THE THERAPEUTIC EFFECT OF INTRATUMORAL INJECTION OF GM-CSF GENE-MODIFIED ALLOGENIC MACROPHAGES ON TUMOR-BEARING MICE

Both the antigen presenting ability and the cytotoxicity of macrophages can be enhanced by GMCSF gene transfer. In the present study, the therapeutic effect of intratumoral injection with GMCSF genemodified allogenic macrophages on tumorbearing mice observed. The peritoneal macrophages of C57BL/6 mice were transfected with GMCSF gene mediated by recombinant adenovirus and the subcutaneous CT26 colon adenocarcinomabearing BALB/c mice were treated by intratumoral injection of the above macrophages. The survival time of the tumorbearing mice were prolonged significantly and some tumor mass disappeared completely. The necroses of the tumor cells and massive infiltration of inflammatory cells were observed 6 days after treatment. 30 days after treatment, only the leftover of tumor cells and the inflammatory cells remained. The data indicated that introtumoral injection of GMCSF genemodified allogenic macrophages displayed more potent therapeutic effect on the preestablished tumorbearing mice.

Morphological features of allogenic nerve segment in rats after subcutaneous embedment

BACKGROUND ： Some studies demonstrate that allogenic peripheral nerve segment embedded subcutaneously significantly reduce the infiltration of lymphocyte and decrease immunological reaction.OBJECTIVE ： To observe the gross shape, optical and electron microscope results of allogenic nerve segment in rats 2 weeks after subcutaneous embedment, and compare with subcutaneous emdedment of autologous nerve segment. DESIGN ： A randomized and controlled experiment.SETTING ： Department of Orthopaedics of Fifth People＇s Hospital of Zhengzhou; Department of Orthopaedics,First Hospital Affiliated to Chongqing Medical University.MATERIALS ： Totally 30 adult healthy Wistar male rats, with body mass of （200±20） g, were enrolled. Ten rats were chosen as the donors of allogenic nerve transplantation. The other 20 rats were randomly divided into 2 groups： allogenic nerve embedment group and autologous nerve embedment group, with 10 rats in each one. JEM-1220 transmission electron microscope （Japan） and Olympus BX50 optical microscope （Japan） were used. METHODS ： This experiment was carried out at the laboratory of Orthopaedic Department, Chongqing Medical University from October 2000 to April 2002. ① Sciatic nerve of donor rats for allogenic nerve transplantation was cut off at 5 mm distant from pelvic strait.15 mm sciatic nerve segment was chosen from lateral part as graft, allogenic nerve embedment group： 15 mm sciatic nerve form the donor rats was embedded in the posterior part of right legs. Autologous nerve embedment group： 15 mm sciatic nerve segment of autologous left side was embedded in the posterior side of right legs. ② Nerve segment embedded subcutaneously was taken out at postoperative 2 weeks and performed gross observation; then 5 samples chosen randomly respectively from 2 groups and given haematoxylin-eosin staining and observation under optical microscope （×400）;The other 5 samples were made into ultrathin sections （0.5μm）and observed under transmission electron microscope（×17 000）. MAIN OUTCOME MEASURES ： Gross shape, optical and electron microscope results of nerve segments of rats between two groups at 2 weeks after subcutaneous embedment. RESULTS ： ① Results of gross observation： Appearance of nerve segment was similar between 2 groups. ② Results of optical observation： medullary sheath denaturation, axonotmesis, vascular engorgement, desmoplasia of adventitia and infiltration of inflammatory cells were all found in both 2 groups. Inflammatory reaction was a little more severe in the allogenic nerve embedment group than in the autologous nerve embedment groups.③Results of electron microscope ： Similar cataplasia and denaturation of medullary sheath and cataplasia of Schwann cell were all found in the 2 groups. CONCLUSION： Some inflammatory reaction occurs after allogenic nerve embedment, but the activity of Schwann cell is similar to that of peripheral nerve after autologous nerve embedment.

After allogenic bone marrow transplantation agent of hemorrhagic cystitis: BK virus

Hemorrhagic cystitis is a common and in its severe form potentially life threatening complication of hematopoietic stem cell transplantation. Hemorrhagic cystitis is defined as a diffuse inflammatory condition of the urinary bladder due to an infectious or noninfectious etiology resulting in bleeding from the bladder mucosa. Hemorrhagic cystitis is characterized by lower urinary tract symptoms including dysuria, hematuria and hemorrhage. The most common cause is a bacterial infection that usually responds promptly to treatment. But chronic and recurrent hemorrhagic cystitis often arises from anticancer chemotherapy or radiotherapy for the treatment of pelvic malignancies. Infectious etiologies are less common causes of chronic hemorrhagic cystitis except in immunocompromised hosts like bone marrow transplant recipients. Hemorrhagic cystitis is a significant complication of bone marrow transplantation which influences economic and survival outcome. Hemorrhagic cystitis can be divided into two classes according to onset time;early and late onset time. Earlyonset hemorrhagic cystitis is commonly associated used with chemo-radiotherapy protocols in some of the preparatory regimens. More than one factor is accused in the etiology of late onset hemorrhagic cystitis. Here, we present a patient whose hematuria started after 54 days from allogeneic stem cell transplantation.

EBV-Associated Post-Transplantation B-Cell Lymphoproliferative Disorder in Patient after Allogenic Stem Cell Transplantation

Epstein-Barr virus (EBV)-associated B-cell post-transplantation lymphoproliferative disorder (PTLD) is a severe complication following solid-organ transplantation (SOT) and allogeneic hematopoietic stem cell transplantation (HSCT). We present a case of a 15-year-old male developing a monomorphic B-cell PTLD after receiving an allogenic stem cell transplant for acute acute myeloid leukemia. A diagnostic lymph node biopsy revealed monomorphic type, B cell phenotype, associated with Epstein-Barr virus, consistent with post-transplant lymphoproliferative disorder (PTLD). The morbidity and mortality of PTLD are high, and there is no standard protocol for treatment of PTLD. To prevent the occurrence of PTLD and early intervention are important for the prognosis of patients.

Factors influencing Frey syndrome after parotidectomy with acellular dermal matrix

BACKGROUND Frey syndrome,also known as ototemporal nerve syndrome or gustatory sweating syndrome,is one of the most common complications of parotid gland surgery.This condition is characterized by abnormal sensations in the facial skin accompanied by episodes of flushing and sweating triggered by cognitive processes,visual stimuli,or eating.AIM To investigate the preventive effect of acellular dermal matrix(ADM)on Frey syndrome after parotid tumor resection and analyzed the effects of Frey syndrome across various surgical methods and other factors involved in parotid tumor resection.METHODS Retrospective data from 82 patients were analyzed to assess the correlation between sex,age,resection sample size,operation time,operation mode,ADM usage,and occurrence of postoperative Frey syndrome.RESULTS Among the 82 patients,the incidence of Frey syndrome was 56.1%.There were no significant differences in sex,age,or operation time between the two groups(P>0.05).However,there was a significant difference between ADM implantation and occurrence of Frey syndrome(P<0.05).ADM application could reduce the variation in the incidence of Frey syndrome across different operation modes.CONCLUSION ADM can effectively prevent Frey syndrome and delay its onset.

Azacitidine maintenance therapy for blastic plasmacytoid dendritic cell neoplasm allograft: A case report

BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare,highly invasive malignant neoplasm.There is no universally accepted standard of care because of its rarity and the dearth of prospective research.It is still challenging for some patients to achieve persistent clinical remission or cure,despite the success of allogeneic hematopoietic stem cell transplantation(allo-HSCT),indicating that there is still a significant recurrence rate.We report a case of prevention of BPDCN allograft recurrence by azacitidine maintenance therapy and review the relevant literature.CASE SUMMARY We report a 41-year-old man with BPDCN who was admitted to hospital due to skin sclerosis for>5 mo’duration.BPDCN was diagnosed by combined clinical assessment and laboratory examinations.Following diagnosis,the patients underwent induction consolidation chemotherapy to achieve the first complete remission,followed by bridging allo-HSCT.Post-transplantation,azacitidine(75 mg/m2 for 7 d)was administered as maintenance therapy,with repeat administration every 4–6 wk and appropriate extension of the chemotherapy cycle.After 10 cycles,the patient has been disease free for 26 mo after transplantation.Regular assessments of bone marrow morphology,minimal residual disease,full donor chimerism,Epstein–Barr virus,and cytomegalovirus all yielded normal results with no abnormalities detected.CONCLUSION Azacitidine may be a safe and effective maintenance treatment for BPDCN following transplantation because there were no overt adverse events during the course of treatment.

Synergy and translation of allogenic bone marrow stem cells after photodynamic treatment of rheumatoid arthritis with tetra sulfonatophenyl porphyrin and TiO2 nanowhiskers

Rheumatoid arthritis （RA） etiology and amelioration remains a challenge in modern therapeutics. Herein, we explored the synergistic effect of allogenic bone marrow stem cell （BMSC） translation and photodynamic treatment of RA with tetra sulfonatophenyl porphyrin （TSPP） and TiO2 nanocomposites as a new strategy for RA theranostics. The translation of BMSCs with miRNAs into infected joints in long bones post-photodynamic therapy is helpful for treating and understanding RA pathophysiology. We observed that allogenic BMSC translation combined with TSPP-TiO2 nanocomposites can significantly （p 〈 0.01） lower the concentrations of serum biomarkers （tumor necrosis factor-α and interleukin-17） in a collagen induced arthritis （CIA） murine model, both in vitro and in vivo, as well as improve other parameters such as arthritis score, BMSC count, complete blood count, and numbers of platelets, red blood cells, and white blood cells. Moreover, a fluorescent TSPP in the feet or long bones and X-ray bioimaging of RA joints revealed the clinical efficacy of BMSCs combined with TSPP-TiO2 nanocomposites. Microarray data analysis illustrated that rnomir-375-3p and rno-mir-196b-3p were up-regulated by approximately 100-fold in the BMSCs of ameliorated RA post-photodynamic therapy with TSPP-TiO2 nanocomposites. Our study not only suggests a new approach for RA theranostics, but also helps in understanding RA pathophysiology.

A risk score system for stratifying the risk of relapse in B cell acute lymphocytic leukemia patients after allogenic stem cell transplantation

Background:For patients with B cell acute lymphocytic leukemia(B-ALL)who underwent allogeneic stem cell transplantation(allo-SCT),many variables have been demonstrated to be associated with leukemia relapse.In this study,we attempted to establish a risk score system to predict transplant outcomes more precisely in patients with B-ALL after allo-SCT.Methods:A total of 477 patients with B-ALL who underwent allo-SCT at Peking University People’s Hospital from December 2010 to December 2015 were enrolled in this retrospective study.We aimed to evaluate the factors associated with transplant outcomes after allo-SCT,and establish a risk score to identify patients with different probabilities of relapse.The univariate and multivariate analyses were performed with the Cox proportional hazards model with time-dependent variables.Results:All patients achieved neutrophil engraftment,and 95.4%of patients achieved platelet engraftment.The 5-year cumulative incidence of relapse(CIR),overall survival(OS),leukemia-free survival(LFS),and non-relapse mortality were 20.7%,70.4%,65.6%,and 13.9%,respectively.Multivariate analysis showed that patients with positive post-transplantation minimal residual disease(MRD),transplanted beyond the first complete remission(≥CR2),and without chronic graft-versus-host disease(cGVHD)had higher CIR(P<0.001,P=0.004,and P<0.001,respectively)and worse LFS(P<0.001,P=0.017,and P<0.001,respectively),and OS(P<0.001,P=0.009,and P<0.001,respectively)than patients without MRD after transplantation,transplanted in CR1,and with cGVHD.A risk score for predicting relapse was formulated with the three above variables.The 5-year relapse rates were 6.3%,16.6%,55.9%,and 81.8%for patients with scores of 0,1,2,and 3(P<0.001),respectively,while the 5-year LFS and OS values decreased with increasing risk score.Conclusion:This new risk score system might stratify patients with different risks of relapse,which could guide treatment.

Recovery from Bell’s palsy after treatment using uncultured umbilical cord-derived mesenchymal stem cells:A case report

BACKGROUND Bell’s palsy is an idiopathic facial palsy with an unknown cause,and 75%of patients heal spontaneously.However,the other 25%of patients continue experiencing mild or severe disabilities,resulting in a reduced quality of life.Currently,various treatment methods have been developed to treat this disease.However,there is controversy regarding their effectiveness,and new alternative treatments are needed.CASE SUMMARY The patient suffered from left-sided facial paralysis due to Bell’s palsy for 7 years.The patient received an uncultured umbilical cord-derived mesenchymal stem cell transplant eight times for treatment.After follow-up for 32 mo,the paralysis was cured,and there was no recurrence.CONCLUSION Uncultured umbilical cord-derived mesenchymal stem cell transplantation may be a potential treatment for patients with Bell’s palsy who do not spontaneously recover.

Allogeneic stem cell transplantation in the treatment of acute myeloid leukemia: An overview of obstacles and opportunities

As an important treatment for acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation(allo-HSCT) plays an important role in reducing relapse and improving long-term survival. With rapid advancements in basic research in molecular biology and immunology and with deepening understanding of the biological characteristics of hematopoietic stem cells, allo-HSCT has been widely applied in clinical practice. During allo-HSCT, preconditioning, the donor, and the source of stem cells can be tailored to the patient’s conditions, greatly broadening the indications for HSCT, with clear survival benefits. However, the risks associated with allo-HSCT remain high, i.e. hematopoietic reconstitution failure, delayed immune reconstitution, graft-versus-host disease, and posttransplant relapse, which are bottlenecks for further improvements in allo-HSCT efficacy and have become hot topics in the field of HSCT. Other bottlenecks recognized in the current treatment of individuals diagnosed with acute myeloid leukemia and subjected to allo-HSCT include the selection of the most appropriate conditioning regimen and post-transplantation management. In this paper, we reviewed the progress of relevant research regarding these aspects.

Protective Effects of Different Hypothermal Preservation Solutions on Structure and Function of Isolated Rat Arteries

Objective:With the increasing application of vascular reconstruction in surgical procedures,allogeneic vessels are becoming more popular in clinical practice due to their abundant sources,precise diameter matching,improved histocompatibility,and higher long-term patency rate.This study aimed to investigate the protective effect of various preservation solutions on the function and structure of the isolated rat abdominal aorta preserved under hypothermal conditions.Methods:The study utilized a total of 150 Sprague-Dawley(SD)rats,with 144 rats allocated to the experimental groups and 6 rats allocated to the control groups.The abdominal aorta of the rats was chosen as the subject of our research.The aorta in the experimental groups were randomly assigned to 4 groups:University of Wisconsin(UW)solution group,histidine-tryptophan-ketoglutarate(HTK)solution group,normal saline(NS)group,and sodium lactate Ringer's solution(RS)group.Samples were subjected to examination after preservation periods of 1 day,3 days,5 days,7 days,14 days,30 days,and 90 days.Evaluation of vascular physiological function involved detecting and assessing vasoconstriction ability and measuring cell viability through the MTT test.Evaluation of the vascular wall structure involved tension tolerance tests and pathological staining.Results:The pathogen-positive rate in the HTK group and NS group at 1 month was 16.7%.Regarding the vascular skeleton structure,both the UW group and HTK group exhibited intact structures after 2 weeks of preservation,with slightly edematous collagen and elastic fibers,which was significantly better than that of the NS group and RS group.In terms of cell activity and contractile function,all preservation groups showed similar effects within 2 weeks.However,after 2 weeks,the UW group showed the most favorable preservation effect(P<0.05).In terms of vascular tension,different groups exhibited similar effects within 1 week.However,after 2 weeks,the UW group showed the best preservation effect(P<0.05).Conclusion:All 4 types of preservation solution had a preservation effect on the structure and function of isolated blood vessels during short-term hypothermal preservation.However,after 2-week preservation,the UW solution was found to be the most suitable solution for the preservation of blood vessels.

Ocular manifestations and quality of life in patients after hematopoietic stem cell transplantation

AIM:To explore the relationship between ocular and systemic conditions and the impact of ocular complications on the quality of life(QOL)in patients after allogeneic hematopoietic stem cell transplantation(ALLO-HSCT).METHODS:Forty-four patients with severe hematopoietic disease were enrolled after ALLO-HSCT at our center from July 2018 to October 2020.They completed two questionnaires:the Ocular Surface Disease Index(OSDI)and the quality-of-life scale for Chinese patients with visual impairment(SQOL-DV1).Ocular conditions and systemic conditions were also assessed.RESULTS:Eye damage was correlated with total bilirubin(P=0.005),and gamma-glutamyl transferase(GGT)(P=0.021).There was no significant correlation between the overall QOL score and OSDI(P=0.8226)or SQOLDV1(P=0.9526)scores.The OSDI and the overall QOL score were not correlated with ocular conditions,including best-corrected visual acuity(BCVA),intraocular pressure,Schirmer tear test II,sodium fluorescein staining,tear film breakup time,and tear meniscus height.SQOLDV1 was correlated with BCVA(P=0.0007),sodium fluorescein staining(P=0.007),and tear film breakup time(P=0.0146).CONCLUSION:In some patients,early ocular symptoms are not evident after ALLO-HSCT,while ocular surface complications can be observed after a comprehensive ophthalmological examination.Especially for those with elevated total bilirubin or GGT,regular ophthalmic follow-up visits are essential to diagnose and treat ocular graft versus host disease(o GVHD),especially for patients with elevated total bilirubin or GGT.

Advantageous tactics with certain probiotics for the treatment of graft-versus-host-disease after hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation(HSCT)becomes a standard form of cellular therapy for patients with malignant diseases.HSCT is the first-choice of immunotherapy,although HSCT can be associated with many complications such as graft-versus-host disease(GVHD)which is a major cause of morbidity and mortality after allogeneic HSCT.It has been shown that certain gut microbiota could exert protective and/or regenerative immunomodulatory effects by the production of short-chain fatty acids(SCFAs)such as butyrate in the experimental models of GVHD after allogeneic HSCT.Loss of gut commensal bacteria which can produce SCFAs may worsen dysbiosis,increasing the risk of GVHD.Expression of G-protein coupled receptors such as GPR41 seems to be upre-gulated in the presence of commensal bacteria,which might be associated with the biology of regulatory T cells(Tregs).Treg cells are a suppressive subset of CD4 positive T lymphocytes implicated in the prevention of GVHD after allogeneic HSCT.Here,we discuss the current findings of the relationship between the modification of gut microbiota and the GVHD-related immunity,which suggested that tactics with certain probiotics for the beneficial symbiosis in gut-immune axis might lead to the elevation of safety in the allogeneic HSCT.

Tissue-engineered rhesus monkey nerve grafts for the repair of long ulnar nerve defects:similar outcomes to autologous nerve grafts

Acellular nerve allografts can help preserve normal nerve structure and extracellular matrix composition. These allografts have low immunogenicity and are more readily available than autologous nerves for the repair of long-segment peripheral nerve defects. In this study, we repaired a 40-mm ulnar nerve defect in rhesus monkeys with tissue-engineered peripheral nerve, and compared the outcome with that of autograft. The graft was prepared using a chemical extract from adult rhesus monkeys and seeded with allogeneic Schwann cells. Pathomo- rphology, electromyogram and immunohistochemistry findings revealed the absence of palmar erosion or ulcers, and that the morphology and elasticity of the hypothenar eminence were normal 5 months postoperatively. There were no significant differences in the mean peak compound muscle action potential, the mean nerve conduction velocity, or the number of neurofilaments between the experimental and control groups. However, outcome was significantly better in the experimental group than in the blank group. These findings suggest that chemically extracted allogeneic nerve seeded with autologous Schwann cells can repair 40-mm ulnar nerve defects in the rhesus monkey. The outcomes are similar to those obtained with autologous nerve graft.

Fulminant gastrointestinal graft-versus-host disease concomitant with cytomegalovirus infection:Case report and literature review

Here,we report a case of fulminant gastrointestinal graft-versus-host disease(GI-GVHD) with cytomegalovirus(CMV) infection in 44-year-old woman.Despite the difficulties associated with the treatment of GIGVHD and GI-CMV disease,the mucosal findings and the clinical course showed marked improvements during long-term clinical observation.The endoscopic findings were remarkable,with diffuse sloughing mucosa in the stomach and highly active inflammation and deep discrete ulcers throughout the colon.Changes in the CMV quantitative polymerase chain reaction results were correlated with the endoscopic mucosal findings and were useful for assessing the efficacy of the treatment.Although a definite diagnosis of GI-GVHD is generally made by endoscopy with biopsy,the gross appearance of this disease can vary depending on the endoscopy.In this paper,we also conduct a literature review of patients with GI-GVHD.

Alopecia treatment using minimally manipulated human umbilical cord-derived mesenchymal stem cells:Three case reports and review of literature

BACKGROUND Alopecia areata(AA)is a common autoimmune disease characterized by hair loss.AA appears in extensive forms,such as progressive and diffusing hair loss(diffuse AA),a total loss of scalp hair(alopecia totalis),and complete loss of hair over the entire body(alopecia universalis).Recently,mesenchymal stem cells(MSCs)have been identified as a therapeutic alternative for autoimmune diseases.For this reason,preclinical and case studies of AA and related diseases using MSCs have been conducted.CASE SUMMARY Case 1:A 55-year-old woman suffered from AA in two areas of the scalp.She was given 15 rounds of minimally manipulated umbilical cord-MSCs(MM-UC-MSCs)over 6 mo.The AA gradually improved 3 mo after the first round.The patient was cured,and AA did not recur.Case 2:A 30-year-old woman,with history of local steroid hormone injections,suffered from AA in one area on the scalp.She was given two rounds of MM-UC-MSCs over 1 mo.The AA immediately improved after the first round.The patient was cured,and AA did not recur.Case 3:A 20-year-old woman,who was diagnosed with alopecia universalis at the age of 12,was given 14 rounds of MM-UC-MSCs over 12 mo.Her hair began to grow about 3 mo after the first round.The patient was cured,and alopecia universalis did not recur.CONCLUSION MM-UC-MSC transplantation potentially treats patients who suffer from AA and related diseases.

Psoriasis treatment using minimally manipulated umbilical cordderived mesenchymal stem cells:A case report

BACKGROUND Psoriasis is a chronic autoimmune disease that usually manifests as a red scaly epidermis,induration,and hyperproliferation of basal keratinocytes.About 2%of the world’s population suffers from psoriasis but there are no clear therapeutics yet.Recently,mesenchymal stem cells(MSCs)have been regarded as a therapeutic alternative for autoimmune diseases,as they possess immunosuppressive effects without risks.Human umbilical cord-derived MSCs effectively regulate immune cells and are characterized by low immunogenicity,which has many advantages in treating immune diseases.CASE SUMMARY The patient was a 47-year-old male,diagnosed with psoriasis in 1995.He had received various treatments for 25 years,but the psoriatic condition was not significantly improved.He was given three rounds of minimally manipulated umbilical cord-derived MSCs over 2 wk.The erythema gradually disappeared.Three months after the 1st round,all erythema completely disappeared,and the psoriasis did not recur.CONCLUSION Minimally manipulated umbilical cord-derived MSC transplantation can potentially treat patients who suffer from psoriasis.

Treatment of acute ischemic stroke by minimally manipulated umbilical cord-derived mesenchymal stem cells transplantation:A case report

BACKGROUND Stroke is one of the major causes of disability and death worldwide.Some treatments for stroke exist,but existing treatment methods have limitations such as difficulty in the regeneration of damaged neuronal cells of the brain.Recently,mesenchymal stem cells(MSCs)have been studied as a therapeutic alternative for stroke,and various preclinical and case studies have been reported.CASE SUMMARY A 55-year-old man suffered an acute stroke,causing paralysis in the left upper and lower limbs.He intravenously transplanted the minimally manipulated human umbilical cord-derived MSCs(MM-UC-MSCs)twice with an 8-d interval.At 65 wk after transplantation,the patient returned to his previous occupation as a veterinarian with no adverse reactions.CONCLUSION MM-UC-MSCs transplantation potentially treats patients who suffer from acute ischemic stroke.

POLYGENETIC COMPOUND ORE DEPOSITS AND THEIR ORIGIN IN THE CONTEXT OF REGULARITIES IN CRUSTAL EVOLUTION

Polygenetic compound ore deposits are here defined as those ore deposits which evidently possess n1any sided genetic characteristics as a comprehensive result of more than one rnineralization stages, from many rnaterial sources, and of many genetic types. They are formed most commonly during the diwa (geo(lepression) stage in the process of crustal evolution and, therefore, spread most widely in diwa regions. At the present stage of our knowledge, they may be subdivided into three principal models and many types of metallogenesis, controlled by different geotectonic conditions and being distributed in time and in space according to the corresponding regularities. This is a newly rccognizcd, third gcnetic type of ore deposits, being not reasonable to be simply referred to either pure endogenic or pure exogenic origin. They are very important and are of great study significance, becausc they comrnonly are rich and have a large amount of reserve with high economic value.