lower limb deformities in hypophosphatemic rickets. METHODS: A retrospective analysis was conducted on 29 patients with severe lower limb deformities of hypophosphatemic rickets who underwent surgical treatment between February 2012 and August 2024. There were 9 males and 20 females. The age ranged from 13 to 53 years, with an average of 24.6 years. All patients were deformities of both lower limbs, presenting as 24 cases of O-shaped legs, 2 cases of wind-blown deformities, and 3 cases of X-shaped legs. Based on the full-length films of both lower limbs in the standing position before operation, the osteotomy planes of the femur, tibia, and fibula were designed. Among them, if both the same-sided thigh and leg were deformed, staged surgeries of both lower limbs were selected. If only the thigh or leg were deformed, simultaneous surgeries of both lower limbs were selected. The femur deformity was corrected immediately after osteotomy at the deformed plane; the osteotomy fragment was temporarily controlled with an external fixator, which was removed after perform internal fixation with a steel plate. After fibular osteotomy, the Ilizarov frame or Taylor frame was installed on the tibia and fibula. The threaded rods were removed and then tibial osteotomy was performed on the deformed plane. Patients using the Taylor frame did not undergo deformity correction during operation. The external fixators were adjusted starting 7 days after operation to correct the varus, valgus, and rotational deformities of the lower limb. Patients using the Ilizarov frame corrected the rotational deformity of the tibia during operation. The external fixator was adjusted starting 7 days after operation to correct the varus and valgus deformities of the lower limb. During the treatment period, the patient could walk with partial weight-bearing on the operated limb with crutches. The external fixator was removed after the bone healed. Before operation and at last follow-up, the medial proximal tibial angle (MPTA), lateral distal tibial angle (LDTA), posterior proximal tibial angle (PPTA), anterior distal tibial angle (ADTA), anatomic lateral distal femoral angle (aLDFA), posterior distal femoral angle (PDFA), and mechanical axis deviation (MAD), lower limb rotation, limb length discrepancy (LLD) were measured. The self-made scoring criteria were adopted to evaluate the degree of lower limb deformity of the patients. RESULTS: All operations were successfully completed, and no complications such as nerve or vascular injury occurred. The adjustment time of the external fixator of the lower limb after operation was 28-46 days, with an average of 37.4 days. The wearing time of the external fixator ranged from 134 to 398 days, with an average of 181.5 days. Mild pin tract infections occurred in 2 limbs. The osteofascial compartment syndrome occurred in 1 limb after operation. No complications related to orthopedic adjustment of the external fixator occurred in other patients. All patients were followed up 6-56 months, with an average of 28.2 months. At last follow-up, full-length films of both lower limbs in the standing position showed that the coronal mechanical axes of the lower limbs of all patients returned to the normal. At last follow-up, MPTA, LDTA, PPTA, aLDFA, PDFA, MAD, lower limb rotation, LLD, and the score of lower limb deformity significantly improved when compared with those before operation ( P<0.05). There was no significant difference in ADTA between pre- and post-operation ( P>0.05). The degree of lower limb deformity were rated as moderate in 2 cases and poor in 27 cases before operation and as excellent in 7 cases, good in 18 cases, and moderate in 4 cases at last follow-up, with an excellent and good rate of 86.2%. CONCLUSION For severe lower limb deformities in hypophosphatemic rickets, immediate correction of deformities with femoral osteotomy and internal plate fixation, as well as gradually correction of deformities with tibiofibular osteotomy and circular external fixation (Ilizarov frame or Taylor frame), have satisfactory therapeutic effects.
Humans ; Male ; Osteotomy/instrumentation* ; Female ; Adult ; Retrospective Studies ; Tibia/abnormalities* ; Adolescent ; Femur/abnormalities* ; Middle Aged ; Fibula/surgery* ; Rickets, Hypophosphatemic/complications* ; Young Adult ; Treatment Outcome ; External Fixators ; Bone Plates ; Lower Extremity Deformities, Congenital/etiology*

This study explored the effect of the Mycobacterium tuberculosis(Mtb)PE/PPE family protein PE_PGRS37 on the growth of Mycobacterium smegmatis(Ms)and macrophage autophagy during Mtb infection.The pe_pgrs37 gene was amplified from Mtb genome through PCR,and the recombinant vector pAIN-PE_PGRS37 was successfully constructed through homologous recombi-nation.pAIN-PE_PGRS37 and pAIN were integrated into Ms through electroshock to construct pAIN-PGRS37/Ms and pAIN/Ms re-combinant bacteria.Western blotting indicated that the PE_PGRS37 protein was correctly expressed in pAIN-PE_PGRS37/Ms.The re-combinant bacteria were inoculated in 7H9/7H10 medium,and their colony morphology and growth curves were observed.No signifi-cant difference in colony morphology was observed between pAIN-PE_PGRS37/Ms and pAIN/Ms.The growth rate significantly in-creased between 10 and 16 h,and a plateau was reached at 26 h.After infection of U937 cells with pAIN-PE_PGRS37/Ms and pAIN/Ms,macrophage autophagy flow was detected with western blotting and immunofluorescence.In the pAIN-PE_PGRS37/Ms-infected group,compared with the pAIN/Ms-infected group,macrophage LC3-II and p62 protein expression was significantly up-regulated(P<0.001)and inhibited autophagosome and lysosome fusion.The intracellular survival of the recombinant bacteria was detected through colony counting,and pAIN-PE_PGRS37/Ms showed significantly greater survival in macrophages at 12 h,24 h,and 48 h than pAIN/Ms(P<0.05).Our results suggested that PE_PGRS37 protein promotes Mycobacterium survival in macrophages by blocking macro-phage autophagy flow,thus inhibiting macrophage autophagy.

OBJECTIVE To investigate the effects of Codonopsis pilosula polysaccharide （CPP） regulating the nuclear factor- erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway on gastric mucosal injury in rats with chronic atrophic gastritis （CAG）. METHODS Rats were randomly divided into control group， model group， CPP low-dose， medium-dose and high-dose groups （CPP 10， 20， 40 mg/kg）， and ML385 group （Nrf2 inhibitor ML385 30 mg/kg+CPP 40 mg/kg）， 10 rats per group. CAG rat model was established using N-methyl-N′- nitro-N-nitrosoguanidine combined with irregular diet， then they were given drugs for consecutive 6 weeks. HE staining was used to observe the pathological changes in gastric tissue morphology； the levels of serum gastrin （GAS）， motilin （MTL）， pepsin （PP）， as well as tumor necrosis factor-α （TNF-α）， interleukin-8 （IL-8） malondialdehyde （MDA） and superoxide dismutase （SOD） in gastric mucosal tissue were detected； TUNEL assay was used to observe gastric mucosal tissue cell apoptosis； immunohistochemical assay was adopted to observe the expressions of Nrf2 and recombinant Bcl2 associated X protein （Bax） in gastric mucosal tissue； Western blot was used to detect the expressions of Nrf2， HO-1， Bax and Bcl-2 proteins in gastric mucosal tissue. RESULTS Compared with the control group， the gastric mucosal tissue was damaged； the levels of GAS， MTL， PP and SOD， and the protein expressions of Nrf2， HO-1 and Bcl-2 were significantly reduced in model group （P＜0.05）， while the levels of MDA， TNF-α and IL-8， the cell apoptosis index， and the protein expression of Bax were significantly increased （P＜0.05）. Compared with model group， CPP low-dose， medium-dose and high- dose groups showed varying degrees of improvement in gastric mucosal histopathology； the levels of the quantitative indicators were significantly reversed （P＜0.05）. Nrf2 inhibitor ML385 significantly attenuated the improvement effect of high-dose CPP on the above indicators in CAG rats （P＜0.05）. CONCLUSIONS CPP can improve gastric mucosal injury in CAG rats， and inhibit oxidative stress， inflammatory response， and cell apoptosis. The mechanism of action may be related to the activation of Nrf2/HO-1 signaling pathway.