In this report,we described a case of a clinical practice,in which the clinical pharmacists was involved in the treatment of a soft tissue sarcoma patient,who was diagnosed with mental disorders induced by regorafenib.The patient was complicated with hypoproteinemia,hepatic insufficiency,leukoencephalopathy and other diseases.Before the treatment,the patient's mental was normal.After continuous administration of regorafenib(40 mg,po,qd)for 5 days,the patient has a sudden loss of consciousness.Clinical pharmacists excluded the possibility of mental disorders caused by tumor brain metastases,exacerbation of leucoencephalopathy or hepatic encephalopathy and the drugs used together.They determined that mental disorders were likely to be related to the use of regorafenib through the association evaluation of adverse reactions.It was considered to be an adverse reaction induced by regorafenib.Therefore,regorafenib treatment was temporarily suspended and symptomatic treatment was given.After 5 days,the patient's mental state improved.In addition,clinical pharmacists monitored the patient for symptomatic treatment,and provided appropriate antitumor drug treatment recommendations based on evidence-based evidence.This case suggests that the clinical use of regorafenib should be vigilant against mental disorders adverse reactions,do a good job of pharmaceutical care,and timely drug analysis and symptomatic treatment after adverse reactions.

Objective:To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods:The prospective multicenter study was conducted in Zhejiang, China from May 1 st, 2019 to January 31 st, 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results:A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P<0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95% CI 0.593-0.771, P<0.01). Conclusion:In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.

Objective:Partial stereotactic ablative boost radiotherapy(P-SABR)is a method to deliver SABR boost to the gross tumor boost volume(GTVb), followed by conventionally fractionated radiotherapy to the whole tumor area(GTV). GTVb is the max volume receiving SABR while ensuring the critical organ-at-risk(OAR)falloff to 3 GyE/f. We investigated the potential advantage of proton therapy in treating bulky non-small cell lung cancer(the tumor length greater than 8 cm).Methods:Nine patients with bulky NSCLC treated with photon P-SABR in our institute were selected. For the treatment planning of proton therapy, the GTVb target area was gradually outwardly expanded based on the photon GTVb target area until the dose to critical OARs reached 3 GyE/f. The GTV and CTV areas remained the same as photon plan. A proton intensity-modulated radiation treatment plan(proton-IMPT), a photon intensity-modulated radiation treatment plan(photon-IMRT)and a photon volumetric modulated arc therapy(photon-VMAT)were created for each patient, respectively. The dosimetric parameters of different treatment plans were compared.Results:The volume ratio of GTVb-photon and GTVb-proton to GTV was(25.4±13.4)% and(69.7±30.0)%,respectively( P<0.001). In photon-IMRT, photon-VMAT, and proton-IMPT plan groups, the mean dose of CTV was(76.1±4.9)Gy, (78.2±3.6)Gy, and(84.7±4.9)Gy, respectively; the ratio of tumor volume with Biologic Effective Dose(BED)≥ 90 Gy to GTV volume was(70.7±21.7)%, (76.8±22.1)%,and(97.9±4.0)%,respectively. The actual dose and BED to the tumor area of the proton-IMPT plan group were significantly higher than those of the photon plan group(both P<0.05). Besides, the OARs dose was significantly decreased in the proton-IMPT group, with(49.2±22.0)%, (56.8±19.0)% and(16.1±6.3)% of the whole lung V5 for photon-IMRT, photon-VMAT and proton-IMPT, respectively(all P<0.001). Conclusions:Larger GTV boost target volume, higher BED and reduced OARs dose can be achieved in proton plans compared with photon plans. Proton P-SABR is expected to further improve the local control rate of bulky NSCLC with fewer adverse effects.

Objective:To evaluate the relationship between serum exosomes and microglial pyroptosis during brain injury in a young rat model of hepatic ischemia-reperfusion (I/R).Methods:Forty-six clean-grade healthy male Sprague-Dawley rats, aged 2-3 weeks, weighing 40-60 g, were allocated into 4 groups using a random number table method: sham operation group (group S, n=10), hepatic I/R group (group I/R, n=13), treatment with serum exosome in sham-operated young rat group (group S-Exosome, n=10), and treatment with serum exosomes in young rats with I/R group (group I/R-Exosome, n=13). The common trunk of the portal vein, left hepatic artery and bile duct was clamped for 60 min resulting in ischemia of 70% of the liver in anesthetized animals.After 6 h of reperfusion, the serum was collected to extract exosomes in S group and I/R group, and the serum exosome suspension 100 μl of S group and I/R group was injected through the tail vein in S-Exosome group and I/R-Exosome group, respectively.The expression of serum exosome marker proteins CD9 and CD81 was determined by Western blot in S group and I/R group.Serum and hippocampi were obtained from each group at 6 h after the corresponding treatment.The expression of NOD-like receptor protein 3 (NLRP3), gasdermin D (GSDMD), pro-caspase-1, cleaved-caspase-1, and apoptosis-associated speck-like protein containing CARD (ASC) in the hippocampus was detected using Western blot, and the expression of GSDMD in hippocampal tissues was determined by immunohistochemistry.The levels of interleukin-1beta (IL-1β), interleukin-18 (IL-18) and tumor necrosis factor-α (TNF-α) in serum and hippocampal tissues and S100β and NSE in serum were determined by enzyme-linked immunosorbent assay.In group I/R-Exosome, 3 rats were selected, and their serum exosomes were extracted, labeled with PKH26 red fluorescence and then injected via the tail vein, and the co-localization between exosomes and microglia was identified by immunofluorescence technique. Results:Compared with group S, the expression of serum CD9 and CD81 was significantly up-regulated in group I/R, the expression of NLRP3, GSDMD, cleaved-caspase-1 and ASC in hippocampal tissues was significantly up-regulated, the levels of IL-18, IL-1β and TNF-α in serum and hippocampal tissues and S100β and NSE in serum were increased in I/R and I/R-Exosome groups ( P<0.05), and no significant change was found in the parameters mentioned above in group S-Exosome ( P>0.05). The positive expression of GSDMD was significantly increased in I/R and I/R-Exosome groups ( P<0.05), no positive expression of GSDMD was found in S and S-Exosome groups ( P>0.05), and the results of immunofluorescence showed the co-localization between exosomes and microglia. Conclusions:The mechanism by which hepatic I/R induces brain injury may be related to serum exosomes-mediated microglial pyroptosis in young rats.

Objective:To explore the amplitude of normal kidney motion in the 3D direction and its influencing factors under free-breathing condition.Methods:Clinical data of 28 patients with a KPS score≥80 who received 4D CT scan from March 2018 to March 2019 were collected. All patients were diagnosed with liver, pancreatic or lung tumors. The kidney was outlined and the geometric center and 3D coordinate values were recorded. The motion of bilateral kidneys in each direction and the 3D direction was calculated. The volume of kidney and surrounding organs, age, sex, height and body mass index (BMI) were recorded. Clinical data were statistically compared by t-test or nonparametric test. Results:The motion of the left and right kidneys in the the sup-inf (SI) direction were the largest up to (8.39±3.18) mm and (7.71±3.55) mm. The motion amplitudes of bilateral kidneys in male patients were significantly larger than those of the female counterparts in the left-right (LR), SI and 3D directions (all P<0.05). The motion amplitudes of bilateral kidneys in patients taller than 165 cm were significantly larger than those of their counterparts with a height of ≤165 cm (all P<0.05). Patients with a BMI≥25 kg/m 2 had significantly larger motion amplitudes of the left kidney in the LR and ant-post (AP) directions compared with those of normal weight counterparts (all P<0.05). The motion amplitude of the left kidney in the AP direction in patients with the left kidney volume of >180 cm 3 was significantly larger than that of patients with smaller left kidney volume ( P=0.014). Age was not significantly associated with kidney motion in each direction ( P>0.05). Conclusions:Kidney motion mainly occurs in the SI direction. The kidney motion amplitudes in male and taller patients are larger. Special attention should be paid to the use of breath motion control device to decrease the normal tissue damage.

Objectives:To investigate the efficacy and toxicity of the full coverage radiation to primary and all metastatic lesions in patients with oligometastatic castration-resistant prostate cancer (CRPC).Methods:Forty-four patients with oligometastatic CRPC was retrospective analyzed from Oct. 2011 to Jun. 2017 at Peking University 1 st Hospital. Before radiotherapy, average age was 72(57-86), the median value of initial PSA was 38.545 (6.640-1 066.000)ng/ml, the median value of PSA nadir after initial androgen deprivation therapy(ADT) was 0.259(0.011-18.762)ng/ml, the time interval between initial ADT to diagnosis of metastatic castration resistant prostate cancer(mCRPC) was 12(4-96) months, and the median PSA value pre-radiotherapy was 3.765(2.040-187.000) ng/ml. There were 23(52.3%)patients with Gleason score 9-10 and 15(34.0%) patients with Gleason score 8. At the time of initial diagnosis, there was 41(93.2%) cases with stage T 3-T 4, 23(52.3%)cases with lymph node metastasis, and 29 (63.9%) case with distant metastasis. The number of metastatic foci before radiotherapy was 1 in 22(50.0%)cases, 2 in 12(27.3%)cases, 3 in 6(13.6%)cases and 4 in 4(9.1%)cases. There were 3 cases of pelvic lymph node metastasis (6.8%), 9 cases of retroperitoneal lymph node metastasis(20.5%), 21 cases of bone metastasis(47.7%), 11 cases of bone metastasis+ lymph node metastasis(25.0%), and no visceral metastasis. Image-guided volumetric modulated arc therapy(IGRT-VMAT) was used to fully cover primary and metastatic foci. The prostate and seminal vesicle were routinely underwent 76Gy/38 fractions, and the bioequivalent dose(BED 3) was 126.67 Gy. For those with pelvic lymph node metastasis, the drainage area of pelvic lymph node was 46Gy/23 fractions. According to the tolerance of different normal tissues around the lesions, the median BED 3 of local radiotherapy dose in the metastatic foci was 112.26(91.14-140.77)Gy. The efficacy and side effects of all these patients were recorded. Kaplan-meier method was used to analyze the overall survival and the new metastasis-free survival. Results:Only 1 patient had grade 3 urinary tract obstruction and underwent indwelling catheter. All the other patients had grade 1-2 toxic and side effects. After a median follow-up of 34.5(9-96) months, the PSA-nadir after radiotherapy was 0.088(0.003-132.000)ng/ml. Forty(90.9%) patients showed a decrease in PSA after radiotherapy, and 34(77.3%) cases. showed a decrease of >80%. The 1, 3, and 5-year overall survival rates were 90.9%, 54.5%, 36.8%, the 1, 3, and 5-year new metastasis free survival rates were 47.7%, 25.0%, 12.9%, respectively.Conclusion:The full coverage radiotherapy to primary and metastatic lesions showed high PSA response rate, the satisfactory survival and tolerable toxicity in oligometastatic CRPC patients.

Objective:To investigate the efficacy and safety of radiotherapy for all metastases in patients with metachronous oligo-metastatic prostate cancer after radical treatment.Methods:From October 2011 to February 2021, 41 patients with prostate cancer with less than 5 metastases after radical treatment were retrospectively analyzed in a single center. The median age at radiotherapy was 68 (57-81) years. Forty patients (98%) received androgen deprivation therapy (ADT). There were 28 patients in the hormone sensitive (HSPC) group and 13 patients in the hormone resistant (CRPC) group. The median initial PSA was 24.4 (7.4-399.0) ng/ml. Tumor stage: T 2 stage 11 patients, T 3 stage 27 patients, T 4 stage 3 patients.30 patients were in N 0 stage and 11 patients in N 1 stage. Gleason score was 7 in 12 patients, 8 in 9 patients, 9 in 18 patients, and 10 in 2 patients.33 patients were treated with surgery, and 8 patients were treated with radiotherapy. The time span from diagnosis to metastasis was 3.1 (0.2-1.8) years. Conventional imaging examination (CT/ MRI/bone scan) before radiotherapy was used in 7 patients, and PSMA PET/CT examination was used in 34 patients.The median PSA before radiotherapy was 1.3(0.1-33.8) ng/ml. There were 62 metastases in 41 patients, including 1 lesion in 28 patients, 2 lesions in 9 patients, 3 lesions in 2 patients, and 5 lesions in 2 patients. Fifty-four patients had bone metastases and eight had retroperitoneal lymph node metastases. Twenty-two bone metastases were located in the pelvis, 18 in the vertebral body, 12 in the ribs, one in the femur and one in the sternum.The median metastatic volume was 5.8(0.2-81.7) cm 3.Daily image-guided rotational intensity modulated radiotherapy was used to cover all metastases.Dose segmentation modes include 37.5Gy/7.5Gy/5F, 60Gy/3Gy/20F, 65-70Gy/2.6-2.8Gy/25F.The median biological effective dose (BED 3) was 120 (67-147) Gy. The primary endpoint was biochemical progression-free survival (BPFS), the secondary endpoints were acute and late toxic side effects, local relapse-free survival (LPFS), and overall survival (OS). Results:The median follow-up time was 21 months (range 5-72 months). All patients completed radiotherapy, and 16 patients had grade 1 to 2 acute toxicity and side effects, and no grade 3 or above acute and late stage side effects. 1-year LPFS was 97.1%.The 1-year and 2-year BPFS were 77.5% and 59.2%, respectively. The median BPFS time was 29 months (range 13.9-44.2 months). Univariate analysis showed that the HSPC group ( P<0.001) and the group with total metastatic volume ≤ 5.8cm 3 ( P=0.010) had higher BPFS. The median BPFS time was 37 months in the retroperitoneal lymph node metastases subgroup and 17 months in the bone metastases subgroup ( P=0.141). In the HSPC group, the median BPFS was 30(22-38) months. After radiotherapy, PSA decreased in all 28 patients, and increased in 6 patients. The median BPFS was 12(4-18) months. In the CRPC group, the median BPFS was 4(0-8) months. PSA decreased in 10 patients (76.9%) after radiotherapy, and PSA decreased in 6 patients. The median BPFS was 5(3-28) months. Three patients’PSA did not decrease after radiotherapy, and they were treated with new endocrine therapy drugs, chemotherapy, immunotherapy and other systemic therapy. Conclusions:For patients with metachronous metastases after radical treatment, full coverage radiotherapy has good safety and high local control rate. HSPC patients and patients with low tumor load could be recommended to receive radiotherapy for all metastatic lesions preferentially, and patients with only retroperitoneal lymph node metastases may have better prognosis after radiotherapy than patients with bone metastases.