Review of the diagnosis and treatment of postoperative bowel obstruction / 中国实用外科杂志

Postoperative intestinal obstruction,also known as postoperative small bowel obstruction(PSBO),is the most common acute abdomen after abdominal operations. The key to the treatment is accurate determination of therapeutic strategy.While avoiding unnecessary operation,delayed operation will cause intestinal obstruction and endanger the patients. PSBO diagnosis was improved owing to the progress of imaging techniques. Contrast enhanced CT can reach 90% in the diagnostic accuracy of intestinal strangulation,necessity of emergency operation and elucidation of etiology. Intestinal decompression via small intestinal decompression tube and subsequent gastrografin challenge can promote resolution of PSBO,increase the success rate of nonoperative management,avoid operation delay,and shorten the length of hospital stay.Operation is indicated for repeated episode of PSBO to eliminating the cause and avoiding recurrence. Elective operation is preferred over emergency. Laparoscopic operation is indicated for simple adhesions,but laparotomy is indicated for complex one. Meticulous operation,either laparoscopic or laparotomic,intestinal protection and eliminating foreign material and tissue debris are the keys to the prophylaxis of PSBO.

Technical difficulties and countermeasures in the source control of intra-abdominal sepsis / 中国实用外科杂志

Source control of intra-abdominal infections is an important part in the treatment of intra-abdominal sepsis,which mainly includes drainage,elimination of necrotic tissue,control of sepsis as well as restoration of anatomy and function of gastrointestinal tract.Source control should be taken immediately after ascertaining intra-abdominal infections.Specific measures of source control include percutaneous drainage,surgery,open abdomen and antimicrobial therapy.The key to percutaneous drainage is accurate location and adequate drainage.When performing surgical drainage,extent of trauma should be restricted while accurate location and avoiding omissions.Accurate timing of open abdomenand definitive abdominal closure,proper selection of temporary abdominal closure method,avoiding complications of OA,and enteral nutrition are essentials of successful definitive abdominal closure and reduction of complications.Effective antimicrobial therapy relies on time,type selection and avoiding antibiotic abuse.Factors should be searched for rigorously after failure to control intra-abdominal sepsis.Comprehensive global treatment is not only the basis but also the countermeasure of source control.

Analysis of intestinal non-Hodgkin lymphoma:A clinical analysis of 34 cases / 中国实用外科杂志

OBJECTIVE: To analyze the clinical characteristics of intestinal non-Hodgkin lymphoma. METHODS: The demographic, clinical, endoscopic and imaging data of patients with intestinal non-Hodgkin lymphoma admitted in Department of General Surgery, General Hospital of Eastern Theater Command from January 2009 to June 2018 were analyzed retrospectively. Rank-sum test and Chi-square test were used. RESULTS: There were 21 B-cell and 13 T/NKcell lymphoma patients.A total of 15 cases including 13 patients of T/NK-cell lymphoma presented with repeatedly fever,hemorrhage of gut and enterobrosis. CONCLUSION: It is necessary to pay attention to T/NK-cell lymphoma if the patient presented with repeatedly fever,hemorrhage of gut and enterobrosis.

Advance in the perioperative management:Enhanced recovery after surgery,perioperative surgical home and perioperative medicine / 中国实用外科杂志

Surgery plays a pivotal role in the treatment of certain diseases,which in turn promotes the development of enhanced recovery after surgery (ERAS). However,with the renewal of concept and technology,it is gradually realized that the key to a successful treatment is not only surgery itself but also preoperative and postoperative management. Patientbased perioperative management is closely related to the prognosis of the disease. Therefore,“perioperative medicine”and“perioperative surgical home (PSH)”are gaining more and more attention from all over the world. These novel concepts aim to cover the whole disease treatment process and improve the prognosis.

Efficient discovery and medicinal research of marine natural products / 中草药

Marine natural products (MNPs) are the source of modern marine drugs, but they have the characteristics of strong guiding function and weak druggability. How to quickly and efficiently discover new bioactive MNPs and optimize their druggability is an important idea for the research and development of innovative marine drugs. This article has made some discussions and suggestions on this emphasis from the origin and characteristics of MNPs, marine microorganisms with specific productivity for MNPs and the strategies of microbial MNPs with high yields and diverse structures, as well as the structural modification for medicinal use of MNPs.

Treatment of Chronic Radiation Intestinal Injury by Ileostomy Combined with Perioperative Nutrition Support Therapy / 肠外与肠内营养

Objective: To review the application of ileostomy combined with perioperative nutrition support therapy in the treatment of chronic radiation intestinal injury. Methods: The clinical data of patients with chronic radiation intestinal injury who received ileostomy combined with perioperative nutrition support therapy in the department of general surgery, Nanjing General Hospital of Nanjing Military Command from January 2012 to December 2016 were retrospectively analyzed. The short-term complications and perioperative nutrition process were recorded, and the long-term prognoses were followed up. Results: Forty-six patients were included in the study. The overall postoperative complication rate was 36. 96％. All the patients restored total enteral nutrition at the time of discharge (18±15) days. There was no post-operative mortality. Thirty-six patients were followed up (follow-up rate of 78. 26％), and the follow-up time was (25 ± 17) months. Tumor recurrence was occurred in 7 patients (19. 44％) during follow-up and 6 deaths (16. 67％). All of the 30 (83. 33％) survived patients maintained total enteral feeding, 27 of whom (75％) returned to normal diet. Twenty-one patients (58. 33％) underwent a second staging ostomy surgery in our hospital and recovered well. Conclusion: For selected patients with chronic radiation intestinal injury, ileostomy combined with perioperative nutrition support therapy could effectively restore intestinal patency and total enteral nutrition, and reduce the mortality.

Surgical treatment for idiopathic abdominal cocoon / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate diagnosis and treatment of abdominal cocoon.</p><p><b>METHODS</b>Clinical data of patients received treatment for abdominal cocoon from January 2000 to January 2011 was retrospectively analyzed.</p><p><b>RESULTS</b>A total of 67 patients underwent treatment in our hospital were analyzed, the preoperatively diagnosis rate was only 47.8% (32/67). Patients who received preoperatively nutrition support have a lower postoperative complication (8/27 vs.13/20, χ(2) = 5.815, P < 0.05) and patients with less extent of intestine involved had a lower early postoperative inflammatory ileus (EPII) rate (9/25 vs. 1/22, χ(2) = 6.912, P < 0.05) when compared with large extent.</p><p><b>CONCLUSIONS</b>Appropriate perioperative management play an important role in the prognosis of abdominal cocoon. The main treatment is surgery while preoperatively nutrition support can reduce postoperative complications.</p>

Damage control surgery directed surgical treatment of Crohn disease / 中华胃肠外科杂志

Damage control surgery (DCS) has been widely used in the management of surgical patients. Crohn disease (CD) patients requiring surgery are usually severe and associated with high surgical risk, while the concept of DCS has not gained adequate attention in surgery for CD. Surgery is indicated in patients with CD to control symptoms, therefore major surgery should not be performed when the general health of the patients is not satisfactory. Use of DCS to guide surgery can reduce risk of treatment and improve clinical outcome The review is to discuss the necessity, objective, and methods of damage control surgery in the surgical treatment of Crohn disease.

Timing of surgery in inflammatory bowel disease / 中华胃肠外科杂志

Surgery is an integral part in the treatment of inflammatory bowel disease. Timely surgery is very necessary and can reduce the risk of postoperative complications. Overemphasizing the importance of medical therapy and prolonged use attempting to evade surgery can not maximize the efficacy of medical treatment, but may miss the optimal chance of surgical treatment. It has already been confirmed that ineffective medical treatment, corticosteroid use, malnutrition and infection are the risk factors of surgical complications and should be avoided. Emergency operation and operation at active stage of IBD also increase the surgical risk. Gastroenterologists should be responsible for the judgment of surgery timing and create surgical conditions for the patients with surgical indications.

Influence of preoperative nutritional support on surgical outcomes of chronic radiation enteritis patients complicated with intestinal obstruction / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the effect of preoperative nutritional support in the management of patients with chronic radiation enteritis (CRE) with intestinal obstruction undergoing resectional surgery.</p><p><b>METHODS</b>Clinical data of 158 CRE patients undergoing diseased bowel resection from 2001 to 2011 were analyzed retrospectively. A total of 130 patients received preoperative nutritional support, including 28 patients with enteral nutrition support, 60 patients with total parenteral nutrition support, and 42 patients with combined nutritional support. The nutritional parameters, procedures, operation-related complications, and postoperative hospital stay were recorded.</p><p><b>RESULTS</b>After aggressive nutritional support in 130 patients, patients nutritional index, such as serum prealbumin, transferrin, serum albumin improved significantly preoperatively, while the change of body mass index and hemoglobin was not significant. Compared to those without preoperative nutritional support, those who received preoperative nutritional support had lower stoma rate (31.5% vs. 53.6%, P=0.027), less postoperative infection rate (13.8% vs. 32.1%, P=0.019), shorter postoperative hospital stay [(14.1±7.3) d vs. (18.8±15.8) d, P=0.013). Enteral nutrition group had less postoperative infection rate (7.1% vs. 21.7%, P=0.017), lower stoma rate (28.6% vs. 48.3%, P=0.02), and shorter postoperative hospital stay [(15.5±9.6) d vs. (21.7±19.0) d, P=0.025) as compared to total parenteral nutrition group.</p><p><b>CONCLUSIONS</b>Preoperative nutritional support can decrease the stoma rate, postoperative infection rate, and shorten hospital stay in CRE patients complicated with intestinal obstruction. If tolerated, enteral nutrition support should be chosen.</p>

Analysis of the monitoring results of iodized salt consumed by residents in Chenzhou city of Hunan province from 2008 to 2011 / 中国地方病学杂志

Objective To understand and master the situation of residents consumption of iodized salt in Chenzhou city of Hunan province,to identify problems and take appropriate interventions to ensure the residents consumption of qualified iodized salt,and to provide a scientific basis for elimination of iodine deficiency disorders (IDD).Methods According to the National Iodized Salt Monitoring Program (Amendment) and the Evaluation Scheme for Elimination of Iodine Deficiency Disorders at the County Level,the monitoring counties,towns and villages were selected in Chenzhou city from 2008 to 2011,the content of iodine in salt was detected using direct titration.The data was analyzed by SPSS 17.0 and Excel 2003.Results A total of 12700 salt samples were tested from 2008 to 2011.The iodized salt coverage rate,the qualified rate of iodized salt,the consumption rate of qualified iodized salt and the rate of non-iodized salt was 99.19％ (12597/12700),96.33％ (12135/12597),95.55％(12135/12700) and 0.81％ (103/12700),respectively.There were significant differences between each year from 2008 to 2011 (x2 =13.99、42.35、48.45、13.99,P all ＜ 0.01).The coefficient of variation was 21.19％.The median and average of iodine content in salt samples was 32.2 mg/kg and 31.9 mg/kg,respectively.Compared with the median and average of iodized salt content,there was no significant difference between each year from 2008 to 2011 (t =2.941,P ＞ 0.05),while there was significant difference among the 11 counties(t =2.983,P ＜ 0.05).Conclusions The goal of eliminating IDD has realized in the city of Chenzhou since 2010.To consolidate the IDD control results,surveillance should be strengthened in future.

Novel surgery for refractory mixed constipation: analysis of the technical notes and outcome to Jinling procedure / 中华外科杂志

<p><b>OBJECTIVE</b>To discuss a new surgical strategy: Jinling procedure (subtotal colectomy combined with modified Duhamel procedure), of which the indications, technical notes and outcomes were analyzed.</p><p><b>METHODS</b>The 590 patients with refractory slow-transit constipation associated with outlet obstruction was strictly included between February 2000 and December 2011. The patients included 103 males and 487 females. Their age were 14-75 years (average 42 ± 13). The 412 patients received laparoscopic-assistant Jinling procedure, and 178 patients with open Jinling procedure. The pre- and post-operation data were collected. The follow up rate were 100%, 98.1%, 95.8% and 92.7% at 3, 6, 12 and 24 months.</p><p><b>RESULTS</b>There was no surgery-related death. Mean hospital day was (12 ± 9) days. Most complications were managed conservatively without significant events. The common complications after surgery were adhesive intestinal obstruction (9.2%), anastomosis bleeding (8.1%) and anastomosis leakage (2.9%). The gastrointestinal quality of life index score was 72 ± 9 preoperatively and increased to 68 ± 11, 99 ± 6, 105 ± 9, 106 ± 9 at 3, 6, 12 and 24 month follow-up, respectively (t = 62.1, -25.1, -126.5, -143.2, P < 0.01). The Wexner constipation scale was 21.9 ± 4.5 preoperatively and decreased to 9.6 ± 2.4, 5.9 ± 2.1, 4.6 ± 1.9, 4.5 ± 1.8 at 3, 6, 12 and 24 month follow-up, respectively (t = 48.6, 61.8, 58.2, 45.9, P < 0.01). The satisfactory rate was 77.5%, 92.1%, 93.0% and 94.1% at 3, 6, 12, and 24 month follow-up.</p><p><b>CONCLUSIONS</b>Jinling procedure provides a good surgical option for refractory slow-transit constipation associated with outlet obstruction.</p>

Impact of disease activity on postoperative recurrence and complications after bowel resection for Crohn's disease / 中华外科杂志

<p><b>OBJECTIVE</b>To determine whether the perioperative disease activity is associated with recurrence and complications after bowel resection for Crohn's disease (CD).</p><p><b>METHODS</b>Clinical data of patients underwent bowel resection for CD at the Nanjing General Hospital of Nanjing Military Command from January 2002 to January 2011 was retrospectively analyzed. Postoperative recurrence and complications in patients with active disease were compared with those in patients with remission.</p><p><b>RESULTS</b>A total of 90 patients underwent bowel resection for CD, active disease were seen in 43 patients at the time of surgery, while the rest 47 patients were in remission. The postoperative cumulative endoscopic recurrence rate was 8.5% at 1 year, 27.7% at 2 years and 44.7% at 3 years in the patients with remission, and was 27.9% at 1 year, 37.2% at 2 years and 53.5% at 3 years in patients with active disease. Data indicated the endoscopic recurrence were statistically significant in the first year after surgery (χ² = 4.605, P = 0.032). Additional, the postoperative complication rates in patients with remission (14.9%) was significantly lower than that in patients with active disease (51.2%) (χ² = 6.979, P < 0.001).</p><p><b>CONCLUSION</b>Patients with active disease at the time of surgery were encountered with early postoperative recurrence and increased complications after intestinal resection for CD.</p>

Management of colon injury in abdominal trauma / 中华胃肠外科杂志

The incidence of colon injury is low but is associated with adverse outcome if managed inadequately.Colostomy and secondary closure has been the traditional management, which is associated with more pain to the patient and a waste of medical resource. Recent studies indicate that physiologic disturbances after trauma is the main risk factor of anastomotic leak , therefore primary repair or resection and anastomosis is feasible if physiological status of the patient is stable as calibrated by New Injury Severity Score and ASA score. For patients with open abdomen or temporary closure,colonic resection can also be performed at definitive abdominal closure in select cases.

Impact of anastomosis type on postoperative recurrence after bowel resection for Crohn disease / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To determine whether side-to-side anastomosis(SSA) is associated with decreased recurrence after bowel resection for Crohn disease(CD) as compared to end-to-side anastomosis(ESA) or end-to-end anastomosis(EEA).</p><p><b>METHODS</b>Patients undergoing bowel resection for CD at the Jinling hospital of Nanjing University School of Medicine from 2002 to 2010 were studied retrospectively. Postoperative recurrence in patients with SSA was compared with that in patients with ESA or EEA.</p><p><b>RESULTS</b>A total of 94 patients underwent bowel resection for CD. Anastomosis type was SSA in 56 patients and ESA or EEA in 38. Postoperatively 52 patients underwent at least one endoscopic evaluation (28 SSA and 24 ESA or EEA). The postoperative cumulative endoscopic recurrence rate was 10.7% at 1 year and 46.4% at 2 years in the SSA group, and was 29.2% at 1 year and 66.7% at 2 year in the ESA/EEA group, the differences were statistically significant(Log-rank P=0.037). The postoperative cumulative clinical recurrence rate was 3.6% at 1 year and 8.9% at 2 years in the SSA group, and was 7.9% at 1 year and 21.1% at 2 year in the ESA/EEA group, the differences were statistically significant(Log-rank P=0.041).</p><p><b>CONCLUSION</b>Side-to-side anastomosis is associated with decreased symptomatic recurrence and endoscopic recurrence as compared to ESA or EEA.</p>

Comparison between staged surgery and one-stage surgery in active complex Crohn disease / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To compare the prognosis between staged surgery and one-stage surgery in active complex Crohn disease(CD).</p><p><b>METHODS</b>Clinical data of 33 patients with active complex CD from February 2006 to September 2010 were analyzed retrospectively.</p><p><b>INCLUSION CRITERIA</b>Patients who were diagnosed with CD by pathology or endoscopy with CD activity index(CDAI)>220 and long history of preoperative steroid use(over 6 months), or complicated with severe preoperative malnutrition. The indications for surgery included enterocutaneous or entero enteric fistula, with/without intra-abdominal abscess, intestinal obstruction, and acute intestinal perforation intra-abdominal sepsis. The surgical procedures, including staged surgery and one-stage definite surgery were chosen by experienced surgeons. All the patients quit smoking and received immunosuppressant therapy (TwHF or azathioprine) together with enteral nutrition supplement for preventing postoperative recurrence. All the patients were followed up after the surgery with regards to CDAI, serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR). Postoperative complications, clinical and endoscopic recurrence were recorded.</p><p><b>RESULTS</b>Of the 33 patients, 14 underwent one-stage definite surgery and 19 received staged surgery. Postoperative complication rates in the two groups were 71% and 26% respectively(P=0.015). The early clinical recurrence rates within postoperative 3 months were 36% and 0(P=0.008). In regard to cumulative probability of post-operative clinical and endoscopic recurrence, staged surgery group was superior to one stage definite surgery group(P=0.000 and 0.006).</p><p><b>CONCLUSION</b>Staged surgery may significantly increase the success rate of operation, reduce postoperative complications and postoperative early relapse, and decrease postoperative recurrence.</p>

Absorbable suture delays postoperative recurrence after bowel resection for Crohn disease / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the effect of anastomosis suture on the postoperative recurrence in patients with Crohn disease(CD).</p><p><b>METHODS</b>A total of 102 patients undergoing intestinal resection for CD at the Jinling Hospital of Nanjing University School of Medicine from Jan. 2002 to Jan. 2010 were studied retrospectively. The postoperative recurrence(endoscopic and clinical) in patients receiving intestinal anastomosis with VICRYL absorbable suture(n=48) was compared with that of patients sewn with normal silk suture(n=54).</p><p><b>RESULTS</b>The 1-, 2-, and 3-year accumulated clinical recurrence rates in the absorbable suture group and silk suture group were 6.3%, 14.6%, 22.9%, and 18.5%, 27.8%, 35.2%, respectively. The differences were not statistically significant(P=0.213). The 1- and 2-year accumulated endoscopic recurrence rates in the absorbable suture group and silk suture group were 14.7%, 38.2% and 22.9%, 62.9%, respectively. The differences were statistically significant(P=0.034).</p><p><b>CONCLUSIONS</b>Compared to silk suture, use of absorbable suture for anastomosis may lower the risk of postoperative endoscopic recurrence after bowel resection in patients with CD. Absorbable suture should be the first choice for intestinal anastomosis in CD patients.</p>

Changes of defecography pre- and post-Jinling procedure for mixed constipation: a prospective single center study / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the anatomy and functional changes of pelvis before and after Jinling procedure (subtotal colectomy and side-to-side colorectal anastomosis) using defecography.</p><p><b>METHODS</b>Fifty patients with refractory mixed constipation received Jinling procedure in the Jinling Hospital between March 2009 and December 2010 and were included in this prospective study. The defecography was performed at one week before surgery and 6 months after Jinling procedure. Longo outlet obstructed score, Wexner constipation score and Wexner incontinence score were also recorded before and after the procedure.</p><p><b>RESULTS</b>After 6 months follow-up, defecography showed that anterior rectocele, prolapse, intussusception, and descending perineum were significantly improved (P<0.01). Anterior rectoceles were significantly reduced in depth from 22.0±1.8 mm to 2.4±0.4 mm (P<0.01). Intussusception decreased from 1.9±0.4 cm to 0.4±0.5 cm (P<0.01). Compared with preoperative score, Longo score and Wexner constipation score were significantly improved from 17.6±3.8 to 5.3±2.0 and from 19.5±4.8 to 5.5±2.4, respectively (P<0.01).</p><p><b>CONCLUSIONS</b>Jinling procedure can correct the anatomy and functional pelvic disorders in mixed constipation. Clinical improvement of obstructed defecation syndrome after Jinling procedure correlates well with morphologic correction of the rectal redundancy.</p>

Enteral nutritional therapy in Crohn disease complicated with incomplete intestinal obstruction / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the efficacy of enteral nutrition(EN) therapy for active Crohn disease(CD) complicated with incomplete intestinal obstruction.</p><p><b>METHODS</b>Clinical data of 37 patients with active CD complicated with incomplete intestinal obstruction treated with EN(n=37) between January 2003 and September 2009 were retrospectively analyzed. CD activity index (CDAI) was between 150 and 450. The patients received total enteral nutrition (TEN) 125 kJ/kg by nasogastric tube or percutaneous endoscopic gastrostomy/jejunostomy(PEG/J) tube. Clinical response was defined as a decrease in CDAI≥70 from baseline since EN therapy, and clinical remission was defined as CDAI<150. Nutritional status, disease activity index, and side effects were recorded at the 0, 4th, and 12th week after EN therapy.</p><p><b>RESULTS</b>Stricture or stenosis location included ileum in 8 (21.6%) patients, ileocolon in 19(51.4%), colon in 4(10.8%), jejunoileum in 5(13.5%), and duodenum in 1(2.7%). At 4 weeks after EN, CDAI significantly decreased(112.0±39.6 vs.174.6±34.7,P<0.05). The ratio of clinical response was 43.2%(16/37) and clinical remission was 72.9%(27/37). At 12 weeks, CDAI was 70.2±32.9, lower than that at week 4(P<0.05). The ratio of clinical response was 70.2%(26/37) and clinical remission was 78.4%(29/37). Other disease activity indexes such as C-reactive protein, erythrocyte sedimentation rate, and nutritional status such as BMI, serum albumin, prealbumin, transferrin and hemoglobin showed similar trend. During therapy, 7 cases had progressive intestinal obstruction resulting in bowel resection, 11 cases had diarrhea and/or abdominal distention due to inadequate infusion of home EN whose symptoms were improved after correction by the doctor.</p><p><b>CONCLUSIONS</b>EN therapy can induce clinical response and remission in CD complicated with incomplete intestinal obstruction, relieve obstruction, alleviate the inflammatory response which plays positive role in the treatment of CD.</p>

Damage control surgery for acute mesenteric ischemia / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To examine the outcome of damage control surgery (DCS) in patients with acute mesenteric ischemia (AMI).</p><p><b>METHODS</b>Clinical data of 15 consecutive AMI cases treated with DCS from May 2001 to March 2009 at the Research Institute of General Surgery, Jinling Hospital were retrospectively analyzed. Eleven patients had acute superior mesenteric vein thrombosis (MVT) on admission, and 4 suffered from acute mesenteric arterial embolism/thrombosis (MAE/MAT). The staged damage control approach included immediate resection of the involved bowel (but no attempts to restore gastrointestinal continuity), open thrombectomy, transfer of the patients to ICU for resuscitation, and thrombolysis prior to the planned definitive reconstructive procedure.</p><p><b>RESULTS</b>Of 15 patients, 10 (66.7%) survived. The mean remnant small bowel length was (209.0+/-53.8) cm (120 to 280 cm). None of the survived patients was parenteral nutrition-dependent. Of the 5 deaths, 2 died of recurrence of thrombosis and necrosis of the remaining bowel,1 of massive gastrointestinal bleeding. One patient abandoned treatment intra-operatively, and another with total small bowel resection abandoned treatment postoperatively.</p><p><b>CONCLUSIONS</b>Damage control approach improves the survival of patients with AMI. Thrombectomy and thrombolysis are necessary for AMI management to prevent progression or further development of the thrombosis.</p>