OBJECTIVE To evaluate the effect of manipulation of Imipenem and cisplatin sodium （ICS） for injection on the consistency of its main drug imipenem （IPN） content， and the stability of different concentrations of ICS solution， to provide a reference for the safe and effective use of ICS in children. METHODS Three operators prepared ICS solutions according to the two commonly used dosage methods for children （10 mL or 20 mL 0.9% Sodium chloride injection to prepare the initial ICS solution and draw the required dose from the initial suspension）. The content of IPN was determined by ultra-high performance liquid chromatography-tandem mass spectrometry after parallel processing. The content consistency of solutions in each group was determined according to the coefficient of variation （CV）＜15% of the IPN content. ICS test solution X1 was prepared according to the instructions， and then test solutions X2 and X3 were prepared by diluting X1 with 0.9% Sodium chloride injection in the volume ratios of 1∶1 and 1∶2， which were stored at room temperature （[ 23.0±0.5） ℃]， in a thermostatic water bath at 30 ℃， and in a refrigerator at 2-8 ℃. The stability of the drug solution was determined by the ratio of the IPN mass concentration measured at the specified temperature and time to the initial （0 h） mass concentration （if the ratio was≥90%， it was considered that the drug solution was stable）. RESULTS CV of IPN content was ＜15% in each group of solutions prepared with two manipulation methods by each operator， indicating a small deviation in IPN content. The solutions at the three concentration levels were stable at room temperature for 6 h or refrigerated for 18 h. The test solutions X1 and X2 were also stable when placed at 30 ℃ for 6 h， but the IPN concentration in test solution X3 decreased by about 20% compared with that of 0 h. CONCLUSIONS The consistency of the content of IPN is good in the two commonly used methods for ICS manipulation in children. The stability of ICS solution is affected by concentration， temperature and time. Lower concentrations at higher temperatures resulted in decreased stability of IPN. Clinical attention should be paid to controlling the amount of solvent as well as temperature and time during preparation and use.

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Objective:To retrospectively analyze the surgical treatment of isolated pulmonary mucormycosis, explore the timing and effect of operation.Methods:Clinical data of patients with isolated pulmonary mucormycosis who underwent surgical treatment from April 2019 to April 2024 were collected and retrospectively analyzed, combined with literature review.Results:The clinical data of 13 patients with pulmonary mucormycosis who underwent operation were collected, including 9 males and 4 females, aged 22~64(45.4±15.4)years old. The basic diseases included diabetes mellitus in 10 cases and hematological malignancy in 3 cases. Seven patients had hemoptysis during the course of the disease. All 13 patients received adequate antifungal therapy before surgery, and 12 patients received bronchoscopic interventional therapy. Ten patients underwent lobectomy, two underwent pneumonectomy, and one underwent a right sleeve pneumonectomy. All patients were cured except one patient with bronchopleural fistula after operation. All patients achieved complete elimination of mucor and also discontinuation of antifungal drug.Conclusion:For isolated pulmonary mucormycosis, on the basis of systemic antifungal treatment, actively seek the opportunity of surgical intervention, can shorten the course of the disease and achieve good therapeutic results.

Objective:To explore the effect of tumor plastic surgery in breast conserving surgery for early breast cancer.Methods:From March 2015 to March 2021, 80 female patients with breast cancer, aged 31 to 55 (43±12) years, who were admitted to the Department of Breast and Thyroid Surgery, the First People′s Hospital of Chenzhou City, Hunan Province, were divided into plastic breast conserving group and conventional breast conserving group, with 40 cases in each group. The plastic surgery breast conserving group used plastic surgery techniques to repair local breast defects after surgery, while the conventional breast conserving group used fascial fat flaps around the cutting edge to repair local defects; the differences in surgical related indicators and postoperative complications were compared between two groups of patients, and the postoperative cosmetic effect was evaluated.Results:Both groups successfully completed the conservative surgery. The operation time, blood loss, and drainage tube retention time in the oncoplastic conservative surgery group were longer than those in the conventional conservative surgery group, and the differences were statistically significant (all P<0.001). The 2nd cut margin expansion rate was 2.5% (1/40) in the oncoplastic conservative surgery group, which was lower than that in the conventional conservative surgery group (20%, 8/40), and the difference was statistically significant ( P=0.034). There were 3 cases of partial necrosis and 2 cases of subcutaneous fat embolism in the oncoplastic conservative surgery group after surgery, and 1 case of partial necrosis and 1 case of subcutaneous fat embolism in the conventional conservative surgery group. All of them healed after drainage and dressing changes. The postoperative aesthetic effect evaluation showed that the excellent rate in the oncoplastic conservative surgery group was 95% (38/40), and the excellent rate in the conventional conservative surgery group was 70% (28/40). The difference was statistically significant ( P=0.003). After a follow-up of 36 to 96 months, no local recurrence or distant metastasis was found in either group. Conclusions:Breast-conserving surgery can enable early breast cancer patients to achieve wider tumor margins and better aesthetic effects, with good safety and is worth clinical application.

Objective:Immune checkpoint inhibitors have a high remission rate in the preoperative application of resectable and potentially resectable non-small cell lung cancer when combined with chemotherapy. For the unresectable stage Ⅲ non-small cell lung cancer, whether the transformation can be achieved through this regimen to provide opportunities for surgical resection is controversial. In this study, we evaluated the pattern of transformation therapy by reviewing the efficacy and safety of preoperative therapy and surgery of this group.Methods:A review of 23 patients undergoing surgical resection after transformation therapy by preoperative immunotherapy combined chemotherapy between November 2019 and November 2021 was performed. All patients must clarify the pathological diagnosis of non-small cell lung cancer by biopsy. After the multi-disciplinary treatment team and preoperative imaging assessment, the diagnosis should be consistent with unresectable stage III as described in the Expert Consensus on Multidisciplinary Management of Stage Ⅲ Non-Small Cell Lung Cancer, 2019 Edition. After 2 to 4 cycles of preoperative anti-PD-1 monoclonal antibody combined with chemotherapy, the surgical team assessed the chance of resection and performed surgery. Important indicators such as surgical resection rate, R0 resection rate, MPR, pCR, incidence of grade 3-5 adverse reactions and various other perioperative data were counted.Results:In the whole group, initial imaging evaluation was 10 of stage cⅢA and 13 of stage cⅢB.15 cases had multiple stations N2 lymph nodes metastasis, 9 had enlarged fused N2 lymph nodes metastasis, 6 had large vessel invasion(T4), and 1 had contralateral mediastinal lymph node metastasis(N3). After preoperative neoadjuvant therapy, 17 cases achieved PR, 3 achieved SD and 3 achieved PD. The surgical resection rate of the whole group was 91.3%(21/23, 1 lobectomy combined with superior vena cava reconstruction, 2 sleeve lobectomy, 5 pneumonectomy, 12 lobectomy/combined lobectomy, 1 wedge resection and 2 unresectable cases), R0 resection rate was 95.2%(20/21). MPR was achieved in 13 cases, 8 of them reached pCR. There were no perioperative deaths, median surgical time was 260(190-460) min, median bleeding volume was 100(50-750) ml, median drainage time was 5(3-9) days, and median hospitalization was 7(5-11) days. Two cases got immunotherapy-related grade 3 adverse reactions, one was interstitial pneumonia and the other was immune-related injury involving the eye, oral and genital mucosa. Two cases got surgical complications and one was persistent lung leakage, which stopped after 46 days of conservative treatment; The other was pleural effusion, which was relieved after drainage.Conclusion:For the unresectable stage Ⅲ NSCLC, immunotherapy combined chemotherapy is an effective preoperative downstage method. It can convert 91.3% cases to resectable ones while achieving a good degree of pathological remission. Its side reactions are generally controllable and safety.

Objective:To explore the clinical efficacy of posterior short-segment internal fixation for the treatment of brucella spondylitis (BS).Methods:The medical records of 34 patients with BS admitted from January 2014 to June 2019 were retrospectively analyzed. There were 22 males and 12 females; the age was 52.3±10.6 years (range 35-72 years). On the basis of standardized use of antibacterial drugs, the lumbar spine posterior short-segment internal fixation was used. Twenty-nine cases underwent simple internal fixation, and posterolateral bone graft fusion, while 5 cases underwent primary debridement, autologous bone grafting and interbody fusion. Monitor erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and test tube agglutination test (SAT) were used to assess inflammation control. Imaging examinations of patients before operation, 1 month after operation, 3 months after operation, 6 months after operation, 1 year after operation to the last follow-up were analyzed to evaluate the condition of intervertebral fusion. The clinical efficacy evaluation was based on the pain visual analog scale (VAS), Japanese Orthopaedic Association (JOA) score, modified MacNab grading, and American Spinal Injury Association (ASIA) grading, as well as surgery-related complications.Results:The operation time of 34 patients was 104.64±16.72 min (range 65-145 min), the average hospital stay was 16.49±7.41 days (range 7-38 d), and the average postoperative follow-up time was 20.2 months (range 12-34 months). At the last follow-up, the ESR and CRP fell to the normal range, and the SAT was negative. At 3 months postoperatively, 11 cases (32.35%) reached Bridwell fusion criteria of grade II, 23 cases (67.65%) of grade III; 3 cases (8.82%) of grade I fusion at 6 months after surgery, 31 cases reached grade II fusion (91.18%); all reached grade I fusion at the last follow-up. After the operation, the symptoms of the waist or lower extremities were significantly relieved. The VAS score was 6.3±1.4 before the operation, 4.1±1.2 at 1 month after the operation, 2.7±1.4 at 3 months after the operation, 1.6±1.0 at 6 months after the operation, and 1.2±0.8 at the last follow-up. The JOA score before surgery was 13.8±2.4, 1 month after surgery 17.6±2.6, 3 months after surgery 21.7±3.1, 6 months after operation 4.9±2.7, and at the last follow-up 25.7±1.8. Compared with the preoperative time nodes of the above indicators, the differences were statistically significant. At the last follow-up, of the 12 patients (2 cases of grade C, 10 cases of grade D) with preoperative neurological dysfunction, 2 cases recovered from grade C to grade D, and 10 cases recovered from grade D to E; the excellent and good rate of modified MacNab grading reached 97.06% (33/34). No extradural hematoma, nerve damage, cerebrospinal fluid leakage and other surgical complications occurred. Only 1 case had wound infection complication, and the prognosis was good after active treatment. There were no recurrences during the follow-up period.Conclusion:On the basis of standardized antimicrobial treatment, posterior lumbar short-segment internal fixation is a safe and effective method for the treatment of BS, and good clinical effects can be obtained.

Objective To explore the role of NT-proBNP in the differentiation of acute pulmonary embolism (APE) from congestive heart failure (CHF) in patients with acute dyspnea.Methods Consecutive 260 patients aged ≥ 60 years complaining of acute dyspnea were collected between June 2010 and October 2015.The patients were divided into two groups of APE and CHF according to their diagnosis standards.The levels of NT-proBNP between the two groups were compared using t test,and receiver operating characteristic curve (ROC curve) was made to show the value of NT-proBNP in differentiation of APE from CHF.Results Patients in APE group had significantly lower median levels of NT-proBNP as compared with patients in CHF group [(2 478.8±1 473.9)ng/L vs.(5 955.4±3 180.1)ng/L,t =-12.020,P ＜ 0.01].The ROC curve of APE existence against serum levels of NT-proBNP showed an optimal cut-point of NT-proBNP of 1 518 ng/L,with specificity up to 98.8％,and the area under the ROC curve for NT-proBNP was 0.877.Conclusions NT-proBNP as a simple and bedside approach to identify APE versus CHF patients with acute dyspnea can help clinicians identify APE early and reduce the rates of misdiagnosis and missed diagnosis of APE.But the confirmative diagnosis of APE is still based on spiral CT angiography.

Objective To establish and assess the new method of APTT assay based on the combinations of Mg2+and Ca2+for lupus anticoagulants(LA)measurements.Methods This prospective study included 309 trisodium citrate anticoagulated plasma samples from 244 random patients and 65 patients with different autoimmune diseases(AID)to establish and assess the method of LA measurement, respectively.Final concentrations of 0,2.0, 4.0, 8.0,16.0 mmol/L Mg2+were added into 25 mmol/L Ca2+solution, and Actin reagent was used to measured plasma APTT of 94 patients.The applied concentration of Mg2+-Ca2+solution was confirmed through the special and significant alteration of APTT from LA-positive and -negative plasma observed in the presence of Mg 2+(test solution).Based on Actin reagent use,the test solution and 25 mmol/L Ca2+solution were applied to measure APTT of patients and normal individuals, respectively, and the ratio of Mg2+-Ca2+-APTT to Ca2+-APTT(Mg2+-Ca2+-APTT indices)and normalized Mg2+-Ca2+-APTT indices(NAR)were calculated, respectively.Mixed plasma NAR was measured,and CV%was calculated to evaluate the repeatability and stability of Mg 2+-Ca2+-APTT method.APTT of 150 patients was measured with the test solution and Actin reagent to calculate Mg 2+-Ca2+-APTT indices, and normalized LA ratio was determined with dRVVT method.The applicability of Mg2+-Ca2+-APTT assay was assessed through comparisons of the results from the two methods.Finally, NAR and NLR of 65 patients with AID(including 26 SLE patients)were measured with Mg2+-Ca2+-APTT assay and dRVVT method, respectively, and ROC curve was also used to assess the efficacy of the two methods for LA measurements.Results In all LA-negative plasma,APTT increased from 28.1 ±4.5 s to 61.2 ±7.9 s in normal APTT group,47.2 ±8.9 s to 97.5 ±10.3 s in increased APTT group,and 27.6 ± 5.1 s to 61.2 ±7.9 s in ACA-positive group when Mg2+increased from 0 to 8 mmol/L in Mg2+-Ca2+solution(F=34.12, 38.9 and 28.35,P<0.01).Following increased Mg2+concentration, APTT shortened from 0 to 4.0 mmol/L, but simultaneously prolonged from 4.0 to 16.0 mmol/L in LA-positive plasma with prolonged or normal APTT(F=31.55 and 39.51, P<0.01), and APTT was significantly higher in 8.0 mmol/L than that in 4.0 mmol/L(P<0.001).The test concentration of Mg 2+/Ca2+solution was 4.0 mmol/L.The within, inter-day CV% of NAR was 1.39%,2.30%, and 3.44%, respectively. According to the judging criteria of <0.966 and >1.034 of Mg2+/Ca2+indices, there was 141 patients with increased indices and NLR <1.20, and 9 patients with decreased ones and NLR≥1.20 in all 150 patients.The area under ROC curve of NAR and NLR for LA detection was 0.913(95%CI:0.848-0.978) and 0.892(95%CI:0.817-0.966), respectively, and the cut-off value was 0.87 and 1.13, respectively. The sensitivity and specificity of NAR(85% and 77%)was higher than that of NLR(81% and 74%), respectively.The accordant rate of positive,negative,and total results between NAR and NLR was 94.4%, 98.5%,and 98%,respectively.Conclusion The method of APTT assay based on Mg2+combining Ca2+for LA measurements is feasible,and can be used to detect plasma LA of patients.

Objective To explore the risk factors of gestational diabetes mellitus and its influence on pregnancy outcome,and to provide guidance for early intervention of gestational diabetes to improve pregnancy outcome in clinic.Methods Totally 159 patients with gestational diabetes mellitus in our hospital from January 2014 to January 2016 as observation group were collected,and at the same time,634 healthy pregnancy women as control group were collected.The risk factors of gestational diabetes mellitus were analyzed by the Logistic regression analysis and comparison of pregnancy outcome between two groups was conducted.Results The patients in the observation group with age ≥ 35 years,overweight or obesity before pregnancy,adverse pregnancy history,family history of diabetes,hypertension and vaginal candida and thyroid peroxidase antibody (TPOAb) compared with the control group,the difference was statistically significant (P ＜ 0.05).Multivariate logistic regression analysis showed that age ≥ 35 years,overweight or obesity before pregnancy,adverse pregnancy history,family history of diabetes,and positive TPOAb were the independent risk factors of gestational diabetes mellitus,OR was 2.441,2.889,1.486,4.879,and 1.323,respectively;the difference was statistically significant (P ＜ 0.05).The incidence of premature rupture of membrane,pregnancy hypertensive disorder,premature birth,polyhydramnios,uterine-incision and postpartum hemorrhage in observation group were higher than those in control group,the difference was statistically significant (P ＜ 0.05).The incidence of giant baby,fetal distress and mild neonatal asphyxia were higher than those in control group,and the difference was statistically significant (P ＜ 0.05).No statistical significance in fetal growth restriction,neonatal malformations between two groups was found (P ＞ 0.05).Conclusions Age ≥35 years,overweight or obesity before pregnancy,adverse pregnancy history,family history of diabetes,and thyroid dysfunction were the independent risk factors of gestational diabetes mellitus,and it has serious effect on pregnancy outcome,so that it should take measures to prevent the independent risk factors.

OBJECTIVETo analyze the epidemiology data on plague in five counties in Zhejiang province and to evaluate the risk of plague in theses areas.

METHODSWe selected five monitoring stations as a risk assessment (Qingyuan county, Longquan city, Yiwu city, Wencheng county, and Ruian city) in Zhejiang province where the plague epidemic more serious in the history. At least one constant site and 1-4 variable sites where plague occurred in history were selected for monitoring. We collected the five counties (cities) surveillance data of indoor rat density, indoor Rattus flavipectus density, the Xenopsylla cheopis index of rat, the Xenopsylla cheopis index of Rattus flavipectus in 1995-2014. Isolation of Yersinia pestis was conducted among 171,201 liver samples and F1 antibody were detected among 228,775 serum samples. Risk matrix, Borda count method, and Delphi approach were conducted to assess risk of the plague of five counties (cities) in Zhejiang province.

RESULTSIndoor rat density in Qingyuan county, Longquan city, Yiwu city, Wencheng county, Ruian city was 1.58%-5.50%, 1.13%-9.76%, 0.56%-3.67%, 2.83%-16.08%, 7.16%-15.96%, respectively; Indoor Rattus flavipectus density of five counties (cities) was 0.08%-2.23%, 0-2.02%, 0-0.54%, 0.71%-5.58%, 0.55%-4.92%, respectively. The Xenopsylla cheopis index of rat in Qingyuan county and Wencheng county was 0.011-0.500 and 0.015-0.227, respectively; The Xenopsylla cheopis index of Rattus flavipectus of Qingyuan county and Wencheng county was 0.119-3.412 and 0.100-1.430, respectively; Ruian City and Yiwu city cannot collected Xenopsylla cheopis, Long quan city only collected the Xenopsylla cheopis index of rat in the five years. Yersinia pestis were not isolated in five counties (cities).There were 3 Apodemus agrarius samples positive of plague F1 antibody test, in Longquan city and Yiwu city in 2005. Borda count method to assess the Longquan city, Yiwu (Borda point were both 321) plague risk was higher than three other regions; Delphi approach to evaluation five counties (cities) belong to the plague had a lower risk areas, according to the level of risk score (Pf) Longquan city and Yiwu (Pf was 0.314, 0.292, respectively) plague risk were higher than three other regions (Pf were all 0.292).

CONCLUSIONThe main host and media were lower in five key plague surveillance counties (cities) of Zhejiang province; The result of Borda count method and Delphi approach for risk assessment indicated that endogenous plague recrudescence was at lower level, but Longquan city and Yiwu city risk were higher than other counties (cities).

Animals ; Cities ; Epidemics ; Epidemiological Monitoring ; Humans ; Murinae ; Plague ; Rats ; Risk Assessment ; Yersinia pestis