Objective: To observe the effects of perinatal exposure to benzo[a]pyrene (B[a]P) on the expression of pancreatic duodenal homeobox-1 (PDX-1) and mitochondrial transcription factor A (TFAM) and mitochondrial DNA copy number in offspring mice, and to explore the role of maternal exposure to B[a]P in the pancreatic function damage of offspring mice. Methods: Forty pregnant rats were randomly divided into the control group, the lowest dose group (2 μg/kg), the low dose group (200 μg/kg), medium dose group (800 μg/kg) and high dose group (1 600 μg/kg), with 8 rats in each group. From day 1 of pregnancy, each exposed group was given 0.2 mL/100 g body weight of B[a]P and corn oil mixture by gavage once a day until 3 weeks after delivery, while the control group was given the same dose of corn oil. The pancreatic tissue of three-week-old mice were collected after abdominal anesthesia for insulin immunohistochemical detection. The protein and mRNA expression levels of PDX-1 and TFAM, as well as mitochondrial DNA copy number were detected. Spearman rank correlation analysis was used to analyze the correlation between B[a]P exposure dose and the above indicators. Results: The insulin-positive area ratio and average optical density of insulin in the medium and the high dose groups were significantly lower than those in the control group (all P<0.05). The insulin-positive area ratio and average optical density of insulin were negatively correlated with the B[a]P dose (rs=-0.862 and -0.858, both P<0.05). The protein expression levels of PDX-1 and TFAM in the high dose group were significantly lower than those in the control group (both P<0.05). The protein expression levels of PDX-1 and TFAM were negatively correlated with the B[a]P dose (rs=-0.756 and -0.799, both P<0.05). The mRNA expression levels of PDX-1 and mitochondrial DNA copy number in the medium and high dose groups were significantly lower than those in the control group, and the mRNA expression level of TFAM in the high dose group was significantly lower than that in the control group (all P<0.05). The mRNA expression levels of PDX-1, TFAM, and mitochondrial DNA copy number were negatively correlated with the B[a]P dose (rs=-0.722, -0.550 and -0.840, all P<0.05). Conclusion Perinatal exposure to B[a]P can induce the damage of islet β cells in offspring rats, which may be related to the decreased expression of PDX-1 and TFAM and the copy number of mitochondrial DNA.

OBJECTIVE To investigate the marketing status， general characteristics， and time trends of rare disease drugs in China. METHODS Based on 121 kinds of rare diseases included in the First Batch of Rare Disease Catalog， the names and marketing approval information of corresponding drugs with indications were obtained from the databases of the Center for Drug Evaluation， National Medical Products Administration and Yaozhi.com， and the relevant characteristic variables were extracted for descriptive statistical analysis. RESULTS As of December 31， 2022， only 32 of 121 rare diseases have therapeutic drugs available for treatment on the market in China， and 79 rare disease drugs have been approved. Among them， 46.84% of the drugs are domestic drugs， 88.61% of the drugs are approved for use in both adults and children； 67.09% are chemicals and 59.49% are injections. According to the ATC classification， Category A （digestive system drugs） is the most， accounting for 20.25%. The number of rare disease drugs on the market each year is the highest in 2021， with an overall upward trend from 2018 to 2021 and a downward trend in 2022. Among rare disease drugs on the market each year， according to the ATC classification， the number of Category L （antineoplastics and immune inhibitors） will be the largest in 2021， being 5. By dosage form， oral medicines were marketed in the largest number in 2022， and injectable medicines in 2021. CONCLUSIONS In recent years， the number of approved rare disease drugs in China has been continuously increasing， but it is still far from meeting the needs of patients， and there is still a lack of domestically approved rare disease drugs. We should further accelerate the research and development of rare disease drugs， and promote the import and replication of rare disease drugs.

OBJECTIVE To investigate the marketing status， general characteristics， and time trends of rare disease drugs in China. METHODS Based on 121 kinds of rare diseases included in the First Batch of Rare Disease Catalog， the names and marketing approval information of corresponding drugs with indications were obtained from the databases of the Center for Drug Evaluation， National Medical Products Administration and Yaozhi.com， and the relevant characteristic variables were extracted for descriptive statistical analysis. RESULTS As of December 31， 2022， only 32 of 121 rare diseases have therapeutic drugs available for treatment on the market in China， and 79 rare disease drugs have been approved. Among them， 46.84% of the drugs are domestic drugs， 88.61% of the drugs are approved for use in both adults and children； 67.09% are chemicals and 59.49% are injections. According to the ATC classification， Category A （digestive system drugs） is the most， accounting for 20.25%. The number of rare disease drugs on the market each year is the highest in 2021， with an overall upward trend from 2018 to 2021 and a downward trend in 2022. Among rare disease drugs on the market each year， according to the ATC classification， the number of Category L （antineoplastics and immune inhibitors） will be the largest in 2021， being 5. By dosage form， oral medicines were marketed in the largest number in 2022， and injectable medicines in 2021. CONCLUSIONS In recent years， the number of approved rare disease drugs in China has been continuously increasing， but it is still far from meeting the needs of patients， and there is still a lack of domestically approved rare disease drugs. We should further accelerate the research and development of rare disease drugs， and promote the import and replication of rare disease drugs.

OBJECTIVE To investigate the transfer and diffusion of berberine hydrochloride(BBH), the main active component of Coptis and Phellodenticum in the system of carboxymethyl chitosan(CMCS)-sodium alginate(SA). METHODS CMCS and SA were stirred in a certain proportion, and D-gluconolactone(GDL) was added to form polyelectrolyte hydrogel. Rheometer was used to study the rheological properties of CMCS-SA hydrogel, including the elastic modulus G′ and the viscous modulus G′′. A BBH diffusion model for CMCS-SA hydrogel was designed, and the relevant rules of BBH permeation through CMCS-SA polyelectrolyte hydrogel were observed by UV-VIS. RESULTS The elastic modulus G′ of the hydrogel was measured when the ratio of CMCS to SA was 3∶1, 2∶1, 1∶1, 1∶2, and 1∶3. When the ratio of CMCS to SA was 1∶1, G′ was the highest, and the crosslinking strength of the hydrogel was the highest. The cumulative amount of BBH transfer was measured by the BBH transfer model, and the diffusion of BBH in CMCS-SA hydrogel was fitted as the skeleton dissolution by Peppas equation, indicating that BBH dissociation and the transfer efficiency increased as the amino group of CMCS decreased or the carboxyl group of SA increased. The elastic modulus G′ of CMCS-SA hydrogel increased with the increase of GDL content. The reason was that the binding force between CMCS and SA molecules gradually increased with the decrease of pH, and the crosslinking degree of the hydrogel was enhanced. When ratio of fixed CMCS to SA was 1∶1 and the GDL content was 0.15 g·mL−1, the formability of CMCS-SA hydrogel was good. In addition, when BBH was transferred in hydrogel with different concentrations of GDL, the transfer efficiency increased with the increase of GDL content. When BBH was delivered in different thickness hydrogel, the delivery efficiency of CMCS-SA hydrogel increased with the decrease of thickness. CONCLUSION The CMCS-SA hydrogel system, as a potential drug carrier for traditional Chinese medicine extracts such as BBH, is expected to serve as a gel carrier for transdermal drug delivery.

Objective: To investigate the benzo[a]pyrene ( B[a]P ) diolepoxide ( BPDE )-DNA adduct levels in offspring rats with intrauterine exposure to B[a]P, and examine the effects of BPDE-DNA adduct levels on pancreatic functional impairment and glucose metabolism in offspring rats. Methods: Forty pregnant rats were randomly divided into the blank control group, standard-dose group, low-dose group, medium-dose group and high-dose group (daily dose of 0, 2, 200, 800, 1 600 μg/kg B[a]P, respectively), of 8 animals in each group. Rats in the B[a]P treatment groups were administered by oral gavage with a mixture of B[a]P and corn oil at a dose of 0.2 mL/100 g body weight since day 1 of pregnancy until 21 days after delivery, while rats in the blank control group were given the same volume of coin oil by oral gavage. The BPDE-DNA adduct levels were measured and the pancreatic development was observed in the offspring rats 2 and 21 days and 12 weeks after birth, and the correlation between pancreas volume index and dose of exposure to B[a]P was examined using Spearman's rank correlation analysis. In addition, glucose metabolism was measured in offspring rats 12 months after birth using glucose tolerance test ( GTT ) and insulin tolerance test ( ITT ). Results: There was no abnormal appearance, death, abortion or preterm birth in pregnant or offspring rats in the five groups, and no significant differences were seen in activity, diet, drinking water or mental status in rats. The greatest level of BPDE-DNA adducts was measured in offspring rats 2 days after birth, with median levels ( interquartile range ) of 1 089.60 ( 586.10 ) to 1 405.49 ( 346.47 ) pg/mL, and no BPDE-DNA adducts were found in offspring rats 12 weeks after birth. The pancreas volume index correlated negatively with the dose of exposure to B[a]P in offspring rats 2 ( rs=-0.620, P=0.001 ) and 21 days after birth ( rs=-0.801, P=0.001 ). Hypoplasia of pancreas with loose tissues was seen in offspring rats 2 days after birth, while well pancreatic development was found in offspring rats 12 weeks after birth, with tight exocrine portion. GTT showed an increase in glucose levels in offspring rats in all five groups following abdominal injection of glucose and declined 30 min post-injection ( F=365.578, P<0.001 ), and ITT showed a tendency towards a decline in glucose levels in offspring rats in all five groups ( F=461.215, P<0.001 ). Conclusions The levels of BPDE-DNA adducts in offspring rats increase with the dose of intrauterine B[a]P exposure, and insulin resistance and impaired glucose tolerance occur 12 months post-exposure to B[a]P. Intrauterine B[a]P exposure affects pancreatic development in offspring rats and causes abnormal glucose metabolism in adult offspring rats.

Objective:To explore the role of internal stenting for preventing biliary anastomotic complications during complex duct-to-duct biliary reconstruction of orthotopic liver transplantation.Methods:From December 1, 2018 to April 30, 2020, intraductal stent was placed in 6 cases of complex biliary tract reconstruction during liver transplantation. Postoperative prognosis, recovery of bilirubin and biliary enzymes, management of intraductal stent and occurrence of postoperative biliary complications were observed.Results:All of them recovered and were discharged smoothly and bilirubin and biliary enzymes normalized before discharge. The average peak values of total bilirubin, alkaline phosphatase, total bile acid and γ-glutamyl transpeptidase were 83.8±56.4 μmol/L, 151.5±76.3 U/L, 301.7±177.0 U/L and 98.4±80.9 μmol/L and the average turning points of total bilirubin, alkaline phosphatase, total bile acid and γ-glutamyl transpeptidase 2.3±1.0, 3.0±1.1, 3.8±1.2 and 1.8±0.8 days; average time of complete recovery of total bilirubin, alkaline phosphatase, total bile acid and γ-glutamyl transpeptidase 7.7±5.1, 5.0±4.9, 23.5±7.6 and 3.8±2.4 days respectively. Intraductal stent was removed by gastroduodenoscopy ( n=3) and slipped off ( n=3). Except for one case of asymptomatic anastomotic stricture at 1 year post-operation, no biliary complications occurred during follow-ups. Conclusions:The placement of intraductal stent during complex biliary reconstruction of liver transplantation can effectively promote the recovery of postoperative liver function, enhance the quality-of-life of patients, effectively avoid the occurrence of biliary anastomotic complications and ensure the safety of patients.

We conducted a randomized, open-label, parallel-controlled, multicenter trial on the use of Shuanghuanglian (SHL), a traditional Chinese patent medicine, in treating cases of COVID-19. A total of 176 patients received SHL by three doses (56 in low dose, 61 in middle dose, and 59 in high dose) in addition to standard care. The control group was composed of 59 patients who received standard therapy alone. Treatment with SHL was not associated with a difference from standard care in the time to disease recovery. Patients with 14-day SHL treatment had significantly higher rate in negative conversion of SARS-CoV-2 in nucleic acid swab tests than the patients from the control group (93.4% vs. 73.9%, P = 0.006). Analysis of chest computed tomography images showed that treatment with high-dose SHL significantly promoted absorption of inflammatory focus of pneumonia, which was evaluated by density reduction of inflammatory focus from baseline, at day 7 (mean difference (95% CI), -46.39 (-86.83 to -5.94) HU; P = 0.025) and day 14 (mean difference (95% CI), -74.21 (-133.35 to -15.08) HU; P = 0.014). No serious adverse events occurred in the SHL groups. This study illustrated that SHL in combination with standard care was safe and partially effective for the treatment of COVID-19.
COVID-19 ; Humans ; Medicine, Chinese Traditional ; Research ; SARS-CoV-2 ; Treatment Outcome

Objective:To investigate the long-term efficacy and safety of alternating double balloon occlusion combined with intra-aneurysm injection of human fibrin binder in the endovascular repair of ruptured abdominal aortic aneurysm (rAAA).Methods:The clinical data of 28 patients with rAAA admitted to Department of Vascular Surgery, the Fourth Affiliated Hospital of Guangxi Medical University from January 2015 to December 2019 were retrospectively analyzed. There were 23 males and 5 females, aged (62±5) years (range: 46 to 88 years).The maximum diameter of the tumors was (65.2±10.5) mm (range: 47.3 to 100.5 mm), all of which were subrenal rAAA. The intraoperative EVAR for abdominal aortic aneurysm was successfully performed under the emergency green channel procedure, and this surgery was assisted used the double balloon occlusion technique in aorta of inferior renal and superior renalcombined with intraoperative human fibrin binder injection technique. Observation indexes included: patients with preoperative preparation, operation time, hospitalization days, surgical treatment success rate and the incidence of postoperative complications, and aortic stent form during the follow-up period, the incidence of leakage, branch stents patency rate and infection rates.Results:The preoperative preparation time of 28 patients was (45.5±8.5) minutes (range:20 to 100 minutes). The operation time was (100.0±15.5) minutes (range:85 to 210 minutes), the ICU stay time was (7±2) days(range:1 to 17 days). The length of hospitalization was (13.5±2.5) days(range:5 to 43 days). The success rate of surgical treatment was 92.9% (26/28). Two patients died, 1 case died of postoperative multifocal lacunar cerebral infarction and massive gastrointestinal hemorrhage, and another elderly patient (84 years old) died of massive abdominal fluid due to preoperative abdominal aortic aneurysm rupture, postoperative complicated with significant abdominal compartment syndrome, and secondary multiple organ failure. Balloon occlusion of the upper renal aorta took (13±2)minutes (range:12 to 30 minutes). The intraoperative injection of fibrin adhesive was (14±2) ml(range:6 to 28 ml) in 22 cases. The incidence of major postoperative complications was 57.1% (16/28). Among the 26 patients who survived the surgery, 69.2% (18/26) completed the 3-year follow-up, and the follow-up time was (30±3) months(range:13 to 36 months). During the follow-up, the aortic stent was in good shape without obvious displacement. The incidence of leakage within 6 months after the operation was 10.7% (3/28), and there was no internal leakage in the patients who were followed up for 36 months after the operation. The patency rate of renal artery and iliac artery branch stents was 16/18. The incidence of stent infection was 7.7% (2/26), 1 case occurred at 1 month and another case at 6 months, respectively. All patients recovered after prolonged intensive anti-infection therapy.Conclusions:Under the standard emergency treatment process, the double balloon alternating occlusion technique combined with the intra-aneurysm injection of human fibrin adhesive technique can assist the successful completion of the endovascular repair of rAAA, effectively improve the success rate of treatment for patients, and reduce the incidence of postoperative leakage and serious complications. The mid-term and long-term results of EVAR for rAAA are good, safe and reliable.

Objective:To investigate the long-term efficacy and safety of alternating double balloon occlusion combined with intra-aneurysm injection of human fibrin binder in the endovascular repair of ruptured abdominal aortic aneurysm (rAAA).Methods:The clinical data of 28 patients with rAAA admitted to Department of Vascular Surgery, the Fourth Affiliated Hospital of Guangxi Medical University from January 2015 to December 2019 were retrospectively analyzed. There were 23 males and 5 females, aged (62±5) years (range: 46 to 88 years).The maximum diameter of the tumors was (65.2±10.5) mm (range: 47.3 to 100.5 mm), all of which were subrenal rAAA. The intraoperative EVAR for abdominal aortic aneurysm was successfully performed under the emergency green channel procedure, and this surgery was assisted used the double balloon occlusion technique in aorta of inferior renal and superior renalcombined with intraoperative human fibrin binder injection technique. Observation indexes included: patients with preoperative preparation, operation time, hospitalization days, surgical treatment success rate and the incidence of postoperative complications, and aortic stent form during the follow-up period, the incidence of leakage, branch stents patency rate and infection rates.Results:The preoperative preparation time of 28 patients was (45.5±8.5) minutes (range:20 to 100 minutes). The operation time was (100.0±15.5) minutes (range:85 to 210 minutes), the ICU stay time was (7±2) days(range:1 to 17 days). The length of hospitalization was (13.5±2.5) days(range:5 to 43 days). The success rate of surgical treatment was 92.9% (26/28). Two patients died, 1 case died of postoperative multifocal lacunar cerebral infarction and massive gastrointestinal hemorrhage, and another elderly patient (84 years old) died of massive abdominal fluid due to preoperative abdominal aortic aneurysm rupture, postoperative complicated with significant abdominal compartment syndrome, and secondary multiple organ failure. Balloon occlusion of the upper renal aorta took (13±2)minutes (range:12 to 30 minutes). The intraoperative injection of fibrin adhesive was (14±2) ml(range:6 to 28 ml) in 22 cases. The incidence of major postoperative complications was 57.1% (16/28). Among the 26 patients who survived the surgery, 69.2% (18/26) completed the 3-year follow-up, and the follow-up time was (30±3) months(range:13 to 36 months). During the follow-up, the aortic stent was in good shape without obvious displacement. The incidence of leakage within 6 months after the operation was 10.7% (3/28), and there was no internal leakage in the patients who were followed up for 36 months after the operation. The patency rate of renal artery and iliac artery branch stents was 16/18. The incidence of stent infection was 7.7% (2/26), 1 case occurred at 1 month and another case at 6 months, respectively. All patients recovered after prolonged intensive anti-infection therapy.Conclusions:Under the standard emergency treatment process, the double balloon alternating occlusion technique combined with the intra-aneurysm injection of human fibrin adhesive technique can assist the successful completion of the endovascular repair of rAAA, effectively improve the success rate of treatment for patients, and reduce the incidence of postoperative leakage and serious complications. The mid-term and long-term results of EVAR for rAAA are good, safe and reliable.

Objective:To explore the clinical evaluation outcomes of COVID-19 risk assessment scale on organ donation and procurement during the pandemic of novel coronavirus pneumonia (NCP) and reduce the incidence of donor-derived infection and medical staff infection.Methods:From January 20 to February 29 in 2020, the organ procurement team adopted the COVID-19 risk assessment scale for evaluating 8 potential donors. They were classified into the levels of high/low/uncertain risk by analyzing the risk levels of donation hospitals, clinical characteristics and exposure history. The coordinators, organ evaluators and ward medical staff adopted essential protective measures. The infection status of 2019-nCoV in the above mentioned staff was examined and graft function in the corresponding recipients were observed.Results:Based upon the COVID-19 risk assessment results, the risk level was high (n=8), low (n=5) and uncertain (n=2) and underwent organ procurement. A total of 19 grafts including liver, kidney, pancreas and heart were harvested and successfully utilized for organ transplantation. During the observation period of 14 days, there was no suspected or confirmed infection of 2019-nCoV among coordinators and medical staff. No graft dysfunction or acute rejection was observed during a follow-up period of 4 to 30 days. No recipient was suspected or confirmed to be infected with 2019-nCoV and 6 of them were negative for 2019-nCoV nucleic acid testing after organ transplantation.Conclusions:During the COVID-19 pandemic, it is safe to proceed with donor organ evaluations and procurements according to the result with the COVID-19 risk assessment scale. Low-risk donor organ donation may be carried out, uncertain risk donor organ donation should be performed cautiously and high-risk donations discouraged.