Zuoguiyin， which first recorded in Jingyue Quanshu written by ZHANG Jiebin in the Ming dynasty， was included in the Catalogue of Ancient Famous Classical Formulas（The Second Batch）. This study followed the Principles of Textual Research on Key Information of Ancient Famous Classical Formulas to determine the key information of Zuoguiyin in ancient and modern literature， such as the formula origin， the composition of the formula and the origin of the drugs. It was found that the composition， dosage， preparation and processing methods of Zuoguiyin were basically the same as the original formula. The original dosage of this formula is 41.03 g of Rehmanniae Radix Praeparata（the fresh or dried tuberous roots of Rehmannia glutinosa， processed by wine stewing or wine steaming）， 7.46 g of Dioscoreae Rhizoma（the dried rhizomes of Dioscorea opposita）， 7.46 g of Lycii Fructus（the dried mature fruit of Lycium barbarum）， 3.73 g of Glycyrrhizae Radix et Rhizoma Praeparata cum Melle（the dried roots and rhizomes of Glycyrrhiza uralensis， processed by honey-roasted method）， 5.595 g of Poria（the sclerotium of Poria cocos）， 5.595 g of Corni Fructus（the dried mature fruit pulp of Cornus officinalis）. The method of administration is to add 600 mL of water to all the herbs， decoct to 140 mL and take before meals. The function of Zuoguiyin is to nourish Yin and tonify the kidney， and it is often used in the treatment of lumbar soreness and ejaculation， night sweating， dry mouth and throat， thirst and desire to drink， glossy red tongue， thin and rapid pulse， etc. Since ancient times， Zuoguiyin has been used to treat a variety of internal and gynaecological diseases as well as diseases of the nervous， circulatory and reproductive systems that are predominantly caused by kidney Yin deficiency. However， there is not much research on the modern application and therapeutic mechanism of this formula， and there is no standardized preparation in the market， so the degree of development and utilization is not high， and there is still a lot of room for research.

Objective:This study aimed to analyze the genomic characteristics of Varicella-Zoster Virus (VZV) strains circulating in Jilin province from 2010 to 2023.Methods:Vesicle fluid from 78 sporadic cases with VZV infection were collected in Jilin province from 2010 to 2023, after detecting by Real-time PCR, 26 specimens (CT<25) were detected by PCR. Open reading frame 22(ORF22), ORF38 and ORF62 were amplified and analyzed. Genotyping was confirmed by SNPs ORF22 (37902, 38019, 38055, 38081 and 38177) and ORF38 (69424). Vaccine strains were indentified from wild-type strains according to ORF38 (69349) and ORF62 (106262, 107252, and 108111). Sequences were analyzed by homologous comparison and phylogenetic analysis.Results:The comparison with Dumas sequence revealed that SNPs (37902, 38055, 38081 and 38177) in ORF22 and ORF38 (69424) have mutations similar to the pOka strain, which belong to clade 2. Compared to the Dumas and Baike strains, all 26 samples were wild-type strains. JL2016-4 strain changes from threonine to asparaginyl at position 38059, JL2021-4 strain changes from arginine to proline at position 37933, from aspartic acid to tyrosine at position 37935, and from aspartic acid at base 38031 to tyrosine. JL2023-1 strain changes from arginine to leucine at position 37933.Conclusions:VZV has been prevalent for 14 years in Jilin province. The main epidemic strains belong to the clade 2. We should strengthen the monitoring of VZV outbreaks and raise the coverage rate of VZV vaccination.

The biological characteristics and pathogenicity of Klebsiella oxytoca isolated from sick carrier pigeons in Gansu province were explored by morphological observations,biochemical testing,16S rRNA PCR analysis,and RNA sequencing.The drug resistance and pathogenicity of the isolated strains were studied by histopathological observation,drug susceptibility testing,and pathogenicity analysis.The livers,lungs,hearts,and other organs of the sick pigeons were bleeding.In addition,the livers were yellow and brittle,and the lungs were purulent.A Gram-negative,short,rod-shaped bacterium was successfully isolated from the sick pigeon.Pink,smooth,moist,and round colonies grew on MacConkey's agar.The result of the indigo matrix test was positive.The homology between the amplified 16S rRNA sequence and MN330093.1 was 100.00％,indicating that the sick pigeon was infected with K.oxytoca.The strain was named GS-BY-GG.K.Oxytoca GS-BY-GG was resistant to 10 drugs,including penicillin,ampicillin,and furazolidone,and sensitive to 5 others,which included florfenicol,meropenem,and gentamicin.Histopathological observation showed bleeding in multiple organs.The liver cells were irregu-larly arranged with brown-yellow pigmentation.Extensive cell necrosis and exfoliation were observed in the trachea and mucosal epithelium,with inflammatory cell infiltration in the mucosal layer.The isolates were highly pathogenic in specific pathogen-free chickens.These findings provide support for the clinical diagnosis and control of K.oxytoca GS-BY-GG.

Objective:To analyze the efficacy and safety of flumatinib,a second-generation tyrosine kinase inhibitor(TKI)independently developed in China,in patients with chronic myelogenous leukemia in chronic phase(CML-CP)who falied first-line and second-line treatment.Methods:The clinical data of 30 CML-CP patients treated with flumatinib in Lianyungang First People's Hospital from January 2020 to September 2022 were collected retrospectively.Among them,15 patients who received imatinib first-line treatment but failed treatment were included in the second-line group,and the other 15 patients who failed second-line treatment with nilotinib or dasatinib were included in the third-line group.The hematological and molecular responses of the patients in the two groups at 3,6 and 12 months of treatment,and the event-free survival(EFS)and adverse reactions of patients at the end of follow-up were statistical analyzed.Results:At 3,6,and 12 months of treatment,10,11,and 12 patients in the second line group achieved major molecular response(MMR),which was higher than that of 3,4,and 5 patients in the third line group(P=0.010,P=0.011,P=0.010).At 3 months of treatment,12 and 13 patients achieved complete hematological response(CHR)and early molecular response(EMR)in the second-line group,which was higher than that of 9 and 13 patients in the third-line group,but the difference between the two groups was not statistically significant(P=0.232,P=1.000);At 6 and 12 months of treatment,6 and 7 patients in the second-line group achieved MR4.5,which were higher than of 3 and 2 cases in the third-line group,but the difference was not statistically significant(P=0.427,P=0.713).The hematological adverse reactions of patients in the second-line group during treatment the period were mainly grade 1-2 thrombocytopenia and anemia,and no grade 3-4 of adverse reactions occurred.In the third-line group,there were 2 cases of grade 1-2 thrombocytopenia,grade 1-2 anemia and white blood cell 3 cases were reduced each,1 case of grade 3-4 anemia,2 cases of grade 3-4 neutropenia.The non-hematological adverse reactions in the second-line group were rash(2 cases),headache(1 case),diarrhea(1 case),fatigue(1 case),limb pain(1 case).There were 1 cases of diarrhea,1 cases of nausea,and 1 cases of edema in the third-line group.There was no statistical significance in hematological and non-hematological adverse reactions between the two groups of patients(P＞0.05).At the end of follow-up,the EFS rate of patients in the second-line group was higher than that in the third-line group(100％vs 93.3％),but the difference was not statistically significant(P=0.317).Conclusion:The second-generation TKI flumatinib independently developed in China,has good curative effect and safety for CML-CP patients who failed first-line and second-line treatment.

Objective:To investigate the clinical efficacy and safety of ixazomib-containing regimens in the treatment of patients with multiple myeloma(MM).Methods:A retrospective analysis was performed on the clinical efficacy and adverse reactions of 32 MM patients treated with a combined regimen containing ixazomib in the Hematology Department of the First People's Hospital of Lianyungang from January 2020 to February 2022.Among the 32 patients,15 patients were relapsed and refractory multiple myeloma(R/RMM)(R/RMM group),17 patients who responded to bortezomib induction therapy but converted to ixazomib-containing regimen due to adverse events(AE)or other reasons(conversion treatment group).The treatment included IPD regimen(ixazomib+pomalidomide+dexamethasone),IRD regimen(ixazomib+lenalidomide+dexamethasone),ICD regimen(ixazomib+cyclophosphamide+dexamethasone),ID regimen(ixazomib+dexamethasone).Results:Of 15 R/RMM patients,overall response rate(ORR)was 53.3％(8/15),among them,1 achieved complete response(CR),2 achieved very good partial response(VGPR)and 5 achieved partial response(PR).The ORR of the IPD,IRD,ICD and ID regimen group were 100％(3/3),42.9％(3/7),33.3％(1/3),50％(1/2),respectively,there was no statistically significant difference in ORR between four groups(x2=3.375,P=0.452).The ORR of patients was 50％after first-line therapy,42.9％after second line therapy,60％after third line therapy or more,with no statistically significant difference among them(x2=2.164,P=0.730).In conversion treatment group,ORR was 88.2％(15/17),among them,6 patients achieved CR,5 patients achieved VGPR and 4 patients achieved PR.There was no statistically significant difference in ORR between the IPD(100％,3/3),IRD(100％,6/6),ICD(100％,3/3)and ID(60％,3/5)regimen groups(x2=3.737,P=0.184).The median progression-free survival(PFS)time of R/RMM patients was 9 months(95％CI:6.6-11.4 months),the median overall survival(OS)time was 18 months(95％CI:11.8-24.4 months).The median PFS time of conversion treatment group was 15 months(95％CI:7.3-22.7 months),the median OS time not reached.A total of 10 patients suffered grade 3-4 adverse event(AE).The common hematological toxicities were leukocytopenia,anemia,thrombocytopenia.The common non-hematological toxicities were gastrointestinal symptoms(diarrhea,nausea and vomit),peripheral neuropathy,fatigue and infections.Grade 1-2 peripheral neurotoxicity occurred in 7 patients.Conclusion:The ixazomib-based chemotherapy regimens are safe and effective in R/RMM therapy,particularly for conversion patients who are effective for bortezomib therapy.The AE was manageable and safe.

Objective:To investigate the efficiency and safety of the pulsatile GnRH therapy in the treatment of male congeni-tal hypogonadotropic hypogonadism(CHH).Methods:We retrospectively analyzed the clinical data on 45 CHH males treated by pulsatile GnRH therapy in our hospital from January 2013 to March 2023.We treated the patients with gonadorelin at 7-15 μg,one pulse/90 min,and followed them up every month in the first 3 months and then every 3 to 6 months after treatment,for an average of 19.1±4.3 months,during which we recorded the height,body weight,penile length,testis volume,Tanner stages,levels of FSH,LH and T,semen parameters and adverse reactions of the patients,followed by comparison of the data obtained with the baseline.Results:The levels of FSH,LH and T of the patients were dramatically elevated after treatment(P<0.01).The T level of the6 ca-ses of cryptorchidism,however,failed to reach the normal value within 18.2±8.6 months of follow-up.Significant improvement was seen in the external genitalia and secondary sexual characteristics of all the patients,and spermatogenesis was observed in the semen in 33 cases(73.3% ),with a mean sperm concentration of(18.2±6.2)106/ml,sperm progressive motility of(19.7±6.5)%,and semen volume of(1.8±0.6)ml.Eight of the cases achieved natural fertility,and another 3 achieved childbirth by assisted re-productive technology.As for adverse events,gynecomastia was observed in 8,subcutaneous induration in 6,and allergic reaction to therapeutic agent in 3 cases.Conclusion:Pulsatile GnRH therapy is an effective and safe strategy for male CHH.However,clini-cians should choose appropriate approaches to different individual cases.

Objective:To investigate the clinical value of emergent endoscopic intervention at different times of acute esophageal and gastric fundal varices bleeding.Methods:From July 2020 to December 2022, data of 207 cases of liver cirrhosis with esophageal and gastric fundal variceal bleeding diagnosed by gastroscopy were retrospectively analyzed, including 74 cases from the Second Affiliated Hospital, Zhejiang University School of Medicine, 41 cases from Affiliated Jinhua Hospital, Zhejiang University School of Medicine, 36 cases from Lanxi People's Hospital, 31 cases from Yongkang First People's Hospital and 25 cases from Pujiang People's Hospital. Patients were divided into 3 groups according to the time of endoscopic intervention and treatment. Patients who received endoscopic treatment within 6 h of hemorrhage were included in group A ( n=68); patients within 6-24 hours were in group B ( n=72). A total of 67 patients selected for conservative drug treatment were included in group C, who did not undergo endoscopic therapy. The prognosis (success rate of hemostasis, early rebleeding rate, mortality rate) and treatment benefit (open diet time, blood transfusion volume, hospital stay, hospital cost) of the 3 groups were compared. Results:The success rates of hemostasis were 100.00% (68/68), 97.22% (70/72), 86.57% (58/67) in group A, B and C respectively with significant difference ( χ2=13.51, P<0.001). The mortalities of the three groups were 0.00% (0/68) in group A, 2.78% (2/72) in group B and 13.43% (9/67) in in group C respectively with significant difference ( χ2 =15.61, P<0.001). The early rebleeding rates of the three groups were 0.00% (0/68) in group A, 2.86% (2/70) in group B, and 13.43% (5/58) in group C respectively with significant difference ( χ2 =3.41, P=0.182). There were significant differences in open diet time (group A: 28.32 ±2.52 h, group B: 37.25±2.45 h, group C: 66.62±2.65 h, F=58.69, P<0.001), blood transfusion volume (group A: 3.62 ± 0.30 U, group B: 5.46 ± 0.37 U, group C: 6.25 ± 0.39 U, F=11.35, P<0.001), hospital stay (group A: 6.58 ± 0.23 d, group B: 7.83 ± 0.34 d, group C: 8.24 ± 0.45 d, F=5.75, P=0.004) and cost (group A: 10 152±821 yuan, group B: 13 568 ± 1 017 yuan, group C: 15 306 ± 1 186 yuan, F=4.96, P=0.008) among the three groups. There was significant difference in Child-Pugh grading among hemostasis-success patients and those who failed ( χ2 =15.63, P<0.001). Conclusion:Early endoscopic diagnosis and treatment in the early 24 hours of acute esophageal and gastric fundal variceal hemorrhage can improve the prognosis and reduce the economic burden of patients with high clinical application value.

AIM: To evaluate the characteristics of choriocapillary blood flow in different patients with diabetic retinopathy(DR)based on the measurement of choriocapillaris(CC)perfusion density(PFD)using ultra-high-speed swept-source optical coherence tomography angiography(SS-OCTA)METHODS: The cross-sectional observational study was conducted on 139 cases(139 eyes)who admitted to the Second People's Hospital of Hefei, including 115 DR cases(115 eyes)and 24 control cases(24 eyes). The color retinal images were graded according to the Early Treatment Diabetic Retinopathy Study(ETDRS)scale, and the DR eyes were classified into non-DR group, nonproliferative diabetic retinopathy(NPDR)group, NPDR combined with diabetic macular edema(DME)group and proliferative diabetic retinopathy(PDR)group. The ultra-high-speed SS-OCTA was used to scan a 3mm×3mm region centered on the macular central fovea, the CC perfusion area was measured by the built-in software, and PFD was calculated. Multivariable linear regressions were used to evaluate the correlation between PFD of CC and DR degree.RESULTS: The degree of DR had a correlation with blood perfusion of CC after adjusting for various confounding factors. When compared to the control group, the PFD of CC in the central fovea of the NPDR group decreased by 9.358 units(95%CI -18.484～-0.232, P=0.045)and 9.284 units in the paracentral fovea(95%CI -18.487～-0.090, P=0.048); In the NPDR combined with DME group, the central fovea CC PFD decreased by 18.173 units(95%CI -28.583～-7.762, P=0.001), while the paracentral fovea decreased by 17.032 units(95%CI -27.521～-6.544, P=0.002); In the PDR group, the central fovea CC PFD decreased by 28.309 units(95%CI -39.978～-16.640, P<0.001), while the paracentral fovea decreased by 25.841 units(95%CI -37.597～-14.085, P<0.001).CONCLUSION: The macular perfusion can be objectively quantified by the measurement of CC PFD with ultra-high-speed SS-OCTA. The CC PFD in the macular region was significantly reduced in more advanced stages of DR. Furthermore, future research should focus on longitudinal studies in the causal relationship between CC perfusion and DR progression.

OBJECTIVE: To investigate the efficacy, prognosis and safety of decitabine combined with modified EIAG regimen in the treatment of patients with relapsed/refractory acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS). METHODS: The clinical data of 44 patients with relapsed/refractory AML and high-risk MDS admitted to our hospital from January 2017 to December 2020 were analyzed retrospectively. The patients were equally divided into D-EIAG group (decitabine combined with EIAG regimen) and D-CAG group (decitabine combined with CAG regimen) according to clinical treatment regimen. The complete response (CR), CR with incomplete hematologic recover (CRi), morphologic leukemia-free state (MLFS), partial response (PR), overall response rate (ORR), modified composite complete response (mCRc), overall survival (OS) time, 1-year OS rate, myelosuppression and adverse reactions between the two groups were compared. RESULTS: In D-EIAG group, 16 patients (72.7%) achieved mCRc (CR+CRi+MLFS), 3 patients (13.6%) achieved PR, and ORR (mCRc+PR) was 86.4%. In D-CAG group, 9 patients (40.9%) achieved mCRc, 6 patients (27.3%) achieved PR, and ORR was 68.2%. Difference was observed in mCRc rate between the two groups (P=0.035), but not in ORR (P>0.05). The median OS time of D-EIAG group and D-CAG group was 20 (2-38) months and 16 (3-32) months, and 1-year OS rate was 72.7% and 59.1%, respectively. There was no significant difference in 1-year OS rate between the two groups (P>0.05). After induction chemotherapy, the median time for absolute neutrophil count recovery to 0.5×10⁹/L in D-EIAG group and D-CAG group was 14 (10-27) d and 12 (10-26) d, for platelet count recovery to 20×10⁹/L was 15 (11-28) d and 14 (11-24)d, the median red blood cell suspension transfusion volume was 8 (6-12) U and 6 (6-12) U, and the median apheresis platelet transfusion volume was 4 (2-8) U and 3 (2-6) U, respectively. There were no statistically significant differences in comparison of the above indicators between the two groups (P>0.05). The hematological adverse reactions of patients were mainly myelosuppression. Grade III-IV hematological adverse events occurred in both groups (100%), with no increase in the incidence of non-hematological toxicities such as gastrointestinal reactions or liver function damage. CONCLUSION Decitabine combined with EIAG regimen in the treatment of relapsed/refractory AML and high-risk MDS can improve remission rate, provide an opportunity for subsequent therapies, and have no increase in adverse reactions compared with D-CAG regimen.
Humans ; Decitabine/therapeutic use* ; Treatment Outcome ; Retrospective Studies ; Cytarabine ; Myelodysplastic Syndromes/drug therapy* ; Leukemia, Myeloid, Acute/drug therapy* ; Bone Marrow Diseases/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

OBJECTIVE: To investigate the factors related to renal impairment in patients with diabetic kidney disease (DKD) from the perspective of integrated Chinese and Western medicine. METHODS: Totally 492 patients with DKD in 8 Chinese hospitals from October 2017 to July 2019 were included. According to Kidney Disease Improving Global Outcomes (KDIGO) staging guidelines, patients were divided into a chronic kidney disease (CKD) 1-3 group and a CKD 4-5 group. Clinical data were collected, and logistic regression was used to analyze the factors related to different CKD stages in DKD patients. RESULTS: Demographically, male was a factor related to increased CKD staging in patients with DKD (OR=3.100, P=0.002). In clinical characteristics, course of diabetes >60 months (OR=3.562, P=0.010), anemia (OR=4.176, P<0.001), hyperuricemia (OR=3.352, P<0.001), massive albuminuria (OR=4.058, P=0.002), atherosclerosis (OR=2.153, P=0.007) and blood deficiency syndrome (OR=1.945, P=0.020) were factors related to increased CKD staging in patients with DKD. CONCLUSIONS Male, course of diabetes >60 months, anemia, hyperuricemia, massive proteinuria, atherosclerosis, and blood deficiency syndrome might indicate more severe degree of renal function damage in patients with DKD. (Registration No. NCT03865914).
Humans ; Male ; Diabetes Mellitus, Type 2 ; Diabetic Nephropathies ; Hyperuricemia ; Kidney ; Proteinuria ; Renal Insufficiency, Chronic/complications*